Phenothiazine - Bipyridinium cyclophanes

FULL PAPER

Phenothiazine؊Bipyridinium Cyclophanes^[‡]

Helmut Bauer,*^[a]Falk Stier,^[a]Christoph Petry,^[a]Andreas Knorr,^[b]Christian Stadler,^[b]and

Heinz A. Staab^[a]

Keywords: Charge-transfer compounds

/

Electron donorϪacceptor cyclophanes

/

Oligooxacyclophanes

/

PhenothiazineϪbipyridinium cyclophanes

The syntheses of oligooxa[8.8]-, -[11.11]-, -[14,14]-, -[17.17]-

and -[20.20]cyclophanes with phenothiazine as donor and bi-

transfer (CT) absorption maxima, the smallest [3.3]cyclo-

phane does not exhibit any CT effect. For the large cyclo-

pyridinium dication as acceptor are described, together with phanes, a preferred conformation with crossed donor and ac-

preparations of the corresponding oligomethylene-[3.3]- ceptor units is proposed. The fluorescence quenching and

and -[4.4]cyclophanes. While the large [8.8]-, [11.11]- and

[14.14]cyclophanes in particular show well-defined charge-

electrochemical behaviour of all phenothiazine−bipyridinium

cyclophanes is discussed.

Scheme 1 shows the outer pyridinium unit of the bipyrid-

inium part lying in a planar fashion above the thiazine ring

of the phenothiazine moiety, positioning its nitrogen atom

over the sulfur atom of the thiazine ring. Another, very sim-

ilar, face-to-face orientation of donor and acceptor, with

even better HOMOϪLUMO overlap, is possible if the inner

pyridinium nitrogen atom of the bipyridinium unit is above

the phenothiazine nitrogen atom (Figure 1).

Introduction

Intermolecular interactions of N-substituted phenothiaz-

ines as donors and bipyridinium dications as acceptors have

been studied with regard to their photoinduced electron-

transfer reactions.^[2]Corresponding intramolecular interac-

tions have been described in compounds with phenothiaz-

ine and bipyridinium components linked through their N

atoms by flexible polymethylene chains^[3,4](Scheme 1). For

Obviously, the face-to-face conformers of the mono-

the dodecamethylene-linked phenothiazineϪbipyridinium linked phenothiazineϪbipyridinium system should consti-

compound 1a, a conformer with a face-to-face orientation tute only a fraction of all the extended non-overlapping

of the donor and acceptor units has been suggested. Com- conformers. Thus, for better investigation of the charge-

pound 1a was reported to display a weak and broad charge- transfer interaction between the phenothiazine donor and

transfer absorption band (λ_maxϭ 550 nm, extinction coeffi- the bipyridinium acceptor, the donorϪacceptor units

cient and solvent not given), which disappeared on addition should be linked by two bridges. Were these bridges long

of α-cyclodextrin (α-CD), giving rise to the open, flat rotax- enough, face-to-face orientations with crossed long axes of

ane-like structure of complex 1b.^[3]

the phenothiazineϪbipyridinium units, similar to that

Scheme 1. Reaction of monolinked phenothiazineϪbipyridinium compounds with α-cyclodextrine

shown in Scheme 1, might be formed (Figure 2). In order

[‡]

[a]

Electron Donor-Acceptor Compounds, 52. Ϫ Part 51: Ref.^[1]

Arbeitsgruppe Organische Chemie, Max-Planck-Institut für

medizinische Forschung

to meet that requirement, polyethylene glycol chains of dif-

ferent lengths were chosen, as shown in compounds 2Ϫ7.

Complexation of such macrocycles with suitable metal ions

might make it possible to generate crown-ether-like struc-

tures exhibiting charge-transfer absorptions of higher in-

tensity, as found with oligooxa[n.n]paracyclophane quinhy-

drones.^[5]The two positive charges of the bipyridinium

Jahnstrasse 29, 69120 Heidelberg, Germany

Fax: (internat.) ϩ 49-(0)6221/486219

[b]

Arbeitskreis Prof. J. Daub, Institut für Organische Chemie der

Universität Regensburg,

Universitätsstraße 31, 93053 Regensburg, Germany

Eur. J. Org. Chem. 2001, 3255Ϫ3278

WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001

1434Ϫ193X/01/0917Ϫ3255 $ 17.50ϩ.50/0

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H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

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component, however, would certainly be a hindrance for the

complexation reactions.

It would also be advisable to compare the oligooxacyclo-

phanes 2Ϫ7 against the phenothiazineϪbipyridinium cyclo-

phanes 8 and 9, containing short (trimethylene and tetra-

methylene) bridges, with the long axes of the donorϪ

acceptor components forced to be nearly parallel.

Figure 1. HOMO of N,2,7-trimethylphenothiazine and LUMO of

N,NЈ-dimethyl-4,4Ј-bipyridinium

In a preliminary communication, the syntheses of the

first doubly bridged macrocyclic phenothiazineϪ

bipyridinium diiodide systems 3aϪ7a, with an oligooxacy-

clophane Ϫ or more precisely cyclophanium Ϫ structure

(another name is oligooxabipyridinophenothiazino-

[3nϩ2]phanium diiodides), were reported.^[6]In these com-

pounds, the phenothiazine 2- and 7-positions are connected

with the bipyridine 4- and 4Ј-positions. Linkage through

simple (CH₂OCH₂)_nbridges could not be achieved in test

attempts with model compounds such as 2,7-bis(alkoxyme-

thyl)-N-methylphenothiazines. The ether groups of 2,7-bis-

(methoxyethyl)-N-methylphenothiazine would cleave even

in water, yielding the corresponding diol. Thus, the oli-

gooxa bridges were connected with the phenothiazine

framework through ester functions, as shown in the

oligooxa[3nϩ2]cyclophanes 3Ϫ7. In the cyclophanes

3aϪ7a, charge-transfer interactions between the iodide an-

ions and the bipyridinium moiety are possible. The iodide

anion in the cyclophanium iodides therefore needed to be

Ϫ

exchanged for anions that do not donate electrons Ϫ BF₄

,

Ϫ

ClO₄and PF₆anions Ϫ if the intramolecular charge-

transfer interactions between the phenothiazine donor and

the bipyridinium acceptor were to be studied exclusively.

In this paper we report on the syntheses and the spectro-

scopic and electrochemical properties of phenothiazineϪ

bipyridinium oligooxa[8.8]-, -[11.11]-, -[14.14]-, -[17.17]-,

and -[20.20]cyclophanes 3Ϫ7, with iodide, tetrafluorobor-

ate, perchlorate and hexafluorophosphate anions. These

compounds were compared with the corresponding oligo-

methylene-bridged [3.3]- and [4.4]cyclophanes 8 and 9.

Figure 2. Some orientations of the phenothiazineϪbipyridinium

oligooxa[3nϩ2]cyclophanes

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Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

Results and Discussion

Syntheses

FULL PAPER

and bis(perchlorates) 3b/cϪ7b/c, four methods were used,

involving treatment of the cyclophanium diiodides

1. with silver tetrafluoroborate or silver perchlorate,

2. with silver oxide and tetrafluoroboric acid or per-

chloric acid,

1. Syntheses of Phenothiazine؊Bipyridinium

Oligooxacyclophanes

3. with sodium perchlorate, and

4. with a Dowex 1 ϫ 8 column loaded with tetrafluoro-

borate or perchlorate.

The [8.8]cyclophanium bis(tetrafluoroborate) 3b and bis-

(perchlorate) 3c were obtained as blue-green powders, the

[11.11]- to [20.20]cyclophanium bis(tetrafluoroborates) and

bis(perchlorates) 4b/cϪ7b/c as dark violet powders slightly

contaminated (1Ϫ2%) with inorganic materials. Because of

these contaminants it was not possible to obtain correct

elemental analyses for the cyclophanium salts.

To achieve cyclizations affording the phenothiazineϪ

bipyridinium oligooxacyclophanes 3aϪ7a with X ϭ I

{oligooxa-(1,1Ј)(4,4Ј)-bipyridino(2,7)phenothiazino[3nϩ2]-

phanium diiodides}, 4,4Ј-bipyridine (10) was doubly al-

kylated with the appropriate 2,7-bis(ω-iodooligooxaalkyl-

carbonylmethyl)-N-methylphenothiazines 11Ϫ16 in re-

fluxing nitromethane over 4Ϫ5 d, using a two-channel syr-

inge pump.

The cyclization components 11Ϫ16 were prepared by two

routes (Scheme 2). The first route involved the transes-

terification of 2,7-bis(methoxycarbonylmethyl)-N-methyl-

phenothiazine (18) with polyethylene glycol chlorohydrins

in the presence of BF₃·OEt₂to give the dichlorides 19Ϫ21,

which were readily converted into the more reactive diiod-

ides 11Ϫ13 by means of a Finkelstein reaction with sodium

iodide. The second route involved the esterification of N-

methylphenothiazine-2,7-diacetic acid (17) with monoiodo-

or mono(p-toluenesulfonyl)oligoethylene glycols to give the

diiodide 14 or the ditosylates 22 and 23, employing the azo-

lide 1,1Ј-carbonylbis(methylimidazolium trifluoromethane-

sulfonate) as condensing agent. Like the dichlorides, com-

For the preparation of the corresponding 4,4Ј-bipyridino- pounds 22 and 23 were treated with sodium iodide to give

2,7-phenothiazino[3nϩ2]phanium bis(tetrafluoroborates) the diiodides 15 and 16.

Scheme 2. Preparation of the phenothiazine cyclization components of the phenothiazineϪbipyridinium oligooxacyclophanes

Eur. J. Org. Chem. 2001, 3255Ϫ3278

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H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

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Scheme 3. Synthesis of N-methylphenothiazine-2,7-diacetic acid

The synthesis of bis(methoxycarbonylmethyl)-N-methyl- methylphenothiazino[3.3 or 4.4]phanium bis(tetrafluoro-

phenothiazine (18) started from the commercially available borates)} were obtained in analogous fashion to the oli-

2-acetylphenothiazine (24), which was converted into the gooxacyclophanes 3bϪ7b, by cyclization of 2,7-bis(iodoal-

known 2,7-diacetyl-N-methylphenothiazine (27) by a circu- kyl)-N-methylphenothiazine 30 and 31 with 4,4Ј-bipyridine

itous route by way of the ketal 25 (Scheme 3). The methyl- and subsequent exchange of the iodide anions for tetra-

ation of the ketal 25 was followed by a FriedelϪCrafts fluoroborate (Scheme 5).

acetylation with CH₃COCl/AlCl₃. This route is strongly re-

Treatment of 2,7-bis(iodoethyl or iodopentyl)-N-

commended, since the alternative direct methylation of 2- methylphenothiazine 29 and 32 with bipyridine 10 did not

acetylphenothiazine (24) resulted in one case in a large ex- yield the cyclized products, because of decomposition of

plosion. An easy synthesis of the dicarboxylic acid 17 and the starting diiodides under the reaction conditions. The

its esterification to 18 was then accomplished by means of iodo compounds 29Ϫ31 were prepared through the dial-

a WillgerodtϪKindler reaction on 27, using sulfur and cohols 35Ϫ37 and the dibromides 38Ϫ40 (Scheme 6).

morpholine.

Elongation of the 2,7-side chains of N-methylphenothiazi-

Under the same reaction conditions as used for the syn- nediacetate 18 by one CH₂group, giving 33, was achieved

thesis of the cyclophanium diiodides 3aϪ7a, it was found by conversion of the dibromide 38 to the dicyanide 41

not to be possible to cyclize diiodide 11 and bipyridine 10 (with sodium cyanide) and subsequent alcoholysis.

to the [5.5]cyclophanium diiodide 2a (Scheme 4). No cyc- Elongation of 18 by two CH₂groups, producing 34, was

lization product could be isolated even when using N- accomplished through a malonic ester synthesis with 2,7-

methylphenothiazine-2,7-diacetic acid (17), 1,1Ј-bis(2Ј-hy- bis(iodoethyl)-N-methylphenothiazine (29), by way of the

droxyethyl)-4,4Ј-bipyridinium bis(trifluorosulfonate) (28) diester 42.

and condensing agent carbonylbis(N-methylimidazolium

trifluorosulfonate) at room temperature.

2,7-Bis(iodopentyl)-N-methylphenothiazine (32) was ob-

tained by cross-coupling of diiodide 29 with allylmagnes-

ium bromide in the presence of nickel dichloride/bis(di-

phenylphosphanyl)ethane as catalyst, followed by hydro-

boration of the diolefin 43 and cleavage of the bis(borane)

2. Syntheses of the Phenothiazine؊Bipyridinium [3.3]- and

[4.4]Cyclophanes

The phenothiazineϪbipyridinium [3.3]- and [4.4]cyclo- with iodine chloride (Scheme 7). The diiodide 29 could eas-

phanes 8b and 9b {correct names: 4,4Ј-bipyridino[2,7]-N- ily be reduced with lithium aluminium hydride, to yield 2,7-

Scheme 4. Attempts to synthesize the [5.5]cyclophanium diiodide 2a

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PhenothiazineϪBipyridinium Cyclophanes

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Scheme 5. Preparation of the phenothiazineϪbipyridinium [3.3]- and [4.4]cyclophanes 8 and 9

Scheme 6. Preparation of the 2,7-bis(iodoalkyl)-N-methylphenothiazines

diethyl-N-methylphenothiazine (44), which was used as a ide anion and the bipyridinium moiety. The [14.14]cyclo-

reference compound in cyclic voltammetric examination of phanium diiodide 5a (in acetonitrile), for example, shows

[3.3]- and [4.4]cyclophanes 8b and 9b.

two CT absorptions at λ ϭ 483 nm (ε ϭ 180) and 550 nm

(sh, ε ϭ 150), the first of which is attributable to the CT

between iodide and bipyridinium, and the second to the CT

between phenothiazine and bipyridinium. In the less polar

Electron Spectra

The UV absorptions of all oligooxa[3nϩ2]cyclophanes solvent dichloromethane, a strongly enhanced absorption is

[λ_maxഠ 250 (strong) and 310Ϫ313 nm (weak)] are practic- observed [λ_CTϭ 477 nm (ε ϭ 920)], composed mainly of

ally identical and appear to be composed simply of the the CT absorption deriving from the less solvated iodide

spectra of the two subunits.

donor and only to a minor extent of the CT between pheno-

In the cyclophanium diiodides 3aϪ7a, CT absorption be- thiazine and bipyridinium. This assignment is based on

tween the phenothiazine donor and the bipyridinium ac- comparison with N,NЈ-dioctyl-4,4Ј-bipyridinium diiodide,

ceptor is superimposed by CT absorptions between the iod- the absorption maximum of which was found at λ ϭ

Eur. J. Org. Chem. 2001, 3255Ϫ3278

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H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

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Scheme 7. Preparation of 2,7-bis(5Ј-iodopentyl)-N-methylphenothiazine (32) and 2,7-diethyl-N-methylphenothiazine (44)

453 nm (ε ϭ 119) in acetonitrile, but at λ ϭ 506 nm (with

a much higher intensity at ε ϭ 1276) in dichloromethane.

The spectrum of the [17.17]cyclophanium bis(perchlor-

ate) 6c is very similar, also featuring only a shoulder at λ ϭ

In contrast with the cyclophanium diiodides 3aϪ7a, se- 530 nm (with ε ϭ 70). When the [20.20]cyclophanium bis-

lective detection of CT between phenothiazine and bipyridi- (perchlorate) 7c was treated with barium perchlorate, no

nium moieties is possible in the cyclophanium bis(tetrafluo- well-defined charge-transfer absorption maximum was ob-

roborates) 3bϪ7b and the bis(perchlorates) 3cϪ7c. In ace- served; the extinction coefficient of the shoulder was merely

tonitrile, the cyclophanium bis(perchlorates) and bis(te- enhanced from ε ϭ 75 to 105. The [14.14]cyclophanium

trafluoroborates) display CT absorptions between λ ϭ 512 bis(perchlorate) 5c exhibits a distinct absorption maximum

and 555 nm. The spectra were measured at concentrations at λ ϭ 555 nm (with ε ϭ 97) (Figure 3). In this case, a

of 5 ϫ 10^Ϫ4mol in order to preclude intermolecular effects. crossed orientation of the donorϪacceptor units Ϫ as in

An acetonitrile solution of the N-methylphenothiazine spe- Figure 2 Ϫ is probably favoured, with a partial overlap of

cies in the form of 18 and the bipyridinium species in the the HOMOϪLUMO orbitals of the phenothiazine and bi-

form of 28 at a concentration of 10^Ϫ2mol/L did not show pyridinium units (Figure 1). The position of the absorption

CT absorption. Since the Vis spectra of the macrocycles maximum corresponds to that of the monolinked

with perchlorate or tetrafluoroborate anions have been phenothiazineϪbipyridinium system 1a (λ_CTϭ 550 nm) in

shown to be practically independent of these counter-ions, Scheme 1. In dichloromethane, the CT absorption max-

only the absorption spectra of the bis(perchlorates) are dis- imum of [14.14]cyclophane 5c is bathochromically shifted

cussed below.

by 38 nm, to λ ϭ 593 nm (ε ϭ 98), because the ground state

In the larger macrocycles, the [20.20]- and [17.17]cyclo- of the cyclophanium bis(perchlorate), which is more polar

phanes 7c and 6c, an orientation with crossed phenothiaz- than the excited state (phenothiazine radical cation Ϫ bipy-

ine and bipyridinium components (as illustrated in Fig- ridinium radical cation), is destabilized in the less polar

ure 2) is possible, but because of their large ring sizes these solvent. The CT absorption of the [11.11]cyclophanium

molecules are rather flexible. Only small CT effects are bis(perchlorate) 4c, which shows λ_CTϭ 554 and ε ϭ 83 in

therefore to be expected in these cases. In fact, the acetonitrile, is similar to that of 5c.

[20.20]cyclophanium bis(perchlorate) 7c just shows a shoul-

The CT absorptions of 4cϪ7c are effectively located in

der at λ ϭ 525 nm (with ε ϭ 75) (Figure 3).

the same region as the bands of the oxidized oligooxacyclo-

phanes containing a phenothiazine radical cation (λ_max

ഠ

530 nm). However, the nature of the CT absorption (broad,

structureless) is quite different from that of the radical tri-

cation or of a superposition of the phenothiazine radical

cation and the bipyridinium radical cation.

In acetonitrile, the smallest of the oligooxacyclophanes,

the [8.8]cyclophanium bis(perchlorate) 3c, as expected,

shows a CT absorption maximum at λ ϭ 512 nm with the

highest extinction coefficient (ε ϭ 165), but the position of

the maximum is hypsochromically shifted relative to those

of 5c (λ_CTϭ 555 nm) and 4c (λ_CTϭ 554 nm). This hyp-

sochromic shift is probably due to the fact that in the

charge-transfer state (excited state) of the oligooxacyclo-

phanes both the bipyridinium and the phenothiazine should

bear positive charges, resulting in a repulsion of the donor

and acceptor. The CT state is consequently accompanied

by a destabilization, which becomes more pronounced, the

smaller the macrocycle. CT absorptions of 3c and 4c could

Figure 3. Vis spectra of the [8.8]-, [11.11]-, [14.14]-, [17.17]- and

[20.20]cyclophanium bis(perchlorates) 3cϪ7c, [3.3]cyclophanium

bis(tetrafluoroborate) 8b, and [4.4]cyclophanium bis(tetrafluoro-

borate) 9b

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PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

not be measured in dichloromethane, because of poor solu- quantum yields ϕ_relwere obtained by integration of the

bility in this solvent.

fluorescence intensities at λ ϭ 370Ϫ600 nm.

The oligomethylene-linked cyclophanes containing short

The quenching is readily explicable in terms of a photoin-

bridges were investigated in the forms of their cyclophan- duced electron transfer process that should be exergonic,

ium bis(tetrafluoroborates). Because of its short bridge, the with an estimated ∆G ഠ Ϫ40 kcal mol^{Ϫ1 [2]}

.

In the charge-

[3.3]cyclophane 8b exists in a coplanar orientation, with separated states of the oligooxacyclophanes, in which both

nearly parallel long axes of the phenothiazine and bipyridi- donor and acceptor bear single positive charges, the donor

nium units. Although fixed almost at the van der Waals (phenothiazine radical cation) and acceptor (bipyridinium

distance, it does not exhibit charge-transfer absorption at radical cation) are able to evade one another at relatively

all (Figure 3). This observation can be explained by the un- large distances. This is not the case with the [3.3]- and

suitable HOMOϪLUMO overlap and the destabilization of [4.4]cyclophanes, in which the positive charges are forced to

the CT state resulting from the Coulombic repulsions of the be at a shorter distance, accompanied by higher energy

positive charges on donor and acceptor. The Vis spectrum charge-separated states because of charge repulsion. They

of the [4.4]cyclophane 9b showed a very broad and weak therefore display fluorescence quenching weaker than that

absorption maximum at λ ϭ 675 nm (with ε ϭ 60) (Fig- of the oligooxacyclophanes. In comparison of the fluores-

ure 3). Absorption at such a high wavelength can hardly be cence quenching of the [3.3]- and [4.4]cyclophanes 8b and

assigned to a CT band, because the repulsion of the donor 9b (ϕ_relϭ 0.35 and 0.2, respectively), the latter shows the

radical cation and acceptor radical cation in the CT state stronger fluorescence quenching (Table 1, Figure 4). This

should produce absorption at a wavelength lower than that result can be explained analogously, by the lower energy

in the [8.8]cyclophane. The absorption probably originates (larger distance between the positive charges) of the charge-

from some unknown impurity.

separated state of the [4.4]cyclophane. An example of the

From these results it may be assumed that only more or geometrical changes accompanying charge separation in a

less perpendicular superposition of the phenothiazine and donorϪacceptor system containing porphyrin (P) as donor

bipyridinium units, best achieved in the larger macrocycles and bipyridinium dication (MV^ϩϩ, methylviologen) as ac-

3c, 4c and 5c, should produce a significant CT effect.

ceptor is described in the literature. In this system the dis-

tance between the donor and acceptor in the ground state

(PϪMV^ϩϩ) was found to be shorter than that in the photo-

induced charge-separated state (P^ϩϪMV^ϩ).^[7]

Fluorescence Spectra

Dimethyl N-methylphenothiazinediacetate (18), a suit-

able reference compound for the phenothiazine components

in the oligooxacyclophanes 3Ϫ7, exhibits absorption max-

ima at λ ϭ 257 (ε ϭ 43.000) and 310 nm (ε ϭ 6.500) in

acetonitrile. A fluorescence band is found at λ ϭ 457 nm,

producing a higher fluorescence quantum yield on excita-

tion at λ ϭ 310 than at 257 nm. Phenothiazine compounds

generally display low fluorescence quantum yields (ϕ

ഠ

rel

0.1) because intersystem crossing from ¹(n, π*) to ³(π,π*) is

the main deactivation path.^[2]Bipyridinium compounds,

such as 1,1Ј-bis(2Ј-hydroxyethyl)-4,4Ј-bipyridinium diiod-

ide, with absorption maxima at λ ϭ 227 (ε ϭ 30.000) and

264 nm (ε ϭ 23.000), are not fluorescent. In a 10^Ϫ5molar

mixture of the phenothiazine diester and the nonfluorescent

bipyridinium salt, phenothiazine fluorescence was not im-

paired. Phenothiazine fluorescence in all phenothiazineϪ

bipyridinium oligooxacyclophanes, however, was quenched

to a large extent (ϕ

ϭ 0.04Ϫ0.1) (Table 1). The relative

rel

Figure 4. Fluorescence spectra of [3.3]cyclophane 8b, [4.4]cyclo-

phane 9b, and of dimethyl N-methylphenothiazine-2,7-diacetate

(18)

Table 1. Relative quantum yields ϕ

the [4.4]cyclophane 9b, the oligooxa[3nϩ2]cyclophanes 3b؊7b, and

dimethyl N-methylphenothiazine-2,7-diacetate (18)

of the [3.3]cyclophane 8b,

rel

NMR Spectra

Compound

ϕ_rel(in CH₃CN)

The two outer (a/d) and the two inner (b/c) protons of

18

1

0.35

0.2

0.07

0.1

0.06

0.08

0.04

N,NЈ-dimethylbipyridinium

bis(tetrafluoroborate)

are

[3.3]cyclophane (8b)

equivalent, and so each pair appears as a doublet in the

NMR spectrum in CD₃CN (Figure 5). The outer and the

inner protons of the bipyridinium components of all oli-

[4.4]cyclophane 9b)

Tetraoxa[8.8]cyclophane (3b)

Hexaoxa[11.11]cyclophane (4b)

Octaoxa[14.14]cyclophane (5b)

Decaoxa[17.17]cyclophane (6b)

Dodecaoxa[20.20]cyclophane (7b)

gooxabipyridinophenothiazinocyclophanium

bis(tetra-

fluoroborates), however, each appear as two pairs of doub-

lets, due to the proximity of the unsymmetrical phenothiaz-

Eur. J. Org. Chem. 2001, 3255Ϫ3278

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H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

ine moiety, and are shifted to higher field relative to N,NЈ- [8.8]cyclophane 3b, however, are not quite in the line with

dimethylbipyridinium bis(tetrafluoroborate). In the series those of the larger oligooxacyclophanes 4bϪ7b. As well as

from [20,20]cyclophane 7b to [11.11]cyclophane 4b, the this, the signal patterns of the phenothiazine hydrogen

high-field shifts of the outer and inner protons of the bipyr- atoms of the [8.8]cyclophane (3b in CD₃CN, for example:

idinium moiety increase, with the shifts of the inner protons pos. 8-4-6-9-3-1) differ significantly from those of the larger

being greater than those of the outer protons cyclophanes (6b in CD₃CN for example: pos. 8-6-4-3-1-9),

(Figure 5).

which are very similar to one another. It is therefore sug-

gested that a somewhat different conformation must be fa-

voured in the [8.8]cyclophane, with no more perpendicular

orientation of the bipyridinium and the N-methylphenothi-

azine moieties. In contrast to the larger macrocycles, which

feature only two averaged signals for the two pairs of

methylene protons CH₂CH₂N^ϩin the bridge, the [8.8]cyclo-

phanium compounds 3aϪc show four separated signals,

due to the closer proximity of the unsymmetrical phenothi-

azine component. Such a differentiation of the two

CH₂CH₂N^ϩpairs in the bridge may also be achieved by

conversion of the [20.20]cyclophane 7a to a dibarium com-

plex by complexation with barium diiodide. This result is

unequivocal proof of the coming closer together of the

phenothiazine and bipyridinium components of the

[20.20]cyclophane as a result of complexation. With the aid

of NOE and COSY experiments, it was possible to assign

all the phenothiazine hydrogen signals, as well as those of

the attached CH₂groups. On irradiation of the various oli-

gooxacyclophanebipyridinium protons, in addition to en-

hancement of the neighbouring protons, transannular

NOEs arising from the phenothiazine protons were also,

surprisingly, observed. These effects were especially pro-

nounced with the oligooxacyclophanes 4Ϫ7, both in dichlo-

romethane and acetonitrile (Figure 6). The intensities of the

transannular NOEs were about 5Ϫ10% of those of the nor-

mal NOEs of the neighbouring bipyridinium protons. The

enhancements of the phenothiazine hydrogen signals were

generally more pronounced on irradiation of the inner bipy-

ridinium hydrogen atoms b/c than on irradiation of the

outer bipyridinium hydrogen atoms a/d. These NOEs evid-

ently demonstrate approaches of the donor and acceptor

units in the cyclophanes 4Ϫ7 for at least several hundreds

of ms. The preferred conformations might be similar to

those in Figure 2.

