Synthesis of porphyrazine-octaamine, hexamine and diamine derivatives

Tetrahedron 61 (2005) 6115–6130

Synthesis of porphyrazine-octaamine, hexamine and

diamine derivatives

Matthew J. Fuchter,^aL. Scott Beall,^aSven M. Baum,^aAntonio Garrido Montalban,^a

Efstathia G. Sakellariou,^aNeelakandha S. Mani,^bTodd Miller,^bBenjamin J. Vesper,^c

c,

Andrew J. P. White,^aDavid J. Williams,^aAnthony G. M. Barrett^a,and Brian M. Hoffman

*

^aDepartment of Chemistry, Imperial College London, London SW7 2AZ, UK

^bDepartment of Chemistry, Colorado State University, Fort Collins, CO 80523, USA

^cDepartment of Chemistry, Northwestern University, Evanston, IL 60208, USA

Received 11 February 2005; revised 14 March 2005; accepted 23 March 2005

Abstract—The syntheses of a variety of substituted diaminomaleonitriles, with variable nitrogen substituents, were undertaken. Linstead

macrocyclization of the resulting diaminomaleonitriles gave access to a wide range of functionalized porphyrazine-octaamines and

hexamines and norphthalocyaninediamines. Conversion of these macrocycles into metallic derivatives and studies of their electronic

absorption, solubility and electrochemistry are described. These ﬂexible tetraazaporphyrins show potential in a range of applications

including biomedical agents, novel charge–transfer complexes, chemical sensors, novel electronic materials and non-linear optics.

1. Introduction

porphyrazines,¹¹as well as a variety of solitaire-macro-

cycles.^8,12,13The platinum(II) solitaire porphyrazines are

potent photosensitizers and have the potential as dual-

warhead anti-cancer agents.¹⁴In addition, we have prepared

several charge-transfer complexes with C₆₀^15,16and utilized

amino-porphyrazine nitrogen donor pockets in metal

sensing applications.¹⁷An important discovery was the

oxidative scission of one of the pyrrole units to yield the

seco-porphyrazines.¹⁸Detailed photophysical studies into

these curious macrocycles unveiled their potent photo-

sensitizing ability for the production of singlet oxygen.¹⁹

We have utilized this feature in the dye catalyzed

photooxygenation of dienes²⁰and have prepared several

novel seco-porphyrazines with variable solubility and

photophysical proﬁles.^21,22Ercolani and co-workers have

prepared a variety of amino-porphyrazines with annulated

heterocyclic rings.^23–27We have exploited this ‘protection’

of the free amino functionality with selenium in the

synthesis of Schiff Base porphyrazines, for application as

molecular scaffolds.^28,29Recently we have also disclosed a

ROM-polymerization-capture-release strategy for the

Tetraazaporphyrins (porphyrazines, pz) can be viewed as

porphyrin analogues, with meso nitrogen atoms replacing

the meso carbon atoms. This alteration results in signiﬁcant

structural and electronic changes within the macrocycle.¹

Porphyrazines, however, have received considerably less

synthetic interest than the related porphyrins and phthalo-

cyanines.^2,3Peripheral heteroatom functionalization of the

macrocycle results in signiﬁcant modulation of their

physical and electronic properties.¹Barrett, Hoffman and

co-workers have published extensively on the synthesis of

porphyrazines bearing thiols, amines or alcohols as ring

substituents, with the conversion of these polydentate

ligands to a variety of coordination complexes.^1,4

Porphyrazines containing peripheral amino substituents

constitute an important class of these ﬂexible molecules.

Since our original report on these electron-rich octaamino-

macrocycles,⁵several structural analogues have been

6

prepared, including trans-A₂B₂

and A₃B type

porphyrazines^7–9and porphyrazine–phthalocyanine

hybrids.¹⁰We have explored the coordination chemistry

of these novel ligands, preparing palladium(II) star-

chromatographically-free

porphyrazines.³⁰

synthesis

of

amino-

Keywords: Porphyrazine; Aminoporphyrazine; Nickel porphyrazines;

Linstead macrocyclization; UV–vis spectroscopy; Electrochemistry.

This report describes the syntheses of diverse amino-

porphyrazines prepared in our laboratories with the aim to

provide information on how the substituents bonded to the

peripheral nitrogens intimately inﬂuence the physical,

*

Corresponding authors. Tel.: C44 207 594 5766; fax: C44 207 594 5805

(A.G.M.); Tel.: C1 847 491 3104; fax: C1 847 491 7713 (B.M.H.);

e-mail addresses: agmb@imperial.ac.uk; bmh@northwestern.edu

doi:10.1016/j.tet.2005.03.090

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M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

chemical and electronic properties of the porphyrazinic

macrocycle.

2. Results and discussion

2.1. Dialkylamino functionalized porphyrazines

The peripheral nitrogen substituents of octaamino-

porphyrazines have a profound inﬂuence on the physical

and chemical properties of the macrocycle. This readily

adaptable effect can be exploited for the synthesis of

porphyrazines which display ﬂexible solubility, variable

electronic absorption spectra and tuneable redox properties.

Following the method of Sheppard and co-workers,³¹tetra-

functionalized maleonitriles were prepared in a controlled

manner and subsequently cyclized to the desired

porphyrazine products. Thus, commercially inexpensive

diaminomaleonitrile (DAMN) was alkylated under strongly

basic conditions to yield tetraalkylated maleonitriles 2a–2c

(53–69%) (Scheme 1). Alternatively, successive reductive

alkylations with benzaldehyde yielded the dibenzyl deriva-

tive 5,³¹which was subsequently converted into the fully

substituted maleonitriles 2d–2e (64–80%). Notably, deriva-

tive 5 has proved a robust derivative for the synthesis of

various functionalized maleonitriles (vide infra).

n

Scheme 2. Reagents and conditions: (a) Mg(OⁿBu)₂, BuOH, D, 24 h. (b)

TFA or AcOH. (c) Ni(OAc)₂, PhCl, DMF, D.

The electronic absorption spectra for the amino-

porphyrazines were consistent with previous observations⁴

and can be rationalized using Gouterman’s four orbital

model.³³Octaamino-porphyrazines have D_4hsymmetry,

with a doubly degenerate lowest unoccupied molecular

orbital (LUMO) (e_g) and two highest occupied molecular

orbitals (HOMOs) that complete the four Gouterman

orbitals with a_1uand a_2usymmetry. The compounds

therefore displayed two visible transitions, a long-wave-

length Q band (w650 nm), corresponding to a_2u/e_gand a

short wavelength B band (Soret) (w350 nm) corresponding

to a_1u/e_g. In addition, heteroatom-substituted

porphyrazines display intense coupling between the non-

bonding, lone pair electrons and the macrocyclic p-system.

The resultant n–p* transitions were visible in the electronic

absorption spectra (w550 nm). The strong coupling of the

non-bonding electrons with the p-system also resulted in

signiﬁcant broadening due to vibrational ﬁne structure. A

representative UV–vis spectrum for porphyrazine 6a is

shown in Figure 1.

Scheme 1. Reagents and conditions: (a) Me₂SO₄or BnBr or CH₂]

CHCH₂Br, NaH, DME or THF, K30 to 20 8C. (b) C₆H₅CHO, MeOH, D.

(c) NaBH₄, MeOH, THF.

Linstead macrocyclization³²of dinitriles 2 gave access to

the octaamino-porphyrazines 6 in reasonable yields

(15–48%) (Scheme 2). The porphyrazines were isolated as

blue-black solids with purple reﬂections. Acidic demetalla-

tion by short exposure to triﬂuoroacetic acid or prolonged

contact with acetic acid gave access to the free base

porphyrazines 7. Remetallation with a variety of metal salts

was then possible using the metal (II) acetate in DMF.⁴In

particular, porphyrazines 7 were converted to the nickel(II)

derivatives 8 in good yield (43–92%). All the octaamino-

porphyrazines prepared were readily soluble in organic

Figure 1. Electronic absorption spectra of 6a.

The electronic absorption data for representative porphyr-

azines 6–8 are listed in Table 1.

solvents,

a feature of the heteroatom-substituted

As can be seen in Table 1, all the macrocycles prepared

displayed qualitatively similar spectra with visible Soret and

Q bands as well as an n–p* transition. However, it is

difﬁcult to glean any structure–absorption trends with

porphyrazines, which is more favorable than the structurally

analogous phthalocyanines. Many of the derivatives were

also crystalline. As a result, X-ray crystal structures have

been solved for 6b and 8e.⁵

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

Table 1. Electronic absorption data for porphyrazines 6–8

6117

pz

R¹, R²

Metal

l_max(log 3)

6a⁷

6b

6d

7a⁷

7c

Me, Me

Bn, Bn

Mg

2H

Ni

335 (4.81), 599 (4.27), 752 (4.33)

368 (4.75), 574 (4.45), 707 (4.51)

350 (4.56), 544 (4.10), 714 (4.38)

334 (4.57), 531 (4.29), 709 (4.16)

333 (4.67), 526 (4.47), 730 (4.36)

330 (4.75), 536 (4.59), 734 (4.44)

325 (4.92), 360 (4.50), 561 (4.42), 704 (4.52)

322 (4.71), 536 (3.95), 654 (4.04), 674 (4.00)

324 (4.72), 511 (4.53), 688 (4.49)

Me, Bn

Me, Me

allyl, allyl

allyl, Bn

Me, Me

Bn, Bn

7e

8a

8b

8e

Ni

allyl, Bn

respect to either the amino substituents or the metal

occupying the porphyrazine cavity. For example, on going

from 6a to 7a to 8a (MZMg to 2H to Ni), the Soret band

remained approximately stationary, whereas the Q band

underwent a blue shift (w43 nm) on conversion to the free

base, with no real change on remetallation with nickel. In

addition, the n–p* transition also underwent a hypso-

chromic effect on demetallation (w68 nm), with a red shift

on insertion of nickel (w30 nm). On changing the

substituents from methyl (R¹ZR²ZMe) to benzyl (R¹Z

R²ZBn) for the magnesium derivatives (6a vs 6b), the

Soret underwent a red shift (w13 nm), whereas the Q band

and n–p* transitions underwent a blue shift (w45 and

w25 nm, respectively). For the nickel macrocycles (8a vs

8b), the Soret underwent no such shift and the Q band and

n–p* transitions underwent a similar shift as observed for

the magnesium derivative. Furthermore, the Soret was split

for 8a, whereas the Q band was split for 8b. In general, the

electronic absorptions of the macrocycles were sensitive to

both the amino-substituents as well as the cavity metal,

although it is hard to predict the differences these changes

will produce.

As expected, the tuning of the amino substituent altered the

solubility proﬁle of the macrocycles. Although porphyr-

azines 12a and 12c showed a greatly enhanced solubility in

polar, protic solvents such as methanol, unfortunately, they

were not water soluble. However, to our delight porphyr-

azine 12b was freely soluble in water, producing a

homogeneous purple solution. Thus, one possibility for

the synthesis of water soluble, neutral amino-porphyrazine

analogues is the substitution of PEG chains of sufﬁcient

length, with free hydroxyl-functionality at the termini. We

2.2. Polyethyleneglycol-amino-functionalized

porphyrazines

Polyetherol-appended thioporphyrazines have already

shown promise as both chemical sensors³⁴and biomedical

imaging and therapeutic agents.^35,36In particular, the

polyethyleneglycol (PEG) chains confer enhanced aqueous

solubility, which makes them ideal candidates for binding

metal ions in water or for medical applications. Recently we

have disclosed the synthesis of one such PEG-function-

alized maleonitrile and its application to the synthesis of a

novel seco-porphyrazine.²¹Alkylation of benzyl derivative

5, with iodo-derivatives 9a³⁷or 9b (formed on treatment of

the mono-protected PEG³⁸with iodine and triphenyl-

phosphine), under the basic conditions gave the maleo-

nitriles 10a and 10b with varying PEG chain lengths. In

addition, reaction with iodide 9c³⁹yielded the methyl-

capped derivative 9c (Scheme 3). Macrocyclization

furnished the PEG substituted amino porphyrazines 11 in

low yield. In the case of THP-protected derivatives 11a and

11b, demetallation and concomitant deprotection using

acidic conditions²¹gave access to the free base macrocycles

12a and 12b. For the methyl-capped product 11c, simple

acidic demetallation occurred on exposure to acetic acid

(Scheme 3). Remetallation within the macrocyclic cavity

was possible for the PEG-appended porphyrazines; for

example 12c was readily converted to its nickel(II)

derivative (not shown).

Scheme 3. (a) I(CH₂CH₂O)_(nC1)R¹(9), Cs₂CO₃, DMF, 50 8C.

(b) Mg(OⁿBu)₂, ⁿBuOH, D, 24 h. (c) AcOH or AcOHHCl, CHCl₃,

MeOH, 20 8C.

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M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

are currently looking to exploit this result in the context of

porphyrazine biomedical agents.

catalyzed amination of 5 using methyl chloroacetate also

provided imine 16 in 77% yield. Therefore, in the presence

of certain electrophiles, benzyl maleonitrile 5 acts more like

a hydride donor than a nucleophile. This is most probably

due to the high acidity of the benzyl protons coupled with

the low solubility of imine 16, driving the reaction in an

undesired direction.

