Synthesis and anion-binding studies of thiaphlorins and covalently linked thiaphlorin-porphyrin dyads

FULL PAPER

DOI: 10.1002/ejoc.200701000

Synthesis and Anion-Binding Studies of Thiaphlorins and Covalently Linked

Thiaphlorin–Porphyrin Dyads

Iti Gupta,^[a]Roland Fröhlich,^[b]and Mangalampalli Ravikanth*^[c]

Keywords: Thiaphlorins / Porphyrins / Anion sensing

A series of thiaphlorins with N₂S₂and N₃S cores have been

prepared in decent yields from readily available precursors.

The thiaphlorins were characterized by all spectroscopic

techniques and the structures of two thiaphlorins were solved

by X-ray crystallography. The spectral studies indicated that

the properties of thiaphlorins were quite different from those

of thiaporphyrins. The methodology used for the synthesis

of thiaphlorins has been extended to synthesize a series of

monofunctionalized thiaphlorins. We also performed func-

tional group transformation of thiaphlorins without decompo-

sition, supporting the conjecture of the stable natures of thia-

phlorins. The crystal structure analysis of two thiaphlorins

indicated that the macrocycles are not planar and that they

each show a marked kink at sp³-hybridised meso carbon.

The functionalized thiaphlorins have been used to synthesize

several novel porphyrin–thiaphlorin dyads as well as a bis-

(thiaphlorin) dyad under mild palladium(0) coupling condi-

tions. Preliminary anion-binding studies carried out on thia-

phlorins and porphyrin–thiaphlorin dyads indicated that they

can bind anions effectively in their protonated forms and that

these systems can also be used as optical sensors.

Germany, 2008)

Introduction

Porphyrins are macrocycles that contain only sp²-hybrid-

ised bridging meso carbon atoms (1.1.1.1- four sp²hy-

bridized carbon atoms) within their frameworks and are

well known for their versatile metal coordination chemis-

try.^[1]On the other hand, calix(4)pyrroles,^[2]the porphyrin

analogues containing pyrroles bridged exclusively by sp³

meso carbon centres (1.1.1.1) have attracted attention re-

cently for their anion-binding chemistry (Scheme 1). Calix-

(4)phyrins^[3]are a class of hybrid molecules containing a

mixture of sp²- and sp³-hybridized meso carbon bridges that

lie at the structural crossroads between porphyrins and ca-

lix(4)pyrroles and have been shown to be good receptors

for cations and, more importantly, for anions. The different

classes of calix(4)phyrins are shown in Scheme 2.

These classes are porphomonomethenes (1.1.1.1 – one

sp²- and three sp³-hybridized meso carbon atoms), porpho-

dimethenes (1.1.1.1 and 1.1.1.1 – two sp²- and two sp³-hy-

bridized meso carbon atoms) and porphotrimethenes

(1.1.1.1 – three sp²- and one sp³-hybridized meso carbon

atoms). Phlorins are a class of porphotrimethenes contain-

Scheme 1. Structures of porphyrins and calix(4)pyrroles.

ing three sp²meso carbon atoms and one sp³one and were

first identified by R. B. Woodward during his landmark

studies directed towards the synthesis of chlorophyll a.^[4]

Phlorins have also been proposed as intermediates in the

catalytic cycle of the haem p460 of hydroxylamine oxidore-

ductase^[5]and also during some syntheses of porphyrins^[6]

and chlorines.^[7]Phlorins have been found to be good anion

sensors and have been obtained on reduction of porphyrins

and metalloporphyrins by photochemical,^[8]radiolytic,^[9]

electrochemical^[10]and chemical^[11]methods. However,

phlorins in general are very unstable for exploration of their

complete potential for various applications. Recently, sev-

eral methods to obtain stable phlorins in metallated and

metal-free forms have become available. Setsune et al.,^[12]

Callot et al.,^[13]Lee et al.,^[14]Furuta et al.^[15]and others^[16]

have independently developed some novel routes by which

to synthesize phlorins starting from porphyrins or oligopyr-

[a] BITS-Pilani, Goa Campus,

Near NH-17B, Bye Pass Road, Zuarinagar, Goa 403726, India

[b] Organisch-Chemisches Institut, Universität Münster,

Corrensstraße 40, 48149 Münster, Germany

[c] Department of Chemistry, Indian Institute of Technology,

Bomay, Powai,

Mumbai 400076, India

E-mail: ravikanth@chem.iitb.ac.in

Supporting information for this article is available on the

WWW under http://ww w .eurjoc.org or from the author.

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Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

Scheme 3. Structures of 21,23-dithia- and 21-thiaphlorins.

Except for our own report, there are to the best of our

knowledge no reports on core-modified calix(4)phyrins to

test their potential for various applications. Our group has

been involved in developing methods to synthesize core-

modified porphyrin building blocks and to use them for the

synthesis of porphyrin dyads, triads, tetrads and pentads

containing two or more different porphyrin subunits.^[18]In

this paper we describe the synthesis of N₂S₂and N₃S phlor-

ins in decent yields from very simple precursors in detail.

The methodology adopted here has been extended to syn-

thesize several monofunctionalized thiaphlorins containing

p-iodophenyl, p-ethynylphenyl, p-bromophenyl, p-cyano-

phenyl and m-nitrophenyl groups etc., and these have been

used further for the synthesis of several novel thiaphlorin–

porphyrin and thiaphlorin–thiaphlorin dyads. Preliminary

anion-binding studies of some of these thiaphlorins and

thiaphlorin–porphyrin dyads and their suitability as optical

sensors is also presented.

Scheme 2. Structures of calix(4)phyrins.

Results and Discussion

Synthesis of Unsymmetrically Substituted 2,5-

Thiophenedimethanols 2–4

roles as precursors. Modification of the phlorin core by re-

placement of one or two nitrogen atoms with heteroatoms

such as sulfur (Scheme 3) and oxygen may lead to core-

The desired diols 2–4 (Scheme 4) were synthesized in two

modified phlorins that may possess interesting metal- and steps starting from thiophene. The 2-thiophenemethanol

anion-binding properties. With this in mind, we recently re- derivative 1 was synthesized in 65% yield by treatment of

ported the synthesis of a series of monofunctionalized thia the thiophene with nBuLi (1.2 equiv.) followed by p-tolylal-

analogues of phlorins and their use in the synthesis of phlo- dehyde (1.2 equiv.) in THF at 0 °C and purified by silica

rin–porphyrin dyads in a communication.^[17]

gel column chromatography.^[18f]After treatment with nBuLi

Scheme 4. Synthesis of unsymmetrically substituted 2,5-thiophenedimethanols 2–4.