In the [4.4]cyclophanium diiodide 9a [PyH a/d: δ ϭ 8.70;

PyH b/c: δ ϭ 8.30 (in CD₃CN)], the outer and the inner

protons of the bipyridinium moiety are shifted to higher

field relative to N,NЈ-didodecylbipyridinium diiodide (δ ϭ

8.95 and 8.42, respectively, in CD₃CN). In contrast to the

oligooxacyclophanium diiodides, however, the outer pro-

tons are more strongly shifted to higher field (δ ϭ 0.25) in

CD₃CN than the inner protons are (δ ϭ 0.12). On irradi-

ation of the outer (a/d) protons of the bipyridinium com-

ponent of the diiodide 9a in CD₃OD, NOEs were observed

for all phenothiazine hydrogen atoms in positions 1, 3, 4, 6,

8 and 9, and NCH₃. If the inner hydrogen atoms were irra-

diated, however, only NOEs from the phenothiazine hydro-

gen atoms at positions 1, 4, 6 and 9 and NCH₃were ob-

Figure 5. ¹H-NMR signals of the bipyridinium units of the

[20.20]cyclophane 7b, the [17.17]cyclophane 6b, the [14.14]cyclo-

phane 5b, the [11.11]cyclophane 4b, the [8.8]cyclophane 3b, and of

the reference compound N,NЈ-dimethylbipyridinium bis(tetra-

fluoroborate) in CD₃CN

These results indicate a growing tendency of these com- served, with NOEs from 3-H and 8-H being absent. This

pounds to form a conformation similar to b in Figure 2. result can be explained by a conformation of the cyclo-

The high-field shifts of the bipyridinium hydrogen atoms of phane 9a in which the long axes of the donor and acceptor

3262

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

units are not exactly superimposed, but a little distorted

relative to each other.

While the donor and acceptor units can rotate at room

temperature in the [4.4]cyclophane 9, this rotation is

hindered in the [3.3]cyclophane 8. Because of this hindered

rotation and the unsymmetrical phenothiazine moiety, the

four outer bipyridinium protons of the [3.3]cyclophanium

diiodide 8a in DMSO exhibit four separate signals a,aЈ,d,dЈ

at δ ϭ 9.0Ϫ9.4, while the four inner protons, which experi-

ence the unsymmetrical environment less, display a pattern

of three signals, resulting from the collapse of the two inner

H signals (b,bЈ) into one. At higher temperature (303 K to

423 K), when rotation of the bipyridinium component is

setting in, the signal patterns of the outer and inner protons

resemble that in the [4.4]cyclophane, except for the greater

shift between these two proton groups (Figure 7).

As far as the signal patterns of the phenothiazine hydro-

gen atoms between the [3.3]- and [4.4]cyclophane are con-

cerned, there is only one small difference, involving the hy-

drogen atoms in pos. 6 and 9 (8b in CD₃CN, for example:

pos. 8-4-3-6-9-1 against 9b in CD₃CN: pos. 8-4-3-9-6-1).

In [3.3]cyclophanium diiodide 8a, through-space NOEs

are found between the bipyridinium protons d,dЈ and the

phenothiazine protons 1-H and 3-H, and also between the

bipyridinium protons a,aЈ and the phenothiazine proton 6-

H and 8-H.

Electrochemistry

Under cyclic voltammetry conditions, at scan rates be-

tween 50 and 500 mV s^Ϫ1, the oligooxa[3nϩ2]cyclophanes

3b؊6b display absolute reversible behaviour for oxidation

to the radical trications, as well as for reduction to radical

cations and the neutral states. Thin layer cyclic voltammog-

rams are stable over several cycles, proving the high stability

of the radicals and the doubly reduced uncharged species.

The [3.3]- and [4.4]cyclophanes 8b and 9b show reversible

oxidation and a quasi-reversible reduction. Thin layer mul-

ticycle experiments on the reduction step revealed a sub-

sequent irreversible reaction of the monocation radicals.

Spectroelectrochemical measurements on 8b and 9b there-

fore had to be carried out with a photodiode array spectro-

meter instead of a slowly scanning continuous wave spectro-

meter.

The oxidation (half-wave) potential of N-methylpheno-

thiazine is much lower (325 mV) Ϫ or put another way, its

donor capacity is much higher Ϫ than that of 2,5-dime-

thoxy-1,4-xylene (778 mV),^[8]while the reduction (half-

wave) potential (Ϫ825 mV) of N,NЈ-dimethylbipyridinium

bis(tetrafluoroborate) is just a little lower than that of 2,5-

dimethylbenzoquinone (Ϫ972 mV).^[8]Nevertheless, with the

N-methylphenothiazine and the bipyridinium dication com-

bined in a [3.3]cyclophane, no charge-transfer absorption

was found, in contrast to the [3.3]cyclophane with a dime-

thoxybenzene donor and a benzoquinone acceptor, which

exhibited a charge-transfer absorption with an extinction

coefficient of about 3000 in the pseudogeminal form.^[9]

The reason for this behaviour of the pheno-

thiazineϪbipyridinium cyclophanes has already been dis-

Figure 6. NOE and reference spectra of [11.11]cyclophanium diiod-

ide 4a in CD₃CN (aЈ,a), of [14.14]cyclophanium diiodide 5a in

CD₂Cl₂(bЈ,b), of [17.17]cyclophanium bis(tetrafluoroborate) 6b in

CD₃CN (cЈ,c) and of [20.20]cyclophanium bis(tetrafluoroborate) 7b

in CD₃CN (dЈ,d)

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3263

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

As expected, the oxidation (half-wave) potential of the

phenothiazineϪbipyridinium [3.3]cyclophane 8b (410 mV)

is higher than that of the corresponding [4.4]cyclophane 9b

(290 mV) because of the stronger Coulombic interaction

with the dicationic bipyridinium component in the smaller

macrocycle. To a small degree, this Coulombic interaction

is also effective in 9b, as can easily be recognized by com-

parison with the oxidation potential of 2,7-diethyl-N-

methylphenothiazine (44) (215 mV) as reference compound.

Alkyl substituents in the 2- and 7-positions of phenothiaz-

ine obviously have a strong influence on the oxidation po-

tential of the phenothiazine compound. This is nicely dem-

onstrated in the oxidation potentials of the series of N-

methylphenothiazine (325 mV), 2,7-bis(methoxycarbonyl-

methyl)-N-methylphenothiazine (18) (300 mV), and 2,7-di-

ethyl-N-methylphenothiazine (44) (215 mV).

The Coulombic effect of the dicationic bipyridinium

component is still effective in the series of the larger

oligooxa[3nϩ2]cyclophanes 3bϪ6b, the oxidation potentials

of which (390, 395, 355, 350 mV, respectively) are higher

than that of the reference compound 2,7-bis(methoxycar-

bonylmethyl)-N-methylphenothiazine (18) (300 mV). It

should be noted that the oxidation potentials of the [8.8]-

and [11.11]cyclophanes 3b and 4b are higher than those of

the [14.14]- and [17.17]cyclophanes 5b and 6b, but are prac-

tically identical within each pair.

The first reduction potentials of the [3.3]- and [4.4]cyclo-

phanes (8b and 9b: each Ϫ815 mV) and of the oli-

gooxa[8.8]-, -[11.11]-, -[14.14]- and -[17.17]cyclophanes

(3bϪ6b: Ϫ795, Ϫ815, Ϫ815 and Ϫ830 mV, respectively) do

not show significant differences within the series or in com-

parison to the N,NЈ-dimethylbipyridinium acceptor (Ϫ825

mV). The somewhat less negative value Ϫ795 mV for the

tetraoxa[8.8]cyclophane 3b is not indicative of an electronic

interaction between the donor and acceptor components, as

this should result in a more negative reduction potential.

Examples of such an interaction are donorϪacceptor ca-

tenanes composed of bipyridinium units and phenol

ethers.^[10]

1

Figure 7. H NMR spectrum of [3.3]cyclophanium diiodide 8a in

[D₆]DMSO and temperature dependence of the signals in the bipyr-

idinium part

The second reduction potentials of the [4.4]cyclophane

9b (Ϫ1220 mV) and of the oligooxacyclophanes (Ϫ1220 to

Ϫ1270 mV) are also of the same magnitude as that of N,NЈ-

dimethylbipyridinium bis(tetrafluoroborate) (Ϫ1245 mV).

cussed in the section concerning electronic and fluores- An exception is the smallest cyclophane 8b, the second re-

cence spectra. duction potential of which (Ϫ1380 mV) differs from that

The redox potentials of the phenothiazineϪbipyridinium of the reference compound by 135 mV. This result may be

cyclophanes and their reference compounds are summar- explained by conformational strain in the doubly reduced

ized in Table 2.

macrocycle containing a bipyridinylidene component.

Table 2. Half-wave redox potentials of phenothiazineϪbipyridinium cyclophanes and their reference compounds

E_1/2[mV vs. F_c]

8b

9b

3b

4b

5b

6b

N-methylphenothiazine 18

44

N,NЈ-dimethylbipyridinium

Ox.

1. Red.

2. Red.

410

Ϫ815

290

Ϫ815

390

Ϫ795

395

Ϫ815

355

Ϫ815

350 325

Ϫ830

300 215

Ϫ825

Ϫ1245

Ϫ1380 Ϫ1220 Ϫ1250 Ϫ1270 Ϫ1250 Ϫ1250

3264

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

Table 3. Absorption maxima of phenothiazineϪbipyridinium cyclophanes and their reference compounds from spectroelectrochemical

(SEC) measurements

Compound

Oxidation

1st Reduction

3b

528 nm (m), 765 (w), 845 (w)

528 nm (m), 758 (w), 843 (w)

527 nm (m), 756 (w), 843 (w)

527 nm (m), 760 (w), 843 (w)

553 nm (m), 790 (w), 870 (w)

536 nm (m), 785 (w), 870 (w)

510 nm (s), 757 (w), 846 (w)

523 nm (m), 751 (w), 841 (w)

536 nm (s), 765 (w), 850 (w)

560 nm (sh), 601 (s), 657 (sh), 722 (m)

560 nm (sh), 603 (s), 658 (sh), 722 (m)

559 nm (sh), 600 (s), 657 (sh), 724 (m)

559 nm (sh), 600 (s), 658 (sh), 723 (w)

580 nm (sh), 610 (m), 675 (w), 747 (w)

570 nm (sh), 606 (m), 660 (sh), 726 (w)

4b

5b

6b

8b

9b

N-Methylphenothiazine

18

44

N,NЈ-Dimethyl-bipyridinium bistetrafluoroborate

558 nm (sh), 601 (m), 665 (sh), 732 (w)

Spectroelectrochemical (SEC) measurements were carried

out to monitor the spectral changes accompanying the ox-

idations of the oligooxa[8.8]-, -[11.11]-, -[14.14]- and -

[17.17]cyclophanes 3bϪ6b. The positions of the long-wave-

length absorptions of the corresponding radical trications

(λ ഠ 525, 760, 845 nm) are almost identical within the series

and do not differ significantly from those of the reference

compound 2,7-bis(methoxycarbonylmethyl)-N-methylphen-

othiazine 18 (λ ϭ 523, 751, 841 nm) (Table 3). In the spec-

troelectrogram of the oxidation of [3.3]cyclophane 8b, a

strong band develops at 553 nm, together with two weak

bands at 790 nm and 870 nm. The corresponding absorp-

tions of the [4.4]cyclophane radical trication 9b^3ϩare loc-

ated at 536 (s), 785 (w) and 870 nm (w). These latter absorp-

tions are nearly identical with that of the oxidized reference

compound 2,7-diethyl-N-methylphenothiazine (44) (λ ϭ

536, 765 and 850 nm), which indicates that there is no elec-

tronic interaction between the chromophores in the radical

trication of the [4.4]cyclophane 9b. However, the absorption

of the oxidized [3.3]cyclophane 8b at λ ϭ 553 nm shows a

bathochromic shift of 17 nm relative to that of the oxidized

[4.4]cyclophane 9b and the reference compound 44. This

may largely be the result of the destabilized ground state of

the [3.3]cyclophane radical trication 8b^3ϩ(strong Cou-

lombic interaction between the positive charges of the

donor and acceptor moieties, which are in closer proximity

in comparison to that in the [4.4]cyclophane radical tri-

cation 9b^3ϩ).

Conclusions

Flexible phenothiazineϪbipyridinium oligooxa[3nϩ2]-

cyclophanium compounds with long (eight-membered to

twenty-membered) bridges, enabling superposition of the

donor and acceptor units in crossed orientations, exhibit

weak but significant CT absorptions. A parallel superposi-

tion of the donorϪacceptor pair, connected by a very short

bridge,

as

achieved

in

the

rigid

pheno-

thiazineϪbipyridinium [3.3]cyclophane, does not produce

any CT effect. This orientation-dependent behaviour of the

phenothiazineϪbipyridinium cyclophanes might be the

consequence of more or less suitable HOMOϪLUMO over-

lap. Among the oligooxacyclophanes, the smallest one Ϫ

the [8.8]cyclophane Ϫ showed the strongest CT absorption,

hypsochromically shifted in comparison to those of the

larger oligooxacyclophanes. The hypsochromic shift can be

explained by growing destabilization of the CT state as the

macrocycle becomes smaller. Quenching of phenothiazine

fluorescence in the cyclophanes is explicable in terms of a

photoinduced electron transfer process through a charge-

separated state, the energy of which should be highest in

the [3.3]cyclophane, because of charge repulsion stronger

than that in the larger oligooxacyclophanes.

Surprisingly, NOEs were detected in the large macro-

cyclic oligooxacyclophanes. It may be assumed that the

donorϪacceptor units may approach in a crossed orienta-

tion on the NMR timescale. The electrochemical and spec-

troelectrochemical behaviour of the oligooxa[3nϩ2]- and of

the [3.3]- or [4.4]cyclophanes is dominated by Coulombic

interaction between the bipyridinium and phenothiazine

units, and does not indicate charge-transfer interaction be-

tween the donor and acceptor units in the ground state.

The spectroelectrochemistry of the reduction of the

oligooxa[3nϩ2]cyclophanes and of the [3.3]- and [4.4]cyclo-

phanes confirmed the typical long wavelength absorption

maximum of the bipyridinium monocation at λ ഠ 600 nm

(Table 3).The spectroelectrograms of reductions of all oli-

gooxacyclophanes and the bipyridinium reference com-

pound to the neutral species counterpart were identical in

the region λ ϭ 300Ϫ800 nm.

These results mean that neither electrochemically nor

spectroelectrochemically significant electronic interactions

could be established, except for Coulombic effects between

the donor and acceptor moieties of the oligooxa-

[3nϩ2]cyclophanes and of the [3.3]- and [4.4]cyclophanes.

Experimental Section

1

General: UV/Vis: Varian Cary 2300. Ϫ H NMR: Bruker HX 360

and AM 500. Ϫ Fluorescence: SPEX Fluorolog F 112 XE. Ϫ MS:

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3265

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

Jeol JMS SX 102 A (FAB spectra in the matrix m-nitrobenzyl alco-

hol/1% trifluoroacetic acid; EI spectra with given temperature T_P

of the probe); Finnigan MAT 212. Ϫ IR: PerkinϪElmer FT-IR

1760 X. Ϫ Cyclic voltammetry: Amel System 5000 (platinum disc

electrode as working electrode, Ag/AgCl electrode as pseudo-refer-

The solution was heated under reflux with filter paper and sub-

sequently filtered through a G-4 glass frit to remove the precipit-

ated silver iodide. The solvent was removed in vacuo and the res-

idue taken up in nitromethane. The residual silver iodide was separ-

ated by centrifugation (10 h). The precipitate was decanted and the

ence electrode, internally calibrated vs. ferrocene). Potentiostat solvent removed in vacuo. After recrystallization from acetonitrile,

EG&G Princeton Applied Research 263 A (glassy carbon electrode 3b (30 mg, 34%) was obtained as a blue-green solid, m.p. 245 °C

1

as working electrode, platinum wire in 3  KCl as counter electrode,

Ag/AgCl as reference electrode). Solvent: acetonitrile; supporting

electrolyte: tetra-n-butylammonium hexafluorophosphate. Ϫ Spec-

troelectrochemistry: PerkinϪElmer Lambda 9 and a spectroelectro-

(decomp.). Ϫ H NMR (360 MHz, [D₆]DMSO): δ ϭ 3.10 (s, 3 H,

NCH₃), 3.55 (s, 2 H, 7Ј-CH₂), 3.63 (s, 2 H, 2Ј-CH₂), 3.72 (m, 4 H,

N^ϩCH₂CH₂ϪOϪCH₂), 3.91 (t, ³J ϭ 4.7 Hz, 2 H, N^ϩCH₂CH₂),

3.96 (t, J ϭ 4.9 Hz, 2 H, N^ϩCH₂CH₂), 4.18 (m, 4 H, CO₂CH₂),

3

chemical cell with an optically transparent thin-layer electrode;^[11]4.74 (t, ³J ϭ 4.8 Hz, 2 H, N^ϩCH₂), 4.82 (t, ³J ϭ 4.7 Hz, 2 H,

for measurement of the less stable radical ions a modified Polytec

photodiode array spectrometer X-dap was used, coupled to a previ-

N^ϩCH₂), 6.70 (d, ⁴J ϭ 1.4 Hz, 1 H, ArH, pos. 1), 6.74 (d, ³J ϭ

3

4

8.4 Hz, 1 H, ArH, pos. 9), 6.75 (dd, J ϭ 7.8, J ϭ 1.5 Hz, 1 H,

ously described spectroelectrochemical cell.^[12]Ϫ Chromatography: ArH, pos. 3), 6.86 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6), 6.95 (d, ³J ϭ

3

4

˚

Column of Silitech silica gel (60Ϫ200 mesh, 60 A), ICN Biochem-

7.8 Hz, 1 H, ArH, pos. 4), 6.99 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H,

ArH, pos. 8), 8.48 (d, ³J ϭ 6.1 Hz, 4 H, PyH), 9.00 (d, ³J ϭ 6.9 Hz,

2 H, PyH), 9.07 (d, ³J ϭ 6.9 Hz, 2 H, PyH). Ϫ ¹H NMR (360 MHz,

CD₃CN): δ ϭ 3.15 (s, 3 H, NCH₃), 3.51 (s, 2 H, 7Ј-CH₂), 3.57 (s,

2 H, 2Ј-CH₂), 3.74 (m, 4 H, N^ϩCH₂CH₂OCH₂), 3.89 (‘‘t’’, 2 H,

N^ϩCH₂CH₂), 3.94 (‘‘t’’, 2 H, N^ϩCH₂CH₂), 4.23 (m, 4 H,

CO₂CH₂), 4.60 (‘‘t’’, 2 H, N^ϩCH₂), 4.73 (‘‘t’’, 2 H, N^ϩCH₂), 6.69

(d, ⁴J ϭ 1.7 Hz, 1 H, ArH, pos. 1), 6.75 (dd, ³J ϭ 8.4, ⁴J ϭ 1.8 Hz,

1 H, ArH, pos. 3), 6.76 (d, ³J ϭ 8.4 Hz, 1 H, ArH, pos. 9), 6.89

(d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6), 6.91 (d, ³J ϭ 7.8 Hz, 1 H, ArH,

pos. 4), 7.05 (dd, ³J ϭ 8.3, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 7.94 (d,

icals; TLC with Riedel-de Hae¨n Si F micro cards. Ϫ Melting

points: Bock monoscope (uncorrected values).

General Procedure for the Synthesis of the Bipyridinophenothiazino-

phanium Diiodides 3a؊7a: Solutions of the diiodides 12Ϫ16

(1.2 mmol) and of 4,4-bipyridine (10) (1.2 mmol) in nitromethane

(each 50 mL) were added over 36 h to 50 mL of boiling nitrometh-

ane, using a two-channel syringe pump (Fa. B. Braun AG, Mel-

sungen). After the mixture had been heated under reflux for the

time indicated, the solvent was removed in vacuo. The residue was

dissolved in 80 mL of trichloromethane, the solution shaken with

water (3 ϫ 100 mL), and the combined aqueous phases were fil-

tered and subsequently lyophilized. The crude materials were puri-

fied and dried in vacuo.

³J ϭ 7.0 Hz, 2 H, PyH), 7.92 (d, J ϭ 7.0 Hz, 2 H, PyH), 8.52 (d,

3

³J ϭ 7.0 Hz, 2 H, PyH), 8.58 (d, J ϭ 7.0 Hz, 2 H, PyH). Ϫ MS

3

(FAB): m/z (%) ϭ 627 (100) [M^ϩϪ 2 BF₄], 714 (28) [M^ϩϪ BF₄].

Ϫ HRMS calcd. for C₃₅H₃₇O₆N₃F₄BS [M^ϩϪ BF₄] 714.2432;

found 714.2463.

Compound 3a: The reaction time after the addition of the cycliza-

tion components 12 and 10 was 3 d. The crude product was dis-

solved in 20 mL of water. After storage of the solution in the refri-

gerator for some days, a dark microcrystalline precipitate had de-

posited; this was recrystallized from water to give 3a (127 mg,

8.2%) as very small, dark green plates, m.p. 262 °C (decomp.) Ϫ

¹H NMR (360 MHz, [D₆]DMSO): δ ϭ 3.11 (s, 3 H, NCH₃), 3.55

(s, 2 H, 7Ј-CH₂), 3.63 (s, 2 H, 2Ј- CH₂), 3.73 (m, 4 H,

N^ϩCH₂CH₂OCH₂), 3.92 (‘‘t’’, 2 H, N^ϩCH₂CH₂), 3.97 (‘‘t’’, 2 H,

NCH₂CH₂), 4.18 (m, 4 H,CO₂CH₂), 4.75 (t, ³J ϭ 4.7 Hz, 2 H,

N^ϩCH₂), 4.84 (t,³J ϭ 4.7 Hz, 2 H, N^ϩCH₂), 6.70 (‘‘d’’, 1 H, ArH,

pos. 1), 6.76 (d, ³J ϭ 8.2 Hz, 2 H, ArH, pos. 3 and pos. 9), 6.86 (d,

Compound 3c: Sodium perchlorate (81 mg, 0.66 mmol) was added

to a solution of [8.8]cyclophanium diiodide 3a (100 mg, 0.11 mmol)

in 100 mL of water. The mixture was heated to reflux, then cooled

in the refrigerator overnight. The deposited precipitate was separ-

ated, taken up in 30 mL of water, heated to reflux again and cooled

to 4 °C overnight. The precipitate was filtered off and washed with

a small amount of water to remove the remaining sodium iodide.