In addition to the physical properties, PEG-appended

aminoporphyrazines display intriguing electronic absorp-

tion spectra. We have previously noted this for the

thioporphyrazine PEG derivatives.⁴For example, 12b

displays a complex spectrum with a split Soret band (327

and 356 nm) as well as a split Q band, which was further

complicated by shoulders (667 and 741 nm). Furthermore,

an intensive n–p* transition was visible at 556 nm.

It was anticipated that the introduction of aliphatic

substituents would avoid this predominant side reaction

and would serve as a better model for further investigations.

Selective dialkylation of DAMN 1 with limited quantities of

alkyl halides (for example methyl iodide) gave mixtures of

substituted products. Likewise, aliphatic aldehydes proved

troublesome in the reductive alkylation pathway (vide

supra). An alternative strategy, which would allow the

introduction of alkyl substituents prior to the formation of

the maleonitrile, was therefore examined. The dimerization

of imines has been previously demonstrated for this

application.^42,43N-(Isopropylamino)acetonitrile 17 was

readily prepared following the procedure of Boyer et al.⁴³

The preparation of imine 19 was carried out by treatment

with tert-butyl hypochlorite followed by dehydrochlorina-

tion with triethylamine^42,44or using calcium hypochlorite as

the chlorination agent followed by elimination with calcium

hydroxide⁴³(49%) (Scheme 4). Alternatively, the use of

N-chlorosuccinimide (NCS) in carbon tetrachloride resulted

in a quantitative conversion to the corresponding N-chloro

derivative 18, as judged by NMR, after 5 min. Subsequent

elimination of intermediate 18 with calcium hydroxide

provided imine 19 in an improved 90% yield. Dimerization

of imine 19 was carried out by reaction with stannic chloride

in dry benzene⁴³and gave N,N⁰-diisopropyldiaminomaleo-

nitrile 20 in 56% yield, along with 7% of the corresponding

trans-isomer (as judged by ¹H NMR) (Scheme 4). Changing

the solvent from benzene to carbon tetrachloride did not

suppress dimerization and gave imine 19, which was used

directly without isolation to provide 20. This provided

multigram quantities of an alternative disubstituted amino-

maleonitrile derivative 20, a useful intermediate in our quest

for other functionalized aminoporphyrazines.

2.3. Carboxymethylamino-functionalized porphyrazines

In order to extend the coordination chemistry of the

aminoporphyrazines and moreover, provide new and varied

macrocycles for application to chemical sensing of metal

ions in solution, the synthesis of an acetic acid function-

alized porphyrazine 6 (R¹ZR²ZCH₂CO₂H) was examined.

The linking of two acetic acid chains to each peripheral

amino group would produce an analogue, which should

mimic ethylenediaminetetracetic acid (EDTA). Previously

reported macrocyclic analogues of EDTA have been

reported to display much higher binding constants with

metal ions.^40,41Unfortunately, this challenging target has

thus far eluded preparation. However, these failed

attempts have led to several important observations, high-

lighting the limitations of both maleonitrile 5 as a

difunctional starting material and the Linstead macro-

cyclization reaction.

Early in these synthetic studies, the direct tetra-function-

alization of DAMN 1, proved to be untenable. Attempted

alkylation with methyl chloroacetate, the orthoester 13

(XZCl, Br), the ortho ester precursor 14 or protected

derivatives of chloroacetaldehyde (e.g., 15) under basic

conditions (NaH or Cs₂CO₃) all failed, resulting either in

decomposition or no reaction (Fig. 2).

Initially attempted alkylation of 20 with alkyl chlorides and

Figure 2.

The use of benzyl derivative 5 was therefore employed for

the synthesis of acetic acid functionalized analogues.

However, curiously, attempts to alkylate maleonitrile 5

with methyl chloroacetate in the presence of sodium hydride

resulted in the formation of the imine 16 (Fig. 2) in 64%

yield. Attempted alkylation with a range of functionally

equivalent electrophiles provided the same result. Palladium

Scheme 4. Reagents and conditions: (a) Ca(OCl)₂, CaCl₂, CH₂Cl₂, 20 8C or

NCS, CCl₄, 55 8C. (b) Ca(OH)₂, CaCl₂, CH₂Cl₂, D. (c) SnCl₄, PhH, 20 8C.

(d) BrCH₂CO₂^tBu, NaH, DMF, K10 to 20 8C.

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

6119

Figure 3. X-ray crystal structure of dinitrile 21.

sodium hydride in THF was unsuccessful, with quantitative

recovery of starting material. However, when DMF was

used as the solvent, dinitrile 21 was obtained in an excellent

84% yield (Scheme 4). A single crystal X-ray analysis

conﬁrmed the structure of dinitrile 21 with the requisite cis-

geometry of the double bond in place (Fig. 3).

Despite these disappointing results, EDTA appended

porphyrazines are still a valuable target in our studies on

the aminoporphyrazines and alternate strategies for their

production are currently being explored in our laboratories.

The current synthetic efforts, however, highlight the

problems associated with maleonitrile 5 as a functional

intermediate and the incompatibility of certain substrates

with Linstead macrocyclization.

Unfortunately, attempted macrocyclization of dinitrile 21

under Linstead conditions using either magnesium butoxide

or propoxide failed to provide any of the corresponding

porphyrazine and resulted in the decomposition of the

starting material. It seems reasonable to assume that the

failure of the reaction could be due to (a) the acidic protons

adjacent to the carbonyl group or (b) steric hindrance of the

tert-butyl ester. It was therefore considered that conversion

of dinitrile 21 to its carboxylic acid counterpart would not

only reduce the acidity of the a-protons, but also the steric

hindrance. Thus, hydrolysis of the tert-butyl ester using neat

TFA, produced a dark brown oil, the identity of which was

established by spectroscopic analysis (NMR, IR, MS).

Exposure of the crude material to magnesium butoxide

resulted only in decomposition and none of the desired

porphyrazine could be isolated.

2.4. Pyridyl functionalized porphyrazines

Following previous reports of cationic porphyrins as

potential DNA-binding and cleavage agents,⁴⁵as well as

sensitizers for photodynamic therapy,⁴⁶we ﬁrst reported the

synthesis of an octacationic pyridyl porphyrazine in 1999.⁴⁷

These novel systems were both freely soluble in water as the

chloride salt and showed strong binding to calf thymus

DNA.⁴⁸Thus, in continuation of these studies, the synthesis

of unsymmetrical pyridyl-substituted aminoporphyrazines

was carried out. The resultant macrocycles should display

rich and varied redox chemistry and could be of use in the

application of non-linear optics due to the presence of both

donor and acceptor functionality.

A statistical, mixed Linstead macrocyclization of pyridyl

In a ﬁnal effort to utilize this methodology in the synthesis

of an acetic acid functionalized porphyrazine, ortho-ester

derivative 22 was converted into the N-alkylaminoacteo-

nitrile derivative 23 (Scheme 5). Although N-chlorination

was straightforward, dehydrohalogenation of the resultant

derivative 24 gave only polymeric intractable products

under a variety of conditions.

Scheme 5. Reagents and conditions: (a) ClCH₂CN, Et₃N, Et₂O, K10 to

20 8C. (b) Ca(OCl)₂, CaCl₂, CCl₄, 20 8C.

Scheme 6. Reagents and conditions: (a) 2a, Mg(OⁿBu)₂, ⁿBuOH, D, 24 h.

(b) TFA. (c) Zn(OAc)₂, DMF, D.

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M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

maleonitrile 25,⁴⁷with aminomaleontrile 2a furnished

porphyrazine 26, the desired (A₃B) hexamine, along with

octaaminoporphyrazine 6a (A₄) (Scheme 6). Traces of cis

and trans A₂B₂porphyrazines were also observable by mass

spectrometry and were isolated as an inseparable mixture.

Exposure of porphyrazine 26 to TFA gave the free base

derivative 27 (30% overall) and subsequent remetallation

under standard conditions gave the zinc(II) macrocycle 28

(63%).

A comparison of the electrochemical data of the novel

pyridyl-appended porphyrazine 27 and the related octa-

amino-porphyrazine 6a is presented in Table 2.

Scheme 7. Reagents and conditions: (a) NaCN, DMSO. (b) I₂, NaOMe,

MeOH, D.

Table 2. Electrochemical data for porphyrazines 27 and 6a

pz^2C/pz^C

pz^C/pz

pz/pz^1K

pz^1K/pz^2K

27

6a

C1.08

K0.06

C0.95

K0.27

K0.29

K1.61

K0.49

—

Measured in dichloromethane, with 0.1 M Bu₄NPF₆as electrolyte, Pt disk

working electrode, at a scan rate of 110 mV s^K1

.

The presence of eight electron donating dimethylamino

groups in ligand 6a results in a system that is extremely

easy to oxidize with a ﬁrst reversible oxidation centered at

E_1/2ZK0.27 V with respect to Fc^C/Fc. Upon replacement

of two NMe₂units by the electron withdrawing pyridyl

groups, the ﬁrst oxidation potential is shifted to E_1/2

Z

C0.95 V, thus, indicating that oxidation of the new system

is, as expected, more difﬁcult. Also as a consequence of the

electron withdrawing pyridyl groups, the ﬁrst reduction

potential of compound 27 is found at K0.29. In contrast, the

electron rich ligand 2a is more difﬁcult to reduce with the

ﬁrst reduction potential centered at K1.61 V. This result

demonstrates how simple modiﬁcation of the porphyrazine

substituents can lead to profound differences in the redox

potentials of the macrocycles.

In addition to the potential biomedical applications of

pyridyl-appended porphyrazines, we have demonstrated the

synthesis of amino porphyrazines bearing pyridyl-based

metal donor pockets 6 (R¹ZBn, R²Z2-pyridylmethyl).¹⁷

Such systems show efﬁcient binding of 4 equiv of a variety

of metal cations including heavy metals such as cadmium(II)

and therefore have potential in sensor applications. In a

continuation of this work, the preparation of a bipyridyl

porphyrazine 36 was initiated. Two strategies were

envisaged, whereby the bipyridyl linkage could be con-

structed pre- or post-macrocyclization. Towards the latter

goal, nitrile 30 was prepared by nucleophilic displacement

of the corresponding chloride 29 (prepared from 2-methoxy-

4-methylpyridine,⁴⁹by chlorination of a transient silyl

derivative synthesized following the method of Katrizky

et al.⁵⁰). Dimerization of 30 with sodium methoxide and

iodine gave the requisite dinitrile 31 (Scheme 7). However,

macrocyclization of dinitrile 31 was problematic, with low

yields of a high polarity material, which could not be fully

puriﬁed. Therefore, introduction of the bipyridyl residue

before the Linstead macrocyclization reaction was

investigated.

Scheme 8. Reagents and conditions: (a) KCN, 18-crown-6, MeCN. (b) I₂,

NaOMe, MeOH, D. (c) NH₃, cat Na, HOCH₂CH₂OH, D. (d) Mg(OⁿBu)₂,

ⁿBuOH, D, 24 h. (e) TFA.

Similar cyanide displacement of acid sensitive chloride

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

6121

Figure 4. X-ray crystal structure of dinitrile 34.

32,⁵¹yielded nitrile 33, which was subsequently oxidatively

dimerized in excellent yield (64% over 2 steps) (Scheme 8).

The trans geometry of dinitrile 34 was elucidated by X-ray

crystallography (Fig. 4). Unfortunately, attempted Linstead

macrocyclization of dinitrile led to decomposition of the

substrate. This was attributed to the slow thermal isomer-

ization of dinitrile 34 and the general sensitive nature of the

substrate. Instead, dinitrile 34 was ﬁrst converted to the

diiminopyrroline 35, upon treatment with ammonia gas

in ethylene glycol at reﬂux catalyzed by sodium 2-hydroxy-

ethoxide.⁵²The crude product 35 was immediately macro-

cyclized to yield the porphyrazine 36, which was

subsequently demetallated with triﬂuoroacetic acid, giving

macrocycle 37, albeit in low yield (ca. 2% from 34)

(Scheme 8).

39a and 39b (Scheme 9). Chromatographic puriﬁcation of

these highly insoluble pigments proved impossible and

therefore the macrocycles were demetallated to give free-

bases 40a and 40b, which were sufﬁciently soluble to purify.

However, the solubility of 40a and 40b precluded further

manipulation and conversion to the nickel (II) derivatives

lead to macrocycles with an even lower solubility proﬁle.

The poor solubility of the norphthalocyanines has been

previously noted.¹⁰

The UV–vis spectra of the octabipyridyl porphyrazines 36

and 37 exhibited qualitatively similar spectra to the

corresponding octapyridyl porphyrazines.⁴⁷The mag-

nesium derivative 36 displayed a Soret band at 337 nm

and a Q band at 537 nm. In addition, there were also strong

absorption bands at higher energy, 241 and 283 nm, which

were assigned to the peripherally attached bipyridyl groups.

The UV–vis spectrum of the demetallated ligand 37

displayed a Soret band at 362 nm and a split Q-band at

593 and 660 nm. Again, higher energy bands at 240 and

283 nm were assigned to the bipyridyl groups. The

applications of these novel bipyridyl porphyrazines is

currently being investigated with particular attention to

their metal binding properties.