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(2.5 equiv.), compound 1 was allowed to react with ketones standard workup, the resulting crude compound was puri-

like acetone, butan-2-one or acetophenone (1.2 equiv.) in fied in order to remove polymeric materials. TLC analysis

THF at 0 °C (Scheme 4). After workup, TLC analysis of after the filtration column showed a fast-moving orange

the crude mixtures showed four spots: two fast-moving spot corresponding to an unidentified product, followed by

minor spots corresponding to the unreacted ketone and 1, a green spot corresponding to the relevant 21,23-dithia-

respectively, and one unknown minor spot, closely followed phlorin 6–8. The crude mixture was subjected to a second

by one major spot corresponding to the required unsym- chromatographic purification. The unidentified orange

metrical diol. The crude mixture was subjected to silica gel product of low polarity (Ͻ1% yield) was collected and the

column chromatography, and unreacted ketone and 1 were desired 21,23-dithiaphlorins 6–8 were then collected as

collected with petroleum ether/ethyl acetate 5–7%. The green compounds in 7–19% yields. Dithiaphlorins 6–8 were

third unknown minor spot was then collected with petro- characterized by spectrometry and spectroscopic techniques

leum ether/ethyl acetate 25–30%, followed by the desired and also in the case of 8 by X-ray crystallographic analysis.

unsymmetrical diol eluted with petroleum ether/ethyl ace- The presence of strong [M]⁺ion peaks in the mass spectra

tate 30–40%. Removal of solvent in vacuo afforded unsym- and matching elemental analyses confirmed the identities

metrical diols 2–4 in 31–57% yields. Since the unsymmetri- of the 21,23-dithiaphlorins 6–8.

1

cal 2,5-thiophenedimethanols 2–4 each have two chiral

The H NMR spectra of 21,23-dithiaphlorins 6–8 were

centres, the additional minor spots observed just above the recorded in CDCl₃both at room temperature and at

1

desired major spots could be due to their diastereomers.^[19]–50 °C. In the H NMR spectrum, the four β-pyrrole pro-

However, we collected the major product in each case and tons gave rise to a sets of four signals, either doublets or

used it for condensation reactions. Although the yields of broad singlets, shifted significantly upfield to the 6.2–

diols are moderate, the ready availability of 1 allows the 7.2 ppm region, indicating the non-aromatic natures of the

easy preparation of the desired unsymmetrical thiophenedi- compounds. The four β-thiophene protons appeared as sets

methanols in about 5 g batches. The diols 2–4 were charac- of two signals: a doublet at ca. 7.2 ppm due to one proton

terized by spectrometric and routine spectroscopic tech- and a multiplet at ca. 7.3 ppm due to three protons. The

niques. The [M – 17]⁺ion peak in the mass spectra and inner NH proton appeared as two broad signals at ca. 11.3

the matching elemental analysis confirmed the formation of and ca. 12.7 ppm, indicating the presence of two tautomers

diols.

in solution. However, when the spectra were recorded in

[D₅]pyridine, only one broad signal at δ = 10.1 ppm was

observed for the NH proton, disappearing on the addition

of a drop of D₂O due to exchange of the NH proton for a

Synthesis of 21,23-Dithiaphlorins 6–8 and 21-Thiaphlorin 9

The 21,23-dithiaphlorins 6–8 were prepared as shown in deuterium atom, confirming the NH signal (see Supporting

Scheme 5. The other desired precursor, the symmetrical 16- Information). The absorption spectra of 6–8 each showed a

thiatripyrrane 5, was synthesized by a literature pro- broad band at ca. 680 nm, together with broad and some-

cedure.^[20]An unsymmetrical diol 2–4 (1 equiv.) was con- times split moderately intense absorption at ca. 420 nm

densed with 16-thiatripyrrane 5 (1 equiv.) in the presence of (Figure 1). The protonated species of 6–8 generated by ad-

a catalytic amount of trifluoroacetic acid at room tempera- dition of few drops of dilute trifluoroacetic acid to 6–8 in

ture, and this was followed by oxidation with DDQ. After dichloromethane each showed a significantly red-shifted

Scheme 5. Synthesis of 21,23-dithiaphlorins 6–8.

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Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

1

strong absorption band at ca. 825 nm, together with two or 12.2 ppm region. The H NMR spectrum of 21-thiaphlorin

three moderately intense broad peaks in the 300–500 nm 9 was very similar to those of the 21,23-dithiaphlorins. The

region (Figure 1).

absorption spectrum of 9 showed a very broad band at ca.

672 nm and two bands in the 300–500 nm region. The pro-

tonated species of 9 also showed similar absorption fea-

tures. The absorption bands of the protonated species of

9 were bathochromically shifted in relation to its neutral

analogue. The absorption bands of 9 and its protonated

species were blue-shifted in relation to the neutral and pro-

tonated species of the 21,23-dithiaphlorins.

Synthesis of Unsymmetrically Substituted 2,5-Thiophene-

dimethanols 10–14

The synthetic methodology discussed above for the prep-

aration of thia analogues of phlorins has been extended fur-

ther to synthesize monofunctionalized thiaphlorins in order

Figure 1. Absorption spectra of 21,23-dithiaphlorin 6 (––) and to use them as building blocks for the synthesis of coval-

6·H⁺(------) recorded in dichloromethane. The concentration of 6

ently linked porphyrin–thiaphlorin and thiaphlorin–thia-

phlorin dyads. To synthesize the monofunctionalized thia-

used was 2.34ϫ10^–5.

phlorins, the functionalized unsymmetrically substituted

The 21-thiaphlorin 9 was synthesized by condensing the 2,5-thiophenedimethanols 10–14 are needed, and these were

diol 2 (1 equiv.) with p-tolylaldehyde (2 equiv.) and pyrrole synthesized as shown in Scheme 7. The 2-thiophenemeth-

(3 equiv.) under acid catalysis conditions (Scheme 6).

anol derivative 15 was synthesized in 43% yield by treat-

The crude mixture containing the desired compound 9 ment of thiophene with nBuLi (1.2 equiv.) followed by reac-

together with 5,10,15,20-tetratolylporphyrin and some un- tion with acetone (1.2 equiv.) in THF and was purified.

identified compound was separated by silica gel column Compound 15 was first treated with nBuLi (2.5 equiv.) then

chromatography and afforded 9 in 3% yield. Compound 9 with an appropriate functionalized aromatic aldehyde

was characterized by all spectroscopic techniques. Its mass (1.2 equiv.) (see Scheme 7).

spectra showed the [M]⁺ion peak, and its elemental analy-

Purification of the crude reaction mixtures by silica gel

sis was in agreement with the proposed composition of 9. column chromatography afforded the pure functionalized

1

In the H NMR, a set of three signals corresponding to six diols 10–14 in 24–62% yields. The functionalized diols 10–

β-pyrrole protons can be seen, further two multiplets and 14 were characterized by common techniques. The diols 10–

one broad singlet, shifted significantly upfield to the 6.5– 14 each showed two signals for OH protons in their infrared

6.9 ppm region. The broad singlet at δ ≈ 7.2 ppm was as- spectra, due to their unsymmetrical natures. The [M]⁺

signed to the two β-thiophene protons. The two inner NH (10%) and [M – 17]⁺(90%) ion peaks in the mass spectra

protons were assigned to either two or three signals in 9.8– confirmed the identities of the diols 10–14.