The crude material was crystallized from acetonitrile and dried to

yield 3c (40 mg, 44%) as a blue-green powder, m.p. 245 °C (de-

comp.). Ϫ ¹H NMR (360 MHz, [D₆]DMSO): δ ϭ 3.11 (s, 3 H,

NCH₃), 3.55 (s, 2 H, 7Ј-CH₂), 3.63 (s, 2 H, 2Ј-CH₂), 3.72 (m, 4

H, N^ϩCH₂CH₂OCH₂), 3.91 (m, 2 H, N^ϩCH₂CH₂), 3.96 (m, 2 H,

N^ϩCH₂CH₂), 4.18 (m, 4 H, CO₂CH₂), 4.74 (‘‘t’’, 2 H, N^ϩCH₂),

3

⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6), 6.96 (d, J ϭ 7.6 Hz, 1 H, ArH,

pos. 4), 7.00 (dd, ³J ϭ 8.2, ⁴J ϭ 1.8 Hz, 1 H, ArH, pos. 8), 8.49

(m, 4 H, PyH), 9.02 (d, ³J ϭ 6.9 Hz, 2 H, PyH), 9.08 (d, ³J ϭ

6.9 Hz, 2 H, PyH); assignment of the signals by NOE; in CD₃CN:

δ ϭ 3.16 (s, 3 H, NCH₃), 3.52 (s, 2 H, 7Ј-CH₂), 3.57 (s, 2 H, 2Ј-

4.82 (‘‘t’’, 2 H, N^ϩCH₂), 6.70 (d, J ϭ 1.3 Hz, 1 H, ArH, pos. 1),

4

3

4

6.75 (d, J ϭ 8.4 Hz, 1 H, ArH, pos. 9), 6.76 (dd, J ϭ 7.9, J ϭ

1.4 Hz, 1 H, ArH, pos. 3), 6.86 (d, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6),

CH₂), 3.74 (m,

4 2 H,

H, N^ϩCH₂CH₂OCH₂), 3.89 (m,

3

4

6.95 (d, J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 7.00 (dd, J ϭ 8.3, J ϭ

N^ϩCH₂CH₂), 3.93 (m, 2 H, N^ϩCH₂CH₂), 4.22 (m, 4 H, CO₂CH₂),

4.61 (t³, J ϭ 4.7 Hz, 2 H, N^ϩCH₂), 4.74 (t, ³J ϭ 4.7 Hz, 2 H,

3

2.2 Hz, 1 H, ArH, pos. 8), 8.48 (d, J ϭ 6.2 Hz, 4 H, PyH), 9.00

(d, ³J ϭ 7.1 Hz, 2 H, PyH), 9.07 (d, ³J ϭ 6.7 Hz, 2 H, PyH). Ϫ

N^ϩCH₂), 6.69 (d, J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 6.75 (dd, J ϭ

7.5, ⁴J ϭ 1.7 Hz, 1 H, ArH, pos. 3), 6.77 (d, ³J ϭ 8.2 Hz, 1 H,

ArH, pos. 9), 6.89 (d, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 6.91 (d, ³J ϭ

3

MS (FAB): m/z (%) ϭ 627 (100) [M^ϩϪ 2 ClO₄], 726 (15) [M^ϩ

Ϫ

ClO₄]. Ϫ HRMS calcd. for C₃₅H₃₇O₁₀N₃ClS [M^ϩϪ ClO₄]

726.1889; found 726.1917.

3

4

7.8 Hz, 1 H, ArH, pos. 4), 7.05 (dd, J ϭ 8.2, J ϭ 2.2 Hz, 1 H,

ArH, pos. 8), 7.94 (2 d, ³J ϭ 7.0 Hz, 4 H, PyH), 8.53 (d, ³J ϭ

Compound 4a: The reaction time after the addition of the cycliza-

tion components 13 and 10 was 3 d. The crude material was dis-

solved in 70 mL of water. After storage of the solution for some

days at 4 °C, 4a (224 mg, 18.9%) deposited as fine, black needles,

which were dried in vacuo at 110 °C, m.p. 138Ϫ139 °C. Ϫ ¹H NMR

(500 MHz, [D₆]DMSO): δ ϭ 3.11 (s, 3 H, NCH₃), 3.48Ϫ3.60 (m,

3

7.0 Hz, 2 H, PyH), 8.60 (d, J ϭ 6.9 Hz, 2 H, PyH). Ϫ IR (KBr):

Ϫ1

ν ϭ 1740 cm (νCϭO). Ϫ MS (FAB): m/z ϭ 627 [M^ϩϪ 2 I]. Ϫ

˜

C₃₅H₃₇I₂N₃O₆S (881.6): calcd. C 47.69, H 4.23, N 4.77, S 3.64;

found C 47.40, H 4.30, N 5.07, S 3.53.

Compound 3b: A solution of silver tetrafluoroborate (44 mg,

0.22 mmol) in 10 mL of water was added to a suspension of 14 H, 2 ϫ CH₂CH₂OCO, 2 ϫ CH₂CH₂O ϩ 7Ј-CH₂), 3.66 (s, 2 H,

[8.8]cyclophanium diiodide 3a (100 mg, 0.11 mmol) in 50 mL of

2Ј-CH₂), 3.89 (‘‘t’’, 2 H, N^ϩCH₂CH₂), 3.92 (‘‘t’’, 2 H, N^ϩCH₂CH₂),

water, and the mixture was stirred for 30 min at room temperature. 4.21 (m, 4 H, CO₂CH₂), 4.79 (‘‘t’’, 2 H, N^ϩCH₂), 4.83 (‘‘t’’, 2H

3266

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

3

N^ϩCH₂), 6.70 (d, J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.76 (‘‘d’’, 1 H,

9.11 (‘‘d’’, 4 H, PyH); in CD₃CN (360 MHz): δ ϭ 3.02 (s, 3 H,

ArH, pos. 1), 6.81 (‘‘dd’’, ³J ϭ 7.8 Hz, 1 H, ArH, pos. 3), 6.94 (‘‘s’’, NCH₃), 3.55Ϫ3.75 (m, 16 H, 2 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂

1 H, ArH, pos. 6), 6.95 (d, ³J ϭ 7.7 Hz, 1 H, ArH, pos. 4), 7.03

ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO), 3.94 (m, 4 H, 2N^ϩCH₂CH₂), 4.36

(dd, ³J ϭ 8.3, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 8), 8.38 (d, ³J ϭ 6.7 Hz, (m, 4 H, 2 CO₂CH₂), 4.71 (m, 4 H, 2N^ϩCH₂), 6.51 (d, ³J ϭ 8.3 Hz,

3

2 H, PyH), 8.41 (d, J ϭ 6.7 Hz, 2 H, PyH), 9.12 (m, 4 H, PyH)

1 H, ArH, pos. 9), 6.65 (‘‘s’’, 1 H, ArH, pos. 1), 6.83 (‘‘AB’’, J ϭ

Ϫ

¹H NMR (CD₃CN, 360 MHz): δ ϭ 3.04 (s, 3 H, NCH₃), 7.5 Hz, 2 H, ArH, pos. 3 ϩ pos. 4), 6.90 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH,

3.55Ϫ3.75 (m, 16 H, 3 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂), 3.98 pos. 6), 7.04 (dd, ³J ϭ 8.3, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 7.85 (d,

(m, 4 H, N^ϩCH₂CH₂), 4.36 (m, 4 H, CO₂CH₂), 4.83 (m, 4 H, ³J ϭ 6.9 Hz, 2 H, PyH), 7.93 (d, J ϭ 6.9 Hz, 2 H, PyH), 8.70 (d,

3

N^ϩCH₂), 6.58 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.73 (d, ⁴J ϭ ³J ϭ 7.0 Hz, 2 H, PyH), 8.76 (d, J ϭ 7.0 Hz, 2 H, PyH). Ϫ MS

3

1.0 Hz, 1 H, ArH, pos. 1), 6.85 (dd, ³J ϭ 7.8, ⁴J ϭ 1.3 Hz, 1 H,

(FAB): m/z (%) ϭ 715 (100) [M^ϩϪ 2 ClO₄], 814 (17) [M Ϫ ClO₄].

ArH, pos. 3), 6.89 (d, ³J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 6.92 (d, ⁴J ϭ Ϫ HRMS calcd. for C₃₉H₄₅O₁₂N₃ClS [M Ϫ ClO₄] 814.2412;

2.0 Hz, 1 H, ArH, pos. 6), 7.06 (dd, ³J ϭ 8.3, ⁴J ϭ 2.1 Hz, 1 H,

found 814.2438.

ArH, pos. 8), 7.89 (d, ³J ϭ 7.0 Hz, 2 H, PyH), 7.98 (d, ³J ϭ 7.0 Hz,

3

Compound 4d: The preparation was analogous to that of 4c, start-

ing from [11.11]cyclophanium diiodide 4a and potassium hexa-

fluorophosphate in water. The precipitated 4d was filtered off, dried

at 50 °C in vacuo and recrystallized from acetonitrile, m.p. 196 °C

(decomp.). Ϫ ¹H NMR (360 MHz, D₂O, only characteristic signals

given): δ ϭ 3.07 (s, 3 H, NCH₃), 3.82 (m, 4 H, NCH₂CH₂), 4.05

2 H, PyH), 8.81 (d, J ϭ 7.0 Hz, 2 H, PyH), 8.87 (d, J ϭ 7.0 Hz,

1 H, PyH). Ϫ ¹H NMR (CD₂Cl₂, 360 MHz): δ ϭ 3.11 (s, 3 H,

NCH₃), 3.60Ϫ3.75 (m, 16 H, 3 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂),

4.08 (m, 4 H, N^ϩCH₂CH₂), 4.42 (m, 4 H, CO₂CH₂), 5.12 (m, 4 H,

N^ϩCH₂), 6.69 (d, ⁴J ϭ 1.4 Hz, 1 H, ArH, pos. 1), 6.71 (d, ³J ϭ

8.4 Hz, 1 H, ArH, pos. 9), 6.89 (dd, ³J not determinable, ⁴J ϭ

1.5 Hz, 1 H, ArH, pos. 3), 6.90 (d, ⁴J ϭ 1.9 Hz, 1 H, ArH, pos. 6),

6.95 (d, J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 7.13 (dd, J ϭ 8.3, J ϭ

2.0 Hz, 1 H, ArH, pos. 8), 8.06 (d, J ϭ 6.9 Hz, 2 H, PyH), 8.17

(d, J ϭ 6.9 Hz, 2 H, PyH), 9.28 (d, J ϭ 6.9 Hz, 2 H, PyH), 9.38

3

(m, 4 H, CO₂CH₂), 4.42 (m, 4 H, N^ϩCH₂), 6.65 (d, J ϭ 8.4 Hz,

3

4

1 H, ArH, pos. 9), 6.73 (‘‘d’’, X part of ABX, 1 H, ArH, pos. 1),

3

6.93 (AB part of ABX, J_ABϭ 7.8 Hz, J_BXϭ 1.3 Hz, ν_Bϭ 6.92,

4

3

ν_Aϭ 6.94, 2 H, ArH, pos. 3 and pos. 4), 7.01 (d, J ϭ 2.0 Hz, 1

3

4

3

H, ArH, pos. 6), 7.15 (dd, J ϭ 8.4, J ϭ 2.1 Hz, 1 H, ArH, pos.

˜

(d, J ϭ 6.9 Hz, 2 H, PyH). Ϫ IR (KBr): ν ϭ 1730, 1712 ν(CϭO).

8), 7.97 (d, ⁴J ϭ 6.9 Hz, 2 H, PyH), 8.05 (d, ⁴J ϭ 6.9 Hz, 2 H,

Ϫ MS (FAB): m/z ϭ 715 [M^ϩϪ 2 I]. Ϫ C₃₉H₄₅I₂O₈N₃S·H₂O

(987.7): calcd. C 47.43, H 4.80 N 4.25, S 3.25; found C 47.28, H

4.59, N 4.37, S 3.29.

3

4

PyH), 8.86 (d, J ϭ 6.9 Hz, 2 H, PyH), 8.92 (d, J ϭ 6.9 Hz, 2 H,

PyH). Ϫ ¹H NMR ([D₆]DMSO): δ ϭ 3.10 (s, 3 H, NCH₃),

3.40Ϫ3.70 (m, 16 H, 2 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂ϩ 2 ϫ

CH₂CH₂OCO), 3.88 (‘‘t’’, 2 H, N^ϩCH₂CH₂), 4.20 (m, 4 H,

2CO₂CH₂), 4.78 (‘‘t’’, 2 H, N^ϩCH₂), 4.82 (‘‘t’’, 2 H, N^ϩCH₂), 6.69

Compound 4b: A solution of [11.11]cyclophanium diiodide 4a

(50 mg, 0.051 mmol) in 100 mL of water was shaken with silver

oxide (100 mg, 0.71 mmol), with ice cooling. The suspension con- (d, ³J ϭ 8.4 Hz, 1 H, ArH, pos. 9), 6.75 (d, ⁴J ϭ 1.3 Hz, 1 H, ArH,

taining the precipitated silver iodide was immediately filtered into

pos. 1), 6.81 (dd, ³J ϭ 7.9, ⁴J ϭ 1.3 Hz, 1 H, ArH, pos. 3), 6.94 (d,

3

a solution of 48% tetrafluoroboric acid (15 µL, 0.08 mmol). The

⁴J ϭ 2.5 Hz, 1 H, ArH, pos. 6), 6.94 (d, J ϭ 7.5 Hz, 1 H, ArH,

violet solution was lyophilized and the crude material crystallized pos. 4), 7.02 (dd, ³J ϭ 8.4, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.36 (d,

4

from acetonitrile, to give 4b (24 mg, 53%) as violet microcrystals,

⁴J ϭ 6.6 Hz, 2 H, PyH), 8.39 (d, J ϭ 6.8 Hz, 2 H, PyH), 9.11 (d,

m.p. 205 °C. Ϫ H NMR (360 MHz, CD₃CN): δ ϭ 3.02 (s, 3 H, ⁴J ϭ 5.8 Hz, 4 H, PyH); in CD₃CN (360, MHz): δ ϭ 3.02 (s, 3 H,

NCH₃), 3.50Ϫ3.80 (m, 16 H, 2 ϫ CH₂CH₂O ϩ 2 ϫ CH₂CH₂OCO NCH₃), 3.55Ϫ3.75 (m, 16 H, 2 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂

ϩ 7Ј-CH₂ϩ 2Ј-CH₂), 3.95 (m, 4 H 2 N^ϩCH₂CH₂), 4.37 (m, 4 H, ϩ 2 ϫ CH₂CH₂OCO), 3.94 (m, 4 H, 2N^ϩCH₂CH₂), 4.36 (m, 4 H,

2 CO₂CH₂), 4.71 (m, 4 H, 2 N^ϩCH₂), 6.50 (‘‘d’’, br., 1 H, ArH, 2CO₂CH₂), 4.70 (m, 4 H, 2 ϫ N^ϩCH₂), 6.49 (d, ³J ϭ 8.3 Hz, 1 H,

1

pos. 9), 6.64 (‘‘s’’, br. 1 H, ArH, pos. 1), 6.83 (‘‘s’’, br. 2 H, ArH,

pos. 3 ϩ 4), 6.90 (‘‘s’’, br. 1 H, ArH, pos. 6), 7.03 (‘‘d’’, br. 1 H,

ArH, pos. 8), 7.83 (d, ³J ϭ 6.9 Hz, 2 H, PyH), 7.91 (d, ³J ϭ 6.9 Hz,

ArH, pos. 9), 6.64 (X part of ABX, not resolved, 1 H, ArH, pos.

1), 6.83 (AB part of ABX, J_ABϭ 7.9 Hz, J_AXϭ 1.4 Hz, ν_Bϭ 6.82,

4

ν_Aϭ 6.84, 2 H, ArH pos. 4 ϩ pos. 3), 6.90 (d, J ϭ 2.1 Hz, 1 H,

3

4

2 H, PyH), 8.69 (d, J ϭ 7.0 Hz, 2 H, PyH), 8.74 (d, J ϭ 7.0 Hz, ArH, pos. 6), 7.04 (dd, J ϭ 8.3, J ϭ 2.1 Hz, 1 H, ArH, pos. 8),

2 H, PyH). Ϫ MS (FAB): m/z (%) ϭ 715 (100) [M^ϩϪ 2 BF₄], 802

(20) [M^ϩϪ BF₄]. Ϫ HRMS calcd. for C₃₉H₅₀O₈N₃F₄SB [M Ϫ

BF₄] 802.2902; found 802.2929.

7.84 (d, J ϭ 7.0 Hz, 2 H, PyH), 7.92 (d, J ϭ 6.9 Hz, 2 H, PyH),

3

8.69 (d, J ϭ 7.0 Hz, 2 H, PyH), 8.74 (d, J ϭ 7.1 Hz, 2 H, PyH).

Ϫ1

˜

Ϫ IR (KBr): ν ϭ 1732 cm (CϭO). Ϫ MS (FAB): m/z (%) ϭ

715 (100) [M Ϫ 2 PF₆], 860 (24) [M^ϩϪ PF₆], 1005 (0.4) [M^ϩ]. Ϫ

C₃₉H₄₅O₈N₃S·2PF₆·H₂O (1023.8): calcd. C 45.75, H 4.63, N 4.10,

S 3.13; found C 45.65, H 4.44, N 3.79, S 3.19.

Compound 4c: Sodium perchlorate (24.7 mg, 0.202 mmol) was ad-

ded to a solution of [11.11]cyclophanium diiodide 4a (100 mg,

0.101 mmol) in 100 mL of water. The reaction mixture was kept in

the refrigerator overnight. The deposited precipitate was filtered off

and washed with a small amount of cold water to remove the re-

Compound 5a: The preparation was according to the general pro-

cedure described above, starting from 14 and 10. The reaction time

maining sodium iodide. The crude material was crystallized from was 4 d. The crude material was dissolved in 30 mL of water and

acetonitrile and dried in vacuo to give 4c (43.4 mg, 47%) as violet purified by chromatography on BIORAD P-2 Gel (fine) with water.

microcrystals, m.p. 238Ϫ240 °C.

¹H NMR (360 MHz, The product was recognizable on the column as a grey blue zone.

[D₆]DMSO): δ ϭ 3.10 (s, 3 H, NH₃), 3.20Ϫ3.60 (m, 14 H, 2 ϫ The fraction was frozen and the solvent removed by lyophilization.

Ϫ

CH₂CH₂O ϩ 7Ј- CH₂ϩ2 ϫ CH₂CH₂OCO), 3.65 (s, 2 H, 2Ј-CH₂), The residue was recrystallized from methanol to give 5a (200 mg,

3.88 (‘‘t’’, 2 H, NCH₂CH₂), 3.91 (‘‘t’’, 2 H, NCH₂CH₂), 4.20 (m, 4 17%) as black-red crystals, m.p. 75 °C (slow sintering). Ϫ ¹H NMR

H, CO₂CH₂), 4.78 (‘‘t’’, 2 H, N^ϩCH₂), 4.82 (‘‘t’’, 2 H, N^ϩCH₂), (360 MHz, [D₆]DMSO): δ ϭ 3.16 (s, 3 H, NCH₃), 3.30Ϫ3.65 (m,

6.69 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.75 (d, ⁴J ϭ 1.3 Hz, 1 H, 24 H, 4 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO),

3

4

ArH, pos. 1), 6.81 (dd, J ϭ 7.8, J ϭ 1.3 Hz, 1 H, ArH, pos. 3), 3.95 (m, 4 H, 2 ϫ N^ϩCH₂CH₂), 4.15 (m, 4 H, 2 ϫ CO₂CH₂), 4.86

6.93 (d, ⁴J ഠ 2.6 Hz, 1 H, ArH, pos. 6), 6.94 (d, ³J ഠ 7.6 Hz, 1 H, (m, 4 H, 2 ϫ N^ϩCH₂), 6.74 (d, ³J ϭ 8.4 Hz, 1 H, ArH, pos. 9),

3

4

ArH, pos. 4), 7.02 (dd, J ϭ 8.3, J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 6.77 (‘‘d’’, 1 H, ArH, pos. 1), 6.79 (dd, ³J ϭ 7.7, ⁴J ϭ 1.5 Hz, ArH,

3

8.35 (d, J ϭ 6.6 Hz, 2 H, PyH), 8.39 (d, J ϭ 6.6 Hz, 2 H, PyH), pos. 3), 6.93 (d, ³J ϭ 7.7 Hz, 1 H, ArH, pos. 4), 6.95 (d, ⁴J ϭ

Eur. J. Org. Chem. 2001, 3255Ϫ3278 3267

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

3

4

1.9 Hz, 1 H, ArH, pos. 6), 7.04 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, CO₂CH₂), 4.71 (m, 4 H, N^ϩCH₂), 6.47 (d, ³J ϭ 8.2 Hz, 1 H, ArH,

ArH, pos. 8), 8.50 (m, 4 H, PyH), 9.21 (m, 4 H, PyH). Ϫ ¹H NMR pos. 9), 6.70 (d, X part of ABX, J_XAϭ 1.5 Hz, 1 H, ArH, pos. 1),

(CD₃CN,360 MHz, only characteristic signals given): δ ϭ 3.10 (s,

3 H, NCH₃), 4.00 (m, 4 H, N^ϩCH₂CH₂), 4.33 (m, 4 H, CO₂CH₂), ν_Aϭ 6.75, pos. 4 ϩ pos. 3), 6.97 (d, J ϭ 2.0 Hz, 1 H, ArH, pos.

4.75 (m, 4 H, N^ϩCH₂), 6.51 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6), 7.00 (dd, ³J ϭ 8.2, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 7.88 (d, ³J ϭ

6.75 (AB part of ABX, J_ABϭ 7.8 Hz, J_AXϭ 1.6 Hz, ν_Bϭ 6.73,

4

3

6.74 (d, X part of ABX, not resolved, 1 H, ArH, pos. 1), 6.77 (AB 6.7 Hz, 2 H, PyH), 7.91 (d, J ϭ 6.8 Hz, 2 H, PyH), 8.77 (d, J ϭ

part of ABX, J_ABϭ 7.8 Hz, J_AXϭ 1.6 Hz, ν_Bϭ 6.75, ν_A6.79, 2 6.8 Hz, 2 H, PyH), 8.82 (d, ³J ϭ 6.8 Hz, 2 H, PyH). Ϫ MS (FAB):

3

H, ArH, pos. 4 and pos. 3), 6.98 (d, J ϭ 1.9 Hz, 1 H, ArH, pos.

m/z (%) ϭ 902 (18) [M^ϩϪ ClO₄], 803 (100) [M^ϩϪ 2 ClO₄]. Ϫ

6), 7.01 (dd, ³J ϭ 8.3, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 7.93 (d, ³J ϭ HRMS calcd. for C₄₃H₆₀N₃ClS [M^ϩϪ ClO₄] 902.2937; found

3

6.9 Hz, 2 H, PyH), 7.96 (d, J ϭ 6.5 Hz, 2 H, PyH), 8.88 (d, J ϭ 902.2940.

6.6 Hz, 2 H, PyH), 8.91 (d, ³J ϭ 7.0 Hz, 2 H, PyH). Ϫ CD₂Cl₂

Compound 6a: The reaction time after the dropwise addition of the

(360 MHz): δ ϭ 3.16 (s, 3 H, NCH₃), 3.55 Ϫ3.85 (m, 24 H, 4 ϫ

CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO), 4.13 (m, 4

H, N^ϩCH₂CH₂), 4.40 (m, 4 H, 2 ϫ CO₂CH₂), 5.08 (m, 4 H,

N^ϩCH₂), 6.54 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.76 (d, ⁴J ϭ

1.6 Hz, 1 H, ArH, pos. 1), 6.78 (d, ³J ϭ 7.7 Hz, 1 H, ArH, pos. 4),

cyclization components 15 and 10 was 6 d. The crude material was

chromatographed twice on BIORAD P2-Gel, using water as eluent.

The fraction containing the product, recognizable on the column

as a broad grey-blue zone, was frozen and the solvent removed in

a lyophilisator to give 6a (138 mg, 10%) as a red-brown powder,

m.p. 65° (slow sintering). Ϫ ¹H NMR (360 MHz, CD₃CN): δ ϭ

3.13 (s, 3 H, NCH₃), 3.40Ϫ3.70 (m, 32 H, 6 ϫ CH₂CH₂O ϩ 7Ј-

CH₂ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO), 3.99 (m, 4 H, N^ϩCH₂CH₂),

4.26 (m, 4 H, CO₂CH₂), 4.74 (m, 4 H, N^ϩCH₂), 6.65 (d, ³J ϭ

8.3 Hz, 1 H, ArH, pos. 9), 6.72 (d, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 1),

3

4

6.86 (dd, J ϭ 7.8, J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 7.00 (d, J ϭ

3

4

2.0 Hz, 1 H, ArH, pos. 6), 7.15 (dd, J ϭ 8.3, J ϭ 2.1 Hz, 1 H,

ArH, pos. 8), 8.10 (m, 4 H, PyH), 9.37 (m, 4 H, PyH). Ϫ IR (KBr):

Ϫ1

ν ϭ 1726 cm (νCϭO). Ϫ MS(FAB): m/z (%) ϭ 803 (100) [M^ϩ

˜

Ϫ 2 I], 402 (16). Ϫ C₄₃H₅₃I₂N₃O₁₀S·0.5 H₂O (1066.8): calcd. C

48.41, H 5.10, N 3.94, S 3.01; found C 48.58, H 5.14, N 4.21,

S 2.97.