Scheme 9. Reagents and conditions: (a) 2, Mg(OⁿBu)₂, ⁿBuOH, D, 24 h. (b)

TFA.

The synthesis of more soluble derivatives was achieved by

the modiﬁcation of the norphthalocyanine cyclization

partner. In particular, 4-n-butylphthalonitrile 38b⁵⁵was

utilized in the Linstead macrocyclization to yield

norphthalocyanines 39c–f, with benzyl, allyl and tetra-

hydropyranoxylethyl substituents (Scheme 9). Demetalla-

tion was achieved to yield the free base macrocycles 40c

and 40d, whereas demetallation and concomitant deprotec-

tion of norphthalocyanine 39f was achieved, furnishing the

di-(hydroxyethylamino)-porphyrazine 40f. All the butyl-

substituted norphthalocyanines were more soluble in

organic solvents than their unsubstituted counterparts.

2.5. Amino functionalized norphthalocyanines

Norphthalocyanines are phthalocyanine–porphyrazine

hybrids, consisting of three phthalonitrile units and one

maleonitrile unit. Previously we reported the synthesis of

norphthalocyanine dithiolates and coordination of these

ligands to a variety of metals, yielding solitaire

porphyrazines.^53,54In addition, we have reported the

preparation of pyridyl-appended systems as novel metal

sensors¹⁷and a bis(dimethylamino)norphthalocyanine,

which was characterized by X-ray crystallography.¹⁰We

initiated the synthesis of several additional amino-appended

norphthalocyanines to investigate how the benzo-substi-

tution of these novel hybrids affects their physical properties

and electronic absorption spectra. Commercially available

phthalonitrile 38a was utilized in a mixed Linstead

macrocyclization with amino-maleonitriles 2b and 2c.

This furnished magnesium norphthalocyanine derivatives

The electronic absorption data for porphyrazines 40a–d are

shown in Table 3.

As can be seen in Table 3, all the macrocycles prepared

displayed qualitatively similar spectra containing Soret

6122

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

Table 3. Electronic absorption data for porphyrazines 40a–d

pz

R¹, R²

R³

l_max(log 3)

40a

40b

40c

40d

allyl, allyl

Bn, Bn

allyl, allyl

Bn, Bn

H

293 (4.46), 338 (4.83), 528sh, 577 (4.42), 649 (4.69), 688 (4.60), 723 (4.60)

292 (4.45), 341 (4.83), 527sh, 583 (4.46), 644 (4.57), 691 (4.56), 727 (4.61)

299 (4.56), 345 (4.89), 524 (4.25), 577sh, 656 (4.62), 691 (4.61), 733 (4.69)

298 (4.58), 347 (4.90), 517 (4.24), 590sh, 655 (4.64), 691 (4.62), 734 (4.74)

ⁿBu

transitions (w340 nm), as well as split Q bands (centered

around 690 nm). In addition, n–p* transitions are observ-

able (w570 nm) as well as high-energy bands at 290 nm.

The splitting of the Q band is due to both the reduced

symmetry of the norphthalocyanine (C_2v), combined with

the reduced symmetry of the free base macrocycles. This

reduction in symmetry destroys the degeneracy of the

LUMO, resulting in two separate orbitals b_2gand b_3g.³³In

general, the substituents of norphthalocyanines 40a–d have

little effect on the position of the bands. Interestingly, the Q

bands of the norphthalocyanines are only slightly blue

shifted in comparison to the corresponding octaamino-

porphyrazines 7 (see Table 1). Parent phthalocyanines

display Q bands around 690 nm, whereas the Q band for

unsubstituted porphyrazines is around 600 nm.⁴Benzo-

substitution therefore results in approximately a 100 nm red

shift. Heteroatom substitution of the porphyrazine macro-

cycle also results in approximately a 100 nm red shift.

Therefore, norphthalocyanines containing three sites of

benzo-substitution and one of amino-substitution result in a

similar Q band shift than parent phthalocyanines or

octaaminoporphyrazines, when compared to unsubstituted

porphyrazines. This indicates that the benzo-substitution,

present in the norphthalocyanines has approximately the

same effect on the energetics of electronic transitions as

amino-substitution does.

(from CaH₂); DMF (predried over BaO, distilled from

neutral Al₂O₃(activity I)); MeOH, n-PrOH, and n-BuOH

(from Mg). All other reagents were purchased from

commercial sources and were used without further puriﬁ-

cation. Thin layer chromatography (TLC) was performed on

Merck Kieselgel 60 F-254 glass plates. Visualization was

accomplished using the quenching of UV ﬂuorescence (l_max

254 nm), and by KMnO₄(basic), ceric molybdate, anisal-

dehyde, and vanillin solutions, followed by heat. Flash

chromatography utilized Merck Kieselgel 60 (230–

400 mesh) or Aluminum oxide 90 active (activity I). Size

exclusion chromatography was performed on Sephadex LH-

20 or Bio-Beads S-X3 supports. All solvents were rotary

evaporated at or below 50 8C under reduced pressure. Cyclic

voltammetry data were recorded with a Cypress Systems

2000 computer-controlled potentiostat. A three electrode

conﬁguration was employed: a platinum disk working

electrode, a silver wire counter electrode, and a silver–

silver chloride reference electrode. Measurements were

made in CH₂Cl₂, freshly distilled from CaH₂, with Bu₄NPF₆

as the supporting electrolyte. All measurements were

calibrated by addition of ferrocene as an internal reference

and E_1/2values were calculated from (E_paCE_pc)/2 at a scan

rate of 110 mV s^K1

.

4.1.1. 2,3-Bis(dibenzylamino)-2(Z)-butene-1,4-dinitrile

(2b). Diamine 1 (10.0 g, 92.6 mmol) in DME (60 mL) was

added with rapid stirring to NaH (60% dispersion in mineral

oil, 17.0 g, 425 mmol) in DME (100 mL) at K22 8C. After

the addition was complete (0.5 h), the brown suspension

was stirred at K22 8C for 0.5 h. PhCH₂Br (69.1 g,

400 mmol) in DME (30 mL) was slowly added and stirring

continued at K22 8C for 1 h, when the mixture was allowed

to warm slowly up to room temperature. The suspension

was ﬁltered through Celite, rotary evaporated and crystal-

lized from EtOAc–hexanes to give dinitrile 2b (23 g, 53%)

as a light brown solid: mp 129–130.5 8C (Et₂O/hexanes);

TLC 0.71 (EtOAc/hexanes 1:1); IR (CHCl₃) 2400, 2186,

3. Conclusions

The synthesis of a wide range of amino-functionalized

porphyrazines has been described in this report. It shows

how the amino-groups, attached to the periphery of the

macrocycle, can be tailored to alter the physical properties

of the porphyrazine as well as its electronic absorption and

reactivity. Some of the macrocycles prepared in this report

are expected to ﬁnd applications as diverse as biomedical

agents, novel charge-transfer complexes, chemical sensors,

novel electronic materials and non-linear optics. We are

currently pursuing this direction and such work will be

reported in due course.

1591, 1579, 1454, 1215, 1152, 1028 cm^K^{1 1}H NMR

;

(270 MHz, CDCl₃) d 4.2 (s, 8H), 7.05 (m, 8H), 7.28 (m,

12H); ¹³C NMR (67.5 MHz, CDCl₃) d 55.9, 115.3, 118.0,

128.1, 128.6, 129.1, 136.4; MS (EI) m/z 468 (M^C%), 377,

260, 181, 91, 65; HRMS (EI) m/z Calcd for C₃₂H₂₈N₄: (M^C%),

468.2316; found: (M^C%), 468.2324. Anal. Calcd for

C₃₂H₂₈N₄: C, 82.01; H, 6.03; N, 11.96. Found: C, 82.15; H,

6.05; N, 11.96%.

4. Experimental

4.1. General procedures

All reactions were conducted in oven or ﬂame dried

glassware under N₂. Reaction temperatures reported refer

to external bath temperatures. Solvents used in chromato-

graphy were BDH AnalR or GPR grade and were used

without further puriﬁcation. Hexanes refers to the alkane

fraction boiling between 40 and 60 8C. Solvents used for

reactions were distilled prior to use: THF, DME, and Et₂O

(from K-Ph₂CO ketal); Et₃N, pyridine, CH₂Cl₂, and MeCN

4.1.2. 2,3-Bis(diallylamino)-2(Z)-butene-1,4-dinitrile

(2c). Following the same procedure as for the preparation

of dinitrile 2b, diamine 1 and allyl bromide gave dinitrile 2c

(8.5 g, 69%) as an orange-yellow oil: TLC R_f0.40 (EtOAc/

hexanes 1:9); IR (ﬁlm) n_max2186, 1643, 1585, 1443, 1403,

1244, 1178, 991, 928 cm^K1; ¹H NMR (CDCl₃, 270 MHz) d

3.71 (8H, d, JZ6.3 Hz), 5.19–5.26 (8H, m), 5.66–5.81 (4H,

m); ¹³C NMR (CDCl₃, 300 MHz) d 54.7, 115.1, 117.1,

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

6123

119.7, 132.9; MS (CI, NH₃) m/z 286 (MCNH₄)^C, 269

(MCH)^C, 227; HRMS (CI, NH₃) Calcd for C₁₆H₂₄N₅(MC

NH₄)^C, 286.2032; found: (MCNH₄)^C, 286.2035. Anal.

Calcd for C₁₆H₂₀N₄: C, 71.61; H, 7.51; N, 20.88. Found: C,

71.51; H, 7.74; N, 20.84.

was diluted with CHCl₃, ﬁltered through Celite and the

ﬁltrate evaporated. AcOH (15 mL) was added and, after

0.5 h in the dark, the mixture was added to ice and H₂O

(100 mL) and the pH adjusted to 7.5 with 1 M NaOH. The

dark precipitate was collected by ﬁltration and washed with

H₂O. Chromatography (SiO₂, EtOAc/hexanes 1:19) gave

porphyrazine 7c (300 mg, 15%) as a dark purple pasty solid:

TLC R_f0.73 (EtOAc/hexanes 1:9); IR (CHCl₃) n_max3301,

1848, 1639, 1573, 1551, 1415, 1190, 1121, 993, 921, 860,

562 cm^K1; UV–vis (CHCl₃) l_max(log 3) 333 (4.67), 526

(4.47), 730 (4.36) nm; ¹H NMR (CDCl₃, 300 MHz) d K1.01

(2H, s), 4.90 (24H, d, JZ6.0 Hz), 5.17 (16H, d, JZ

10.0 Hz), 5.37 (16H, d, JZ17.0 Hz), 6.10–6.23 (16H, m);

¹³C NMR (CDCl₃, 125 MHz) d 55.0, 116.7, 136.3, 148.5;

FABMS m/z 1075 (M^C%), 1034.

4.1.3. 2,3-Di(benzyl(methyl)amino)-2(Z)-butene-1,4-

dinitrile (2d). Following the same procedure as for the

preparation of dinitrile 2b, diamine 5³¹and dimethyl sulfate

gave dinitrile 2d (7.0 g, 64%) as a colorless solid: mp 86 8C

(EtOAc/hexane); TLC 0.55 (EtOAc/hexanes 2:3); IR (ﬁlm)

2184, 1593, 1450, 1429, 1284, 1233, 947, 881, 710, 675,

654 cm^K1; ¹H NMR (200 MHz, CDCl₃) d 2.74 (s, 6H), 4.20

(s, 4H), 7.15 (m, 4H), 7.34 (m, 6H); ¹³C NMR (75 MHz,

CDCl₃) d 40.5, 58.7, 115.0, 117.5, 128.0, 128.4, 128.8,

136.1. Anal. Calcd for C₂₀H₂₀N₄: C, 75.91; H, 6.37; N,

17.71. Found: C, 75.99; H, 6.54; N, 17.89%.

4.1.7. 2,3,7,8,12,13,17,18-Octakis(allyl(benzyl)amino)-

porphyrazine (7e). Dry n-PrOH (375 mL), Mg turnings

(2.6 g, 109 mmol) and I₂(1 crystal) were heated at reﬂux for

24 h. After cooling to room temperature, dinitrile 2e (10 g,

27.2 mmol) in n-PrOH (20 mL) was added and the mixture

heated at reﬂux for 36 h. After cooling to room temperature,

the deep purple mixture was diluted with CH₂Cl₂(300 mL),

ﬁltered through Celite and the ﬁltrate evaporated. Chroma-

tography (Al₂O₃EtOAc/hexanes 5:95) gave porphyrazine

7e (MZMg) (2.0 g, 20%) as a purple solid, which was used

without further puriﬁcation. AcOH (20 mL) was added to

porphyrazine 7c (MZMg) (570 mg, 0.38 mmol) and the

mixture stirred at room temperature for 3 h. The blue-purple

solution was slowly added to ice and H₂O (300 mL) and the

pH adjusted to 7.5 using aqueous 2.0 M NaOH. The dark

precipitate was ﬁltered off and washed repeatedly with H₂O.