Scheme 6. Synthesis of 21-thiaphlorin 9.

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FULL PAPER

Compounds 16–20 were characterized by NMR, mass, ab-

sorption and elemental analysis. The monofunctionalized

21,23-dithiaphlorins 16–20 each showed a strong [M]⁺ion

peak in the mass spectrum, and the elemental analyses were

in agreement with the proposed compositions of the com-

1

pounds. The β-pyrrole protons cause H NMR signals in

the 6.3–7.1 ppm region as sets of three or four peaks. Sets

of two multiplets in the 7.1–7.3 ppm region were assigned

to the four β-thiophene protons.

Monofunctionalized 21-Thiaphlorins 21–24

The monofunctionalized 21-thiaphlorins 21–24, contain-

ing functional groups such as iodophenyl, bromophenyl, cy-

anophenyl and nitrophenyl at their meso-positions were

synthesized by using the appropriate diols (Scheme 8, b).

Condensation of the appropriate functionalized 2,5-thio-

phenedimethanol (1 equiv.) with p-tolylaldehyde (2 equiv.)

and pyrrole (3 equiv.) in dichloromethane under nitrogen in

the presence of catalytic amounts of trifluoroacetic acid at

room temperature, followed by oxidation with DDQ, gave

Scheme 7. Synthesis of functionalized unsymmetrically substituted

2,5-thiophenedimethanols 10–14.

Monofunctionalized 21,23-Dithiaphlorins 16–20

The monofunctionalized 21,23-dithiaphlorins 16–20 were a crude mixture of the desired compound along with

synthesized by condensing each of the appropriate diols 10– 5,10,15,20-tetratolylporphyrin and some unidentified

14 (1 equiv.) with 16-thiatripyrrane 5^[20]under mild acid ca- macrocycles (Scheme 8, b). Column chromatographic puri-

talysis conditions (Scheme 8, a). Purification by silica gel fication on silica with petroleum ether/ethyl acetate 5–10%

column chromatography with petroleum ether/ethyl acetate afforded pure 21–24 as green solids in 3–5% yields.

5–15% afforded the desired monofunctionalized 21,23-di-

The functionalized 21-thiaphlorins 21–24 were charac-

thiaphlorins 16–20 as the second bands in 12–20% yields. terized by spectrometric and spectroscopic techniques. The

Scheme 8. Synthesis of monofunctionalized 21,23-dithiaphlorins 16–20 and 21-thiaphlorins 21–24.

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Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

mass spectra of 21–24 each showed a molecular ion peak Table 1. Crystal data and data collection parameters for 8 and

17·H⁺.

at the expected molecular weight, and the elemental analy-

ses were in agreement with the compositions of the com-

pounds. In the H NMR, the signals of the six β-pyrrole

and the two β-thiophene protons were found in the 6.4–

7.3 ppm region (see Supporting Information). The two in- Dimensions [mm]

Parameters

8

17·H⁺

1

Empirical formula

Formula weight

C₄₈H₃₈N₂S₂

706.92

C₄₂H₃₄N₂S₂BrI₃·0.5C₆H₆

1130.50

0.25ϫ0.20ϫ0.05

monoclinic

13.440 (1)

15.667 (1)

20.937 (1)

90

103.82 (1)

90

4283.5 (12)

P2₁/c

0.35ϫ0.15ϫ0.05

monoclinic

8.990 (1)

16.034 (1)

25.816 (1)

90

98.78 (1)

90

3677.7 (5)

P2₁/n

Crystal system

ner NH protons produced sets of two or three broad sing-

a [Å]

lets in the 9.9–12.0 ppm region. In [D₅]pyridine, two broad

b [Å]

signals were observed for the inner NH protons at low tem-

c [Å]

α [°]

β [°]

perature, and these disappeared on addition of a drop of

D₂O, due to exchange of NH protons for deuterium atoms,

confirming the identities of the NH protons (see Support-

ing Information). The absorption spectra of 21–24 and their

protonated species showed features similar to those of 9 and

its protonated species, respectively.

γ [°]

V [Å³]

space group

Z

4

1.83

0.064

4

µ(Mo-K_α) [cm^–1

Residuals: R₁

]

32.53

0.085

Reflections measured 19039

T [K] 198 (2)

12124

198 (2)

X-ray Diffraction Analysis

The X-ray structures of 8^[21]and the protonated form of

17^[21]were solved. The crystal structures are shown in Fig-

ure 2 and the crystal data are presented in Table 1.

into two types: a) thiophene I and pyrrole I (lying between

the two sp²meso carbon atoms), and b) thiophene II and

pyrrole II (lying between sp³and sp²meso carbon atoms).

The dihedral angels between the mean core planes and the

thiophene I, II and pyrrole I, II units of 8 and 17·H⁺are

tabulated in Table 2. It is very clear from Table 2 that in

thiaphlorin 8 the thiophene II and pyrrole II units are much

more deviated from the mean plane than the thiophene I

and pyrrole I units. The presence of one sp³meso carbon

forces the thiophene II and pyrrole II units to tilt away from

the mean core plane in the macrocycles 8 and 17·H⁺.

Furthermore, the pyrrole II unit is more deviated from the

mean core plane than the thiophene II unit in both macro-

cycles.

Table 2. Selected bond lengths and dihedral angles in 8 and 17·H⁺,

Figure 2. X-ray crystal structures of a) 8 and b) 17·H⁺Thermal

ellipsoids are shown at the 50% probability level. In the bottom

view, meso aryl groups have been removed for clarity.

together with free thiophene and free pyrrole units.

Ring

C_α–X [Å]

C_α–C_β[Å]

C_β–C_β[Å] Є [°]

Free thio-

phene

Free pyrrole

1.714

1.370

1.423

1.417

–

It is clear from the figure that both 8 and 17·H⁺are non-

planar and possess marked kinks at their sp³-hybridized

meso carbons. In dithiaphlorin 8, the nonbonding N···N

(4.69 Å) and S···S (3.43 Å) distances are slightly larger than

those in meso-tetraphenyl-21,23-dithiaporphyrin (S₂TPP)

[N···N (4.65 Å) and S···S (3.07 Å)], indicating that 8 is less

planar than S₂TPP.^[22]Similarly the nonbonding N···N

(4.84 Å) and S···S (3.39 Å) distances in the protonated di-

thiaphlorin 17·H⁺were found to be greater than those in

S₂TPP, showing that 17·H⁺is not planar, due to the pres-

ence of one meso sp³carbon.