3

4

3

6.82 (dd, J ϭ 7.8, J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 6.86 (d, J ϭ

7.7 Hz, 1 H, ArH, pos. 4), 6.94 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6),

3

4

Compound 5b: A column filled with DOWEX 1 ϫ 8 (Cl^Ϫform)

was rinsed with a 5% solution of sodium tetrafluoroborate until

chloride was no longer detectable with AgNO₃. The column was

then rinsed with water to remove the remaining sodium tetrafluoro-

7.07 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.15 (‘‘t’’, 4 H,

3

PyH), 8.86 (d, J ϭ 7.0 Hz, 2 H, PyH), 8.91 (d, J ϭ 7.0 Hz, 2 H,

PyH); in CD₂Cl₂: δ ϭ 3.18 (s, 3 H, NCH₃), 3.50Ϫ3.75 (m, 32 H, 6

ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO), 4.12 (m,

borate. The [14.14]cyclophanium diiodide 5a (100 mg) in 30 mL of 4 H, N^ϩCH₂CH₂), 4.36 (m, 4 H, CO₂CH₂), 5.05 (m, 4 H, N^ϩCH₂),

water (brown solution) was layered on the column, and slowly (1

drop/s) eluted with water. The violet fraction containing the prod- part of ABX, 1 H, ArH, pos. 1), 6.85 (AB part of ABX, J_AB

uct was frozen and lyophilized to give 5b (76 mg, 83%) as a dark 7.7 Hz, J_BXϭ 1.4 Hz, ν_Aϭ 6.87, ν_Bϭ 6.84, pos. 4 and pos. 3),

violet solid, m.p. 79Ϫ80 °C. Ϫ ¹H NMR (360 MHz, CD₃CN, only 6.97 (d, J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 7.11 (dd, J ϭ 8.3, J ϭ

6.66 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.77 (‘‘d’’, not resolved, X

ϭ

4

3

4

characteristic signals given): δ ϭ 3.02 (s, 3 H, NCH₃), 3.93 (m, 4

2.1 Hz, 1 H, ArH, pos. 8), 8.24 (m, 4 H, PyH), 9.32 (d, ³J ϭ 6.9 Hz,

H, 2 ϫ N^ϩCH₂CH₂), 4.37 (m, 4 H, 2 ϫ CO₂CH₂), 4.71 (m, 4 H, 2 H, PyH), 9.37 (d, ³J ϭ 6.9 Hz, 2 H, PyH). Ϫ If the crude material

3

2 ϫ N^ϩCH₂), 6.48 (d, J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.64 (d, X

was chromatographed on P2-Gel using an aqueous buffer of 0.11

part of ABX, ⁴J ϭ 1.2 Hz, 1 H, ArH, pos. 1), 6.83 (AB part of mol/L acetic acid and 0.1 mol/L triethylamine as eluent, with sub-

ABX, J_ABϭ 7.8 Hz, J_AXϭ 1.4 Hz, ν_Bϭ 6.82, ν_Aϭ 6.84, pos. 4

sequent ion exchange on DOWEX 1 ϫ 8 (I^Ϫform) to transform the

ϩ pos. 3), 6.89 (d, J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 7.04 (dd, J ϭ compound into the iodide form again, the amorphous red-brown

4

3

8.3, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 7.83 (d, ³J ϭ 6.9 Hz, 2 H,

cyclophane contained encapsulated triethylammonium iodide.

PyH), 7.91 (d, J ϭ 6.9 Hz, 2 H, PyH), 8.69 (d, J ϭ 7.0 Hz, 2 H, Yield 250 mg (13%), m.p. 70 °C (sintering). Ϫ ¹H NMR (360 MHz,

3

PyH), 8.74 (d, J ϭ 7.0 Hz, 2 H, PyH). Ϫ MS (FAB): m/z (%) ϭ [D₆]DMSO): δ ϭ 3.22 (s, 3 H, NCH₃), 3.40Ϫ3.55 (m, 30 H, 6 ϫ

890 (32) [M^ϩϪ BF₄], 803 (100) [M^ϩϪ 2 BF₄], 402 (30). Ϫ HRMS CH₂CH₂O ϩ 7Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO), 3.63 (s, 2 H, 2Ј-CH₂),

calcd. for C₄₃H₆₀BF₄N₃O₁₀S [M^ϩ

890.3505.

Ϫ

BF₄] 890.3481; found 3.97 (m, 4 H, NCH₂CH₂), 4.14 (m, 4 H, CO₂CH₂), 4.86 (m, 4 H,

NCH₂), 6.82 (m, 3 H, ArH, pos. 1 ϩ pos. 9 ϩpos. 3), 6.99 (m, 2H

3

4

ArH, pos. 6 ϩ pos. 4), 7.07 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH,

Compound 5c: Sodium perchlorate (24.7 mg, 0.202 mmol) was ad-

ded to a solution of [14.14]cyclophanium diiodide 5a (107.7 mg,

0.101 mmol) in 30 mL of water. The reaction mixture was stored

overnight in the refrigerator. The precipitate was filtered off and

washed with a small amount of cold water to remove the remaining

sodium iodide. The crude material was recrystallized from aceto-

nitrile and dried in vacuo to yield 5c (43.6 mg, 43%) as a microcrys-

pos. 8), 8.64 (m, 4 H, PyH), 9.25 (m, 4 H, PyH); triethylammonium

3

iodide: δ ϭ 1.17 (t, J ϭ 7.3 Hz, 3 H), 3.07 (q, J ϭ 7.2 Hz, 2 H);

in CD₂Cl₂: δ ϭ 3.23 (s, 3 H, NCH₃), 3.50Ϫ3.75 (m, 32 H, 6 ϫ

CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO), 4.10 (m, 4

H, N^ϩCH₂CH₂), 4.37 (m,

4 H, CO₂CH₂). 5.02 (m, 4 H,

N^ϩCH₂CH₂), 6.73 (d, ³J ϭ 8.4 Hz, 1 H, ArH, pos. 9), 6.80 (d, ⁴J ϭ

1.5 Hz, 1 H, ArH, pos. 1), 6.86 (dd, ³J ϭ 7.8, ⁴J ϭ 1.6 Hz, 1 H,

talline product, m.p. 112Ϫ113 °C.

Ϫ

¹H NMR (360 MHz,

ArH, pos. 3), 6.93 (³J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 6.99 (d, J ϭ

4

2.0 Hz, 1 H, ArH, pos. 6), 7.12 (dd, ³J ϭ 8.3, ⁴J ϭ 2.0 Hz, 1 H,

ArH, pos. 8), 8.35 (m, 4 H, PyH), 9.31 (d, ³J ϭ 6.3 Hz, 2 H, PyH),

[D₆]DMSO, only characteristic signals given): δ ϭ 3.16 (s, 3 H,

NCH₃), 3.62 (s, 2 H, 2Ј-CH₂), 3.96 (m, 4 H, N^ϩCH₂CH₂), 4.16 (m,

4 H, 2 ϫ CO₂CH₂), 4.84 (m, 4 H, 2 ϫ N^ϩCH₂), 6.73 (d, ³J ϭ

8.4 Hz, 1 H, ArH, pos. 9), 6.77 (d, ⁴J ϭ 1.9 Hz, 1 H, ArH, pos. 1),

9.35 (d, ³J ϭ 6.5 Hz, 2 H, PyH); triethylammonium iodide: δ ϭ

1.43 (t, ³J ϭ 7.3 Hz), 3.13 (q, J ϭ 7.3 Hz). Ϫ IR (KBr): ν ϭ

3

˜

3

4

3

1724 cm^Ϫ1(CϭO). Ϫ MS (FAB): m/z ϭ 871 (100%) [M Ϫ 2 I]. Ϫ

C₄₇H₃₁I₂N₃O₁₈S·1.2Et₃NHI (1420.8): calcd. C 45.82, H 5.69, N

4.11, S 2.26; found C 45.88, H 5.68, N 4.22, S 2.61.

6.80 (dd, J ϭ 7.8, J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 6.93 (d, J ϭ

7.7 Hz, 1 H, ArH, pos. 4), 6.96 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6),

3

4

7.03 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.48 (m, 4 H,

3

PyH), 9.19 (d, J ϭ 6.8 Hz, 2 H, PyH), 9.21 (d, J ϭ 6.8 Hz, 2 H,

PyH). Ϫ ¹H NMR (CD₃CN, only characteristic signals given): δ ϭ Compound 6b: A column filled with DOWEX 1 ϫ 8 (Cl^Ϫform)

3.09 (s, 3 H, NCH₃), 3.99 (m, 4 H, N^ϩCH₂CH₂), 4.33 (m, 4 H, was rinsed with a 5% solution of sodium tetrafluoroborate until

3268

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

chloride could no longer be detected (AgNO₃test). After the col-

umn had been washed with 2 L of water to remove sodium tetra-

pos. 3 and 4), 7.08 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6), 7.23 (dd,

4

3

³J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.38 (d, J ϭ 6.1 Hz, 4

fluoroborate, the cyclophanium diiodide 6a (56 mg, 0.049 mmol) H, PyH), 9.11 (m, 4 H, PyH); triethylammonium iodide: δ ϭ 1.40

was applied to the column and eluted slowly with water (1 drop/s)

to afford a violet product fraction, which was frozen and lyophil-

(t, ³J ϭ 7.3 Hz), and δ ϭ 3.32 (q, ³J ϭ 7.3 Hz). Ϫ¹H NMR

(CD₂Cl₂): δ ϭ 3.28 (s, 3 H, NCH₃), 3.50Ϫ3.60 (m, 30 H, 15 CH₂O)

ized. Compound 6b was obtained as a faint pink powder, which 3.64Ϫ3.69 (m, 10 H, 3 CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂), 4.07 (m, 4 H,

changed into a dark violet solid on action of moisture. Yield

N^ϩCH₂CH₂), 4.27 (m, 4 H, CO₂CH₂), 5.00 (m, 4 H, N^ϩCH₂), 6.79

(38.7 mg, 74%), m.p. 80 °C (gradual sintering). Ϫ¹H NMR (d, ⁴J ϭ 1.5 Hz, 1 H, ArH, pos. 1), 6.79 (d, ³J ϭ 8.2 Hz, 1 H, ArH,

(360 MHz, CD₃CN): δ ϭ 3.13 (s, 3 H, NCH₃), 3.30Ϫ3.65 (m, 32 pos. 9), 6.86 (dd, ³J ϭ 7.9, ⁴J ϭ 1.5 Hz, 1 H, ArH, pos. 3), 6.98 (d,

4

H, 6 ϫ CH₂CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂ϩ 2 ϫ CH₂CH₂OCO),

³J ϭ 8.3 Hz, 1 H, ArH, pos. 4), 7.00 (d, J ϭ 2.5 Hz, 1 H, ArH,

3.97 (m, 4 H, N^ϩCH₂CH₂), 4.24 (m, 4 H, CO₂CH₂), 4.70 (m, 4 H, pos. 6), 7.12 (dd, ³J ϭ 8.2, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.53 (d,

3

N^ϩCH₂), 6.64 (d, J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.70 (d, X part ³J ϭ 5.2 Hz, 4 H, PyH), 9.32 (m, 4 H, PyH); triethylammonium

3

of ABX, J_XBϭ 1.4 Hz, 1 H, ArH, pos. 1), 6.84 (AB part of ABX, iodide: δ ϭ 1.43 (t, J ϭ 7.3 Hz) and δ ϭ 3.15 (q, J ϭ 7.3 Hz). Ϫ

Ϫ1

˜

IR (KBr): ν ϭ 1728 cm (CϭO). Ϫ MS (FAB): m/z (%) ϭ 980

J

_ABϭ 7.8 Hz, J_BXϭ 1.5 Hz, ν_Aϭ 6.86, ν_Bϭ 6.81, 2 H, ArH, pos.

4 and pos. 3), 6.93 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6), 7.06 (dd, (100) [MH Ϫ 2 I], 1107 (7) [MH Ϫ I]. C₅₁H₆₉I₂N₃O₁₄S (M^ϩ, 1233).

³J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.12 (d, J ϭ 7.2 Hz, 2 Ϫ C₅₁H₆₉I₂N₃O₁₄S·1.8(C₂H₅)₃NHI (1646.4): calcd. C 45.09, H

H, PyH), 8.14 (d, J ϭ 7.2 Hz, 2 H, PyH), 8.81 (d, J ϭ 6.9 Hz, 2 5.99, N 4.09, S 1.95; found C 45.33, H 6.17, N 4.39, S 2.23. Ϫ To

4

3

1

H, PyH), 8.86 (d, J ϭ 6.9 Hz, 2 H, PyH). Ϫ H NMR (CD₂Cl₂):

δ ϭ 3.15 (s, 3 H, NCH₃), 3.45Ϫ3.75 (m, 32 H, 6 ϫ CH₂CH₂O ϩ was chromatographed twice on BIORAD P2-Gel, using water as

7Ј-CH₂2Ј-CH₂CH₂CH₂OCO), 4.02 (m, H, eluent. The product fraction appearing on the column as a broad

free the product from triethylammonium iodide, the crude material

ϩ

2

ϫ

4

N^ϩCH₂CH₂), 4.28 (m, 4 H, CO₂CH₂), 4.81 (m, 4 H, N^ϩCH₂), 6.61 grey-blue zone was frozen and the solvent removed in the lyophilis-

(d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.68 (d, X part of ABX, J_XBϭ

1.0 Hz, 1 H, ArH, pos. 1), 6.84 (AB part of ABX, J_ABϭ 7.7 Hz,

ator to give 7a (113 mg, 8%) as a dark brown powder, m.p. 55 °C

1

(slow sintering). Ϫ H NMR (360 MHz, [D₆]DMSO, only charac-

J

_BXϭ 1.2 Hz, ν_Aϭ 6.87, ν_Bϭ 6.82, 2 H, ArH, pos. 4 and pos. 3), teristic signals given): δ ϭ 3.23 (s, 3 H, NCH₃), 3.96 (m, 4 H,

4

3

4

6.93 (d, J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 7.06 (dd, J ϭ 8.3, J ϭ N^ϩCH₂CH₂), 4.12 (m,

4

H, CO₂CH₂), 4.86 (m, N^ϩCH₂),

2.0 Hz, 1 H, ArH, pos. 8), 8.25 (m, 4 H, PyH), 9.00 (d, ³J ϭ 7.0 Hz,

6.81Ϫ6.85 (m, 3 H, ArH, pos. 1 and 3 and 9), 7.00 (d, ⁴J ϭ 1.6 Hz,

2 H, PyH), 9.02 (d, ³J ϭ 7.0 Hz, 2 H, PyH). Ϫ MS (FAB): m/z 1 H, ArH, pos. 6), 7.02 (d, ³J ϭ 8.1 Hz, 1 H, ArH, pos. 4), 7.08

(%) ϭ 978 (12) [M Ϫ BF₄], 891 (100) [M Ϫ 2 BF₄]. Ϫ HRMS (dd, ³J ϭ 8.3, ⁴J ϭ 1.9 Hz, 1 H, ArH, pos. 8), 8.68 (d, ³J ϭ 6.0 Hz,

calcd. for C₄₇H₆₁BF₄N₃O₁₂S [M Ϫ BF₄] 978.4005; found 978.4039.

4 H, PyH), 9.27 (m, 4 H, PyH). Ϫ ¹H NMR (D₂O, only character-

istic signals given): δ ϭ 3.12 (s, 3 H, NH₃), 4.07 (m, 4 H,

N^ϩCH₂CH₂), 4.33 (m, 4 H, CO₂CH₂), 4.87 (m, 4 H, N^ϩCH₂), 6.66

(d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.78 (d, X part of ABX, J_XAϭ

1.4 Hz, 1 H, ArH, pos. 1), 6.84 (AB part of ABX, J_ABϭ 8.0 Hz,

Compound 6c: The preparation was analogous to that of compound

6b, with a 5% solution of sodium perchlorate and starting from the

[17.17]cyclophanium diiodide 6a (40 mg, 0.035 mmol), yielding 6c

as a waxy dark violet solid (30.9 mg, 81%), m.p. 90 °C (sintering).

J

_AXϭ 1.4 Hz, ν_Aϭ 6.86, ν_Bϭ 6.82, 2 H, ArH, pos. 3 and pos. 4),

¹H NMR (360 MHz, [D₆]DMSO, only characteristic signals

4

3

4

Ϫ

6.98 (d, J ϭ 1.9 Hz, 1 H, ArH, pos. 6), 7.12 (dd, J ϭ 8.6, J ϭ

given): δ ϭ 3.21 (s, 3 H, NCH₃), 3.96 (m, 4 H, N^ϩCH₂CH₂), 4.14

2.2 Hz, 1 H, ArH, pos. 8), 8.22 (m, 4 H, PyH), 8.99 (m, 4 H, PyH).

(m, 4 H, CO₂CH₂), 4.85 (m, 4 H, N^ϩCH₂), 6.80 (m, 3 H, ArH,

pos. 1 ϩ 3 ϩ 9), 6.98 (m, 2 H, ArH, pos. 4 ϩ 6), 7.06 (dd, J ϭ

8.4, J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.62 (2 d, J ϭ 7.0 Hz, 4 H,

PyH), 9.23 (d, J ϭ 6.8 Hz, 2 H, PyH), 9.24 (d, J ϭ 6.8 Hz, 2 H,

PyH). Ϫ MS (FAB): m/z (%) ϭ 990 (26) [M^ϩϪ ClO₄], 891 (100)

[M^ϩϪ 2 ClO₄], 697 (28). Ϫ HRMS calcd. for C₄₇H₆₁N₃ClS [M Ϫ

ClO₄] 990.3461, found 990.3492.

1

Ϫ H NMR (CD₃CN, only characteristic signals given): δ ϭ 3.16

3

(s, 3 H, NCH₃), 3.94 (m, 4 H, N^ϩCH₂CH₂), 4.22 (m, 4 H,

4

3

CO₂CH₂), 4.73 (m, N^ϩCH₂), 6.69 (d, J ϭ 8.3 Hz, 1 H, ArH, pos.

3

4

3

9), 6.74 (d, J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 6.81 (dd, J ϭ 7.8 Hz,

1 H, ArH, pos. 3), 6.88 (d, ³J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 6.93

(d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6), 7.06 (dd, ³J ϭ 8.3, ⁴J ϭ 2.0 Hz,

1 H, ArH, pos. 8), 8.22 (m, 4 H, PyH), 8.88 (m, 4 H, PyH). Ϫ¹H

NMR (CD₂Cl₂): δ ϭ 3.24 (s, 3 H, NH₃), 3.50Ϫ3.80 (m, 40 H, 18

CH₂O ϩ7Ј-CH₂ϩ 2Ј-CH₂), 4.06 (m, 4 H, N^ϩCH₂CH₂), 4.31 (m,

Compound 7a: The reaction time after the addition of the cycliza-

tion components 16 and 10 was 7 d. The crude material was puri-

fied by twofold chromatography on P2-Gel, using an aqueous buf-

fer of 0.11 mol/L acetic acid and 0.1 mol/L triethylamine as eluent.

Ion exchange on DOWEX 1 ϫ 8 (I^Ϫform) retransformed the com-

pound into the iodide. After drying in the lyophilisator, 7a (145 mg,

9%) was obtained as a brown powder containing encapsulated trie-

3

4 H, CO₂CH₂), 5.04 (m, 4 H, N^ϩCH₂), 6.76 (d, J ϭ 8.4 Hz, 1 H,

3

ArH, pos. 9), 6.82 (‘‘d’’, 1 H, ArH, pos. 1), 6.86 (dd, J ϭ 7.8 Hz,

3

⁴J not determinable, 1 H, ArH, pos. 3), 6.98 (d, J ϭ 7.7 Hz, 1 H,

ArH, pos. 4), 7.00 (d, ⁴J ϭ 1.8 Hz, 1 H, ArH, pos. 6), 7.11 (dd,

4

3

³J ϭ 8.3, J ϭ 1.8 Hz, 1 H, ArH, pos. 8), 8.58 (d, J ϭ 6.5 Hz, 4

3

H, PyH), 9.29 (d, J ϭ 6.1 Hz, 4 H, PyH).

thylamine, m.p. 60 °C (sintering).

Ϫ

¹H NMR (360 MHz,

[D₆]DMSO): δ ϭ 3.24 (s, 3 H, NCH₃), 3.41 (m, 29 H, CH₂O), 3.55 Compound 7b: A DOWEX 1 ϫ 8 (I^Ϫform) column was rinsed with

(m, 9 H, CH₂), 3.64 (s, 2 H, 2Ј-CH₂), 3.98 (m, 4 H, N^ϩCH₂CH₂), a 5% solution of sodium tetrafluoroborate until the silver nitrate

4.12 (m, 4 H, CO₂CH₂), 4.89 (m, 4 H, N^ϩCH₂), 6.81Ϫ6.84 (m, 2 test for chloride was negative. The column was then rinsed with

3

H, pos. 1 and 3), 6.84 (d, J ϭ 8.5 Hz, 1 H, ArH, pos. 9), 7.01 (d, 2 L of water to remove the remaining sodium tetrafluoroborate and

3

⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 7.02 (d, J ϭ 8.2 Hz, 1 H, ArH, subsequently loaded with [20.20]cyclophanium diiodide 7a (50 mg,

pos. 4), 7.07 (dd, ³J ϭ 8.3, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 8.71 (d, 0.041 mmol), dissolved in 30 mL of water (brown solution). Slow

³J ϭ 6.6 Hz, 4 H, PyH), 9.30 (m, 4 H, PyH); triethylammonium elution (1 drop/s) afforded 7b as a violet product fraction, which

iodide: δ ϭ 1.18 (t, ³J ϭ 7.3 Hz, 3 H) and δ ϭ 3.08 (q, ³J ϭ 7.3 Hz, was lyophilized to give a faint pink powder, which transformed into

2 H); in D₂O: δ ϭ 3.24 (s, 3 H, NCH₃), 3.55Ϫ3.90 (m, 40 H, 18 a waxy dark violet solid on action of moisture. Yield 38 mg, sin-

CH₂O ϩ 7Ј-CH₂and 2Ј-CH₂), 4.18 (m, 4 H, N^ϩCH₂CH₂), 4.42 tering from 60 °C. Ϫ ¹H NMR (360 MHz, CD₃CN, only character-

3

(m, 4 H, CO₂CH₂), 4.98 (m, 4 H, N^ϩCH₂), 6.80 (d, J ϭ 8.4 Hz, istic signals given): δ ϭ 3.19 (s, 3 H, NCH₃), 3.93 (m, 4 H,

1 H, ArH, pos. 9), 6.89 (s, 1H. ArH, pos. 1), 6.96 (m, 2 H, ArH,

N^ϩCH₂CH₂), 4.20 (m, 4 H, CO₂CH₂), 4.70 (m, 4 H, N^ϩCH₂), 6.72

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3269

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

(d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.74 (d, ⁴J ϭ 1.7 Hz, 1 H, ArH,

Compound 8a: A solution of 2,7-bis(3-iodopropyl)-N-methylpheno-

pos. 1), 6.82 (dd, ³J ϭ 7.8, ⁴J ϭ 1.7 Hz, 1 H, ArH, pos. 3), 6.92 (d, thiazine (30) (180 mg, 0.33 mmol) in 30 mL of trichloromethane,

4

³J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 6.95 (d, J ϭ 2.1 Hz, 1 H, ArH, and a solution of 4,4Ј-bipyridine (10) (51.2 mg, 0.33 mmol) were

pos. 6), 7.07 (dd, ³J ϭ 8.3, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 8.23

added to 30 mL of refluxing nitromethane using a two-channel syr-

(m, 4 H, PyH), 8.84 (m, 4 H, PyH). Ϫ ¹H NMR (CD₂Cl₂, only inge pump (0.5 mL/h). The solution was heated under reflux for a

characteristic signals given): δ ϭ 3.17 (s, 3 H, NCH₃), 4.00 (m, 4

further 24 h. The solvent was evaporated in vacuo and the residue

H, N^ϩCH₂CH₂), 4.30 (m, 4 H, CO₂CH₂), 4.75 (m, 4 H, N^ϩCH₂), was treated with petroleum ether to remove starting materials. The

3

6.64 (d, J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.68 (d, X part of ABX, remaining solid was extracted several times with hot methanol. The

J_XBϭ 1.3 Hz, 1 H, ArH, pos. 1), 6.84 (AB part of ABX, J_AB

ϭ

combined methanol solution was cooled to room temperature and

7.8 Hz, J_BXϭ 1.3 Hz, ν_Aϭ 6.86, ν_Bϭ 6.82, 2 H, ArH, pos. 4 and filtered, and the solvent was removed in vacuo. The crude material

pos. 3), 6.94 (d, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 7.07 (dd, ³J ϭ 8.2, was crystallized first from methanol, then from water to afford the

3

⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 8.23 (d, J ϭ 6.9 Hz, 2 H, PyH),

title compound 8a as a black solid (20 mg, 9.1%) with m.p. 290

3

1

8.26 (d, J ϭ 6.9 Hz, 2 H, PyH), 8.90 (d, J ϭ 7.0 Hz, 2 H, PyH), °C. Ϫ H NMR (360 MHz, [D₆]DMSO): δ ϭ 2.50Ϫ2.70 (m, 4 H,

3

8.92 (d, J ϭ 7.0 Hz, 2 H, PyH). Ϫ MS (FAB): m/z (%) ϭ 1066.5

CH₂CH₂CH₂), 2.80Ϫ2.95 (m, 4 H, ArϪCH₂), 3.05 (s, 3 H, NCH₃),

(18) [M^ϩϪ BF₄], 979.5 (100) [M^ϩϪ 2 BF₄], 891 (16), 490 (49). 4.85 (m, 4 H, N^ϩCH₂), 6.22 (s, 1 H, ArH, pos. 1), 6.52 (d, ³J ϭ

Ϫ HRMS: calcd. for C₅₁H₆₉BF₄N₃O₁₄S [M^ϩϪ BF₄] 1066.4529;

8.3 Hz, 1 H, ArH, pos. 9), 6.62 (d, ⁴J ϭ 1.4 Hz, 1 H, ArH, pos. 6),

found 1066.4565.