Chromatography (SiO₂, EtOAc/hexanes 1:19) gave por-

phyrazine 7e (MZ2H) (460 mg, 82%) as a purple solid:

TLC R_f0.6 (Et₂O/hexanes 1:4); IR (CH₂Cl₂) n_max3304,

4.1.4. 2,3-Di(allyl(benzyl)amino)-2(Z)-butene-1,4-di-

nitrile (2e).⁵Dinitrile 5 (10.0 g, 34.7 mmol) was added

with rapid stirring to NaH (60% in mineral oil; 3.1 g,

76.4 mmol) in dry THF (350 mL) at K22 8C. After 30 min,

allyl bromide (16.8 g, 139.0 mmol) was added and stirring

continued at K22 8C for 2 h. The mixture was allowed to

warm up to room temperature. After stirring for 2 h, distilled

H₂O (40 mL) was added, the aqueous layer was extracted

with Et₂O (3!200 mL), and the solvent evaporated.

Chromatography (SiO₂, Et₂O/hexanes 9:1 to 1:1) gave

dinitrile 2e (10.3 g, 80%) as a viscous yellow oil: TLC R_f

0.16 (Et₂O/hexanes 9:1); IR (ﬁlm) n_max2185, 1642, 1590,

1581, 1495, 1454, 750, 700 cm^K^{1 1}H NMR (CDCl₃,

;

270 MHz) d 3.65 (4H, d, JZ6.3 Hz), 4.25 (4H, s), 5.11–5.24

(4H, m), 5.56–5.68 (2H, m), 7.11–7.34 (10H, m); ¹³C NMR

(CDCl₃, 67.5 MHz) d 54.7, 55.4, 114.8, 117.1, 119.5, 127.9,

128.4, 128.8, 132.3, 136.1; MS (EI) m/z 368 (M)^C, 277;

HRMS (EI) m/z Calcd for C₂₄H₂₄N₄: (M^C%), 368.2001;

found: (M^C%), 368.2011. Anal. Calcd for C₂₄H₂₄N₄: C,

78.22; H, 6.57; N, 15.22. Found: C, 78.11; H, 6.76; N, 15.15.

1644, 1572, 1548, 1494, 1452, 1414, 1297, 924, 873 cm^K1

;

UV–vis (CH₂Cl₂) l_max(log 3) 330 (4.75), 536 (4.59), and

734 (4.44) nm; ¹H NMR (CDCl₃, 270 MHz) d K0.93 (2H, s,

NH), 4.70 (16H, d, JZ6.4 Hz), 5.09 (8H, dd, JZ2.0,

10.0 Hz) 5.23 (8H, dd, JZ2.0, 17.0 Hz), 5.34 (16H, s),

5.97–6.07 (8H, m), 7.10–7.18 (24H, m), 7.30–7.34 (16H,

m); ¹³C NMR (CDCl₃, 125 MHz) d 54.9, 55.2, 117.1, 126.7,

128.2, 128.7, 136.0, 136.5, 139.7, 148.5; FABMS m/z 1475

(M^C%), 1435, 1385. Anal. Calcd for C₉₆H₉₈N₁₆: C, 78.11;

H, 6.70; N, 15.19. Found: C, 78.12; H, 6.71; N, 14.96.

4.1.5. (2,3,7,8,12,13,17,18-Octa(benzyl(methyl)amino)-

porphyrazinato)-magnesium(II) (6d). PrOH (100 mL)

and Mg turnings (550 mg, 22.6 mmol) were heated to reﬂux

for 10 h and cooled to room temperature. Dinitrile 2d (2.0 g,

6.3 mmol) was added and the mixture was heated to reﬂux

for 48 h. The blue suspension was ﬁltered off through celite

and the solids leached with CH₂Cl₂(150 mL). Rotary

evaporation and chromatography (Al₂O₃EtOAc/hexanes)

gave 6d (500 mg, 25%) as a dark blue amorphous solid:

TLC 0.60 (EtOAc/hexanes 2:3); IR (nujol) 1567, 1450,

1394, 1065, 730, 696 cm^K1; UV–vis (PhCl) l max (log 3)

350 (4.56), 544 (4.10), 714 (4.38) nm; ¹H NMR (300 MHz,

CDCl₃) d 3.44 (s, 24H), 5.32 (s, 16H), 7.16 (m, 24H), 7.32

(m, 16H); ¹³C NMR (75 MHz, CDCl₃) d 42.7, 60.8, 126.9,

128.4, 128.9, 139.5, 140.5, 152.8; HRMS (FAB) m/z Calcd

for C₈₀H₈₀MgN₁₆: (M^C%), 1288.6602; found: (M^C%),

1288.6912.

4.1.8. (2,3,7,8,12,13,17,18-Octakis(dimethylamino)por-

phyrazinato)nickel(II) (8a). Porphyrazine 7a⁷(60 mg,

0.09 mmol), anhydrous Ni(OAc)₂(160 mg, 0.9 mmol),

PhCl (15 mL) and DMF (5 mL) were heated to reﬂux with

stirring overnight. After cooling to room temperature, the

mixture was ﬁltered through celite and the solids leached

with Et₂O and CHCl₃. The ﬁltrate was evaporated, dissolved

in heptanes, re-evaporated and chromatographed (SiO₂

Et₂O). The colored band remaining on the silica was eluted

with MeOH and evaporated. Size exclusion chromato-

graphy (Sephadex LH20 CHCl₃) gave 8a (28 mg, 43%) as a

black amorphous solid: TLC 0.84 (EtOAc/hexanes 3:2); IR

(nujol) 1599, 1385, 1092 cm^K1; UV–vis (CH₂Cl₂) l max

(log 3) 325 (4.92) 360 (4.90), 561 (4.42), 704 (4.52) nm; ¹H

NMR (300 MHz, CDCl₃) d 3.63 (s); ¹³C NMR (75 MHz,

CDCl₃) d 45.3, 138.5, 144.1; HRMS (FAB) m/z Calcd for

4.1.6. 2,3,7,8,12,13,17,18-Octa(diallylamino)porphyra-

zine (7c). Dry n-PrOH (22 mL), Mg turnings (68 mg,

2.8 mmol) and I₂(1 crystal) were heated to reﬂux for 24 h.

After cooling to room temperature, dinitrile 2c (2 g,

7.5 mmol) in dry n-PrOH (5 mL) was added and reﬂux

continued for 24 h. After cooling, the deep purple mixture

6124

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

C₃₂H₄₈N₁₆Ni: (MCH^C), 715.3680, (M^C%), 714.3601;

found: (MCH^C), 715.3726, (M^C%), 714.3708.

evaporated to give another white oily solid. This procedure

was repeated with Et₂O (50 mL) to give a clear slightly

yellow oil. Chromatography (SiO₂, EtOAc/hexanes 1:3)

gave iodide 9b (11.8 g, 80%) as a clear yellow oil: TLC R_f

0.35 (EtOAc/hexanes 1:3); IR (ﬁlm) n_max1453, 1440, 1352,

1261, 1200, 1124, 1077, 1034, 988, 872, 814, 618 cm^K1; ¹H

NMR (CDCl₃, 270 MHz) d 1.49–1.74 (6H, m), 3.24 (2H, t,

JZ7 Hz), 3.48–3.88 (14H, m), and 4.60–4.63 (1H, m); ¹³C

NMR (CDCl₃, 67.5 MHz) d 2.9, 19.4, 25.4, 30.5, 62.1, 66.6,

70.2, 71.9, 98.9; MS (CI, NH₃) m/z 362 (MCNH₄)^C, 345

(MCH)^C, 278, 261; HRMS (CI, NH₃) m/z Calcd for

C₁₁H₂₂O₄I: (MCH)^C, 345.0563; found: (MCH)^C,

345.0559.

4.1.9. (2,3,7,8,12,13,17,18-Octakis(dibenzylamino)por-

phyrazinato)nickel(II) (8b). CF₃CO₂H (10 mL) was

added to porphyrazine 6b⁵(200 mg, 0.29 mmol), the

mixture stirred at room temperature for 12 h and added to

ice and the pH adjusted to 7.5 using aqueous NaOH (1.0 M).

The dark precipitate was ﬁltered off and chromatographed

(SiO₂EtOAc/hexane) to provide 7b (170 mg, 86%) as a

black amorphous solid: TLC 0.85 (EtOAc/hexanes 3:2);

HRMS (FAB) m/z Calcd for C₁₂₈H₁₁₄N₁₆: (MCH^C),

1875.9490, found: (MCH^C), 1875.9456. The crude

porphyrazine 7b was used directly without further puriﬁ-

cation. The crude porphyrazine 7b (160 mg, 0.085 mmol),

anhydrous Ni(OAc)₂(300 mg, 1.7 mmol), PhCl (10 mL)

and DMF (10 mL) were heated to reﬂux with stirring for

12 h. After evaporation, the residue was dissolved in

CH₂Cl₂and ﬁltered through celite. The ﬁltrate was

evaporated and chromatographed (SiO₂EtOAc/hexanes)

to give porphyrazine 8b (98 mg, 59%) as a purple-black

amorphous solid: TLC 0.63 (EtOAc/hexanes 2:3); IR

(nujol) 1576, 1493, 1448, 765, 689 cm^K1; UV–vis (PhCl)

l max (log 3) 322 (4.71), 536 (3.95), 654 (4.04), 674 (4.00)

4.1.12. 2,3-Di(benzyl(2-tetrahydropyranyloxyethyl)-

amino)-2-butene-1,4-dinitrile (10a). Dinitrile 5 (250 mg,

0.87 mmol) and THPOCH₂CH₂I 9a³⁷(890 mg, 3.5 mmol)

in dry DMF (2.5 mL) was added over 1 h to a rapidly

stirring suspension of Cs₂CO₃(620 mg, 1.9 mmol) in dry

DMF (2.5 mL). After the addition was complete, the

mixture was heated at 40 8C for 5 h and allowed to cool to

room temperature. After 12 h, the mixture was poured into

ice and H₂O (50 mL) and extracted with EtOAc (2!

20 mL). The combined organic layers were washed with

H₂O (2!30 mL), brine (1!20 mL), dried (MgSO₄: K₂CO₃

1:1), and the solvent evaporated. Chromatography (SiO₂,

EtOAc/hexanes 1:3) gave dinitrile 10a (390 mg, 83%) as a

mixture of E and Z isomers as a clear amber oil: TLC R_f

0.29, 0.42 (EtOAc/hexanes 1:3); IR (ﬁlm) n_max2200, 1563,

1495, 1453, 1390, 1348, 1202, 1128, 1075, 1035, 976, 751,

701 cm^K1; ¹H NMR (CDCl₃, 300 MHz) d 1.46–1.85 (12H,

m), 3.25–3.53 (4H, m), 3.75–3.85 (4H, m), 4.30–4.66 (4H,

m), 7.17–7.35 (10H, m); ¹³C NMR (CDCl₃, 75 MHz) d 19.4,

25.4, 30.6, 50.6, 55.9, 62.3, 65.0, 99.0, 115.2, 116.9, 127.8,

128.5, 128.8, 136.9; MS (CI, NH₃) m/z 545 (MCH)^C, 461

(M-THPCH)^C; HRMS (CI, NH₃) m/z Calcd for

C₃₂H₄₁N₄O₄: (MCH)^C, 545.3128; found: (MCH)^C,

545.3102. Anal. Calcd for C₃₂H₄₀N₄O₄: C, 70.56; H, 7.40;

N, 10.29. Found: C, 70.65; H, 7.26; N, 10.04.

1

nm; H NMR (300 MHz, CDCl₃) d 4.1 (s, 32H), 7.10 (m,

32H), 7.25 (m, 48H); ¹³C NMR (75 MHz, CDCl₃) d 57.5,

114.3, 120.5, 128.2, 129.1, 136.2; MS (FAB) m/z 1932 (M^C%),

1841, 1749, 1737.

4.1.10. (2,3,7,8,12,13,17,18-Octakis(allyl(benzyl)amino)-

porphyrazinato)nickel(II) (8e). Porphyrazine 7e (100 mg,

0.034 mmol), anhydrous Ni(OAc)₂(84.0 mg, 0.34 mmol),

PhCl (7 mL) and DMF (2.3 mL) were heated at reﬂux with

stirring for 18 h. After cooling to room temperature, the

mixture was ﬁltered through Celite, the solids leached with

CHCl₃and the ﬁltrate evaporated. Chromatography (SiO₂,

Et₂O/hexanes 1:25) gave porphyrazine 8e (96 mg, 92%) as a

purple solid: mp 112–114 8C; TLC R_f0.50 (Et₂O/hexanes

1:9); IR (CHCl₃) n_max1576, 1511, 1493, 1438, 1320, 1186,

1123, 918, 698 cm^K1; UV–vis (CH₂Cl₂₁) l_max(log 3) 324

(4.72), 511 (4.53), and 688 (4.49) nm; H NMR (CDCl₃,

270 MHz) d 4.62 (16H, d, JZ6.0 Hz), 5.07 (8H, dd, JZ2.0,

10.0 Hz) 5.20 (8H, dd, JZ2.0, 17.0 Hz), 5.31 (16H, s),

5.94–6.04 (8H, m), 7.11–7.34 (40H, m); ¹³C NMR (CDCl₃,

125 MHz) d 55.3, 55.6, 117.2, 126.8, 128.3, 128.7, 136.1,

138.0, 140.0, 143.7; FABMS m/z 1532 (MCH)^C, 1491,

1441; HRFABMS m/z Calcd for C₉₆H₉₆N₁₆Ni: (M^C%),

1530.7357; found: (M^C%), 1530.7359. Anal. Calcd for

C₉₆H₉₆N₁₆Ni: C, 75.23; H, 6.31; N, 14.62. Found: C, 75.13;

H, 6.45; N, 14.43.