1.370

1.382

8

Thiophene I

Thiophene II 1.725(3), 1.736(3)

Pyrrole I

Pyrrole II

17

1.783(3), 1.780(2)

1.427(5), 1.417(5)

1.365(5), 1.380(5)

1.440(5), 1.462(5)

1.369(5), 1.374(5)

1.365(5)

1.406(5)

1.357(5)

1.400(5)

34.1

67.9

22.4

74.6

1.314(3), 1.317(3)

1.433(4), 1.447(4)

Thiophene I

1.733(11), 1.770(11) 1.415(14), 1.402(16) 1.354(14)

12.2

7.8

9.0

Thiophene II 1.740(12), 1.736(12) 1.351(16), 1.365(16) 1.390(16)

Pyrrole I

Pyrrole II

1.372(13), 1.401(13) 1.428(16), 1.426(14) 1.353(15)

1.377(14), 1.386(14) 1.392(15), 1.381(16) 1.381(16)

25.9

The nonplanarity of 8 and 17·H⁺was clearly reflected in

their dihedral angels between their mean core planes con-

The relevant bond lengths in the heterocyclic rings in

sisting of 24 atoms and the planes of the individual pyrrole thiaphlorins 8 and 17·H⁺, together with those in free thio-

or thiophene. In each macrocycle, the mean core plane of phene and free pyrrole, are also listed in Table 2. Closer

24 atoms was highly distorted, with a mean deviation of inspection of Table 2 shows that significant changes in C_α–

4.41 Å for 8 and 4.58 Å for 17·H⁺. The thiophene and pyr- X, C_α–C_βand C_β–C_βbond lengths are observed in 8 and

role rings in thiaphlorins 8 and 17·H⁺can be categorised 17·H⁺in relation to those in free thiophene and free pyr-

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role.^[23]The inner NH atom in 8 is present on the pyrrole

N (pyrrole II), which is adjacent to the meso sp³carbon.

The macrocycles 8 and 17·H⁺each adopt a ruffled confor-

mation, due to the nonplanarity induced by the presence

of one meso sp³carbon. To accommodate the deformation

caused by the meso sp³carbon atom, the pyrrole and the

thiophene units in 8 and 17 each adopt an alternate confor-

mation.

Synthesis of Covalently Linked 21,23-Dithiaphlorin–

Porphyrin Dyads 25–28 and 21-Thiaphlorin–Porphyrin

Dyads 29, 30

To show the applicability of the monofunctionalized

thiaphlorins, we synthesized a series of covalently linked un-

symmetrical dyads 25–28 (Scheme 9). The diarylethyne-

bridged covalently linked unsymmetrical dyad 25 contain-

ing 21,23-dithiaphlorin and ZnN₄porphyrin subunits was

synthesized by coupling of 16 with the zinc(II) complex of

5,10,15-tri(mesityl)-20-(p-ethynylphenyl)porphyrin^[24]in tol-

uene/triethylamine at 50 °C in the presence of catalytic

amounts of AsPh₃/Pd₂(dba)₃under inert atmosphere^[25]

Scheme 10. Synthesis of covalently linked 21,23-dithiaphlorin–por-

phyrin dyad 25.

The diarylethyne-bridged dyad 27 containing 21,23-di-

(Scheme 10). The crude compound was purified by column thiaphlorin and N₃S porphyrin subunits was synthesized in

chromatography on neutral alumina with petroleum ether/ 48% yield by coupling of 16 with 5-(p-ethynylphenyl)-

ethyl acetate 3–5% and afforded dyad 25 in 35% yield. The 10,15,20-tris(p-octyloxyphenyl)-21-thiaporphyrin^[18f]under

dyad 26 was synthesized in 69% yield by demetallation of similar palladium coupling conditions.^[25]The phenyl-

25 with trifluoroacetic acid at room temperature.

ethyne-bridged dyad 28 containing 21,23-dithiaphlorin and

Scheme 9. Covalently linked thiaphlorin–porphyrin dyads 25–30.

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Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

N₃S porphyrin subunits was synthesized in 20% yield under mainly to the ZnN₄porphyrin subunit, completely masking

the same mild palladium(0)-assisted coupling conditions the absorption of the 21,23-dithiaphlorin subunit in that

through the coupling of 16 with 5-ethynyl-10,15,20-tri(p- region. Interestingly, it is possible to protonate the 21,23-

tolyl)-21-thiaporphyrin^[18g]

.

dithiaphlorin subunit with trifluoroacetic acid without

To synthesize dyad 29, the 21-thiaphlorin building block causing any demetallation of the ZnN₄porphyrin subunit.

21 was coupled with 5-ethynylphenyl-10,15,20-trimesityl- Comparison of the absorption spectra of dyad 25 and of its

zinc(II)porphyrin^[24]in toluene/triethylamine at 50 °C in the protonated species as shown in Figure 3 clearly indicated

presence of AsPh₃/Pd₂(dba)₃as catalyst, followed by stan- that the protonation had occurred at the 21,23-dithiaphlo-

dard workup and chromatography on neutral alumina with rin subunit site without causing any demetallation of the

petroleum ether/ethyl acetate to give dyad 29 in 33% yield. porphyrin subunit.

The dyad 29 was treated with trifluoroacetic acid in dichlo-

romethane for 12 h to give after purification the free base

dyad 30 as a green–violet solid in 70% yield.

The dyads 25–30 are highly soluble in all common or-

ganic solvents and were characterized by NMR, mass and

1

absorption spectroscopic techniques. In the H NMR, the

dyads 25–27 each showed peaks corresponding to both mo-

nomeric units. For dyad 25, the four β-pyrrole protons of

the 21,23-dithiaphlorin subunit gave signals upfield in the

6.4–6.9 ppm region as a set of four signals whereas the sig-

nals of the eight β-pyrrole protons of the ZnN₄porphyrin

subunit appeared downfield as a set of three signals in the

8.7–8.9 ppm region (see Supporting Information). The sig-

nals of the two β-thiophene protons of the 21,23-dithi-

aphlorin subunit also appeared upfield as two multiplets in

the 6.9–7.2 ppm region. The inner NH signal of the 21,23-

dithiaphlorin subunit of dyad 25 was detected downfield.

Figure 3. Absorption spectra of dyad 25 (––) and 25·H⁺(-----) re-

The dyad 26, containing 21,23-dithiaphlorin and N₄por-

corded in dichloromethane (concentration of 25 used was

phyrin subunits, and the dyad 27, containing 21,23-di-

thiaphlorin and 21-thiaporphyrin subunits, both showed ¹H

NMR spectral features similar to those of dyad 25. Com-

1.97ϫ10^–6). The inset shows expansion of 500–1000 nm region.