6.72 (d, ³J ϭ 7.9 Hz, 1 H, ArH, pos. 3), 6.81 (d, ³J ϭ 7.7 Hz, 1 H,

3

4

ArH, pos. 4), 6.84 (dd, J ϭ 8.3, J ϭ 1.5 Hz, 1 H, ArH, pos. 8),

Compound 7c:The preparation was analogous to that of 7b, starting

from the [20.20]cyclophanium diiodide 7a and using sodium per-

chlorate instead of sodium tetrafluoroborate. The fraction of the

eluate containing 7c was violet. After freezing of this fraction and

removal of the solvent in the lyophilisator, a faint pink powder was

obtained. This turned waxy and dark violet on action of traces of

8.23 (m, 1 H, PyH), 8.28 (m, 2 H, PyH), 8.34 (m, 1 H, PyH), 9.07

3

(d, J ϭ 6.2 Hz, 1 H, PyH), 9.24 (d, J ϭ 6.3 Hz, 1 H, PyH), 9.29

3

(d, J ϭ 6.0 Hz, 1 H, PyH), 9.38 (d, J ϭ 6.4 Hz, 1 H, PyH). Ϫ¹H

NMR (CD₃CN): 2.50Ϫ2.70 (m, H, CH₂CH₂CH₂),

δ

ϭ

4

2.90Ϫ3.05 (m, 4 H, ArCH₂), 3.10 (s, 3 H, NCH₃), 4.85 (m, 4 H,

N^ϩCH₂), 6.24 (d, ⁴J ϭ 1.4 Hz, 1 H, ArH, pos. 1), 6.57 (d, ³J ϭ

8.3 Hz, 1 H, ArH, pos. 9), 6.66 (d, ⁴J ϭ 1.9 Hz, 1 H, ArH, pos. 6),

1

moisture. Yield 35.3 mg (73%), sintering from 68 °C. Ϫ H NMR

3

4

3

(360 MHz, CD₃CN): δ ϭ 3.19 (s, 3 H, NCH₃), 3.35Ϫ3.65 (m, 40

6.76 (dd, J ϭ 7.8, J ϭ 1.4 Hz, 1 H, ArH, pos. 3), 6.85 (d, J ϭ

7.8 Hz, 1 H, ArH, pos. 4), 6.87 (dd, ³J ϭ 8.3, ⁴J ϭ 2.0 Hz, 1 H,

ArH, pos. 8), 7.89 (m, 1 H, PyH), 8.06 (m, 2 H, PyH), 8.16 (m, 1

H, PyH), 8.73 (‘‘d’’, 1 H, PyH), 8.90 (‘‘d’’, 1 H, PyH), 8.98 (‘‘d’’,

1 H, PyH), 9.16 (‘‘d’’, 1 H, PyH). Ϫ C₂₉H₂₉I₂N₃S (705.4). Ϫ MS

(FAB): m/z (%) ϭ 578 (7) [M^ϩϪ I], 451 (100) [M^ϩϪ 2 I]. Ϫ

HRMS calcd. for C₂₉H₂₉IN₃S [M^ϩϪ I] 578.1127; found 578.1146.

H, 18 CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂), 3.94 (m, 4 H, N^ϩCH₂CH₂), 4.20

3

(m, 4 H, CO₂CH₂), 4.68 (m, 4 H, N^ϩCH₂), 6.72 (d, J ϭ 8.3 Hz,

1 H, ArH, pos. 9), 6.74 (d, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 6.82

(dd, ³J ϭ 7.8, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 6.92 (d, ³J ϭ 7.8 Hz,

1 H, ArH, pos. 4), 6.95 (d, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 7.07

4

(dd, ³J ϭ 8.3, J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 8.21 (m, 4 H, PyH),

3

8.80 (d, J ϭ 7.0 Hz, 2 H, PyH), 8.82 (d, J ϭ 7.1 Hz, 2 H, PyH).

Ϫ C₅₁H₆₉O₂₂N₃Cl₂S (1179.1). Ϫ MS (FAB): m/z (%) ϭ 1078 (34) Compound 8b: A column filled with DOWEX-50 1 ϫ 8 (Cl^Ϫform)

[M^ϩϪ ClO₄], 980 (100) [M^ϩϪ 2 ClO₄], 490 (42). Ϫ HRMS calcd. was rinsed with aqueous sodium tetrafluoroborate until chloride

for C₅₁H₆₉ClN₃O₁₈S [M^ϩϪ ClO₄] 1078.3942; found 1078.3964.

was no longer detectable. To remove excess sodium tetrafluorobor-

ate, it was washed with 2 L of water. A solution of 8a (42 mg, 0.06

mol) in 50 mL of water was then loaded onto the column. Elution

with water, evaporation of the solvent in a rotary evaporator and

crystallization of the residue from water gave 8b (30 mg, 80%) as

green crystals, m.p. Ͼ 300 °C. Ϫ ¹H NMR (500 MHz, CD₃CN):

δ ϭ 2.50Ϫ2.70 (m, 4 H, CH₂CH₂CH₂), 2.90Ϫ3.10 (m, 4 H,

7a·Bis(barium diiodide): A saturated solution of barium diiodide in

acetone was added to a solution of 7a (25 mg, 0.015 mmol) in

10 mL of acetone until precipitation had finished. The precipitate

was filtered off and dried at 40 °C in vacuo to give 7a (6.7 mg,

22%) as a red brown powder. Ϫ ¹H NMR (360 MHz, CD₃CN):

δ ϭ 3.22 (s, 3 H, NCH₃), 3.50Ϫ3.80 (m, 40 H, 18 CH₂O ϩ 7Ј-CH₂

ϩ 2Ј-CH₂), 4.05 (‘‘t’’, 2 H, N^ϩCH₂CH₂), 4.09 (‘‘t’’, 2 H,

4

ArCH₂), 4.85 (m, 4 H, N^ϩCH₂), 6.22 (d, J ϭ 1.7 Hz, 1 H, ArH,

pos. 1), 6.56 (d, ³J ϭ 8.6 Hz, 1 H, ArH, pos. 9), 6.67 (d, ⁴J ϭ

3

N^ϩCH₂CH₂), 4.46 (m, 4 H, CO₂CH₂), 4.64 (t, J ϭ 4.6 Hz, 2 H,

3

4

1.7 Hz, 1 H, ArH, pos. 6), 6.78 (dd, J ϭ 7.7, J ϭ 1.7 Hz, 1 H,

3

N^ϩCH₂), 4.70 (t, J ϭ 4.7 Hz, 2 H, N^ϩCH₂), 6.77 (d, ³J ϭ 8.4 Hz,

3

4

ArH, pos. 3), 6.88 (dd, J ϭ 8.6, J ϭ 1.7 Hz, 1 H, ArH, pos. 8),

6.89 (d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4), 7.85 (m, 1 H, PyH), 8.00,

1 H, ArH, pos. 9), 6.80 (‘‘d’’, 1 H, ArH, pos. 1), 6.88 (dd, ³J ϭ

7.9 Hz, ⁴J ill-defined, 1 H, ArH, pos. 3), 6.97 (d, ³J ϭ 7.7 Hz, 1 H,

3

(m, 3 H, PyH), 8.65 (‘‘d’’, 1 H, PyH), 8.81 (‘‘d’’, 1 H, PyH), 8.88

(‘‘d’’, 1 H, PyH), 8.97 (‘‘d’’, 1 H, PyH). Ϫ MS (FAB): m/z (%) ϭ

538 (16) [M^ϩϪ BF₄], 451 (100) [M^ϩϪ 2 BF₄]. Ϫ HRMS calcd.

for C₂₉H₂₉BF₄N₃S [M^ϩϪ BF₄] 538.2111; found 538.2108.

3

4

ArH, pos. 4), 6.98 (s, 1 H, ArH, pos. 6), 7.11 (dd, J ϭ 8.3, J ϭ

3

1.9 Hz, 1 H, ArH, pos. 8), 8.26 (d, J ϭ 6.8 Hz, 2 H, PyH), 8.30

(d, J ϭ 6.8 Hz, 2 H, PyH), 8.89 (d, J ϭ 6.7 Hz, 2 H, PyH), 8.94

(d, J ϭ 6.7 Hz, 2 H, PyH). Ϫ IR (KBr): ν ϭ 1699 cm (CϭO).

3

Ϫ1

˜

Ϫ MS (FAB): m/z (%) ϭ 1891 (24) [MH^ϩϪ I], 1764 (89) [MH^ϩCompound 9a: A solution of 2,7-bis(4-iodobutyl)-N-methylpheno-

Ϫ 2 I], 1637 (30) [MH^ϩϪ 3 I], 1372 (27) [MH^ϩϪ BaI₄], 980 (100) thiazine (31) (190 mg, 0.33 mmol) in 30 mL of trichloromethane,

[MH^ϩϪ Ba₂I₆] if M^ϩϭ C₅₁H₆₉Ba₂I₆N₃O₁₄S. Ϫ MS (FAB) of a and a solution of 4,4Ј-bipyridine (10) (51.2 mg, 0.33 mmol) in

mixture of 7a (triethylammonium adduct) and Ba(SCN)₂: m/z

30 mL of nitromethane were added simultaneously whilst stirring

(%) ϭ 980 (100) [C₅₁H₇₀N₃O₁₄S], 1234 (3) [C₅₁H₇₀N₃O₁₄SI₂], 1303 to 30 mL of refluxing nitromethane, using a two-channel syringe

(5) [C₅₁H₇₀N₃O₁₄SBa(SCN)I], 1430 (5) [C₅₁H₇₀N₃O₁₄SBa₂(SCN)₃],

1488 (5) [C₅₁H₇₀N₃O₁₄SBa₂(SCN)₄], 1499 (5) [C₅₁H₇₀N₃O₁₄S-

pump (0.4 mL/h). The solution was heated under reflux for a fur-

ther 24 h. The solvents were removed in vacuo and the residue

Ba₂(SCN)₂I], 1543 (10) [C₅₁H₆₉N₃O₁₄SBa₂(SCN)₂(CF₃CO₂H)I], treated with boiling petroleum ether to separate unconverted cyc-

1557 (10) [C₅₁H₇₀N₃O₁₄SBa(SCN)I₃], 1612 (10) [C₅₁H₆₉N₃O₁₄S- lization components. The remaining solid product was recrystal-

Ba₂(SCN)₂(CF₃CO₂H)I], 1626 (5) [C₅₁H₇₀N₃O₁₄SBa₂(SCN)₂I₂]. Ϫ lized several times from acetonitrile until a green powder was ob-

C₅₁H₆₉I₂N₃O₁₄S·2BaI₂(2016.3): calcd. C 30.38, H 3.45, N 2.08, S tained and was then recrystallized from methanol to afford 9a

1.59; found C 28.65, H 3.44, N 2.04, S 1.29.

(16 mg, 6.65%) as very fine, light green needles, m.p. 256Ϫ257 °C.

3270

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

Ϫ

¹H NMR (500 MHz, [D₄]methanol): δ ϭ 1.35Ϫ1.55 (m, 2 H, 48 h, the precipitated sodium chloride was filtered off and the solv-

N^ϩCH₂CH₂), 2.00Ϫ2.15 (m, 2 H, N^ϩCH₂CH₂), 2.15Ϫ2.30 (m, 4

ent removed in vacuo. The remaining crude material was chromato-

H, Ar CH₂CH₂), 2.30Ϫ2.40 (m, 2 H, ArCH₂), 2.45Ϫ2.70 (m, 2 H, graphed on silica gel, using cyclohexane/ethyl acetate (2:1) as elu-

ArCH₂), 4.40Ϫ4.55 (m, 2 H, N^ϩCH₂), 4.65Ϫ4.75 (m, 2 H, ent, to give 12 (1.63 g, 62%) as a yellow oil, R_fϭ 0.5. Ϫ Method

N^ϩCH₂), 6.05 (d, ⁴J ϭ 1.3 Hz, 1 H, ArH, pos. 1), 6.34 (d, ³J ϭ B: Methyl trifluoromethanesulfonate (1.34 mL, 2.0 g, 12.2 mmol)

2.0 Hz, 1 H, ArH, pos. 6), 6.48 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), was added dropwise at 0 °C to a solution of carbonyldiimidazole

3

4

3

6.57 (dd, J ϭ 7.6, J ϭ 1.7 Hz, 1 H, ArH, pos. 3), 6.73 (d, J ϭ (1.0 g, 6.1 mmol) in 10 mL of nitromethane. This solution was ad-

3

4

7.6 Hz, 1 H, ArH, pos. 4), 6.79 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ded in one portion to a suspension of N-methylphenothiazine-2,7-

ArH, pos. 8), 8.55 (d, ³J ϭ 6.3 Hz, 4 H, PyH), 8.99 (d, ³J ϭ 6.7 Hz, diacetate 17 (1.0 g) in 40 mL of nitromethane. After 1Ϫ2 h, diethyl-

2 H, PyH), 9.01 (d, ³J ϭ 6.7 Hz, 2 H, PyH). Ϫ¹H NMR (CD₃CN,

ene glycol monoiodide (1.9 g, 9 mmol) was added to the clear solu-

360 MHz, only characteristic signals given): δ ϭ 4.37 (m, 2 H, tion with stirring, and the mixture was stirred for a further 12 h.

4

N^ϩCH₂), 4.62 (m, 2 H, N^ϩCH₂), 6.03 (d, J ϭ 1.6 Hz, 1 H, ArH, Nitromethane was then removed in vacuo and exchanged for

pos. 1), 6.36 (d, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6), 6.45 (d, ³J ϭ

150 mL of ethyl acetate. After washing with 5% sodium hydrogen

3

4

8.2 Hz, 1 H, ArH, pos. 9), 6.55 (dd, J ϭ 7.6, J ϭ 1.7 Hz, 1 H, carbonate and removal of the solvent in vacuo, the residue was

ArH, pos. 3), 6.75 (d, ³J ϭ 7.6 Hz, 1 H, ArH, pos. 4), 6.76 (dd, chromatographed on silica gel, using cyclohexane/ethyl acetate

4

3

³J ϭ 8.3, J ϭ 2.1 Hz, 1 H, ArH, pos. 8), 8.29 (d, J ϭ 6.8 Hz, 2 (1:1) as eluent, to yield 12 (1.93 g, 87%) as a yellow oil. A correct

3

1

H, PyH), 8.30 (d, J ϭ 6.8 Hz, 2 H, PyH), 8.68 (d, J ϭ 6.9 Hz, 2 elemental analysis could not be obtained Ϫ H NMR (500 MHz,

H, PyH), 8.71 (d, ³J ϭ 6.9 Hz, 2 H, PyH). Ϫ MS (FAB): m/z (%) ϭ

[D₆]benzene): δ ϭ 2.69Ϫ2.76 (m, 7 H, CH₂I and NCH₃), 2.73 (s,

606 (2.5) [M^ϩϪ I], 479 (100) [M^ϩϪ 2 I]. Ϫ HRMS calcd. for 3 H, NCH₃), 3.08Ϫ3.18 (m, 8 H, CH₂O), 3.27 (s, 2 H, 7Ј-CH₂),

C₃₁H₃₃IN₃S [M^ϩϪ I] 606.1440; found 606.1405.

3.33 (s, 2 H, 2Ј-CH₂), 3.98 (m, 4 H, CH₂O), 6.32 (d, J ϭ 8.3 Hz,

3

1 H, ArH, pos. 9), 6.51 (d, ⁴J ϭ 1.2 Hz, 1 H, ArH, pos. 1), 6.69

Compound 9b: A solution of the cyclophanium diiodide 9a (15 mg,

3

4

3

(dd, J ϭ 7.7, J ϭ 1.3 Hz, 1 H, ArH, pos. 3), 6.93 (dd, J ϭ 8.3,

0.02 mmol) in a water/methanol mixture (3:1) was loaded onto a

⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 6.97 (d, J ϭ 7.7 Hz, 1 H, ArH,

3

Ϫ

DOWEX-50 1 ϫ 8 (BF₄form) column prepared as described for

pos. 4), 7.01 (d, ⁴J ϭ 1.9 Hz, 1 H, ArH, pos. 6). Ϫ IR (NaCl film):

ν˜ ϭ 1735 cm^Ϫ1(νCϭO). Ϫ MS (EI, T_Pϭ 386 °C): m/z (%) ϭ 726

(18), 725 (100) [M^ϩ].

8b. After elution with methanol/water (3:1), the solvents were re-

moved in vacuo and the residue crystallized from water to give 9b

(9.4 mg, 70%) as very fine, green needles, sintering from 250 °C.

Ϫ

¹H NMR (500 MHz, [D₄]methanol): δ ϭ 1.33Ϫ1.55 (m, 2 H, Diethylene Glycol Monoiodide: A solution of diethylene glycol

ArCH₂CH₂), 2.00Ϫ2.15 (m, 2 H, ArCH₂CH₂), 2.15Ϫ2.30 (m, 4 H, monochloride (Fluka) (10 g, 40 mmol) in 80 mL of acetone, satur-

N^ϩCH₂CH₂), 2.30Ϫ2.43 (m, 2 H, ArCH₂), 2.43Ϫ2.70 (m, 2 H, ated with sodium iodide, was heated under reflux for 24 h. The

ArCH₂), 4.35Ϫ4.50 (m, 2 H, N^ϩCH₂), 4.60Ϫ4.73 (m, 2 H, solvent was then removed in vacuo and the residue distilled under

4

N^ϩCH₂), 6.03 (d, J ϭ 1.7 Hz, ArH, pos. 1), 6.33 (d, J ϭ 2.0 Hz, reduced pressure to yield a dark brown (because of elementary iod-

1 H, ArH, pos. 6), 6.45 (d, ³J ϭ 8.1 Hz, 1 H, ArH, pos. 9), 6.54

(dd, ³J ϭ 7.5, ⁴J ϭ 1.7 Hz, 1 H, ArH, pos. 3), 6.72 (d, ³J ϭ 7.5 Hz, wise addition of a sulfuric sodium sulfite solution until the mixture

ine) liquid, which was purified by dissolution in acetone and drop-

3

4

1 H, ArH, pos. 4), 6.76 (dd, J ϭ 8.1, J ϭ 2.0 Hz, 1 H, ArH, pos. was decolourised. After removal of the solvents, the residue was

8), 8.50 (d, ³J ϭ 6.4 Hz, 2 H, PyH), 8.51 (d, ³J ϭ 6.4 Hz, 2 H,

redistilled in vacuo to give the product (10.5 g, 61%) as a light

PyH), 8.96 (d, J ϭ 6.7 Hz, 2 H, PyH), 8.99 (d, J ϭ 6.7 Hz, 2 H, yellow oil, b.p. 73Ϫ75 °C, 0.03 mbar. Ϫ ¹H NMR (360 MHz,

3

PyH). Ϫ MS (FAB): m/z (%) ϭ 566 (8) [M^ϩϪ BF₄], 479 (100) CDCl₃): δ ϭ 2.12 (s, 1 H, OH), 3.25 (t, J ϭ 6.5 Hz, 2 H, CH₂I),

3

[M^ϩϪ 2BF₄]. Ϫ HRMS calcd. for C₃₁H₃₃BF₄N₃S [M^ϩϪ BF₄]

3.59 (m, 2 H, CH₂OH), 3.71 (m, 4 H, CH₂). Ϫ MS (EI, T_Pϭ 32

°C): m/z (%) ϭ 217 (0.2), 216 (1) [M^ϩ] 185 (8), 155 (100), 127 (5),

89 (17). Ϫ C₄H₉IO₂(216.0): calcd. C 22.24, H 4.20; found C 22.57,

H 4.37.

566.2424; found 566.2418.

2,7-Bis(2Ј-iodoethoxycarbonylmethyl)-N-methylphenothiazine (11):

Sodium iodide (4 g, 26 mmol) was added to a solution of the

dichloride 19 (1.28 g, 2.8 mmol) in 50 mL of butanone, and the 2,7-Bis(8Ј-iodo-3Ј,6Ј-dioxaoctyloxycarbonylmethyl)-N-methylpheno-

mixture was heated under reflux with stirring for 48 h. Precipitated

sodium chloride was filtered off, the solvent was removed in vacuo

and the residue was chromatographed on silica gel, using cyclohex-

ane/ethyl acetate (1:1) as eluent, to give 11 (470 mg, 26%) as a yel-

low oil (R_fϭ 0.6, cyclohexane/ethyl acetate, 1:1). Ϫ ¹H NMR

thiazine (13): The preparation was analogous to that of 12, starting

from dichloride 21 (8.77 g, 13.7 mmol) in 110 mL of acetone to

afford 13 (9.40 g, 84%) as a yellow oil, R_fϭ 0.4 (silica gel; ethyl

acetate/cyclohexane 1:2) or R_fϭ 0.7 (RP-18 Gel; methanol/10%

water). A correct elemental analysis was not obtained; the product

1

(360 MHz, [D₆]benzene): δ ϭ 2.68 (m, 4 H, CH₂I), 2.76 (s, 3 H, was sufficiently pure, however, for synthetic purposes. Ϫ H NMR

NCH₃), 3.23 (s, 2 H, 7Ј-CH₂), 3.28 (s, 2 H, 2Ј-CH₂), 3.92 (m, 4 H, (360 MHz, [D₆]benzene): δ ϭ 2.73 (s, 3 H, NCH₃), 2.83 (m, 4 H,

3

4

CO₂CH₂), 6.33 (d, J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.49 (d, J ϭ CH₂I), 3.26 (m, 20 H, CH₂O ϩ 2Ј-CH₂and 7Ј-CH₂), 4.08 (m, 4

1.6 Hz, 1 H, ArH, pos. 1), 6.65 (dd, J ϭ 7.8, J ϭ 1.6 Hz, 1 H, H, CO₂CH₂), 6.32 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.53 (d, ⁴J ϭ

3

4

3

4

3

4

ArH, pos. 3), 6.90 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH, pos. 8), 1.6 Hz, 1 H, ArH, pos. 1), 6.70 (dd, J ϭ 7.8, J ϭ 1.7 Hz, 1 H,

6.94 (d, ³J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 6.99 (d, ⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 3), 6.94 (dd, J ϭ 8.2, J ϭ 2.0 Hz, 1 H, ArH, pos. 8),

3

4

Ϫ1

ArH, pos. 6). Ϫ IR (NaCl, film): ν ϭ 1737 cm (νCϭO). Ϫ MS

6.96 (d, ³J ϭ 7.7 Hz, 1 H, ArH, pos. 4), 7.02 (d, ⁴J ϭ 2.0 Hz, 1 H,

˜

(EI, T_Pϭ 280 °C): m/z (%) ϭ 639 (6), 638 (15), 637 (100) [M^ϩ], ArH, pos. 6). Ϫ IR (NaCl, film): ν˜ ϭ 1737 and 1735 cm^Ϫ1(νCϭ

438 (15), 425 (11), 239 (16), 238 (11), 194 (16). Ϫ C₂₁H₂₁I₂NO₄S O). Ϫ MS (EI, T_Pϭ 393 °C): m/z (%) ϭ 814 (10), 813 (29) [M^ϩ],

(637.3): calcd. C 39.58, H 3.32, N 2.20, S 5.03; found C 40.02, H 199 (11), 155 (100), 142 (84), 141 (12), 128 (22), 127 (37), 88 (22).

3.43, N 2.21, S 5.33.