4.1.13. 2,3-Di(benzyl(8-tetrahydropyranyloxy-3,6-dioxa-

octyl)amino)-2-butene-1,4-dinitrile (10b). Following the

same procedure as for the preparation of dinitrile 10a,

dinitrile 5 and THPO(CH₂CH₂O)₂CH₂CH₂I 9b gave

dinitrile 10b (6.98 g, 91%) as a mixture of E and Z isomers

as a clear amber oil: TLC R_f0.68 (EtOAc); IR (ﬁlm) n_max

2185, 1587, 1494, 1453, 1125, 1076, 1035, 988, 873,

701 cm^K1; ¹H NMR (CDCl₃, 270 MHz) d 1.46–1.84 (12H,

m), 3.19–3.27 (4H, m), 3.45–3.68 (16H, m), 3.81–3.90 (4H,

m), 4.27, 4.38 (4H, 2 s), 4.59–4.62 (2H, m), 7.15–7.35 (10H,

m); ¹³C NMR (CDCl₃, 67.5 MHz) d 19.5, 25.4, 30.6, 50.6,

52.8, 55.9, 58.7, 62.20, 62.25, 66.6, 68.9, 69.3, 70.51, 70.55,

98.9, 114.1, 115.0, 116.7, 119.3, 127.8, 128.4, 128.6,

128.65, 128.72, 136.3, 136.9; MS (CI, NH₃) m/z 721

(MCH)^C, 634, 553; HRMS (CI, NH₃) m/z Calcd for

C₄₀H₆₀N₅O₈: (MCNH₄)^C, 738.4442; found: (MCNH₄)^C,

738.4495. Anal. Calcd for C₄₀H₆₀N₅O₈: C, 66.64; H, 7.83;

N, 7.77. Found: C, 66.57; H, 7.53; N, 7.66.

4.1.11. 1-Iodo-8-tetrahydropyranyloxy-3,6-dioxaoctane

(9b). I₂(15.5 g, 61 mmol) was slowly added rapidly with

stirring to THPO(CH₂CH₂O)₂CH₂CH₂OH³⁸(10 g,

43 mmol), Ph₃P (14.6 g, 55.5 mmol), and imidazole

(4.0 g, 58.5 mmol) in MeCN (50 mL) and Et₂O (75 mL) at

0 8C. The brown-black slurry was stirred at 0 8C for 1.5 h,

the mixture was diluted with Et₂O (900 mL), ﬁltered, and

washed with saturated aqueous Na₂S₂O₃(3!250 mL),

saturated aqueous CuSO₄(3!250 mL), H₂O (3!250 mL),

dried (MgSO₄: K₂CO₃1:1), ﬁltered, and rotary evaporated

to give a white oily solid. Et₂O was added (100 mL), the

suspension was ﬁltered and the ﬁltrate was rotary

4.1.14. 2,3-Di(benzyl(3,6,9-trioxadecyl)amino)-2-butene-

1,4-dinitrile (10c). Following the same procedure as for the

preparation of dinitrile 10a, dinitrile 5 and Me(OCH₂CH₂)₃I

9c³⁷gave dinitrile 10c (5.0 g, 83%) as a clear amber oil:

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

6125

TLC R_f0.11 (EtOAc/hexanes 1:1); IR (ﬁlm) n_max2197,

1584, 1493, 1453, 1111, 747, 701 cm^K1; ¹H NMR (CDCl₃,

300 MHz) d 3.27 (4H, t, JZ5.2 Hz), 3.37 (6H, s), 3.49 (4H,

t, JZ5.2 Hz), 3.50–3.60 (16H, m), 4.40 (4H, s), 7.19 (6H,

m), 7.29 (4H, m); ¹³C NMR (CDCl₃, 75 MHz) d 50.6, 56.0,

59.0, 69.0, 70.5, 70.58, 70.61, 72.0, 115.1, 116.8, 127.8,

128.4, 128.8, 137.0; MS (CI, NH₃) m/z 581 (MCH)^C, 491;

HRMS (CI, NH₃) m/z Calcd for C₃₂H₄₅N₄O₆: (MCH)^C,

581.3339, found: (MCH)^C, 581.3366. Anal. Calcd for

C₃₂H₄₄N₄O₆: C, 66.18; H, 7.64; N, 9.65. Found: C, 65.94;

H, 7.34; N, 9.64.

turnings (2.09 g, 86.2 mmol) were heated to 300 8C under

vacuum, allowed to cool to room temperature under dry N₂.

Dry n-PrOH (450 mL) and I₂(1 crystal) were added and the

suspension heated at reﬂux for 24 h. After cooling to room

temperature, dinitrile 10c (5.0 g, 8.6 mmol) in dry n-PrOH

(10 mL) was added and the suspension heated at reﬂux for

60 h. After cooling to room temperature, the purple-black

suspension was diluted with CHCl₃(400 mL), ﬁltered

through Celite, and rotary evaporated. CHCl₃(100 mL)

was added, and the suspension was ﬁltered to remove the

remaining ﬁne solids. Rotary evaporation and chromato-

graphy (SiO₂EtOAc/hexanes 1:1 to EtOAc/MeOH 95:5)

gave porphyrazine 11c (400 mg, 8%) as a purple oil: TLC R_f

0.5 (CHCl₃: Me₂CO 7:3); IR (ﬁlm) n_max1559, 1452, 1290,

1195, 1110, 1029, 850, 736, 701 cm^K1; UV–vis (CHCl₃)

l_max(log 3) 330 (4.63), 365 (4.66), 577 (4.36), and 708

4.1.15. 2,3,7,8,12,13,17,18-Octakis(benzyl(2-tetrahydro-

pyranyloxyethyl)amino)-porphyrazinato)magnesium(II)

(11a). Dry n-BuOH (2.5 mL), I₂(1 crystal) and Mg turnings

(0.11 g, 4.6 mmol) were heated at reﬂux for 24 h. After

cooling to room temperature, dinitrile 10a (250 mg,

0.46 mmol) in dry n-BuOH (2.5 mL) was added and the

suspension heated at reﬂux for 24 h. After cooling to room

temperature, the purple-black suspension was diluted with

CHCl₃(10 mL), ﬁltered through Celite, and rotary evapor-

ated. Chromatography (SiO₂, EtOAc/hexanes 1:3 to 2:3)

gave porphyrazine 11a (36 mg, 14%) as a purple oil: TLC R_f

0.30 (EtOAc/hexanes 1:2); IR (CHCl₃) n_max1601, 1556,

1

(4.51) nm; H NMR (CDCl₃, 270 MHz) d 2.92 (24H, s),

3.01–3.04 (16H, m), 3.13–3.17 (16H, m), 3.19–3.23 (16H,

m), 3.31–3.35 (16H, m), 3.70–3.74 (16H, m), 4.51–4.54

(16H, m), 5.40 (16H, s), 7.08–7.11 (24H, m), 7.42–7.45

(16H, m); ¹³C NMR (CDCl₃, 125 MHz) d 51.1, 56.1, 58.4,

69.9, 70.2, 70.3, 70.4, 71.4, 126.4, 128.1, 128.5, 137.2,

140.9, 151.9; FABMS m/z 2347 (MCH)^C, and 2256. Anal.

Calcd for C₁₂₈H₁₇₆MgN₁₆O₂₄: C, 65.50; H, 7.56; N, 9.55.

Found: C, 65.28; H, 7.39; N, 9.32.

1493, 1452, 1285, 1122, 1070, 1032, 975, 733, 698 cm^K1

;

UV–vis (CHCl₃) l_max(log 3) 347sh, 359 (4.77), 516sh, 569

(4.38), 713 (4.58) nm; ¹H NMR (CDCl₃, 300 MHz) d 0.88–

1.56 (48H, m), 3.20–4.70 (56H, m), 5.45 (16H, m), 7.08–

7.92 (40H, m); FABMS m/z 2201 (MCH)^C, 2110. Anal.

Calcd for C₁₂₈H₁₅₈MgN₁₆O₁₆: C, 69.85; H, 7.24; N, 10.18.

Found: C, 69.57; H, 7.00; N, 10.08.

4.1.18. (2,3,7,8,12,13,17,18-Octakis(benzyl(2-hydroxy-

ethyl)amino)porphyrazine) (12a). AcOH (4 drops) was

added with stirring to porphyrazine 11a (30 mg, 14 mmol) in

CHCl₃(2 mL) and MeOH (0.5 mL) at room temperature.

After 1 h and 2.5 h respectively, concd HCl (1 drop) and

1 M NaOH (1.5 mL) were added and the layers separated.

The aqueous layer was extracted with CHCl₃(1!10 mL)

and the combined organic extracts rotary evaporated.

Chromatography (SiO₂, CHCl₃/MeOH 95:5 to 90:10) gave

porphyrazine 12a (17 mg, 80%) as a purple solid: TLC R_f

0.45 (CHCl₃/MeOH 90:10); IR (CHCl₃) n_max3336, 3297,

1568, 1548, 1494, 1453, 1378, 1310, 1174, 1135, 1060, 741,

699 cm^K1; UV–vis (CHCl₃) l_max(log 3) 335 (4.63), 556

4.1.16. (2,3,7,8,12,13,17,18-Octakis(benzyl(8-tetrahydro-

pyranyloxy-3,6-dioxa-octyl)amino)porphyrazinato)mag-

nesium(II) (11b). Mg turnings (1.35 g, 35.6 mmol) were

heated to 300 8C under vacuum, allowed to cool to room

temperature under dry N₂. Dry n-PrOH (250 mL) and I₂(1

crystal) were added and the suspension heated at reﬂux for

24 h. After cooling to room temperature, dinitrile 10b

(4.0 g, 5.6 mmol) in dry n-PrOH (10 mL) was added and the

suspension heated at reﬂux for 60 h. After cooling to room

temperature, the purple-black suspension was diluted with

CHCl₃(200 mL), ﬁltered through Celite, and rotary

evaporated. The dark residue was dissolved in CHCl₃

(50 mL), ﬁltered through Celite to remove the remaining

particulates, and rotary evaporated. Chromatography (SiO₂,

EtOAc/hexanes 1:2 to EtOAc/MeOH 9:1) gave

porphyrazine 11b (320 mg, 8%) as a purple oil: TLC R_f

0.32 (EtOAc/MeOH 95:5); IR (ﬁlm) n_max1561, 1555, 1452,

1351, 1285, 1200, 1122, 1076, 1034, 987, 703 cm^K1; UV–

vis (CH₂Cl₂) l_max(log 3) 333 (4.69), 365 (4.75), 574 (4.47),

1

(4.32), 725 (4.32) nm; H NMR (CDCl₃, 300 MHz) d 0.09

(2H, s), 3.65 (16H, br s), 3.73 (16H, br s), 5.33 (16H, s), 6.13

(8H, br s), 7.12–7.28 (40H, m); FABMS m/z 1508 (MC

H)^C, 1417, 1326.

4.1.19. (2,3,7,8,12,13,17,18-Octakis(benzyl(8-hydroxy-

3,6-dioxaoctyl)amino)-porphyrazine) (12b). AcOH (4

drops) was added with stirring to porphyrazine 11b

(30 mg, 10.3 mmol) in CHCl₃(2 mL) and MeOH

(0.5 mL). After 1 h, conc HCl (1 drop) was added and

stirring continued for 1.5 h. 1 M NaOH (1.5 mL) was added,

the layers were separated, the aqueous layer was extracted

with CHCl₃(1!10 mL) and the combined organic extracts

rotary evaporated. Gel permeation chromatography

(Sephadex LH20 CHCl₃) gave porphyrazine 12b (18 mg,

80%) as a purple oil: TLC R_f0.75 (MeOH/MeCN 1:1;

Whatman MKC₁₈F Reversed Phase TLC Plates); IR (ﬁlm)

n_max3412, 3303, 1551, 1492, 1449, 1130, 1074, 742,

701 cm^K1; UV–vis (CHCl₃) l_max(log 3) 328 (4.62), 348sh,

556 (4.53), 661sh, 740sh nm; ¹H NMR (CDCl₃, 300 MHz) d

K0.94 (2H, s) 3.28–3.83 (80H, m), 4.42 (16H, br s), 5.33

(16H, s), 7.08–7.35 (40H, m); ¹³C NMR (CDCl₃, 100 MHz)

d 50.8, 55.9, 61.5, 70.15, 70.23, 72.4, 126.7, 128.2, 128.5,

136.0, 140.0, 148.0; FABMS m/z 2212 (M^C%), 2122, 1106

1

and 711 (4.57) nm; H NMR (CDCl₃, 270 MHz) d 1.08–

1.62 (48H, m), 2.77–2.85 (8H, m), 3.12–3.19 (8H, m), 3.21–

3.50 (64H, m), 3.67–3.70 (16H, m), 3.89–3.91 (8H, m),

4.51–4.60 (16H, m), 5.38 (16H, br s,), 7.05–7.09 (24H, m),

7.40–7.43 (16H, m); ¹³C NMR (CDCl₃, 100 MHz) d 18.9,

24.9, 30.0, 51.2, 55.5, 61.4, 66.3, 70.0, 70.17, 70.23, 70.4,

98.2, 126.4, 128.0, 128.3, 137.1, 140.9, 151.5; FABMS m/z

2908 (MCH)^C, 2818. Anal. Calcd for C₁₆₀H₂₂₄MgN₁₆O₃₂:

C, 66.09; H, 7.76; N, 7.71. Found: C, 65.79; H, 7.46; N, 7.56.