The dyad 26 showed a broad absorption band of the

parison of the chemical shifts of the various protons of the 21,23-dithiaphlorin subunit at 699 nm and four Q-bands of

dyads 25–27 with those of the corresponding individual mo- the N₄porphyrin subunit in the visible region, together with

nomeric units indicates only minor differences, suggesting one strong Soret band, mainly of the N₄porphyrin subunit,

that the 21,23-dithiaphlorin and porphyrin subunits in dy- at 420 nm. In dyad 27, the absorption bands of the 21,23-

ads 25–27 interact very weakly.

dithiaphlorin subunit and the N₃S porphyrin subunit over-

The phenylethyne-bridged dyad 28 showed peaks corre- lapped and showed a broad band at 685 nm along with

sponding to its constituent monomeric units. The chemical three other Q-bands at 627, 556 and 518 nm mainly corre-

shifts of the protons corresponding to the N₃S porphyrin sponding to the N₃S porphyrin subunit. The dyad 27 also

subunit with the ethyne group directly at the meso position showed a single strong Soret band at 435 nm, correspond-

were affected, whereas the protons of the 21,23-dithiaphlo- ing mainly to the N₃S porphyrin subunit. The dyad 28

rin subunit with the phenyl group at the meso position re- showed ill-defined Q-bands and one strong Soret band,

mained unaffected. The β-thiophene and β-pyrrole protons which were bathochromically shifted in relation to 5-eth-

of the N₃S-porphyrin subunit in dyad 28 were shifted down- ynyl-10,15,20-tri(p-toyl)-21-thiaporphyrin^[18g]because of

field in relation to 5-ethynyl-10,15,20-tri(p-tolyl)-21-thia- the strong interaction between the two subunits. In all these

porphyrin,^[18g]indicating a strong interaction between the dyads, it is possible to protonate the 21,23-dithiaphlorin

two subunits.

The absorption spectra of dyads 25–28 are each essen- subunit.

tially a linear combination of the spectra of the correspond- The dyads 29 and 30 were identified by clear NMR spec-

subunit selectively without protonation of the porphyrin

1

ing monomers with only minor differences in wavelength tra and by [M]⁺ion peaks in their mass spectra. In the H

maxima and band shapes, indicating that the monomeric NMR of dyad 29, the six β-pyrrole H signals of the 21-

subunits essentially retain their individual identities in the thiaphlorin subunit appeared upfield as a set of three sig-

dyads 25–28. In the visible region, the dyad 25 showed a nals in the 6.5–7.0 ppm region, while the signals of the eight

broad absorption at 700 nm corresponding to the 21,23-di- β-pyrrole protons of the ZnN₄porphyrin subunit appeared

thiaphlorin subunit and two absorption bands at 550 and downfield as a set of three broad signals in the 8.7–8.9 ppm

590 nm corresponding to the ZnN₄porphyrin subunit (Fig- region. The two β-thiophene H signals of the 21-thiaphlorin

ure 3). In addition to the visible bands, the dyad 25 also subunit appeared as a multiplet at 7.3 ppm. Dyad 30

1

showed a strong Soret band at 422 nm, corresponding showed similar H NMR features. The visible absorption

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1891

I. Gupta, R. Fröhlich, M. Ravikanth

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1

spectra of dyad 29 showed a broad absorption at 681 nm chromatography on neutral alumina (Scheme 11). The H

corresponding to the 21-thiaphlorin subunit and two bands NMR spectra of dyad 33 showed a set of four signals for

at 550 and 590 nm corresponding to the ZnN₄porphyrin the eight β-pyrrole protons and two sets of signals for the β-

subunit. In addition, the dyad 29 also showed a strong Soret thiophene protons of both the 21,23-dithiaphlorin subunits.

band at 432 nm, corresponding mainly to the ZnN₄porphy- The dyad 33 also showed two broad singlets for inner NH

rin subunit. The visible absorption spectrum of dyad 30 protons at δ = 11.9 and 13.1 ppm. The absorption spectrum

showed a broad absorption at 679 nm for the 21-thiaphlorin of dyad 33 showed a broad absorption at 706 nm and mul-

subunit and four Q-bands in the 500–650 nm region corre- tiple absorption bands in the 300–450 nm region.

sponding to the N₄porphyrin subunit. The dyad 30 also

showed a strong Soret band at 419 nm, corresponding

mainly to the N₄porphyrin subunit. In dyads 29 and 30, it

is possible to protonate the 21-thiaphlorin subunit selec-

tively.

Anion-Binding Studies

The calix(4)pyrroles, calix(4)phyrins and their expanded

analogues are well known for their strong abilities to coor-

dinate anions.^[26]The driving force for anion coordination

in these macrocycles is mainly through electrostatic interac-

tions and hydrogen bonds. The thiaphlorins synthesized

Bis(21,23-dithiaphlorin) Dyad 33

To synthesize bis(21,23-dithiaphlorin) dyad 33, the other here have been found to have less affinity for anion coordi-

required 21,23-dithiaphlorin building block 31, with a p- nation in neutral form, due to smaller numbers of inner

ethynylphenyl group at the meso position, was synthesized hydrogen atoms, which would be expected to be involved in

as shown in Scheme 11. The 21,23-dithiaphlorin 16, with a anion binding through hydrogen-bonding interactions. Sim-

meso p-iodophenyl group, was treated with (trimethylsilyl)- ilar observations were made earlier with calix(4)phyrins

acetylene in toluene/triethylamine in the presence of AsPh₃with N₄cores^[26]and expanded heteroporphyrins.^[27]How-

and Pd₂(dba)₃at 50 °C under inert atmosphere^[25]for 24 h. ever, these macrocycles were found to be effective in anion

After purification 31 was obtained in 65% yield. Deprotec- coordination in their protonated forms. It should be noted

tion of 31 with tetrabutylammonium fluoride (TBAF) at that the protonated forms of thiaphlorins absorb very

room temperature in dry THF gave 32 in 64% yield. Com- strongly in the visible region relative to their neutral species,

pound 32 showed a singlet at 3.2 ppm in the ¹H NMR, which helps in carrying out anion-binding experiments

corresponding to the CCH proton and a molecular ion using optical spectroscopic techniques. Preliminary binding

peak in its mass spectrum, confirming the identity of the studies of the protonated forms of 21,23-dithiaphlorin 6

compound.

and the covalent thiaphlorin–porphyrin dyads 25 and 27

The diarylethyne-bridged bis(dithiaphlorin) dyad 33 con- with various tetrabutylammonium salts were carried out in

taining two 21,23-dithiaphlorin subunits was synthesized in order to test their abilities to coordinate anions.

24% yield by coupling of 16 with 32 under mild palla-

The protonated forms of thiaphlorin 6 and thiaphlorin–

dium(0) coupling conditions as used for the preparation of porphyrin dyad 25 show strong absorptions in their 800–

other dyads, followed by purification by column 860 nm regions, so the changes in the electronic spectra on

Scheme 11. Synthesis of bis(21,23-dithiaphlorin) dyad 33.

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Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

addition of anions were used to study anion complexation.