2,7-Bis(11Ј-iodo-3Ј,6Ј,9Ј-trioxaundecyloxycarbonylmethyl)-N-

2,7-Bis(5Ј-iodo-3Ј-oxapentyloxycarbonylmethyl)-N-methylpheno- methylphenothiazine (14): A solution of 3,3Ј-dimethylcarbonyldiim-

thiazine (12). ؊ Method A: Sodium iodide was added to a boiling idazolium bis(triflate) (prepared from 1 g of carbonyldiimidazole

solution of the dichloride 20 (2.0 g, 3.6 mmol) in 60 mL of but-

anone until the solution was saturated. After heating for a further

as in the preparation of 12, method B) was added in one portion to

a suspension of N-methylphenothiazine-2,7-diacetic acid (17) (1 g,

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3271

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

3.3 mmol) in 40 mL of nitromethane. The suspension was stirred 2,7-Bis(17Ј-iodo-3Ј,6Ј,9Ј,12Ј,15Ј-pentaoxaheptadecyloxy-

until the dissolution was complete (1Ϫ2 h). Tetraethylene glycol

carbonylmethyl)-N-methylphenothiazine (16): The preparation was

monoiodide (2.73 g, 8.5 mmol) was then added and stirring was analogous to that of 15, starting with ditosylate 23 (1.86 g,

continued overnight. After concentration and dissolution in

200 mL of ethyl acetate, the solution was washed with a 5% solu-

tion of sodium hydrogen sulfate (50 mL). The organic phase was

dried with sodium sulfate, the solvent removed in vacuo and the

residue subjected to chromatography on silica gel, with ethyl acet-

1.6 mmol). After purification, 16 (1.05 g, 61%) was obtained as a

yellow oil, R_f(ethyl acetate/5% ethanol) ϭ 0.5. Ϫ ¹H NMR

(360 MHz, [D₆]benzene): δ ϭ 2.77 (s, 3 H, NCH₃), 2.86 (t, ³J ϭ

6.7 Hz, 4 H, CH₂I), 3.29Ϫ3.45 (m, 44 H, CH₂O ϩ 7Ј-CH₂ϩ 2Ј-

CH₂), 4.10 (m, 4 H, CO₂CH₂), 6.35 (d, ³J ϭ 8.3 Hz, 1 H, ArH,

pos. 9), 6.54 (d, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 6.70 (dd, ³J ϭ 7.8,

ate/cyclohexane (4:1) as eluent, to give 14 (1.25 g, 45%) as a yellow

1

3

4

oil, R_fϭ 0.7. Ϫ H NMR (360 MHz, [D₆]benzene): δ ϭ 2.73 (s, 3 ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 6.94 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1

3

H, NCH₃), 2.83 (m, 4 H, CH₂I), 3.25Ϫ3.38 (m, 28 H, CH₂O ϩ2Ј-

H, ArH, pos. 8), 6.95 (d, J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 7.00 (d,

3

4

Ϫ1

˜

J ϭ 2.0 Hz, 1 H, ArH, pos. 6). Ϫ IR (NaCl, film): ν ϭ 1737 cm

CH₂ϩ 7Ј-CH₂), 4.10 (m, 4 H, CO₂CH₂), 6.32 (d, J ϭ 8.3 Hz, 1

H, ArH, pos. 9), 6.52 (d, ⁴J ϭ 1.7 Hz, 1 H, ArH, pos. 1), 6.69 (dd, (νCϭO). Ϫ MS (EI, T_Pϭ 389): m/z (%) ϭ 987 (5), 901 (10), 863

4

3

³J ϭ 7.8, J ϭ 1.7 Hz, 1 H, ArH, pos. 3), 6.93 (dd, J ill-defined,

(5) [M^ϩϪ I Ϫ 2 ϫ CH₂CH₂O], 814 (20), 776 (16), 725 (11), 659

4

3

J ϭ 2.2 Hz, 1 H, ArH, pos. 8), 6.95 (d, J ϭ 7.7 Hz, 1 H, ArH, (13), 284 (13), 240 (25), 239 (23), 238 (28). 155 (100). Ϫ

pos. 4), 7.01 (d, ⁴J ϭ 2.1 Hz, 1 H, ArH, pos. 6). Ϫ IR (NaCl film): C₄₁H₆₁I₂NO₁₄S (1077.8): calcd. C 45.69, H 5.70, N 1.30, S 2.97;

ν ϭ 1737 cm^Ϫ1(νCϭO). Ϫ MS (EI, T_Pϭ 380 °C): m/z (%) ϭ 901 found C 45.74, H 5.81, N 1.42, S 2.90.

˜

(100) [M^ϩ], 813 (94), 773 (47), 685 (18), 482 (11), 443 (11), 240

N-Methylphenothiazin-2,7-diyldi(acetic acid) (17): A mixture of 2,7-

(17), 239 (32), 238 (34), 224 (13), 207 (14), 194 (25), 156 (13), 155

(71), 128 (33), 127 (20), 119 (27), 89 (12). Ϫ C₃₃H₄₅I₂NO₁₀S (901.6):

calcd. C 43.96, H 5.03, N 1.55, S 3.56; found C 44.35, H 5.00, N

1.70, S 3.96.

diacetyl-N-methylphenothiazine (27) (80 g, 270 mmol), morpholine

(150 mL, 144 g, 1.65 mol) and sulfur (30 g, 0.93 mol) was heated

to 135 °C (oil bath temp.) for 6 h. The morpholine was then re-

moved in vacuo and the residue was taken up in a solution of

potassium hydroxide (160 g, 2.8 mol) in 200 mL of water and

600 mL of ethanol and heated under reflux for 5 h. After removal

of ethanol in vacuo, the solution was diluted with water to 2 L and

filtered. The filtrate was then acidified with 2  hydrochloric acid

to afford, after standing overnight, a precipitate which was filtered

off and reprecipitated from a sodium hydrogen carbonate solution

with dilute hydrochloric acid. A dark brown solid (86 g, 97%) was

obtained; for purification this was recrystallized twice from water

to give 17 as slightly yellow platelets. For the preparation of the

pure di(acetic acid) 17 the route via the dimethyl ester was fa-

voured. Sodium hydroxide (1  150 mL) was added to a suspension

of dimethyl ester 18 (15 g, 42 mmol) in 450 mL of methanol and

the mixture was stirred at room temperature for 2 h. After removal

of methanol in vacuo, the solution was diluted with water to

800 mL and acidified with hydrochloric acid. The mixture was

stirred for a further 30 min, and the precipitate was filtered off,

washed with water and dried at 70 °C in a drying oven to give 17

(13.9 g, nearly quant.) as a slightly yellow powder, m.p. 172Ϫ175

°C. Ϫ ¹H NMR (360 MHz, [D₆]DMSO): δ ϭ 3.28 (s, 3 H, NCH₃),

3.46 (s, 2 H, CH₂), 3.52 (s, 2 H, CH₂), 6.86 (m, 3 H, ArH), 7.06

(m, 3 H, ArH), 12.26 (s, 2 H, CO₂H). Ϫ IR (KBr): ν˜ ϭ 1701 cm^Ϫ1

(νCϭO). Ϫ MS (EI, T_Pϭ 312 °C): m/z (%) ϭ 330 (20), 329 (100)

[M^ϩ], 315 (28), 314 (44), 285 (26), 284 (30), 270 (23), 269 (17), 238

(14), 224 (20). Ϫ C₁₇H₁₅NO₄S (329.4): calcd. C 61.99, H 4.59, N

4.25, S 9.74; found C 61.70, H 4.49, N 4.55, S 9.52.

Tetraethylene Glycol Monoiodide: A solution of tetraethylene glycol

mono(p-toluenesulfonate) (20 g, 57 mmol) in 200 mL of acetone

saturated with sodium iodide (about 40 g of NaI, 220 mmol) was

heated under reflux for 15 h. Precipitated sodium p-toluenesulfon-

ate was filtered off, the solvent was evaporated and the residue was

taken up in 200 mL of ethyl acetate. Insoluble salts were filtered

off, the filtrate was concentrated in vacuo and the residue was dis-

tilled under reduced pressure. The distillate, which was discoloured

by elementary iodine, was diluted with 20 mL of acetone, and

treated with a sulfuric sodium sulfite solution until the solution

was colourless. After removal of the solvent in a rotary evaporator,

the residue was redistilled in vacuo to give the monoiodide (13.02 g,

1

71%) as a colourless oil, b.p. 140Ϫ142 °C, 0.02 mbar. Ϫ H NMR

3

(360 MHz, CDCl₃): δ ϭ 2.55 (s, 1 H, OH), 3.23 (t, J ϭ 6.7 Hz, 2

H, CH₂I), 3.60 (m, 2 H, CH₂OH), 3.64 (m, 8 H, CH₂O), 3.70 (m,

4 H, CH₂O). Ϫ MS (EI, T_Pϭ 95 °C): m/z (%) ϭ 287 (0.1) [M^ϩ

Ϫ

OH], 198 (10), 155 (100), 89 (18). Ϫ C₈H₁₇IO₄(304.1): calcd. C

31.60, H 5.63; found C 31.33, H 5.85.

2,7-Bis(14Ј-iodo-3Ј,6Ј,9Ј,12Ј-tetraoxatetradecyloxycarbonylmethyl)-

N-methylphenothiazine (15): A solution of ditosylate 22 (1.72 g,

1.6 mmol) in 40 mL of acetone, saturated with sodium iodide, was

heated under reflux for 12 h. After removal of the solvent in vacuo,

the residue was taken up in 150 mL of ethyl acetate and washed

with 30 mL of water. The organic phase was filtered, the solvent

was removed in vacuo and the residue was subjected to chromato-

Dimethyl N-Methylphenothiazine-2,7-diyldi(acetate) (18): Conc.

graphy on silica gel, eluting with ethyl acetate/5% ethanol, to afford

sulfuric acid (25 mL) was added to a suspension of crude di(acetic

1

15 (1.3 g, 82%) as a yellow oil, R_fϭ 0.6. Ϫ H NMR (360 MHz, acid) 17 (40 g, 121 mmol) in 600 mL of methanol and the mixture

3

[D₆]benzene: δ ϭ 2.76 (s, 3 H, NCH₃), 2.85 (t, J ϭ 6.3 Hz, 4 H, was heated under reflux for 15 h. After removal of the solvent in a

CH₂I), 3.27Ϫ3.43 (m, 36 H, CH₂O ϩ 7Ј-CH₂ϩ 2Ј-CH₂), 4.10 (m,

4 H, CO₂CH₂), 6.33 (d, J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.53 (d, methane. The solution was washed with 200 mL of water (2 ϫ),

rotary evaporator, the residue was taken up in 50 mL of dichloro-

3

4

⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 1), 6.69 (dd, J ϭ 7.8 Hz, J ϭ 2.0, 1 dried with sodium sulfate and concentrated in vacuo to give a

3

4

H, ArH, pos. 3), 6.94 (dd, J ϭ 8.3, J ϭ 2.0 Hz, 1 H, ArH, pos. pitchy residue, which was treated (3Ϫ4 ϫ) with hot hexane until

8), 6.95 (d, ³J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 7.00 (d, J ϭ 2.0 Hz, 1 complete solidification. The black, viscous residue was taken up in

4

Ϫ1

˜

H, ArH, pos. 6). Ϫ IR (NaCl, film): ν ϭ 1738, 1733 cm (νCϭ

dichloromethane and filtered through silica gel. The filtrate was

O). Ϫ MS (EI, T_Pϭ 409 °C): m/z (%) ϭ 989 (100) [M^ϩ], 902 (44), concentrated and the residue crystallized from hexane to afford 18

901 (90), 862 (84), 813 (12), 774 (18), 293 (14), 240 (17), 239 (21), (21.5 g, 50%) as lemon-yellow, very light platelets, m.p. 75Ϫ77 °C.

238 (20), 194 (16), 169 (25), 167 (21), 156 (14), 155 (80), 149 (83).

Ϫ C₃₇H₅₃I₂NO₁₂S (989.7): calcd. C 44.90, H 5.40, N 1.42, S 3.24; 3.59 (s, 2 H, CH₂CO), 3.60 (s, 3 H, CH₃O), 3.61 (s, 3 H, CH₃O),

Ϫ

¹H NMR (360 MHz, [D₆]DMSO): δ ϭ 3.29 (s, 3 H, NCH₃),

found C 44.89, H 5.37, N 1.43, S 3.48.

3.65 (s, 2 H, CH₂CO), 6.87 (m, 3 H, ArH), 7.08 (m, 3 H, ArH). Ϫ

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3272

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

IR (KBr): ν˜ ϭ 1737 cm^Ϫ1(νCϭO). Ϫ MS (EI, T_Pϭ 201 °C): m/z

General Procedure for the Syntheses of 22 and 23 by Esterification

(%) ϭ 358 (22), 357 (100) [M^ϩ], 343 (14), 342 (40), 298 (37), 297 of 17 with Oligoethylene Glycol p-Toluenesulfonates: A solution pre-

(11), 283 (13); 238 (17), 224 (19). Ϫ C₁₉H₁₉NO₄S (357.4): calcd. C

pared from carbonyldiimidazole (CDI) (1 g, 6.1 mmol) and methyl

63.84, H 5.36, N 3.92, S 8.97; found C 63.86, H 5.38, N 4.14, trifluoromethylsulfonate (1.34 mL, 2 g, 12.2 mmol) was added at 0

S 8.76.

°C in one portion to a suspension of the di(acetic acid) 17 (1 g,

3.03 mmol) in 40 mL of nitromethane. After 1Ϫ2 h, the oligoethy-

lene glycol monotosylate (7.5 mmol, 2.94 g of pentaethylene glycol

monotoluenesulfonate or 6.60 g of hexaethylene glycol monotol-

uenesulfonate) was added to the clear solution whilst stirring. Stir-

ring was continued for 12 h. The solvent was evaporated in vacuo,

and the residue was taken up in 200 mL of ethyl acetate and washed

twice with 50 mL of a 5% solution of sodium hydrogen carbonate.

The organic phase was dried by passing through a paper filter. For

purification, the crude material was subjected to chromatography

on silica gel.

General Procedure for the Preparation of Bis(ω-chlorooligoethylene

glycol)-Modified N-Methylphenothiazines 19؊21 : BF₃·OEt₂(5

drops) was added to a suspension of phenothiazine dimethyl ester

18 (2 g) and the reported amount of the ω-chlorooligoethylene

glycol and the mixture was heated to 130 °C for 15 h. The oily

product was taken up in 250 mL of ethyl acetate, and the solution

was washed with water and dried with sodium sulfate. The solvent

was then removed in vacuo.

2,7-Bis(2Ј-chloroethoxycarbonylmethyl)-N-methylphenothiazine

(19): 2-Chloroethanol (50 mL) was used. After workup, the crude

oil crystallized on drying in vacuo. It was sufficiently pure for syn-

thetic purposes. For characterization it was chromatographed on

silica gel using dichloromethane as eluent ( R_fϭ 0.8) to afford 19

(1.68 g, 66%) as yellow, intergrown needles, m.p. 65 °C. Ϫ ¹H NMR

(360 MHz, [D₆]benzene): δ ϭ 2.70 (s, 3 H, NCH₃), 2.98 (t, ³J ϭ

5.5 Hz, 4 H, CH₂Cl), 3.20 (s, 2 H, 7Ј-CH₂), 3.25 (s, 2 H, 2Ј-CH₂),

N-Methyl-2,7-bis[14Ј-(p-toluenesulfonyl)-3Ј,6Ј,9Ј,12Ј-tetra-

oxatetradecyloxycarbonylmethyl]phenothiazine (22): Yield: 1.94 g

(60%) of a yellow oil, R_f(silica gel, ethyl acetate) ϭ 0.4. Ϫ ¹H

NMR (360 MHz, [D₆]benzene): δ ϭ 1.90 (s, 6 H, tosyl CH₃), 2.79

3

(s, 3 H, NCH₃), 3.25Ϫ3.42 (m, 36 H, CH₂), 3.94 (t, J ϭ 4.7 Hz, 4

3

H, CH₂OTS), 4.11 (m, 4 H, CO₂CH₂), 6.37 (d, J ϭ 8.3 Hz, 1 H,

4

3

ArH, pos. 9), 6.55 (d, J ill-defined, 1 H, ArH, pos. 1), 6.70 (dd,

3.86 (m, 4 H, CO₂CH₂), 6.28 (d, J ϭ 8.4 Hz, 1 H, ArH, pos. 9),

³J ϭ 7.8 Hz, ⁴J ill-defined, 1 H, ArH, pos. 3), 6.78 (d, ³J ϭ 8.1 Hz,

4

3

4

6.47 (d, J ϭ 1.4 Hz, 1 H, ArH, pos. 1), 6.62 (dd, J ϭ 8.1, J ϭ

4

1.8 Hz, 1 H, ArH, pos. 3), 6.89 (dd, ³J and ⁴J ill-defined, 1 H, ArH,

4 H, tosyl H), 6.94 (m, 2 H, ArH, pos. 4 and pos. 8), 6.98 (d, J ϭ

3

pos. 8), 6.92 (d, ³J ill-defined, 1 H, ArH, pos. 4), 6.97 (d, ⁴J ill-

1.9 Hz, 1 H, ArH, pos. 6), 7.74 (d, J ϭ 8.2 Hz, 4 H, tosyl H). Ϫ

Ϫ1

˜

IR (NaCl, film): ν ϭ 1734 cm (νCϭO). Ϫ MS (EI, T_Pϭ 377

˜

defined, 1 H, ArH, pos. 6). Ϫ IR (KBr): ν ϭ 1733 cm (νCϭO).

°C): m/z (%) ϭ 818 (1) [M Ϫ CH₃C₆H₄SO₂(OCH₂CH₂)₂OH], 729

(2), 619 (4), 557 (4), 469 (4), 443 (3), 310 (4), 238 (7), 199 (16), 172

(51), 155 (24), 108 (24), 107 (36), 92 (11), 91 (100), 90 (11), 89 (21),

88 (71), 87 (11). Ϫ C₅₁H₆₇NO₁₈S₃(1078.3): calcd. C 56.81, H 6.27,

N 1.30, S 8.92; found C 56.91, H 6.36, N 1.46, S 8.79.

Ϫ MS (EI, T_Pϭ 235 °C): m/z (%) ϭ 457 (14), 456 (13), 455 (68),

453 (100), 440 (13), 405 (22), 393 (17), 391 (43), 376 (16), 348 (19),

346 (49), 333 (33), 284 (36), 238 (33). Ϫ C₂₁H₂₁Cl₂NO₄S (454.4):

calcd. C 55.51, H 4.66, N 3.08, S 7.06; found C 55.58, H 4.50, N

3.21, S 7.09.

2,7-Bis(5Ј-chloro-3Ј-oxapentyloxycarbonylmethyl)-N-methylpheno-

thiazine (20): Use of diethylene glycol monochloride (5-chloro-3-

oxapentan-1-ol, 30 g) as starting material and chromatography of

the oily crude product on silica gel with cyclohexane/ethyl acetate

(1:2) yielded 20 (1.8 g, 60%) as a yellow oil (R_fϭ 0.6). Ϫ ¹H NMR

(360 MHz, [D₆]benzene): δ ϭ 2.70 (s, 3 H, NCH₃), 3.00Ϫ3.20 (m,

12 H, 2 CH₂Cl and 4 CH₂O), 3.25 (s, 2 H, 7Ј-CH₂), 3.31 (s, 2 H,

N-Methyl-2,7-bis[17Ј-(p-toluenesulfonyl)-3Ј,6Ј,9Ј,12Ј,15Ј-penta-

oxaheptadecyloxycarbonylmethyl]phenothiazine (23): Yield 4.5 g

(63%) of a yellow oil after chromatography with ethyl acetate/eth-

anol (95:5), R_fϭ 0.4 (silica gel, ethyl acetate). A correct elemental

analysis could not be obtained. Ϫ ¹H NMR (360 MHz, [D₆]ben-

zene): δ ϭ 1.83 (s, 6 H, tosyl CH₃), 2.77 (s, 3 H, NCH₃), 3.25Ϫ3.46

(m, 44 H, CH₂), 3.95 (m, 4 H, CH₂OTS), 4.12 (m, 4 H, CO₂CH₂),

3

4

6.35 (d, ³J ϭ 8.3 Hz, 1 H, ArH, pos. 9), 6.55 (d, J ϭ 1.4 Hz, 1 H,

2Ј-CH₂), 3.99 (m, 4 H, CO₂CH₂), 6.30 (d, J ϭ 8.2 Hz, 1 H, ArH,

pos. 9), 6.49 (d, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 6.66 (dd, ³J ϭ 7.8,

ArH, pos. 1), 6.72 (m, 5 H, 4 tosyl H ϩ 1 ArH, pos. 3), 6.95 (m, 2

3

4

⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 6.91 (dd, J ϭ 8.2, J ϭ 2.0 Hz, 1

H, ArH, pos. 4 and pos. 8), 7.00 (d, 1.9 Hz, 1 H, ArH, pos. 6), 7.75

3

Ϫ1

H, ArH, pos. 8), 6.93 (d, J ϭ 7.8 Hz, 1 H, ArH, pos. 4), 6.98 (d,

˜

(d, J ϭ 8.3 Hz, 4 H, tosyl H). Ϫ IR (NaCl, film): ν ϭ 1737 cm

⁴J ϭ 2.0 Hz, 1 H, ArH, pos. 6). Ϫ IR (KBr): ν˜ ϭ 1737, 1733 cm^Ϫ1

(νCϭO). Ϫ MS (EI, T_Pϭ 323 °C): m/z (%) ϭ 545 (17), 544 (21),

543 (75), 542 (30), 541 (100) [M^ϩ], 390 (18), 238 (12). Ϫ HRMS

calcd. for C₂₅H₂₉Cl₂NO₆S [M^ϩ] 541.1093; found 541.1184.

(νCϭO). Ϫ MS (EI, T_Pϭ 359 °C): m/z (%) ϭ 729 (3), 641 (6), 293

(6), 239 (10), 238 (15), 207 (9), 199 (16), 181 (6), 172 (10). 91 (64),

89 (18), 88 (100).

General Procedure for the Preparation of Oligoethylene Glycol

Monotoluenesulfonates: p-Toluenesulfonyl chloride (6.7 g, 35 mmol)

in pyridine (12 mL) was added dropwise at 0 °C with stirring to a

solution of oligoethylene glycol (88 mmol, 17 g of tetraethylene

glycol, 21 g pentaethylene glycol or 25 g hexaethylene glycol) in

50 mL of dichloromethane. Stirring was continued overnight. After

shaking twice with 20 mL of 2  hydrochloric acid, the organic

phase was dried by filtering through a paper filter. The solvent was

evaporated in a rotary evaporator under vacuum and the remaining

colourless oil was subjected to gradient elution chromatography on

silica gel with ethyl acetate/cyclohexane (ethyl acetate from 0.33 to

1.0). For characterization the product was chromatographed on

RP-18 silica gel with methanol/water (60:40). The procedure could

be carried out without problem at larger scales.

2,7-Bis(8Ј-chloro-3Ј,6Ј-dioxaoctyloxycarbonylmethyl)-N-methyl-

phenothiazine (21): Triethylene glycol monochloride (8-chloro-3,6-

dioxaoctan-1-ol, 9 g) was used. The crude oil was chromatographed

on silica gel with cyclohexane/ethyl acetate (1:2) to give 21 (1.59 g,

44%) as a yellow oil (R_fϭ 0.3), which was sufficiently pure for

synthetic purposes. For characterization, the oil was further chro-

matographed on RP-18 gel with methanol/water (10:1) (R_fϭ 0.4).

Ϫ

¹H NMR (360 MHz, [D₆]benzene): δ ϭ 2.71 (s, 3 H, NCH₃),

3.25 (m, 24 H, 8 CH₂O, 7Ј-CH₂, 2Ј-CH₂, 2 CH₂Cl), 4.06 (m, 4 H,

3

CO₂CH₂), 6.30 (d, J ϭ 8.2 Hz, 1 H, ArH, pos. 9), 6.51 (‘‘s’’, 1 H,

ArH, pos. 1), 6.67 (‘‘d’’, 1 H, ArH, pos. 3), 6.92 (m, 2 H, ArH,

pos. 8 and pos. 4), 6.95 (‘‘s’’, 1 H, ArH, pos. 6). Ϫ IR (NaCl, film):

ν ϭ 1735, 1732 cm^Ϫ1(νCϭO). Ϫ MS (EI, T_Pϭ 263 °C): m/z (%) ϭ

˜

631 (2), 629 (3)[M^ϩ], 218 (47), 182 (12), 181 (10), 177 (14), 167

(11), 162 (18), 161 (10), 149 (25), 147 (26). Ϫ HRMS calcd. for

C₂₉H₃₇Cl₂NO₈S [M^ϩ] 629.1616; found 629.1566.