4.1.17. (2,3,7,8,12,13,17,18-Octakis(benzyl(3,6,9trioxa-

decyl)amino)-porphyrazinato)magnesium(II) (11c). Mg

6126

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

(M)^2C. Anal. Calcd for C₁₂₀H₁₆₂N₁₆O₂₄$CHCl₃: C, 62.32;

H, 7.04; N, 9.61. Found: C, 62.50; H, 6.90; N, 9.41.

(285 mg, 2.1 mmol) in CCl₄(5 mL), N- isopropylamino-

acetonitrile 17 (210 mg, 2.1 mmol) in CCl₄(1 mL) was

added dropwise. After 5 min the reaction mixture

was allowed to cool to ambient temperature. The suspension

was ﬁltered, and the ﬁltrate was heated to reﬂux for 6 h in

the presence of powdered calcium hydroxide (316 mg,

4.3 mmol) and anhydrous CaCl₂(40 mg, 0.4 mmol).

Filtration, evaporation and distillation of the solvent gave

cyanide 19 (184 mg, 90%) as a colorless oil.

4.1.20. 2,3,7,8,12,13,17,18-Octakis(benzyl(3,6,9-trioxa-

decyl)amino)porphyrazine (12c). AcOH (2.5 mL) was

added to porphyrazine 11c (MZMg) (35 mg, 15 mmol)

under N₂in the dark. After 2 h, the purple solution was

slowly added to ice and H₂O (100 mL) and neutralized with

1 M NaOH, extracted with CHCl₃(3!20 mL), and dried

(MgSO₄). Rotary evaporation and chromatography (SiO₂

CHCl₃: Me₂CO 4:1) gave porphyrazine 12c (30 mg, 86%)

as a viscous purple oil: TLC R_f0.5 (CHCl₃: Me₂CO 7:3); IR

(CHCl₃) n_max3301, 1571, 1550, 1495, 1452, 1292, 1248,

1105, 1029, 850, 715, 700 cm^K1; UV–vis (CHCl₃) l_max

(log 3) 327 (4.60), 356 (4.60), 556 (4.60), 667sh, and 741sh

4.1.23. N,N⁰-Diisopropyl-N,N⁰-di-((tert-butyloxycar-

bonyl)methyl)diamino-maleonitrile (21). SnCl₄(12 mL,

26.6 g, 0.102 mol) in dry PhH (100 mL) was added over 1 h

to N-isopropylformimidoyl cyanide 19 (8.2 g, 0.09 mol) in

dry PhH (50 mL), at 0 8C.⁴³The mixture was stirred

overnight at 20 8C. H₂O (200 mL) and Et₂O (300 mL) were

added and the organic layer separated. The organic phase

was washed with aqueous NaHCO₃(200 mL) and H₂O

(200 mL), dried (MgSO₄) and rotary evaporated.

Chromatography (Al₂O₃, hexanes/EtOAc 7:3) followed by

sublimation (80 8C/20 mm) gave N,N⁰-diisopropyldiamino-

maleonitrile 20 (5.2 g, 63%) as bright yellow crystals (2

isomers, Z/E 9:1): mp 74 8C; R_f0.39 (hexanes/EtOAc 7:3);

IR (ﬁlm) n_max3361, 2205, 1603, 1465, 1366, 1178,

1

nm; H NMR (CDCl₃, 270 MHz) d K1.05 (2H, s), 3.22

(24H, s), 3.24–3.34 (64H, m), 3.59–3.64 (16H, m), 4.34–

4.40 (16H, m), 5.29 (16H, s), 7.04–7.11 (24H, m), 7.29–7.36

(16H, m); ¹³C NMR (CDCl₃, 100 MHz) d 50.9, 55.2, 58.8,

70.1, 70.2, 71.7, 126.6, 128.1, 128.5, 136.0, 140.2, 148.0;

FABMS m/z 2323 (MCH)^C. Anal. Calcd for

C₁₂₈H₁₇₈N₁₆O₂₄: C, 66.13; H, 7.72; N, 9.64. Found: C,

65.88; H, 7.63; N, 9.66.

1

1126 cm^K1; H NMR (300 MHz, CDCl₃) d 4.20 (heptet,

4.1.21. (2,3,7,8,12,13,17,18-Octakis(benzyl(3,6,9-trioxa-

decyl)amino)-porphyrazinato)nickel(II). Porphyrazine

12c (MZ2H) (15 mg, 6.5 mmol) and Ni(OAc)₂(15 mg,

65 mmol) in DMF (1 mL) and PhCl (2 mL) were heated at

100 8C for 4 h. After allowing to cool to room temperature,

the dark purple solution was ﬁltered through Celite, rotary

evaporated and chromatographed (SiO₂CHCl₃: Me₂CO

4:1) to yield the nickel(II) porphyrazine (13 mg, 84%) as a

viscous purple oil: TLC R_f0.40 (CHCl₃: Me₂CO 8:2); IR

(ﬁlm) n_max1578, 1513, 1494, 1449, 1351, 1322, 1250, 1195,

1111, 1030, 851, 745, 701 cm^K1; UV–vis (CHCl₃) l_max

(log 3) 312 (4.68), 379sh, 532 (4.46), and 680 (4.38) nm; ¹H

NMR (CDCl₃, 270 MHz) d 3.21 (24H, s), 3.26–3.28 (64H,

m), 3.63 (16H, s), 7.09–7.17 (24H, m), 7.35–7.38 (16H, m);

¹³C NMR (CDCl₃, 100 MHz) d 51.0, 56.0, 58.9, 70.2, 70.26,

70.30, 70.7, 126.6, 128.2, 128.5, 137.3, 140.3, 143.3;

FABMS m/z 2381 (M^C%), 2290. Anal. Calcd for

C₁₂₈H₁₇₆N₁₆O₂₄Ni: C, 64.55; H, 7.45; N, 9.41. Found: C,

64.73; H, 7.26; N, 9.18.

JZ6.3 Hz, 2H, CH, E), 3.54 (heptet, JZ6.3 Hz, 2H, CH, Z),

3.28 (bs, 2H), 1.36 (d, JZ6.3 Hz, 12H, E), 1.18 (d, JZ

6.3 Hz, 12H, Z); ¹³C NMR (75 MHz, CDCl₃) d 114.7, 113.0,

48.1, 23.5; MS (EI) m/z 192 (M^C%). The dinitrile 20 was

used directly without further puriﬁcation. NaH (44 mg,

1.1 mmol, 60% dispersion in mineral oil, 10% excess) was

added rapidly to dinitrile 20 (96 mg, 0.5 mmol) in DMF

(10 mL) at K10 8C. After 2 h, t-butyl bromoacetate

(0.29 mL, 2 mmol) in DMF (10 mL) was added to the

dark green solution, which was stirred at K10 8C for 2 h,

allowed to warm up to 20 8C, poured onto ice (50 mL) and

extracted with Et₂O (3!50 mL). The combined extracts

were dried (MgSO₄), rotary evaporated and chromato-

graphed (SiO₂hexanes/EtOAc 9:1) to give dinitrile 21

(177 mg, 84%) as yellow crystals: mp 78 8C (EtOAc); R_f0.6

(hexanes/EtOAc 7:3); IR (ﬁlm) n_max2203, 1740, 1561,

1461, 1370, 1226, 1154 cm^K1; ¹H NMR (300 MHz, CDCl₃)

d 3.82–3.79 (m, 6H, CH), 1.48 (s, 18H), 1.16 (d, JZ6.6 Hz,

12H); ¹³C NMR (75 MHz, CDCl₃) d 169.1, 117.4, 115.2,

82.1, 52.2, 46.7, 28.0, 20.6; MS (CI, NH₃) m/z 438 (MC

NH₄)^C, 421 (MCH)^C, 420 (M^C%). Anal. Calcd for

C₂₂H₃₆N₄O₄: C, 62.83; H, 8.63; N, 13.32. Found: C,

63.10; H, 8.51; N 13.43.

4.1.22. N-Isopropylformimidoyl cyanide (19).⁴³Calcium

hypochlorite (21.5 g, 0.09 mol, 60%) and anhydrous CaCl₂

(1.6 g, 0.015 mol) were added to (isopropylamino)aceto-

nitrile 17^43,56(8.7 g, 0.09 mol) in CH₂Cl₂(200 mL). The

mixture was stirred for 2 days at ambient temperature,

ﬁltered, and the ﬁltrate was heated to reﬂux for 2 days in the

presence of powdered calcium hydroxide (13.0 g, 0.18 mol)

and anhydrous CaCl₂(1.6 g, 0.015 mol) until the N-chloro-

N-isopropylaminoacetonitrile 18 was not detected by GC/

MS. The mixture was ﬁltered, rotary evaporated and

distilled to give cyanide 19 (4.2 g, 64%) as a colorless oil

(Z/E 64:36): bp 60 8C /20 mm; IR (ﬁlm) n_max1620, 1465,

4.1.24. 1-((N-Cyanomethyl)aminomethyl)-4-methyl-

2,6,7-trioxabicyclo[2,2,2]octane (23). ClCH₂CN (2.6 mL,

3.1 g, 0.40 mol) in Et₂O (20 mL) was added dropwise to

1-(aminomethyl)-4-methyl-2,6,7-trioxabicyclo[2,2,2]-

octane 22⁵⁷(6.4 g, 0.40 mol) and Et₃N (6.2 mL, 4.5 g,

0.45 mol) in Et₂O (300 mL) at K10 8C. After stirring

overnight at 20 8C, rotary evaporation and chromatography

(Al₂O₃hexanes/EtOAc 7:3) gave nitrile 23 (4.4 g, 55%) as a

white solid: mp 31 8C; R_f0.35 (hexanes/EtOAc 1:1); IR

(ﬁlm) n_max3347, 2235, 1723, 1472, 1405, 1356, 1286, 1193,

1

1384, 1366, 1143 cm^K1; H NMR (300 MHz, CDCl₃) d

7.39 (s, 1H, E), 7.28 (s, 1H, Z), 4.07 (heptet, JZ6.3 Hz, 1H,

Z), 3.60 (heptet, JZ6.3 Hz, 1H, E), 1.25 (d, JZ6.3 Hz,

12H); ¹³C NMR (75 MHz, CDCl₃) d 133.5 (E), 128.9 (Z),

115.0 (Z), 108.0 (CN, E), 63.4 (CHMe₂, E), 60.5 (CHMe₂,

Z), 23.2; MS (EI) m/z 96 (M^C%). Alternatively, to a

preheated (55 8C) suspension of N-chlorosuccinimide

1148, 1115, 1052, 989, 935, 882, 749 cm^K^{1 1}H NMR

;

(300 MHz, CDCl₃) d 3.93 (s, 6H), 3.68 (s, 2H), 2.89 (s, 2H),

1.71 (s, 1H), 0.83 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) d

117.9, 107.4, 72.5, 52.4, 37.1, 30.5, 14.3; MS (CI, NH₃) m/z

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

6127

199 (MCH)^C. Anal. Calcd for C₉H₁₄N₂O₃: C, 54.53; H,

7.12; N, 14.13. Found: C, 54.83; H, 7.02; N, 13.92.

EtOAc/MeOH 7:1) gave the zinc porphyrazine 28 (4 mg,

63%) as a dark blue solid: R_f0.2 (EtOAc/MeOH 9:1); IR

(CH₂Cl₂) 1650, 1608, 1380, 1313, 1097, 1018, 873 cm^K1

;

UV–vis (CH₂Cl₂) l_max(log 3) 357 (4.77), 593 (4.46) nm; ¹H

NMR (270 MHz, pyridine-d₅) d 3.60 (s, 12H), 3.80 (s, 12H),

3.89 (s, 12H), 8.16 (d, JZ5.9 Hz, 4H), 9.01 (d, JZ5.9 Hz,

4H); ¹³C NMR (67.5 MHz, pyridine-d₅) d 43.4, 44.5, 45.5,

127.3, 129.0, 143.8, 146.8, 152.0, 160.0, 161.7; MS (FAB)

m/z 789 (M^C%); HRMS (FAB) calc for C₃₈H₄₅N₁₆Zn: (MC

H)^C, 789.3304; found: (MCH)^C, 789.3275.