In the case of dyad 27, the calix(4)phyrin subunit can be

selectively protonated without protonating the thiaporphy-

rin subunit, and the changes in the strong fluorescence

of the thiaporphyrin subunit on addition of increasing

amounts of anions were used to study the anion complex-

ation. In a typical experiment, an aliquot (3 mL) of the pro-

tonated solution of thiaphlorin 6 or thiaphlorin–porphyrin

dyad 25 or 27 in dichloromethane was placed in the spectro-

metric cell and increasing amounts of the tetrabutylammo-

nium halide salt dissolved in dichloromethane were added

by Hamilton Micro syringe. The addition of the salt solu-

tion changed the colour of the host solution from greenish

yellow to brown. Immediately the absorption spectra of the

solutions in the desired region for 6·H⁺and 25·H⁺and the

emission spectral changes for 27·H⁺were recorded in the

overlay mode. The addition of increasing amounts of the

salt resulted in the gradual decrease in the absorbance of

the protonated host 6·H or 25·H⁺with no shift in the ab-

sorption peak maxima or gradual increase in the emission

intensity of the 21-thiaporphyrin subunit in case of dyad

27·H⁺. In these experiments, the concentration of the host

(6·H⁺, 25·H⁺or 27·H⁺) was kept constant and the change

in absorbance (∆A) or in emission intensity (∆I) was calcu-

lated at a particular λ value where the spectral change was

maximum. The ∆A or ∆I was plotted against the concentra-

tion of the added anion guest (C). The data were fitted with

the aid of the Origin (version 6.0) software package. The

binding constants were calculated with a 1:1 anion binding

model according to the formula shown in Equation (1).^[28]

Figure 4. a) UV/Vis titration curve for protonated dithiaphlorin

6·H⁺with increasing amounts of tetrabutylammonium bromide

salt in dichloromethane. b) The curve-fitting plot of the change in

absorbance (∆A) vs. the concentration of Br^–anion. The concentra-

tion of the dithiaphlorin used was 2.13ϫ10^–5 and the concentra-

tion range of the Br^–used was 6.29ϫ10^–6 to 1.06ϫ10^–4. The

spectra were measured at 825 nm at 22 °C.

(1)

A represents the absorbance of host solution (thiaphlorin

or thiaphlorin–porphyrin dyad), R is the initial fixed con-

centration of the host, C is the concentration of the added

guest (tetrabutylammonium salt), A_cis the difference in ab-

sorbance of host–guest complex and the free host (thiaphlo-

Similar anion-binding titrations were carried out for

rin or thiaphlorin–porphyrin dyad), and K_arepresents the 6·H⁺with tetrabutylammonium iodide, chloride, thiocyan-

association constant. We used the same equation to calcu- ide and hydrogen sulfate salts (see Supporting Information),

late the binding constant for dyad 27·H⁺, using the changes and the calculated binding constants are presented in

in the fluorescence intensity in place of absorbance changes. Table 3. The data indicated that the protonated 6 showed

The shape of the observed titration curves and good fit to higher affinities for bromide and iodide than for other

1:1 binding profiles indicated the formation of 1:1 complex anions, as evident in their binding constants K_a.

in solution.

Preliminary anion-binding studies by the absorption

The effect of addition of increasing amounts of tetrabu- spectroscopic technique were also carried out with the pro-

tylammonium bromide salt on the absorption spectra of the tonated form of dyad 25, containing 21,23-dithiaphlorin

protonated form of 6 is shown in Figure 4 (a). It is clear and ZnN₄porphyrin subunits. Dyad 25 with the zinc(II)

from the Figure that 6·H⁺showed a strong peak at 825 nm, ion in the porphyrin subunit was selectively protonated at

which decreased in its intensity when it was titrated with the 21,23-dithiaphlorin subunit by careful addition of dilute

increasing amounts of anion salts, confirming the binding trifluoroacetic acid without inducing the demetallation of

of anion. Figure 4 (b) shows the plot of ∆A vs. concentra- the porphyrin subunit. When the dyad 25·H⁺was titrated

tion of tetrabutylammonium bromide salt. The binding with tetrabutylammonium iodide, the decrease in the inten-

constant was calculated using the above formula, and a sity of the absorption band at 840 nm, with a clean fit to a

good fit to a 1:1 binding profile indicated the formation of 1:1 binding profile, suggested the binding of the anion at

a 1:1 thiaphlorin–anion complex.

the 21,23-dithiaphlorin site in 1:1 stoichiometry. Similar ob-

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1893

I. Gupta, R. Fröhlich, M. Ravikanth

FULL PAPER

Table 3. Binding constant (K_a) data for 6·H⁺, 25·H⁺and 27·H⁺in

dichloromethane at 22 °C determined by absorption and fluores-

cence spectroscopic techniques.

The dyad 27, which contains free base N₃S porphyrin

and 21,23-dithiaphlorin subunits, was tested for binding of

iodide ion by fluorescence.^[29]Since the N₃S porphyrin sub-

unit is a good fluorophore, we assumed that it should be

usable to sense the anion binding that occurs at the proton-

ated 21,23-dithiaphlorin site by showing changes in its emis-

sion band. Increasing amounts of tetrabutylammonium io-

dide salt solution in dichloromethane were therefore added

to the selectively protonated dyad 27·H⁺, and the fluores-

cence of the 21-thiaporphyrin subunit was monitored by ex-

citation at 520 nm (Figure 5, a). Addition of increasing

amounts of iodide ion resulted in the gradual enhancement

of the intensity of the 21-thiaporphyrin fluorescent band

(λ_em= 692 nm), suggesting that the iodide ion was bound

at the protonated 21,23-dithiaphlorin site in dyad 27·H⁺.

Thus, in dyad 27, the binding of iodide ion at the 21,23-

dithiaphlorin site was sensed by observing the changes in

the fluorescence intensity of the 21-thiaporphyrin subunit,

suggesting that the dyad 27 should be usable as a fluores-

cence sensor. The binding stoichiometry is 1:1 as indicated

by a good fit to 1:1 binding profile (Figure 5, b). Thus,

while a detailed study is needed, these preliminary investi-

gations have indicated that the thiaphlorins and thiaphlo-

rin–porphyrin dyads bind anions effectively, as judged from

optical studies.

Compound

Anion^[a]

K_a(^–1)

6·H⁺

25·H⁺

27·H⁺

Cl^–

Br^–

I^–

4.8 (9)ϫ10^{3 [b]}

2.1 (1)ϫ10^{4 [b]}

1.5 (4)ϫ10^{4 [b]}

3.3 (7)ϫ10^{3 [b]}

1.8 (2)ϫ10^{3 [b]}

4.6 (4)ϫ10^{4 [b]}

2.3 (2)ϫ10^{4 [b]}

6.2 (8)ϫ10^{3 [c]}

–

HSO₄

SCN^–

Br^–

I^–

[a] Anions used were in the form of their Bu₄N⁺(TBA) salts. The

errors in all fits are Ͻ Ϯ15%. [b] Absorption spectroscopy. [c] Fluo-

rescence spectroscopy; λ_ex= 520 nm.

servations were made for tetrabutylammonium bromide ion

as well (see Supporting Information). Thus, the dyad 25 is

a novel system that binds anions and cations.