11-Hydroxy-3,6,9-trioxaundecyl-1-p-toluenesulfonate:^[13]Yield 8.2 g

(67%) of a colourless oil. In ref.^[12]the oil was used directly as crude

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3273

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

material, obtained in 77% yield, but not characterized. R_f(silica

gel, ethyl acetate) ϭ 0.65; R_f(RP-18, methanol/water 60:40) ϭ 0.6;

warm slowly to Ϫ40 °C. When the clear solution had reached room

temperature, 200 mL of 2  hydrochloric acid was added and stir-

ring was continued for another 3 h. The tetrahydrofuran was re-

gradient chromatography on silica gel with cyclohexane/ethyl acet-

1

ate from 3:1 to 0:1. Ϫ H NMR (360 MHz, CDCl₃): δ ϭ 2.33 (s, 1 moved in vacuo. The residue was dissolved in 500 mL of trichloro-

H, OH), 2.43 (s, 3 H, tosyl CH₃), 3.56Ϫ3.70 (m, 14 H, CH₂O),

methane and washed twice with 200 mL of water. The organic

4.15 (t, J ϭ 4.1 Hz, 2 H, CH₂O-tosyl), 7.32 (d, J ϭ 7.9 Hz, 2 H, phase was filtered through silica gel. After evaporation of the solv-

3

tosyl H), 7.78 (d, J ϭ 7.9 Hz, 2 H, tosyl H). Ϫ IR (NaCl, film):

ent the residual oil was crystallized from ethanol to give 26 (93 g,

Ϫ1

ν ϭ 3457 cm (ν OH), 1357, 1178 cm^Ϫ1(ν SϭO). Ϫ MS (EI, 95%) as bright yellow prisms, m.p. 68.5 °C (ref.^[14]70 °C). Because

T_Pϭ 271 °C): m/z (%) ϭ 349 (0.4), 348 (0.8) [M^ϩ], 305 (1.7), 273 the crystallization of 26 normally takes several weeks, it is recom-

(2.1), 243 (8), 217 (4), 200 (7.5), 199 (100), 155 (67), 91 (89), 89 mended that the deep yellow oil be used for further conversions. Ϫ

(56), 88 (11), 87 (15). Ϫ C₁₅H₂₄O₇S (348.4): calcd. C 51.71 H 6.95 ¹H NMR (360 MHz, CDCl₃): δ ϭ 2.55 (s, 3 H, CH₃CO), 3.39 (s,

˜

3

4

S 9.20; found C 51.43, H 7.07, S 9.31.

3 H, NCH₃), 6.80 (dd, J ϭ 8.0, J ϭ 1.0 Hz, 1 H, ArH, pos. 9),

3

4

3

6.92 (dt, J ϭ 7.5, J ϭ 1.0 Hz, 1 H, ArH, pos. 8), 7.09 (dd, J ϭ

14-Hydroxy-3,6,9,12-tetraoxatetradecyl-1-p-toluenesulfonate: Yield

7.7 g (56%) of a colourless oil. R_f(silica gel, ethyl acetate/ 20 %

ethanol) ϭ 0.65. Gradient elution chromatography on silica gel

with cyclohexane/ethyl acetate (4:1), pure ethyl acetate and finally

ethyl acetate/ethanol (4:1). Ϫ ¹H NMR (360 MHz, CDCl₃): δ ϭ

2.40 (s, 3 H, tosyl CH₃), 2.47 (s, 1 H, OH), 3.54Ϫ3.67 (m, 18 H,

CH₂O), 4.12 (t, ³J ϭ 4.4 Hz, 2 H, CH₂O-tosyl), 7.30 (d, ³J ϭ

7.5, ⁴J ϭ 1.5 Hz, 1 H, ArH, pos. 6), 7.14 (d, ³J ϭ 8.0 Hz, 1 H,

3

4

ArH, pos. 4), 7.16 (dt, J ϭ 8.0, J ϭ 1.5 Hz, 1 H, ArH, pos. 7),

4

3

4

7.34 (d, J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 7.45 (dd, J ϭ 8.0, J ϭ

1.6 Hz, 1 H, ArH, pos. 3). Ϫ IR (KBr). ν ϭ 1675 cm (νCϭO).

Ϫ1

˜

Ϫ MS (EI, T_Pϭ 202 °C): m/z (%) ϭ 256 (15) [M^ϩϩ1], 255 (100)

[M^ϩ], 240 (65), 213 (18), 197 (21). Ϫ The preparation of 26^[14]by

treatment of 2-acetylphenothiazine (24) (for example, 15 g,

62 mmol) with methyl iodide (for example, 20 mL, 315 mmol) in

methanol (65 mL) in a sealed tube at 110 °C (CAUTION!) for 24 h

is very dangerous. In one case an explosion occurred, probably as

a result of a reaction between the hydroiodic acid produced and

methyl iodide to give elementary iodine and methane.

3

8.4 Hz, 2 H, tosyl H), 7.76 (d, J ϭ 8.4 Hz, 2 H, tosyl H). Ϫ IR

(NaCl, film): ν˜ ϭ 3460 cm^Ϫ1(νOH), 1357, 1178 cm^Ϫ1(νSϭO). Ϫ

MS (EI, T_Pϭ 205 °C): m/z (%) ϭ 393 (0.3), 392 (0.5) [M^ϩ], 317

(1.4), 305 (2), 261 (2), 243 (8), 199 (100), 155 (59), 91 (88), 89 (65),

87 (29). Ϫ C₁₇H₂₈O₈S (392.5): calcd. C 52.02, H 7.20, S 8.17; found

C 52.14, H 7.38, S 7.95.

2,7-Diacetyl-N-methylphenothiazine (27):^[15]A solution of 2-acetyl-

N-methylphenothiazine (26) (93 g, 365 mmol) and acetyl chloride

(41 g, 522 mmol) in 500 mL of carbon disulfide was added drop-

wise at room temperature to a suspension of aluminium trichloride

(220 g, 1.62 mol) in 500 mL of carbon disulfide. The mixture was

then refluxed for 14 h, the solvent was removed by evaporation in

vacuo and the residue was hydrolysed with ice. The solid was fil-

tered under suction, dried and recrystallized from ethyl acetate to

afford 27 (81.2 g, 75%) as green yellow crystals, m.p. 221 °C (ref.^[14]

17-Hydroxy-3,6,9,12,15-pentaoxaheptadecyl-1-p-toluenesulfonate:

Yield 8.88 g of a colourless oil, R_f(silica gel, ethyl acetate/20 %

ethanol) ϭ 0.5. Gradient elution chromatography on silica gel with

cyclohexane/ethyl acetate (4:1), pure ethyl acetate and finally ethyl

acetate/ethanol (4:1). Ϫ H NMR (360 MHz, CDCl₃): δ ϭ 2.45 (s,

3 H, tosyl CH₃), 2.52 (br. s, 1 H, OH), 3.58Ϫ3.72 (m, 23 H, CH₂O),

1

3

4.16 (t, J ϭ 4.8 Hz, 2 H, CH₂O-tosyl), 7.33 (d, J ϭ 8.4 Hz, 2 H,

3

tosyl H), 7.80 (d, J ϭ 8.4 Hz, 2 H, tosyl H). Ϫ IR (NaCl, film):

ν ϭ 3470 cm (νOH), 1355, 1177 cm^Ϫ1(νSϭO). Ϫ MS (EI, T_P

ϭ

Ϫ1

1

˜

61%, m.p. 223 °C). Ϫ H NMR (360 MHz, CDCl₃): δ ϭ 2.52 (s, 3

95 °C): m/z ϭ 436 (0.1) [M^ϩ], 349 (1), 287 (3), 199 (100), 155 (27),

91 (95), 89 (80), 87 (28), 73 (14). Ϫ C₁₉H₃₂O₉S (436.5): calcd. C

52.28, H 7.39, S 7.35; found C 52.04, H 7.53, S 7.10.

H, CH₃CO), 2.57 (s, 3 H, CH₃CO), 3.44 (s, 3 H, NCH₃), 6.81 (d,

3

³J ϭ 8.5 Hz, 1 H, ArH, pos. 9), 7.17 (d, J ϭ 7.9 Hz, 1 H, ArH,

pos. 4), 7.39 (d, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 1), 7.51 (dd, ³J ϭ 7.9,

4

⁴J ϭ 1.6 Hz, 1 H, ArH, pos. 3), 7.68 (d, J ϭ 2.1 Hz, 1 H, ArH,

2-(2-Methyl-1,3-dioxolan-2-yl)-10H-phenothiazine (25): Ethylene

glycol (100 g, 1.61 mol) and BF₃·OEt₂(2 mL) were added to a sus-

pension of 2-acetylphenothiazine (24) (Aldrich, 100 g, 415 mmol)

in 1 L of benzene. The mixture was refluxed in a DeanϪStark ap-

paratus for 36 h and then washed twice with 500 mL of water. After

concentration of the organic phase in a rotary evaporator, the re-

sulting brown oil was crystallized from 600 mL of cyclohexane to

3

4

pos. 6), 7.78 (dd, J ϭ 8.5, J ϭ 2.1 Hz, 1 H, ArH, pos. 8). Ϫ IR

Ϫ1

˜

(KBr): ν ϭ 1673, 1663 cm (νCϭO). Ϫ MS (EI, T_Pϭ 249 °C):

m/z (%) ϭ 298 (12) [M^ϩϩ 1], 297 (100) [M^ϩ], 282 (33), 254 (12),

240 (13).

1,1Ј-Bis(2ЈЈ-hydroxyethyl)-4,4Ј-bipyridinium Bis(trifluoromethane-

sulfonate) (28): Silver trifluoromethylsulfonate (1.43 g, 5.6 mmol)

was added to a stirred suspension of 1,1Ј-bis(2ЈЈ-hydroxyethyl)-4,4Ј-

bipyridinium diiodide (1.4 g, 2.8 mmol) (see below) in 200 mL of

nitromethane and stirring was continued for 1 h. The yellow-orange

colour of the bipyridinium diiodide disappeared and a yellow pre-

cipitate of AgI was formed. The mixture was filtered and the filtrate

was concentrated in vacuo to give a colourless powder. After

recrystallization from trichloromethane/nitromethane (1:2), com-

pound 28 (1.29 g, 86%) was obtained as a colourless powder with

1

give 25 (110 g, 93%) as yellow plates, m.p. 90Ϫ91 °C. Ϫ H NMR

(360 MHz, [D₆]DMSO): δ ϭ 1.51 (s, 3 H, CH₃), 3.68 (m, AAЈ, 2

H, CH₂), 3.95 (m, BBЈ, 2 H, CH₂), 6.64Ϫ6.99 (m, 7 H, ArH), 8.58

(s, 1 H, NH); (CDCl₃): δ ϭ 1.63 (s, 3 H, CH₃), 3.75 (m, AAЈ, 2 H,

CH₂), 4.05 (m, BBЈ, 2 H, CH₂), 5.99 (s, 1 H, NH), 6.50Ϫ7.00 (m,

Ϫ1

˜

7 H, ArH). Ϫ IR (KBr): ν ϭ 3334 cm (νNH). Ϫ MS (EI, T_P

ϭ

143 °C): m/z (%) ϭ 286 (19), 285 (100) [M^ϩ], 271 (11), 270 (61),

226 (33), 225 (11), 199 (13), 198 (42), 197 (13), 193 (18), 154 (12).

Ϫ C₁₆H₁₅NO₂S (285.4): calcd. C 67.34, H 5.30, N 4.91, S 11.24;

found C 67.30, H 5.30, N 5.04, S 11.29.

1

m.p. 168 °C (decomp.). Ϫ H NMR (360 MHz, [D₆]DMSO): δ ϭ

3.94 (t, ³J ϭ 4.9 Hz, 4 H, CH₂OH), 4.76 (t, ³J ϭ 4.8 Hz, 4 H,

N^ϩCH₂), 5.30 (br., 2 H, OH), 8.78 (d, ³J ϭ 6.9 Hz, 4 H, ArH),

9.30 (d, ³J ϭ 6.9 Hz, 4 H, ArH). Ϫ C₁₆H₁₈F₆S₂N₂O₈(544.4): calcd.

C 35.30, H 3.30, N 5.15, S 11.78; found C 35.20, H 3.28, N 5.20,

S 11.79.

2-Acetyl-N-methylphenothiazine (26):^[14]A solution of butyllithium

in hexane (1.6 , 300 mL, 480 mmol) was added at Ϫ80 °C to a

solution of ketal 25 (110 g, 385 mmol) in 650 mL of absolute tetra-

hydrofuran. The orange colour of the resulting solution changed

to deep black, then brown before the bright yellow lithiophenothia-

1,1Ј-Bis(2ЈЈ-hydroxyethyl)-4,4Ј-bipyridinium Diiodide:^[16]A mixture

zine compound deposited. Methyl iodide (35 mL, 550 mmol) was of 4,4Ј-bipyridine (1.56 g, 10 mmol) and iodoethanol (5.2 g,

added dropwise to the stirred suspension, which was allowed to

2.4 mL, 30 mmol) in 30 mL of nitromethane was refluxed for 2 h.

3274

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

During this time a yellow orange precipitate was formed; this was

filtered off under suction and washed first with nitromethane, then

7.4 Hz, 2 H, ArCH₂), 3.19 (m, 4 H, CH₂I), 3.36 (s, 3 H, NCH₃),

6.61 (d, ⁴J ϭ 1.4 Hz, 1 H, ArH, pos. 1), 6.73 (m, 2 H, ArH, pos. 9

3

with ether. After drying at 60 °C in vacuo, the product (3.74 g, and pos. 3), 6.95 (m, 2 H, ArH, pos. 6 and pos. 8), 7.05 (d, J ϭ

74%) was obtained as a yellow orange powder, m.p. 252 °C (de-

7.8 Hz, 1 H, ArH, pos. 4). Ϫ MS (EI, T_Pϭ 289 °C): m/z (%) ϭ

comp.). In reference^[15]the yield was 71% and the m.p. 250 °C (de-

578 (16), 577 (100) [M^ϩ], 120 (41). Ϫ C₂₁H₂₅I₂NS (576.9): calcd.

1

comp.). Ϫ H NMR (360 MHz, [D₆]DMSO): δ ϭ 3.95 (br., 4 H, C 43.69, H 4.37, I 43.96, N 2.43, S 5.55; found C 43.62, H 4.46, I

3

CH₂OH), 4.79 (t, J ϭ 4.8 Hz, 4 H, N^ϩCH₂), 5.28 (br., 2 H, OH), 44.00, N 2.52, S 5.36.

3

8.82 (d, J ϭ 6.9 Hz, 4 H, ArH), 9.33 (d, J ϭ 6.9 Hz, 4 H, ArH).

2,7-Bis(5Ј-iodopentyl)-N-methylphenothiazine (32): BoraneϪtetra-

hydrofuran complex (1 , 0.6 mL) was slowly added at 0 °C by

syringe to a solution of 2,7-bis(pent-4-en-1-yl)-N-methylphenothia-

zine (43) (310 mg, 0.89 mmol) in 15 mL of tetrahydrofuran. The

reaction mixture was heated to 50 °C for 1 h, then cooled to room

temperature. To destroy the excess of borane, 0.6 mL of methanol

was added, followed by 1.8 mL of 1  sodium acetate in methanol.

Finally, iodine chloride (192 mg) was added dropwise. The mixture

was stirred for 45 min, then poured into 50 mL of water. The excess

of iodine chloride was destroyed with sodium thiosulfate. After re-

moval of the tetrahydrofuran in vacuo, the residue was extracted

with two 50-mL portions of trichloromethane, then washed with

50 mL of water. The combined organic phases were concentrated

and subjected to chromatography on silica gel with cyclohexane/

toluene (2:1). The solvent was evaporated under reduced pressure

to give 32 (220 mg, 25%) as a yellow oil, R_fϭ 0.6. Ϫ ¹H NMR

(500 MHz, CDCl₃): δ ϭ 1.43 [m, 4 H, (CH₂)₂CH₂(CH₂)₂], 1.62 (m,

Ϫ1

˜

Ϫ IR (KBr): ν ϭ 3306 cm (νOH). Ϫ MS (EI, T_Pϭ 333 °C): m/

z (%) ϭ 156 (100) [M^ϩϪ 2 ϫ CH₂CH₂I], 128 (85), 127 (30). Ϫ

C₁₄H₁₈I₂N₂O₂(500.1): calcd. C 33.62, H 3.63, I 50.75, N 5.60;

found C 33.76, H 3.60, I 50.70, N 5.72.

2,7-Bis(2Ј-iodoethyl)-N-methylphenothiazine (29): 2,7-Bis(2Ј-bromo-

ethyl)-N-methylphenothiazine (38) (2.0 g, 4.68 mmol) was dissolved

in 100 mL of acetone, saturated with sodium iodide, and the mix-

ture was refluxed for 18 h. After the mixture had been allowed to

cool down to room temperature, the precipitated sodium bromide

was filtered off. The solvent was removed in a rotary evaporator

at reduced pressure, and the residue was dissolved in 100 mL of

trichloromethane and washed with two 100-mL portions of water.

After filtration through silica gel, the solvent was distilled off in

vacuo. The residue was crystallized at Ϫ20 °C from dichlorome-

thane/petroleum ether to give 29 (2.2 g, 90%) as slightly yellow

crystals, m.p. 126Ϫ127 °C. Ϫ ¹H NMR (500 MHz, CDCl₃): δ ϭ

3.07 (t, ³J ϭ 7.8 Hz, 2 H, CH₂I), 3.13 (t, ³J ϭ 7.7 Hz, 2 H, CH₂I),

3.29 (t, ³J ϭ 7.6 Hz, 2 H, ArCH₂), 3.32 (t, ³J ϭ 7.7 Hz, 2 H,

ArCH₂), 3.37 (s, 3 H, NCH₃), 6.62 (‘‘d’’, 1 H, ArH, pos. 1), 6.75

(d, ³J ϭ 8.1 Hz, 1 H, ArH, pos. 9), 6.76 (dd, not resolved, 1 H,

ArH, pos. 3), 6.96 (d, ⁴J ϭ 1.8 Hz, 1 H, ArH, pos. 6), 6.99 (dd,

3

4 H, ArCH₂ϪCH₂ϪCH₂), 1.84 (m, 4 H, CH₂CH₂I), 2.51 (t, J ϭ

3

7.7 Hz, 2 H, ArCH₂), 2.57 (t, J ϭ 7.8 Hz, 2 H, ArCH₂), 3.17 (t,

3

³J ϭ 7.0 Hz, 2 H, CH₂I), 3.19 (t, J ϭ 7.0 Hz, 2 H, CH₂I), 3.36 (s,

3 H, NCH₃), 6.61 (‘‘d’’, 1 H, ArH, pos. 1), 6.74 (m, 2 H, ArH, pos.

3

9 and pos. 3), 6.96 (m, 2 H, ArH, pos. 6 and pos. 8), 7.04 (d, J ϭ

7.7 Hz, 1 H, ArH, pos. 4). Ϫ MS (EI, T_Pϭ 260 °C): m/z (%) ϭ

605 (83) [M^ϩ], 477 (100) [M Ϫ HI], 437 (27) [M Ϫ (CH₂)₃Iϩ1],

349 (23), 294 (45), 252 (50), 224 (54), 194 (44), 180 (18), 127 (63),

91 (17), 55 (30). Ϫ HRMS calcd. for C₂₃H₂₉I₂NS [M^ϩ] 605.0110;

found 605.0099.

4

3

³J ϭ 8.2, J ϭ 1.7 Hz, 1 H, ArH, pos. 8), 7.07 (d, J ϭ 7.7 Hz, 1

H, ArH, pos. 4). Ϫ MS (EI, T_Pϭ 278 °C): m/z (%) ϭ 522 (14),

521 (100) [M^ϩ], 394 (15), 266 (12), 134 (17). Ϫ C₁₇H₁₇I₂NS (521.2):

calcd. C 39.19, H 3.29, I 48.69, N 2.79, S 6.15; found C 39.49, H

3.42, I 48.50, N 2.78, S 5.88.

2,7-Bis[2Ј-(methoxycarbonyl)ethyl]-N-methylphenothiazine (33): A

vigorous stream of hydrogen chloride was passed through a suspen-

sion of 2,7-bis(2Ј-cyanoethyl)-N-methylphenothiazine (41) (5.5 g,

17.2 mmol) in 800 mL of abs. methanol, with ice cooling and stir-

ring. During this procedure the methanol began to boil and the

colour changed from bright yellow to red-brown. After boiling had

ceased, hydrogen chloride was bubbled through the solution for a

further 3 h at room temperature. The stirring was continued over-

night. The mixture was poured onto 1 L of ice and the methanol

evaporated under reduced pressure. The aqueous phase was ex-

tracted with three 200-mL portions of trichloromethane. The com-

bined organic phases were concentrated and subjected to chroma-

tography on silica gel, with ethyl acetate/cyclohexane (1:2). The

product fraction (R_fϭ 0.39) was crystallized from hexane to yield

33 (3.6 g, 55%) as light yellow crystals, m.p. 78Ϫ80 °C. Ϫ ¹H NMR

(360 MHz, CDCl₃): δ ϭ 2.61 (m, 4 H, CH₂CO), 2.84 (t, ³J ϭ

2,7-Βis(3Ј-iodopropyl)-N-methylphenothiazine (30): 2,7-Bis(3Ј-bro-

mopropyl)-N-methylphenothiazine (39) (1.0 g, 3.04 mmol) was dis-

solved in 20 mL of acetone, saturated with sodium iodide, and the

mixture was refluxed for 10 h. The deposited sodium bromide was

filtered off and the solvent removed in vacuo. The residue was

taken up in dichloromethane, the mixture was filtered and the fil-

trate was concentrated in a rotary evaporator to give a yellow oil,

which after treatment with petroleum ether at Ϫ20 °C yielded 30

1

(900 mg, 54%) as an orange-yellow solid, m.p. 38 °C. Ϫ H NMR

(360 MHz, CDCl₃): δ ϭ 2.09 (m, 4 H, CH₂CH₂CH₂), 2.63 (t, ³J ϭ

6.0 Hz, 2 H, ArCH₂), 2.69 (t, ³J ϭ 7.0 Hz, 2 H, ArCH₂), 3.12Ϫ3.20

4

(m, 4 H, CH₂I), 3.36 (s, 3 H, NCH₃), 6.64 (d, J ϭ 1.5 Hz, 1 H,

ArH, pos. 1), 6.75 (m, 2 H, ArH, pos. 9 and pos. 3), 6.98 (m, 2 H,

3

ArH, pos. 6 and pos. 8), 7.05 (d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4).

Ϫ MS (EI, T_Pϭ 289 °C): m/z (%) ϭ 550 (30), 549 (100) [M^ϩ], 394

(27), 239 (11). Ϫ C₁₉H₂₁I₂NS (549.3): calcd. C 41.55, H 3.85, I

46.21, N 2.55, S 5.84; found C 41.29, H 3.93, I 46.03, N 2.60,

S 5.94.

3

7.5 Hz, 2 H, ArCH₂), 2.90 (t, J ϭ 7.6 Hz, 2 H, ArCH₂), 3.34 (s, 3

H, NCH₃), 3.66 (s, 3 H, CH₃O), 3.67 (s, 3 H, CH₃O), 6.64 (d, ⁴J ϭ

1.5 Hz, 1 H, ArH, pos. 1), 6.75 (m, 2 H, ArH), 6.98 (m, 2 H, ArH),

3

˜

7.03 (d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4). Ϫ IR (KBr): ν ϭ 1742

cm^Ϫ1(νCϭO). Ϫ MS (EI, T_Pϭ 248 °C): m/z (%) ϭ 386 (15), 385

(100) [M^ϩ], 371 (17), 285 (25). Ϫ C₂₁H₂₃NO₄S (385.5): calcd. C

65.43, H 6.01, N 3.63, S 8.32; found C 65.47, H 6.04, N 3.50,

S 8.42.

2,7-Bis(4Ј-iodobutyl)-N-methylphenothiazine (31): The preparation

was analogous to that of 30, starting from 2,7-bis(4Ј-bromobutyl)-

N-methylphenothiazine (40) (1.75 g, 3.62 mmol) and 30 mL of

acetone, saturated with sodium iodide. After crystallization from

petroleum ether at Ϫ20 °C, compound 31 (1.44 g, 69%) was ob-

2,7-Bis[3Ј-(methoxycarbonyl)propyl]-N-methylphenothiazine (34): In

analogy to a method described in ref.^[17]2,7-bis[3Ј,3Ј-bis(methoxy-

1

tained as yellow crystals, m.p. 83Ϫ84 °C. Ϫ H NMR (360 MHz,

CDCl₃): δ ϭ 1.68 (m, 4 H, CH₂CH₂CH₂CH₂), 1.84 (m, 4 H, carbonyl)propyl]-N-methylphenothiazine (42) (3.6 g, 6.81 mmol),

CH₂CH₂CH₂CH₂), 2.53 (t, ³J ϭ 7.4 Hz, 2 H, ArCH₂), 2.59 (t, ³J ϭ tetramethylammonium acetate (18 g) and water (0.4 mL) in 50 mL

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3275

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

of 1,3-dimethylimidazolidin-2-one were heated to 140 °C for 10 h.