4.1.25. 1-(N-Chloro-(N-cyanomethyl)aminomethyl)-4-

methyl-2,6,7-trioxabicyclo[2,2,2]octane (24). Amine 23

(0.6 g, 3 mmol) in CCl₄(10 mL) was heated to reﬂux with

calcium hypochlorite (0.72 g, 5.1 mmol, 60%) and

anhydrous CaCl₂(55 mg, 0.5 mmol) for 30 min. The

suspension was ﬁltered and the solvent evaporated to give

chloramine 24 (0.6 g, 86%) as a white solid: mp 79 8C; IR

(CCl₄) n_max1703, 1398, 1354, 1281, 1205, 1101, 1059,

1024, 993, 976, 933, 889 cm^K1

;

¹H NMR (300 MHz,

4.1.28. 2-Methoxy-4-pyridylacetonitrile (30). Finely

powdered NaCN (0.46 g, 9.4 mmol) was added to 4-(chloro-

methyl)-2-methoxypyridine 29 (0.98 g, 6.2 mmol) in dry

DMSO (50 mL), the mixture stirred for 8 h, diluted with

H₂O (300 mL) and extracted with Et₂O (8!100 mL). The

combined extracts were dried (MgSO₄), rotary evaporated

and chromatographed (deactivated SiO₂hexanes/EtOAc

7:3) to give nitrile 30 (0.74 g, 76%), as a white solid: mp

106 8C (CHCl₃); R_f0.23 (deactivated silica, hexanes/EtOAc

7:3); IR (DRIFTS) n_max2248, 1939, 1614, 1563, 1486,

1455, 1401, 1324, 1221, 1184, 1152, 1040, 928, 813,

CDCl₃) d 4.13 (s, 2H), 3.91 (s, 6H), 3.34 (s, 2H), 0.85 (s,

3H); ¹³C NMR (75 MHz, CDCl₃) d 113.7, 107.0, 72.5, 65.1,

51.2, 30.6, 14.4; MS (CI, NH₃) m/z 233 (M^C%).

4.1.26. 2,3-Dipyridyl-7,8,12,13,17,18-hexakis(dimethyl-

amino)porphyrazine (27). Mg (19.5 mg, 0.8 mmol),

n-BuOH (10 mL) and I₂(3 small crystals) were heated to

reﬂux under N₂for 24 h. After cooling, dinitrile 2a (180 mg,

1.09 mmol) and dipyridylmaleonitrile 25⁴⁷(36 mg,

0.15 mmol) were added, the mixture was heated at 110 8C

for 12 h under N₂, ﬁltered (Celite) and the solids washed

with CH₂Cl₂. Rotary evaporation and chromatography

(SiO₂hexanes/EtOAc 9:1; CHCl₃/MeOH 9:1) gave the

crude Mg-porphyrazine 26 as a blue solid: R_f0.2 (CHCl₃/

MeOH 9:1); MS (FAB) m/z 749 (M^C%); HRMS (FAB)

Calcd for C₃₈H₄₅N₁₆Mg: (MCH)^C, 749.3863; found: (MC

H)^C, 749.3866. A small amount of a mixture of the cis- and

trans tetrapyridyl-tetrakis(dimethylamino)porphyrazines

were isolated by chromatography (SiO₂hexanes/EtOAc

9:1; CHCl₃/MeOH 9:1; CHCl₃/MeOH 6:1) of the crude

product obtained from the previous reaction, as conﬁrmed

by mass spectroscopy: MS (FAB) m/z 817 (M^C%); HRMS

(FAB) Calcd for C₄₄H₄₁N₁₆Mg: (MCH)^C, 817.3551;

found: (MCH)^C, 817.3510. Porphyrazine 26 was demetal-

lated without any further puriﬁcation. CF₃CO₂H (7 mL) was

added to the partially puriﬁed porphyrazine 26 (87 mg,

0.116 mmol), the mixture stirred at 20 8C for 30 min under

N₂and poured onto ice and H₂O (50 mL) and the suspension

neutralized with 1 M NaOH. The solid was collected by

ﬁltration, redissolved in CH₂Cl₂, dried (MgSO₄), rotary

evaporated and chromatographed (SiO₂EtOAc/MeOH 9:1)

to give porphyrazine 27 (25 mg, 30%) as a dark purple solid:

mp >350 8C; R_f0.4 (EtOAc/MeOH 9:1); IR (CH₂Cl₂) 3299,

768 cm^K^{1 1}H NMR (300 MHz, CDCl₃) d 8.17 (d, JZ

;

5.3 Hz, 1H), 6.85 (dd, JZ5.3, 1.3 Hz, 1H), 6.74 (d, JZ

1.3 Hz, 1H), 3.95 (s, 3H), 3.71 (s, 2H); ¹³C NMR (75 MHz,

CDCl₃) d 164.9, 147.8, 141.5, 116.3, 116.0, 110.1, 53.7,

23.1; MS (CI, NH₃) m/z 149 (MCH)^C. Anal. Calcd for

C₈H₈N₂O: C, 64.85; H, 5.44; N, 18.91. Found: C, 64.90; H,

5.57; N, 19.02.

4.1.29. 2,3-Di-(4-(2-methoxy)pyridyl)fumaronitrile (31).

I₂(1.8 g, 7.15 mmol) was added to nitrile 30 (0.58 g,

3.9 mmol) in MeOH (10 mL), the mixture heated to reﬂux

under N₂for 1 h, cooled to room temperature and NaOMe,

from Na (0.2 g, 8.6 mmol) in MeOH (5 mL) was added

dropwise. The mixture was heated to reﬂux for 3 h, during

which time a brown precipitate formed, allowed to cool, the

solid ﬁltered off and redissolved in CHCl₃. The solution was

ﬁltered, rotary evaporated and the residue recrystallized

from CHCl₃to give dinitrile 31 (0.22 g, 38%) as a light

brown solid: mp 167 8C (CHCl₃); R_f0.63 (deactivated

silica, hexanes/EtOAc 1:1); IR (ﬁlm) n_max2222, 1602, 1550,

1483, 1451, 1397, 1325, 1198, 1111, 1041, 867, 822,

787 cm^K^{1 1}H NMR (300 MHz, CDCl₃) d 8.38 (d, JZ

;

5.5 Hz, 2H), 7.27 (dd, JZ5.5, 1.5 Hz, 2H), 7.15 (d, JZ

1.5 Hz, 2H), 4.02 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) d

165.0, 148.7, 140.9, 125.8, 114.9, 114.8, 110.5, 54.1; MS

(CI, NH₃) m/z 293 (MCH)^C. Anal. Calcd for C₁₆H₁₂N₄O₂:

C, 65.75; H, 4.14; N, 19.17. Found: C, 66.08; H, 4.36; N,

19.39.

1596, 1500, 1388, 1321, 1199, 1081, 1058, 869, 748 cm^K1

;

UV–vis (CH₂Cl₂) l_max(log 3) 339 (4.49), 539 (4.38) nm; ¹H

NMR (300 MHz, CDCl₃) d 3.48 (s, 12H), 3.72 (s, 12H), 3.9

(s, 12H), 7.89 (d, JZ5.8 Hz), 8.72 (d, JZ5.8 Hz); ¹³C NMR

(75 MHz, CDCl₃) d 43.6, 45.0, 45.7, 126.6, 127.1, 135.6,

138.9, 140.2, 143.9, 145.4, 149.7, 149.9, 151.0, 163.6; MS

(FAB) m/z 727 (M^C%); HRMS (FAB) calc for C₃₈H₄₇N₁₆:

(MCH)^C, 727.4169; found: (MCH)^C, 727.4134. Anal.

Calcd for C₃₈H₄₆N₁₆: C, 62.79; H, 6.38; N, 30.83. Found: C,

62.87; H, 6.38; N, 30.65.

4.1.30. 2,2⁰-Bipyridyl-4-acetonitrile (33). Finely powdere₀d

KCN (0.26 g, 4 mmol) was added to 4-chloromethyl-2,2 -

bipyridine 32⁵¹(0.1 g, 0.5 mmol) and 18-crown-6 (26 mg,

0.01 mmol) in CH₃CN (10 mL), the mixture stirred for 4 h,

diluted with H₂O (100 mL) and extracted with CH₂Cl₂(4!

75 mL). The combined extracts were dried (MgSO₄), rotary

evaporated, and rapidly chromatographed (deactivated SiO₂

hexanes/EtOAc 7:3) to give nitrile 33 (90 mg, 92%) as a

white solid: mp 105 8C (EtOAc); R_f0.9 (deactivated silica,

hexanes/EtOAc 7:3); IR (DRIFTS) n_max2246, 1604, 1586,

4.1.27. (2,3-Dipyridyl-7,8,12,13,17,18-hexa(dimethyl-

amino)porphyrazinato)-zinc(II) (28). Porphyrazine 27

(6.2 mg, 0.008 mmol) and anhydrous Zn(OAc)₂(1.7 mg,

0.009 mmol) in dry DMF (10 mL) were heated at 100 8C for

16 h under N₂. The mixture was allowed to cool, ﬁltered

(Celite) and the solids washed with CH₂Cl_2.Rotary

evaporation and chromatography (SiO₂EtOAc/MeOH 9:1;

1561, 1462, 1401, 1253, 1067, 992, 932, 853, 788, 751 cm^K1

¹H NMR (300 MHz, CDCl₃) d 8.74–8.71 (m, 2H), 8.50–8.47

;

6128

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

(m, 2H), 7.92(td, JZ7.8,1.8 Hz, 1H), 7.44–7.40 (m, 2H), 3.90

(s, 2H); ¹³C NMR (75 MHz, CDCl₃) d 156.9, 155.1, 150.0,

149.2, 140.0, 137.1, 124.2, 122.7, 121.3, 120.3, 116.5, 23.4;

MS (CI, NH₃) m/z 212 (MCNH₄)^C, 196 (MCH)^C. Anal.

Calcd for C₁₂H₉N₃: C, 73.83; H, 4.65; N, 21.52. Found: C,

74.17; H, 4.79; N, 21.45.

93.3 mmol) and dinitrile 2c (1.0 g, 3.7 mmol) were added

and heated at reﬂux was resumed for 24 h. After cooling, the

deep purple mixture was diluted with CHCl₃, ﬁltered

through celite and the ﬁltrate evaporated under reduced

pressure. Chromatography (SiO₂, CHCl₃/MeOH 99:1 to

95:5) gave the crude norphthalocyanine 39a as a greenish

solid. CF₃CO₂H (20 mL) was added and the mixture

allowed to stand in the dark for 1 h, added to ice and H₂O

(200 mL) and the pH adjusted to 7.5 using aqueous 1.0 M

NaOH. The dark precipitate was ﬁltered off and washed

repeatedly with H₂O. Chromatography (SiO₂, PhMe/

hexanes 6:4 to 7:3) gave norphthalocyanine 40a (175 mg,

7%) as a blue solid: mp 188–192 8C; TLC R_f0.45 (CHCl₃);

IR (CHCl₃) n_max3294, 1561, 1552, 1514, 1498, 1408, 1334,

1306, 1116, 1023, 996, 923, 706 cm^K1; UV–vis (CHCl₃)

l_max(log 3) 293 (4.46), 338 (4.87), 528sh, 577 (4.42), 649

(4.59), 688 (4.60), 723 (4.60) nm; ¹H NMR (CDCl₃,

500 MHz) d K3.40 (2H, s), 4.97 (8H, d, JZ6.3 Hz), 5.34

(4H, d, JZ10.1 Hz), 5.51 (4H, dd, JZ1.6, 17.1 Hz), 6.38–

6.44 (8H, m), 7.35 (2H, d, JZ5.3 Hz), 7.62 (2H, t, JZ

6.9 Hz), 7.66 (2H, t, JZ6.9 Hz), 7.91 (2H, d, JZ6.9 Hz),

8.17 (2H, d, JZ6.9 Hz), 8.45 (2H, d, JZ6.9 Hz); ¹³C

(CDCl₃, 125 MHz) d 55.6, 117.4, 122.0, 122.2, 122.6,

128.9, 129.0, 129.7, 133.0, 134.1, 136.2, 139.1, 139.9,

140.9, 141.5, 156.0, 158.4; FABMS m/z 1309 (2 MCH)^C,

654 (M^C%), 572; HRFABMS m/z Calcd for C₄₀H₃₅N₁₀:

(MCH)^C, 655.3046; found: (MCH)^C, 655.3073. Anal.

Calcd for C₄₀H₃₄N₁₀: C, 73.37; H, 5.23; N, 21.39. Found: C,

73.26; H, 5.39; N, 21.13.

4.1.31. 2,3-Di-(4-(2,2⁰-bipyridyl))fumaronitrile (34).

Following the same procedure as for the preparation of

dinitrile 31, nitrile 33 gave dinitrile 34 (0.41 g, 70%) as a

white solid: mp 2418C (CHCl₃); IR (DRIFTS) n_max2222,

1583, 1547, 1461, 1391, 1253, 1211, 1111, 1072, 993, 920,

1

846, 791 cm^K1; UV/vis l_max(log 3) 286 (4.68); H NMR

(300 MHz, CDCl₃) d 8.94 (d, JZ5.0 Hz, 2H), 8.93 (s, 2H),

8.75 (d, JZ5.1 Hz, 2H), 8.49 (d, JZ7.8 Hz, 2H), 7.90 (td,

JZ7.8, 1.6 Hz, 2H), 7.74 (dd, JZ5.1, 2.0 Hz, 2H), 7.41

(ddd, JZ7.8, 5.0, 1.6 Hz, 2H); ¹³C NMR (75 MHz, CDCl₃)

d 158.0, 154.5, 150.5, 149.5, 139.7, 137.2, 126.5, 124.6,

121.6, 121.4, 119.9, 115.0; MS (CI, NH₃) m/z 387 (MC

H)^C. Anal. Calcd for C₂₄H₁₄N₆: C, 74.60; H, 3.65; N, 21.75.