Conclusions

In conclusion, we have described the synthesis of 21,23-

dithia- and 21-thiaphlorins, each containing one sp³meso

carbon, from easily available precursors. The method

adopted to synthesize the thiaphlorins is simple and versa-

tile and allows the synthesis of any desired 21,23-dithia and

21-thia analogues of phlorins in metal-free form. The syn-

thetic strategy has been used further to synthesize the

monofunctionalized 21,23-dithia- and 21-thiaphlorins. The

monofunctionalized 21,23-dithia- and 21-thiaphlorins have

been used to synthesize a series of covalently linked thia-

phlorin–porphyrin dyads. We have also carried out func-

tional group transformation on thiaphlorin to show that

they are quite stable and have synthesized a bis(thiaphlorin)

dyad for future use.

Preliminary anion-binding studies indicated that the thia-

phlorins and thiaphlorin–porphyrin dyads exhibits very

interesting anion binding properties, so the thiaphlorins and

the thiaphlorin–porphyrin dyads represent a new class of

anion sensors. It is anticipated that more attention will be

given in future to the synthesis of various hetero analogues

of calix(n)phyrins to test their potential for cation- and,

more importantly, anion-binding studies. Although the pre-

liminary studies showed that the thiaphlorins and thiaphlo-

rin–porphyrin dyads are good anion-complexing agents, a

detailed study is needed to understand the complete poten-

tial of these systems to act as anion-binding agents/anion

sensors. The synthesis of various hetero analogues of dif-

ferent classes of calix(n)phyrins and detailed anion-binding

studies will be carried out in these laboratories in the near

future.

Figure 5. a) Fluorescence titration of thiaphlorin–porphyrin dyad

27·H⁺with increasing amounts of tetrabutylammonium iodide in

dichloromethane. b) The curve fitting plot of the change in fluo-

rescene intensity (∆I) vs. the concentration of I^–anion. The

8.82ϫ10^–6 dichloromethane solution of dyad 27 was selectively

protonated by addition of 1.5 µL of 2ϫ10^–3 trifluoroacetic acid

in dichloromethane (the TFA concentration was 9.67ϫ10^–7).

The dyad 27·H⁺was excited at 520 nm and the concentration range

of iodide salt used was 1.06ϫ10^–6 to 7.32ϫ10^–6.

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Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

(neat): ν = 3394 (OH), 3271 (OH) cm^–1. ES-MS: C H SO , calcd.

˜

15 18

2

Experimental Section

av. mass 262.4; obsd. m/z: 245.1 [M – 17]⁺(90%). C₁₅H₁₈O₂S

(262.4): calcd. C 68.67, H 6.92, S 12.22; found C 68.48, H 6.73, S

12.46.

2-(Thiophen-2-yl)propan-2-ol (15): Dry, distilled ether (40 mL) was

placed in a 250 mL three-necked, round-bottomed flask fitted with

a rubber septum and gas inlet tube, and the flask was flushed with

argon for 10 min. Tetramethylethylenediamine (TMEDA, 3.5 g,

4.6 mL, 30.457 mmol) and n-butyllithium (20 mL of ca. 15% solu-

tion in hexane) were added to the stirred solution, and the reaction

temperature was maintained at 0 °C (ice bath). Thiophene (2.1 g,

2.0 mL, 25.381 mmol) was added, and the solution was stirred for

1 h at 0 °C. As the reaction progressed, a white turbid solution

formed, indicating the formation of the 2-lithiated salt of thio-

phene. An ice-cold solution of dry acetone (3.6 g, 4.5 mL,

63.453 mmol) in dry THF (20 mL) was then added and the system

was stirred for an additional 15 min at 0 °C. The reaction mixture

was brought to room temperature. The reaction was quenched by

adding an ice-cold NH₄Cl solution (50 mL, ca. 1 ). The organic

layer was diluted with diethyl ether and washed several times with

water and brine and dried with anhydrous Na₂SO₄. The solvent

was removed in a rotary evaporator under reduced pressure to af-

ford the crude compound. TLC analysis mainly showed two spots

corresponding to the unreacted thiophene and the desired alcohol.

The crude compound was loaded onto silica and eluted with petro-

leum ether. The unchanged thiophene was removed with a petro-

leum ether/ethyl acetate (98:2) solvent mixture, and the desired

mono-ol 15 was then collected with a petroleum ether/ethyl acetate

(94:6) solvent mixture. The solvent was removed in a rotary evapo-

rator to afford 15 as a yellow oil (1.6 g, 44% yield). ¹H NMR

(300 MHz, CDCl₃, 25 °C, TMS): δ = 1.66 (s, 6 H), 2.15 (br. s, 1

H), 6.94 (m, 2 H), 7.18 (m, 1 H) ppm. ¹³C NMR (75 MHz, CDCl₃):

δ = 32.04, 71.10, 121.87, 123.61, 126.46, 128.29, 154.32 ppm. IR

2-{(5-[Hydroxy(p-tolyl)methyl]thiophen-2-yl}butan-2-ol (3): The li-

thiated derivative of 1, generated as described above, was treated

with an ice-cold solution of but-3-en-2-one (1.8 g, 2.2 mL,

24.473 mmol) in THF (25 mL), followed by standard workup and

column chromatographic purification on silica with petroleum

ether/ethyl acetate (65:35) to give the desired diol 3 as a brown oil

1

in 47% yield (1.3 g). H NMR (300 MHz, CDCl₃, 25 °C, TMS): δ

= 0.88 (m, 3 H), 1.55 (s, 3 H), 1.83 (m, 2 H), 1.97 (br. s, 1 H), 2.35

(s, 3 H), 2.48 (br. s, 1 H), 5.94 (s, 1 H), 6.70 (m, 2 H), 7.17 (d, J =

8.1 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H) ppm. ¹³C NMR (75 MHz,

CDCl₃): δ = 8.66, 21.23, 29.38, 29.46, 37.26, 72.40, 74.18, 121.98,

124.44, 129.22, 137.70, 140.22, 146.60, 153.12 ppm. IR (neat): ν =

˜

3384 (OH), 3272 (OH) cm^–1. ES-MS: C₁₆H₂₀SO₂, calcd. av. mass

276.4; obsd. m/z: 273.1 [M – 17]⁺(90%). C₁₆H₂₀O₂S (276.4): calcd.

C 69.53, H 7.29, S 11.60; found C 69.39, H 7.23, S 11.24.