CH₂CH₂CH₂CH₂), 2.54 (t, ³J ϭ 7.4 Hz, 2 H, ArCH₂), 2.60 (t, ³J ϭ

The solvent was evaporated in vacuo and the residue chromato- 7.6 Hz, 2 H, ArCH₂), 3.36 (s, 3 H, NCH₃), 3.65 (m, 4 H, CH₂OH),

4

graphed on silica gel with cyclohexane/ethyl acetate (4:1) to yield

6.62 (d, J ϭ 1.5 Hz, 1 H, ArH, pos. 1), 6.74 (m, 2 H, ArH), 6.96

34 (2.3 g, 80%) as a yellow oil, R_fϭ 0.35. Ϫ H NMR (360 MHz, (m, 2 H, ArH), 7.04 (d, ³J ϭ 7.7 Hz, 1 H, ArH, pos. 4). Ϫ IR

1

3

Ϫ1

˜

CDCl₃): δ ϭ 1.80 (m, 4 H, CH₂CH₂CH₂), 2.30 (t, J ϭ 7.7 Hz, 2 (NaCl, film): ν ϭ 3419 cm (νOH). Ϫ MS (EI, T_Pϭ 273 °C):

H, CH₂CO₂), 2.32 (t, ³J ϭ 7.5 Hz, 2 H, CH₂CO₂), 2.55 (t, ³J ϭ m/z (%) ϭ 358 (16), 357 (100) [M^ϩ], 298 (15). Ϫ C₂₁H₂₇NO₂S

3

7.7 Hz, 2 H, ArCH₂), 2.60 (t, J ϭ 7.8 Hz, 2 H, ArCH₂), 3.35 (s, 3 (357.5): calcd. 70.55, H 7.61, N 3.92, S 8.97; found C 70.44, H 7.60,

H, NCH₃), 3.66 (s, 6 H, CO₂CH₃), 6.61 (d, ⁴J ϭ 1.5 Hz, 1 H, ArH,

pos. 1), 6.74 (m, 2 H, ArH), 6.96 (m, 2 H, ArH), 7.04 (d, ³J ϭ

7.7 Hz, 1 H, ArH, pos. 4). Ϫ IR (NaCl, film): ν˜ ϭ 1742 cm^Ϫ1(νCϭ

O). Ϫ MS (EI, T_Pϭ 297 °C): m/z (%) ϭ 414 (17), 413 (100) [M^ϩ],

326 (14). Ϫ C₂₃H₂₇NO₄S (413.5): calcd. C 66.80, H 6.58, N 3.39,

S 7.75; found C 66.65, H 6.56, N 3.58, S 7.84.

N 4.15, S 8.86.

2,7-Bis(2Ј-bromoethyl)-N-methylphenothiazine (38): Triphenylphos-

phane (2.1 g, 8 mmol) was added to a solution of 2,7-bis(2Ј-hydro-

xyethyl)-N-methylphenothiazine (35) (1.0 g, 3.32 mmol) and tetra-

bromomethane (2.65 g, 8 mmol) in 50 mL of absolute tetrahydrofu-

ran and the solution was stirred at 55 °C for 5 h. The deposited

triphenylphosphane oxide was filtered off, the solvent was removed

in vacuo and the mixture was taken up in cyclohexane/toluene

(3:2). After filtration through silica gel, the filtrate was concen-

trated and the residue was crystallized from dichloromethane/pet-

roleum ether at Ϫ20 °C to give 38 (720 mg, 51%) as yellow green

needles, m.p. 128Ϫ130 °C. Transformations at larger scales were

possible without problem. Ϫ ¹H NMR (360 MHz, CDCl₃): δ ϭ

3.05 (t, ³J ϭ 7.4 Hz, 2 H, ArCH₂), 3.11 (t, ³J ϭ 7.4 Hz, 2 H,

2,7-Bis(2Ј-hydroxyethyl)-N-methylphenothiazine (35): A solution of

2,7-bis[(methoxycarbonyl)methyl]-N-methylphenothiazine

(18)

(3.0 g, 8.4 mmol) in 500 mL of tetrahydrofuran was added dropwise

with stirring, at room temperature, to a suspension of lithium alu-

minium hydride (6.0 g, 150 mmol) in 500 mL of tetrahydrofuran.

The mixture was stirred at room temperature for a further 2 h and

subsequently refluxed for 2 h. After cooling, the excess of LiAlH₄

was destroyed by addition of 2  hydrochloric acid, the tetrahy-

drofuran was evaporated in vacuo and the residue was taken up in

dichloromethane. After washing of the organic phase with water

and drying with sodium sulfate, the solvent was removed and the

residue was crystallized from methanol/water to give 35 (15 g, 58%)

3

ArCH₂), 3.36 (s, 3 H, NCH₃), 3.50 (t, J ϭ 7.4 Hz, 2 H, CH₂Br),

3.53 (t, ³J ϭ 7.4 Hz, 2 H, CH₂Br), 6.63 (d, ⁴J ϭ 1.3 Hz, 1 H, ArH,

pos. 1), 6.78 (m, 2 H, ArH), 7.00 (m, 3 H, ArH). Ϫ MS (EI, T_P

ϭ

246 °C): m/z (%) ϭ 429 (32), 428 (11), 427 (100) [M^ϩ], 425 (33),

412 (14), 334 (16), 332 (21). Ϫ C₁₇H₁₇Br₂NS (427.2): calcd. C 47.79,

H 4.01, N 3.28, S 7.51; found C 47.59, H 4.02, N 3.34, S 7.63.

1

as slightly yellow, fibrous needles, m.p. 127Ϫ128 °C. Ϫ H NMR

(360 MHz, [D₆]DMSO): δ ϭ 2.61 (t, ³J ϭ 6.7 Hz, 2 H, ArCH₂),

3

2.67 (t, J ϭ 7.0 Hz, 2 H, ArCH₂), 3.27 (s, NCH₃), 3.52 (m, 2 H,

2,7-Bis(3Ј-bromopropyl)-N-methylphenothiazine (39): The prepara-

tion was analogous to that of 38, starting with 2,7-bis(3Ј-hydroxyp-

ropyl)-N-methylphenothiazine (36) (2.0 g, 6.08 mmol), tetrabromo-

methane (4.85 g, 14.65 mmol) and triphenylphosphane (3.85 g,

14.65 mmol) in 100 mL of abs. tetrahydrofuran. Stirring was at 55

°C for 24 h. Yield 1.8 g (65%) of colourless crystals, m.p. 55 °C. Ϫ

¹H NMR (500 MHz, CDCl₃): δ ϭ 2.13 (m, 4 H, CH₂CH₂CH₂),

2.69 (t, ³J ϭ 7.0 Hz, 2 H, ArCH₂), 2.74 (t, ³J ϭ 7.2 Hz, 2 H,

ArCH₂), 3.35Ϫ3.43 (m, 7 H, 2 ϫ CH₂Br and NCH₃at 3.38), 6.65

(‘‘s’’, 1 H, ArH, pos. 1), 6.74 (m, 2 H, ArH), 6.99 (m, 2 H, ArH),

ArCH₂CH₂), 3.59 (m, 2 H, ArCH₂CH₂), 4.53 (m, 1 H, OH), 4.55

(m, 1 H, OH), 6.81 (m, 3 H, ArH), 7.01 (m, 3 H, ArH). Ϫ IR

(KBr): ν˜ ϭ 3242 (br.) (νOH). Ϫ MS (EI, T_Pϭ 225 °C): m/z ϭ

302 (12), 301 (100) [M^ϩ], 287 (9), 286 (12), 270 (60), 224 (11). Ϫ

C₁₇H₁₉NO₂S (301.4): calcd. C 67.74, H 6.36, N 4.65, S 10.64; found

C 67.97, H 6.42, N 4.64, S 10.78.

2,7-Bis(3Ј-hydroxypropyl)-N-methylphenothiazine (36): The pre-

paration was analogous to that of 35, starting with lithium alumi-

nium hydride (1.1 g, 28.8 mmol) in 100 mL of abs. tetrahydrofuran

3

and

2,7-bis[2Ј-(methoxycarbonyl)ethyl]-N-methylphenothiazine

7.06 (d, J ϭ 7.8 Hz, 1 H, ArH, pos. 4). Ϫ MS (EI, T_Pϭ 289 °C):

m/z (%) ϭ 457 (53), 456 (22), 455 (100) [M^ϩ], 454 (11), 453 (49), 440

(17), 348 (40), 346 (40). Ϫ C₁₉H₂₁Br₂NS (454.8): calcd. C 50.13, H

4.65, Br 35.10, N 3.08, S 7.04; found C 50.14, H 4.75, Br 35.25, N

3.18, S 7.25.

(33) (3.7 g, 9.61 mmol) in 100 mL of abs. tetrahydrofuran. Re-

fluxing time was 8 h. After removal of the tetrahydrofuran in va-

cuo, the residue was taken up in trichloromethane. Crystallization

from methanol/water yielded 36 (2.21, 70%) as light brown crystals,

1

m.p. 119Ϫ120 °C. Ϫ H NMR (360 MHz, CDCl₃): δ ϭ 1.85 (m, 4

3

H, CH₂CH₂CH₂), 2.61 (t, ³J ϭ 8.0 Hz, 2 H, ArCH₂), 2.66 (t, J ϭ

2,7-Bis(4Ј-bromobutyl)-N-methylphenothiazine (40): The prepara-

tion was analogous to that of 39, starting with 2,7-bis(4Ј-hydroxy-

butyl)-N-methylphenothiazine (37) (2.0 g, 5.6 mmol), tetrabromo-

methane (4.5 g, 13.6 mmol) and triphenylphosphane (3.6 g,

13.6 mmol) in 80 mL of abs. tetrahydrofuran. Yield 1.81 g (67%) of

3

8.0 Hz, 2 H, ArCH₂), 3.35 (s, 3 H, NCH₃), 3.64 (t, J ϭ 6.4 Hz, 2

H, CH₂OH), 3.66 (t, ³J ϭ 6.4 Hz, 2 H, CH₂OH), 4.81 (br., 2 H,

4

OH), 6.63 (d, J ϭ 1.5 Hz, 1 H, ArH, pos. 1), 6.75 (m, 2 H, ArH),

3

6.95 (m, 2 H, ArH), 7.03 (d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4). Ϫ IR

1

(KBr): ν˜ ϭ 3305 cm^Ϫ1(br., νOH). Ϫ MS (EI, T_Pϭ 289 °C): m/z

(%) ϭ 331 (21), 330 (14), 329 (100) [M^ϩ], 299 (10), 284 (11), 254

(11). Ϫ C₁₉H₂₃NO₂S (329.2): calcd. C 69.27, H 7.04, N 4.25, S

9.73; found C 68.99, H 7.03, N 4.34, S 9.81.

yellow needles, m.p. 71 °C. Ϫ H NMR (360 MHz, CDCl₃): δ ϭ

1.74 (m, 4 H, CH₂CH₂CH₂CH₂), 1.88 (m, 4 H, CH₂CH₂CH₂CH₂),

2.54 (t, ³J ϭ 7.4 Hz, 2 H, ArCH₂), 2.60 (t, ³J ϭ 7.6 Hz, 2 H,

4

ArCH₂), 3.36 (s, 3 H, NCH₃), 3.42 (m, 4 H, CH₂Br), 6.61 (d, J ϭ

1.4 Hz, 1 H, ArH, pos. 1), 6.75 (m, 2 H, ArH), 6.99 (m, 2 H, ArH),

7.06 (d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4). Ϫ MS (EI, T_Pϭ 361 °C):

2,7-Bis(4Ј-hydroxybutyl)-N-methylphenothiazine (37): The prepara-

tion was analogous to that of 35, starting with lithium aluminium

hydride (260 mg, 6.86 mmol) in 25 mL of abs. tetrahydrofuran and

2,7-bis[3Ј-(methoxycarbonyl)propyl]-N-methylphenothiazine (34)

(1.42 g, 3.43 mmol) in 25 mL of abs. tetrahydrofuran. The refluxing

time was 12 h. After evaporation of the tetrahydrofuran in vacuo,

3

m/z (%) ϭ 485 (35), 484 (18), 483 (100) [M^ϩ], 482 (10), 481 (36), 362

(15), 360 (15), 224 (40), 119 (14). Ϫ C₂₁H₂₅Br₂NS (483.3): calcd. C

52.19, H 5.21, Br 33.07, N 2.90, S 6.63; found C 52.00, H 5.22, Br

33.28, N 3.00, S 6.62.

the residue was taken up in ethyl acetate and filtered through silica 2,7-Bis(2Ј-cyanoethyl)-N-methylphenothiazine (41): In analogy to

gel. Crystallization from cyclohexane/ethyl acetate afforded 37

the method described in ref.^[18]a solution of 2,7-bis(2Ј-bromo-

(1.0 g, 82%) as colourless needles, m.p. 71Ϫ72 °C. Ϫ ¹H NMR ethyl)-N-methylphenothiazine (38) (2.0 g, 4.68 mmol) and sodium

(360 MHz, CDCl₃): δ ϭ 1.21 (br., 2 H, OH), 1.56Ϫ1.68 (m, 8 H, cyanide (514 mg, 14.7 mmol) in 10 mL of abs. dimethyl sulfoxide

3276

Eur. J. Org. Chem. 2001, 3255Ϫ3278

PhenothiazineϪBipyridinium Cyclophanes

FULL PAPER

was heated to 70 °C for 24 h. After removal of the solvent in vacuo,

the residue was taken up in dichloromethane and precipitated with

2,7-Diethyl-N-methylphenothiazine (44): Lithium aluminium hy-

dride (800 mg, 21.0 mmol) was added to a solution of 2,7-bis(2Ј-

petroleum ether at Ϫ20 °C to afford 41 (915 mg, 87%) as a yellow bromoethyl)-N-methylphenothiazine (38) (1.12 g, 2.75 mmol) in

solid, m.p. 149 °C. Ϫ ¹H NMR (360 MHz, CDCl₃): δ ϭ 2.56 (t, 50 mL of anhydrous tetrahydrofuran, and the mixture was heated

³J ϭ 7.4 Hz, 2 H, CH₂CN), 2.60 (t, ³J ϭ 7.2 Hz, 2 H, CH₂CN), under reflux for 10 h. After the mixture had cooled to room tem-

2.85 (t, ³J ϭ 7.3 Hz, 2 H, ArCH₂), 2.90 (t, ³J ϭ 7.3 Hz, 2 H,

perature, hydrochloric acid (2 , 10 mL) was added dropwise, and

ArCH₂), 3.37 (s, 3 H, NCH₃), 6.67 (d, ⁴J ϭ 1.6 Hz, 1 H, ArH, pos. the solvent was removed in vacuo. The residue was taken up in

4

1), 6.78 (m, 2 H, ArH, pos. 9 and pos. 3), 6.99 (d, J ϭ 2.1 Hz, 1

dichloromethane. After filtration and evaporation of the solvent

3

4

H, ArH, pos. 6), 7.04 (dd, J ϭ 8.1, J ϭ 2.1 Hz, 1 H, ArH, pos. under reduced pressure in a rotary evaporator, compound 44

8), 7.08 (d, ³J ϭ 7.8 Hz, 1 H, ArH, pos. 4). Ϫ IR (KBr): ν˜ ϭ 2243 (700 mg, 95%) was obtained as a yellow oil; R_fϭ 0.67 (cyclohex-

cm^Ϫ1(νCϵN). Ϫ MS (EI, T_Pϭ 218 °C): m/z (%) ϭ 319 (47) [M^ϩ], ane/ethyl acetate, 1:1). Ϫ ¹H NMR (500 MHz, CDCl₃): δ ϭ 1.19

292 (23) [M Ϫ HCN], 279 (44), 278 (53), 277 (100) [M Ϫ HCN Ϫ (t, ³J ϭ 7.5 Hz, 3 H, CH₂CH₃), 1.22 (t, ³J ϭ 7.6 Hz, 3 H,

CH₃], 201 (16), 199 (13), 183 (11), 119 (14), 77 (19). Ϫ C₁₉H₁₇N₃S CH₂CH₃), 2.55 (q, ³J ϭ 7.6 Hz, 2 H, ArCH₂), 2.60 (q, ³J ϭ 7.6 Hz,

(319.3): calcd. C 71.44, H 5.36, N 13.15, S 10.04; found C 71.18, 2 H, ArCH₂), 3.37 (s, 3 H, NCH₃), 6.64 (d, ⁴J ϭ 1.4 Hz, 1 H, ArH,

H 5.52, N 12.96, S 9.98.

pos. 1), 6.73 (d, ³J ϭ 8.0 Hz, 1 H, ArH, pos. 9), 6.77 (dd, ³J ϭ 7.7,

⁴J ϭ 1.7 Hz, 1 H, ArH, pos. 3), 6.98 (m, 2 H, ArH, pos. 8 and pos.

3

6), 7.05 (d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4). Ϫ MS (EI, T_Pϭ 238

2,7-Bis[3Ј,3Ј-bis(methoxycarbonyl)propyl]-N-methylphenothiazine

(42): In analogy to the method described in ref.^[19]a 0.5  meth-

anolic sodium methoxide solution (50 mL) was added dropwise by

syringe pump (0.5 mL/h), under reflux, to a solution of 2,7-bis(2Ј-

iodoethyl)-N-methylphenothiazine (29) (4.97 g, 9.53 mmol) and di-

methyl malonate (3.8 g, 28.6 mmol) in 100 mL of abs. tetrahydrofu-

ran. The solution was heated for a further 2 d, then cooled and

filtered. The solvent was removed in vacuo, and the residue was

taken up in ethyl acetate and filtered through silica gel. After evap-

oration of the solvent in a rotary evaporator under reduced pres-

°C): m/z (%) ϭ 270 (19), 269 (100) [M^ϩ], 255 (17), 254 (95), 239

(17), 224 (26), 194 (16), 192 (10). Ϫ C₁₇H₁₉NS (269.2): calcd. C

75.84, H 7.06, N 5.20, S 11.90; found C 75.88, H 7.34, N 4.98,

S 11.66.

Acknowledgments

sure, compound 42 (3.7 g, 74%) was obtained as a yellow oil; R_fϭ We heartily thank Dr. William E. Hull of the Deutsches Krebsfor-

0.51 (cyclohexane/ethyl acetate 1:1). Ϫ ¹H NMR (360 MHz, schungszentrum (DKFZ), Zentrale Spektroskopie, for discussion

CDCl₃): δ ϭ 2.19 (m, 4 H, CH₂CH), 2.55 (t, ³J ϭ 7.2 Hz, 2 H, of the NOE spectra of the phenothiazineϪbipyridinium oligoox-

3

ArCH₂), 2.60 (t, J ϭ 7.2 Hz, 2 H, ArCH₂), 3.35 (s, 3 H, NCH₃), acyclophanes. We also thank Mrs. C. Bernd and Dr. M. Rentzea

3.38 (m, 2 H, CH₂CH), 3.73 (s, 12 H, OCH₃), 6.61 (d, ⁴J ϭ 1.5 Hz, for carrying out the mass spectra and their elucidation.

1 H, ArH, pos. 1), 6.74 (m, 2 H, ArH), 6.96 (m, 2 H, ArH), 7.04

3

(d, J ϭ 7.7 Hz, 1 H, ArH, pos. 4). Ϫ IR (KBr): ν˜ ϭ 1737 cm^Ϫ1

(νCϭO). Ϫ MS (EI, T_Pϭ 280 °C): m/z (%) ϭ 531 (16), 530 (31),

[1]

H. A. Staab, D.-Q. Zhang, C. Krieger, Liebigs Ann./Receuil

529 (100) [M^ϩ], 515 (12), 471 (16), 398 (17), 397 (58), 384 (25), 382

1997, 1551Ϫ1556.

(13), 252 (22), 250 (18), 237 (15), 132 (14). Ϫ C₂₇H₃₁NO₈S (529.4):

calcd. C 61.23, H 5.90, N 2.64, S 6.05; found C 60.97, H 6.13, N

2.63, S 6.18.

[2]

Y. Kawanishi, N. Kitamura, S. Tazuke, J. Phys. Chem. 1986,

90, 2469Ϫ2475; ibid. 6034Ϫ6037.

[3]

H. Yonemura, H. Saito, S. Matsushima, H. Nakamura, T. Mat-

suo, Tetrahedron Lett. 1989, 30, 3143Ϫ3146.

[4]

[5]

H. Yonemura, H. Nakamura, T. Matsuo, Chem. Phys. Lett.

1989, 155, 157Ϫ161; Chem. Phys. 1992, 162, 69Ϫ78.

Preliminary communication: H. Bauer, J. Briaire, H. A. Staab,

Tetrahedron Lett. 1985, 26, 6175Ϫ6178; Full paper: H. Bauer,

M. Lang, H. A. Staab, Europ. J. Org. Chem., in preparation;

see also H. Bauer, V. Matz, M. Lang, C. Krieger, H. A. Staab,

Chem. Ber. 1994, 127, 1993Ϫ2008.

C. Petry, M. Lang, H. A. Staab, H. Bauer, Angew. Chemie 1993,

105, 1791Ϫ1795; Angew. Chem. Int. Ed. Engl. 1993, 32,

1711Ϫ1714.

M. J. Shephard, M. N. Paddon-Row, J. Phys. Chem. A. 1999,

103, 3347Ϫ3350; K. A. Joliffe, T. B. M. Bell, K. P. Ghiggino,

S. J. Langford, M. N. Paddon-Row, Angew. Chem. 1998, 110,

960Ϫ963.

N-Methyl-2,7-bis(pent-4-en-1-yl)phenothiazine (43): In analogy to

the method described in ref.^[20][1,2-bis(diphenylphosphanyl)-

ethane]nickel(II) chloride NiCl₂(dppe)₂(132 mg, 0.25 mmol) was

added to a solution of 2,7-bis(2Ј-iodoethyl)-N-methylphenothiazine

(29) (1.0 g, 1.92 mmol) in 15 mL of anhydrous tetrahydrofuran fol-

lowed at Ϫ78 °C over 30 min by a 1  solution of allylmagnesium

bromide (4.8 mL) in tetrahydrofuran. The mixture was allowed to

warm to room temperature whilst stirring over 2 h, and was then

refluxed for a further 2 h. After it had cooled to room temperature,

hydrochloric acid (2 , 10 mL) was added. The solvent was re-

moved in vacuo and the residue was shaken with trichloromethane/

water. The organic phase was concentrated and the residue chroma-

tographed on silica gel with cyclohexane/toluene (10:1) to give 43

(337 mg, 51%) as a slightly yellow oil, R_fϭ 0.32. Ϫ ¹H NMR

[6]

[7]

[8]

[9]

T. Geiger, Dissertation, University of Heidelberg, 1978.

H. A. Staab, C. P. Herz, C. Krieger, M. Rentzea, Chem. Ber.

1983, 116, 3813Ϫ3830.

(500 MHz, CDCl₃):

δ ϭ 1.64Ϫ1.73 (m, 4 H, ArCH₂CH₂),

[10]

3

P. R. Ashton, R. Ballardini, V. Balzani, A. Credi, M. T. Gan-

2.05Ϫ2.11 (m, 4 H, CH₂CHϭCH₂), 2.52 (t, J ϭ 7.6 Hz, ArCH₂),

2.58 (t, ³J ϭ 7.8 Hz, 2 H, ArCH₂), 3.36 (s, 3 H, NCH₃), 4.96Ϫ5.05

´

dolfi, S. Menzer, L. Perez-Garcıa, L. Prodi, J. F. Stoddart, M.

Venturi, A. J. P. White, D. J. Williams, J. Am. Chem. Soc. 1995,

117, 11171Ϫ11197.

4

(m, 4 H, CHϭCH₂), 5.79Ϫ5.86 (m, 2 H, CHϭCH₂), 6.62 (d, J ϭ

1.1 Hz, 1 H, ArH, pos. 1), 6.73 (m, 2 H, ArH), 6.95 (m, 2 H, ArH),

[11]

[12]

[13]

J. Salbeck, Anal. Chem. 1993, 65, 2161Ϫ2173.

J. Salbeck, J. Electroanal. Chem. 1992, 340, 169Ϫ195.

M. Kimura, K. Kajita, N. Onoda, S. Morosawa, J. Org. Chem.

1990, 55, 4887Ϫ4892.

G. Cauquil, A. Casadevall, C. R. Acad. Sci. 1954, 238,

908Ϫ911.

3

7.04 (d, J ϭ 7.6 Hz, 1 H, ArH, pos. 4). Ϫ IR (NaCl, film): ν˜ ϭ

1640 cm^Ϫ1(νCHϭCH₂). Ϫ MS (EI): m/z (%) ϭ 349 (100) [M^ϩ],

334 (10), 309 (12), 294 (34), 262 (10). Ϫ C₂₃H₂₇NS (349.5): calcd.

C 79.03, H 7.79, N 4.01, S 9.17; found C 79.15, H 7.80, N 4.09,

S 9.03.

[14]

Eur. J. Org. Chem. 2001, 3255Ϫ3278

3277

H. Bauer, F. Stier, C. Petry, A. Knorr, C. Stadler, H. A. Staab

FULL PAPER

[15]

[19]

[20]

G. Cauquil, A. Casadevall, Bull. Soc. Chim. Fr. 1955,

C. F. Lane, H. L. Myatt, J. Daniels, H. B. Hopps, J. Org. Chem.

1974, 39, 3052Ϫ3054.

1061Ϫ1075.

[16]

J. Volke, V. Volkova, Collect. Czech. Chem. Commun. 1969,

34, 2037Ϫ2047.

A. P. Krapcho, Synthesis 1982, 805Ϫ822, there p. 811.

L. Friedman, H. Shechter, J. Org. Chem. 1960, 25, 877Ϫ879.

G. Consiglio, F. Morandini, O. Piccolo, J. Am. Chem. Soc.

1981, 103, 1846Ϫ1847.

[17]

Received January 30, 2001

[18]

[O01039]

3278

Eur. J. Org. Chem. 2001, 3255Ϫ3278

Article Doi

Phenothiazine - Bipyridinium cyclophanes

DOI: 10.1002/1099-0690(200109)2001:17<3255::AID-EJOC3255>3.0.CO;2-0

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