Found: C, 74.61; H, 3.73; N, 21.85.

4.1.32. 2,3,7,8,12,13,17,18-Octakis((2-(2-pyridyl)-4-pyri-

dyl)porphyrazine (37). Na (17 mg, 0.75 mmol) was added

to dinitrile 34 (0.29 g, 0.75 mmol) in ethylene glycol

(100 mL) and NH₃bubbled through the suspension for

3 h, during which turned dark green. The solution was

ﬁltered hot and the ﬁltrate was poured onto ice (200 mL)

and extracted with CHCl₃(4!100 mL). The combined

extracts were dried (MgSO₄) and rotary evaporated to give

crude 3,4-di-(4-(2,2⁰-bipyridyl))pyrroline-2,5-diimine 35 as

a dark green oily residue that was used in the subsequent

step without further puriﬁcation. n-BuOH (100 mL), Mg

(0.4 g) and I₂(2 small crystals) were heated to reﬂux for

12 h under N₂. The suspension was cooled and the crude

diimine 35 in n-BuOH (5 mL) added and the mixture further

heated at reﬂux for 12 h. The dark green suspension was

allowed to cool, ﬁltered (Celite) and the solids washed with

CH₂Cl₂. After rotary evaporation, the dark green residue

was dissolved in TFA (10 mL). After 30 min at 20 8C under

N₂, the mixture was poured onto ice and H₂O (50 mL),

neutralized with 4 M NaOH, and ﬁltered. The precipitate

was ﬁltered off and washed thoroughly with H₂O, dissolved

in a minimum of CH₂Cl₂, dried (Na₂SO₄) and the solvent

rotary evaporated. Double gel ﬁltration (Sephadex LH20

CHCl₃; Biobeads SX3 CHCl₃), gave porphyrazine 37

(23 mg, 2% from 34) as a dark green solid: mp 328 8C

(CHCl₃); IR (ﬁlm) n_max2191, 1583, 1249, 1093, 989,

793 cm^K1; UV–vis l_max240, 283, 362, 593, 660, CH₂Cl₂;

¹H NMR (300 MHz, CDCl₃) d 8.74–8.50 (m, 16H), 8.36–

8.13 (m, 16H), 7.83–7.73 (m, 8H), 7.32–7.28 (m, 16H),

–1.70 (s, 2H); ¹³C NMR (75 MHz, CDCl₃) d 156.9, 155.5,

150.4, 150.0, 149.1, 149.0, 148.8, 137.2, 136.9, 136.8,

125.1, 124.4, 124.3, 124.2, 123.9, 123.8, 122.6, 121.5,

121.4, 121.3, 121.1, 121.0, 120.4, 119.6, 119.2; MS (FAB)

m/z 1549 (MCH)^C; HRMS (FAB) m/z Calcd for

C₉₆H₅₉N₂₄(MCH)^C, 1547.5355; found: (MCH)^C,

1547.5396.

4.1.34. 2,3-Bis(dibenzylamino)norphthalocyanine (40b).

Following the same procedure as for the preparation of

norphthalocyanine 40a, dinitriles 2b and 38a gave

norphthalocyanine 40b (20 mg, 20%) as a blue solid: mp

243–245 8C; TLC R_f0.55 (CHCl₃); IR (CHCl₃) n_max3294,

1549, 1513, 1495, 1453, 1334, 1320, 1116, 992, 875 cm^K1

;

UV–vis (CHCl₃) l_max(log 3) 292 (4.45), 341 (4.83), 527sh,

583 (4.46), 644 (4.57), 691 (4.56), 727 (4.61) nm; ¹H NMR

(CDCl₃, 300 MHz) d K1.87 (2H, s), 5.78 (8H, s), 7.21–7.31

(12H, m), 7.49–7.53 (8H, m), 7.72 (2H, t, JZ7.0 Hz), 7.80

(2H, t, JZ7.0 Hz), 8.36–8.39 (2H, m), 8.57 (2H, d, JZ

7.0 Hz), 8.70 (2H, d, JZ7.0 Hz); ¹³C NMR (CDCl₃,

100 MHz) d 56.1, 121.7, 121.9, 127.0, 128.5, 128.7,

128.8, 129.2, 132.2, 133.8, 138.7, 139.4, 139.6, 140.3,

141.2, 155.6, and 158.2; FABMS m/z 855 (MCH)^C, 763,

672, 581; HRFABMS m/z Calcd for C₅₆H₄₃N₁₀: (MCH)^C,

855.3672; found: (MCH)^C, 855.3689. Anal. Calcd for

C₅₆H₄₂N₁₀: C, 78.67; H, 4.95; N, 16.38. Found: C, 78.43; H,

5.24; N, 16.02.

4.1.35. 2,3-Bis(diallylamino)-9,10,18,19,27,28-hexabutyl-

norphthalocyanine (40c). Following the same procedure as

for the preparation of norphthalocyanine 40a, dinitriles 2c

and 38b gave norphthalocyanine 40c (17 mg, 4%) as a dark

blue solid: mp 183–185 8C; TLC R_f0.46 (CHCl₃/hexanes

1:1); IR (CHCl₃) n_max3296, 1552, 1515, 1456, 1320, 1107,

996, 923, 720 cm^K1; UV–vis (CHCl₃) l_max(log 3) 299

(4.56), 345 (4.89), 524 (4.25), 577sh, 656 (4.62), 691 (4.61),

1

733 (4.69) nm; H NMR (CDCl₃, 300 MHz) d K0.89 (2H,

4.1.33. 2,3-Bis(diallylamino)norphthalocyanine (40a).

Dry n-BuOH (250 mL), Mg turnings (880 mg, 36 mmol)

and I₂(1 crystal) were heated at reﬂux for 24 h. After

cooling to room temperature, phthalonitrile 38a (12.0 g,

br s), 1.15–1.19 (18H, m), 1.70–1.74 (12H, m), 1.95–2.02

(12H, m), 3.07–3.22 (12H, m), 5.00 (8H, d, JZ5.8 Hz), 5.25

(4H, d, JZ10.1 Hz), 5.46 (4H, d, JZ16.9 Hz), 6.37–6.46

(2H, m), 8.71 (2H, s), 8.89 (2H, s), 9.20 (2H, s); ¹³C NMR

M. J. Fuchter et al. / Tetrahedron 61 (2005) 6115–6130

6129

(CDCl₃, 100 MHz) d 14.2, 23.1, 23.3, 33.3, 33.5, 33.6, 33.7,

33.9, 34.0, 55.6, 117.1, 122.1, 122.6, 123.1, 132.1, 133.7,

136.5, 137.3, 138.1, 140.4, 142.3, 142.4, 142.9, 144.2,

155.7, 158.9; FABMS m/z 991 (MCH),^C950, 908, 868;

HRFABMS Calcd for C₆₄H₈₃N₁₀: (MCH)^C, 991.6802;

found: (MCH)^C, 991.6872. Anal. Calcd for C₆₄H₈₂N₁₀: C,

77.54; H, 8.34; N, 14.13. Found: C, 77.31; H, 8.24; N, 13.89.

8.79 (2H, s), 9.05 (2H, s), 9.32 (2H, s); ¹³C NMR (CDCl₃,

125 MHz) d 14.2, 23.1, 23.2, 33.5, 33.6, 33.7, 33.8, 33.9,

34.0, 56.0, 58.8, 61.3, 122.5, 123.0, 123.5, 127.1, 128.4,

128.6, 132.5, 135.1, 137.2, 137.6, 139.5, 140.8, 143.0,

143.2, 155.5, 159.4; FABMS m/z 1099 (MCH),^C1008,

916; HRFABMS m/z Calcd for C₇₀H₈₇N₁₀O₂: (MCH)^C,

1099.7013; found: (MCH)^C, 1099.6948. Anal. Calcd for

C₇₀H₈₆N₁₀O₂: C, 76.47; H, 7.88; N, 12.74. Found: C, 76.44;

H, 7.72; N, 12.70.

4.1.36. 2,3-Bis(dibenzylamino)-9,10,18,19,27,28-hexa-

butylnorphthalocyanine (40d). Following the same

procedure as for the preparation of norphthalocyanine

40a, dinitriles 2b and 38b gave norphthalocyanine 40d

(100 mg, 10%) as a dark blue solid: mp 247–249 8C; TLC R_f

0.42 (CHCl₃/hexanes 1:1); IR (CHCl₃) n_max3292, 1566,

Acknowledgements

We thank GlaxoSmithKline for the generous endowment (to

A.G.M.B.), the Royal Society and the Wolfson Foundation

for a Royal Society Wolfson Research Merit Award (to

A.G.M.B.), the Wolfson Foundation for establishing the

Wolfson Centre for Organic Chemistry in Medical Sciences

at Imperial College London, the Engineering and Physical

Sciences Research Council, the National Science

Foundation and Schering AG for generous support of our

studies.

1514, 1495, 1451, 1320, 1108, 1027, 989, 746, 698 cm^K1

;

UV–vis (CHCl₃) l_max(log 3) 298 (4.58), 347 (4.90), 517

1

(4.24), 590sh, 655 (4.64), 691 (4.62), 734 (4.74) nm; H

NMR (CDCl₃, 300 MHz) d K0.40 (2H, br s), 1.12–1.20

(18H, m), 1.60–1.78 (12H, m), 1.88–2.05 (12H, m), 3.07–

3.26 (12H, m), 5.68 (8H, s), 7.19–7.23 (12H, m), 7.38–7.41

(8H, m), 8.66 (2H, s), 9.07 (2H, s), 9.36 (2H, s); ¹³C (CDCl₃,

125 MHz) d 14.18, 14.21, 23.1, 23.2, 33.4, 33.6, 33.66,

33.74, 33.8, 34.0, 56.6, 122.4, 122.8, 123.3, 126.8, 128.3,

128.7, 132.3, 133.6, 137.3, 138.1, 139.5, 140.5, 142.56,

142.61, 143.6, and 144.3; FABMS m/z 1192 (MCH)^C,

1101, 1009; HRFABMS m/z Calcd for C₈₀H₉₁N₁₀: (MC

H)^C, 1191.7428; found: (MCH)^C, 1191.7353. Anal. Calcd

for C₈₀H₉₀N₁₀: C, 80.63; H, 7.61; N, 11.75. Found: C,

80.34; H, 7.38; N, 12.05.

Supplementary data

Supplementary data associated with this article can be

found, in the online version, at doi:10.1016/j.tet.2005.03.

090

4.1.37. 2,3-Bis(allyl(benzyl)amino)-9,10,18,19,27,28-

hexabutylnorphthalocyanine (40e). Following the same

procedure as for the preparation of norphthalocyanine 40a,

dinitriles 2e and 38b gave norphthalocyanine 40e (25 mg,

6%) as a dark blue solid: mp 168–170 8C; TLC R_f0.72

(CHCl₃/hexanes 1:1); IR (CHCl₃) n_max3297, 1549, 1514,

References and notes

1

1496, 1452, 1321, 1106, 1033, 983, 767, 699 cm^K1; H

NMR (CDCl₃, 300 MHz) d K0.74 (2H, br s), 1.17 (18H, t,

JZ7.1 Hz), 1.66–1.75 (12H, m), 1.88–2.00 (12H, m), 3.05–

3.16 (12H, m), 5.00 (4H, d, JZ5.8 Hz), 5.22 (2H, d, JZ

10.3 Hz), 5.39 (2H, d, JZ16.7 Hz), 5.74 (4H, s), 6.26–6.32

(2H, m), 7.20–7.28 (6H, m), 7.51 (4H, d, JZ6.5 Hz), 8.62

(2H, s), 8.97 (2H, s), 9.22 (2H, s); ¹³C NMR (CDCl₃,

125 MHz) d 14.2, 23.1, 23.2, 33.4, 33.6, 33.7, 33.9, 34.0,

56.0, 56.7, 117.3, 122.4, 122.8, 123.2, 126.8, 128.2, 128.8,

132.2, 133.9, 136.1, 137.4, 138.2, 139.7, 140.7, 142.5,

142.6, 143.4, 144.3, 155.8, 159.1; FABMS m/z 1091 (MC

H),^C1049, 999, 958; HRFABMS m/z Calcd for C₇₂H₈₇N₁₀:

(MCH)^C, 1091.7115; found: (MCH)^C, 1091.7058. Anal.

Calcd for C₇₂H₈₆N₁₀: C, 79.23; H, 7.94; N, 12.83. Found: C,

79.48; H, 7.75; N, 12.61.

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Article Doi

Synthesis of porphyrazine-octaamine, hexamine and diamine derivatives

DOI: 10.1016/j.tet.2005.03.090

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