1-{5-[Hydroxy(p-tolyl)methyl]thiophen-2-yl}-1-phenylethanol

(4):

The lithiated derivative of 1 was treated with an ice cold solution

of acetophenone (2.2 g, 2.1 mL, 18.355 mmol) in THF (25 mL).

Workup and silica gel column chromatographic purification using

petroleum ether/ethyl acetate (70:30) gave diol 4 in 31% yield

(0.8 g). ¹H NMR (400 MHz, CDCl₃, 25 °C, TMS): δ = 1.94 (s, 3

H), 2.33 (s, 3 H), 2.49 (br. s, 2 H), 5.89 (s, 1 H), 6.66 (m, 2 H), 7.15

(d, J = 6 Hz, 2 H), 7.28 (m, 5 H), 7.46 (m, 2 H) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 21.25, 31.99, 72.39, 74.85, 123.78, 123.83,

124.27, 124.32, 125.45, 126.38, 126.42, 127.27, 128.19, 129.26,

137.71, 137.74, 140.18, 147.12, 147.88, 153.28 ppm. IR (neat): ν =

˜

3409 (OH), 3277 (OH) cm^–1. ES-MS: C₂₀H₂₀SO₂, calcd. av. mass

324.4; obsd. m/z: 307.4 [M – 17]⁺(90%). C₂₀H₂₀O₂S (324.4): calcd.

C 74.04, H 6.21, S 9.88; found C 74.44, H 6.51, S 9.68.

(neat): ν = 3389 (OH) cm^–1. ES-MS: C H SO, calcd. av. mass

˜

7

10

142.2; obsd. m/z: 125.2 [M – 17]⁺, 90%. C₇H₁₀OS (142.2): calcd. C

59.12, H 7.09, S 22.55; found C 59.01, H 7.03, S 22.49.

5,5-Dimethyl-10,15,20-tri(p-tolyl)-21,23-dithiaphlorin (6): Com-

2-{[5-Hydroxy(p-tolyl)methyl]thiophen-2-yl}propan-2-ol (2): Dry,

distilled ether (35 mL) was placed in a 250 mL three-necked, round-

bottomed flask fitted with a rubber septum and gas inlet tube, and

the flask was flushed with argon for 10 min. Tetramethylethylenedi-

amine (TMEDA, 1.9 g, 2.4 mL, 16.152 mmol) and n-butyllithium

(12 mL of a ca. 15% solution in hexane) were added to the stirred

solution, and the reaction temperature was maintained at 0 °C in

an ice bath. Compound 1 (1.5 g, 7.342 mmol) was added, and the

solution was stirred for 1 h. An ice-cold solution of dry acetone

(1.0 g, 1.3 mL, 18.355 mmol) in dry THF (30 mL) was then added

to the turbid solution and the system was stirred for additional

15 min at 0 °C. The reaction mixture was brought to room tem-

perature. An ice-cold NH₄Cl solution (50 mL, ca. 1 ) was added

to quench the reaction. The organic layer was washed several times

with water and brine and dried with anhydrous Na₂SO₄. The sol-

vent was removed in a rotary evaporator under reduced pressure

to afford the crude compound, which was loaded onto silica and

eluted with petroleum ether. The unchanged mono-ol was removed

with a petroleum ether/ethyl acetate (95:5) solvent mixture, the two

other unidentified minor spots were removed in petroleum ether/

ethyl acetate (90:10), and the desired diol 2 was then collected with

a petroleum ether/ethyl acetate (70:30) solvent mixture. The solvent

was removed in a rotary evaporator to afford 2 as a brown oil in

pound

2 (0.4 g, 1.524 mmol) and 16-thiatripyrrane 5 (0.6 g,

1.524 mmol) were condensed in CH₂Cl₂(40 mL) under nitrogen

at room temperature in the presence of trifluoroacetic acid (0.1 g,

0.1 mL, 1.524 mmol). The reaction mixture was stirred under nitro-

gen for 1 h. DDQ (0.3 g, 1.524 mmol) was added and stirring was

continued in air for an extra 1 h. The crude mixture was purified

by silica gel column chromatography, and the desired N₂S₂-phlorin

6 was collected with petroleum ether/ethyl acetate (94:6). The sol-

vent was removed in a rotary evaporator, to afford the N₂S₂-phlorin

6 as a green solid in 19% yield (0.2 g); m.p. Ͼ250 °C. ¹H NMR

(300 MHz, CDCl₃, –50 °C, TMS): δ = 1.86 (s, 6 H), 2.45 (s, 9 H),

6.29 (br. s, 1 H), 6.49 (br. s, 1 H), 6.90 (br. s, 1 H), 7.10 (br. s, 1

H), 7.28 (m, 8 H), 7.43 (m, 4 H), 7.52 (m, 4 H), 11.32 (br. s, 1 H),

12.72 (br. s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 21.43,

29.62, 39.06, 106.77, 121.37, 128.54, 128.77, 129.49, 131.37, 131.97,

132.55, 134.69, 137.14, 138.24, 140.34 ppm. UV/Vis: λ_max

(εϫ10³Lmol^–1cm^–1) = 327 (23.86), 415 (32.24), 686 nm (19.37).

ES-MS: C₄₃H₃₆N₂S₂, calcd. av. mass: 644.8; obsd. m/z: 645.2 [M]⁺.

C₄₃H₃₆N₂S₂(644.8): calcd. C 80.08, H 5.63, N 4.34, S 9.94; found C

80.28, H 5.71, N 4.38, S 9.86.

5-Ethyl-5-methyl-10,15,20-tri(p-tolyl)-21,23-dithiaphlorin (7): Sam-

ples of 3 (0.4 g, 1.447 mmol) and 16-thiatripyrrane 5 (0.6 g,

1.447 mmol) were condensed under same reaction conditions as

described for compound 6. The crude product was purified by silica

1

57% yield (1.1 g). H NMR (400 MHz, CDCl₃, 25 °C, TMS): δ =

1.57 (s, 6 H), 2.32 (s, 3 H), 3.11 (br. s, 2 H) 5.85 (s, 1 H), 6.63 (d,

J = 3.3 Hz, 1 H), 6.70 (d, J = 3.9 Hz, 1 H), 7.12 (d, J = 7.5 Hz, 2 gel column chromatography and afforded the desired compound 7

H), 7.28 (d, J = 8.1 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ as a green solid in 13% yield (0.1 g); m.p. Ͼ250 °C. ¹H NMR

= 21.11, 29.11, 31.91, 53.71, 72.11, 101.97, 121.35, 123.09, 124.19,

(300 MHz, CDCl₃, 25 °C, TMS): δ = 1.26 (s, 3 H), 1.73 (m, 2 H),

124.81, 126.21, 129.04, 137.49, 140.32, 146.77, 154.08 ppm. IR 2.15 (s, 3 H), 2.46 (m, 9 H), 6.29 (d, J = 3.6 Hz, 1 H), 6.50 (d, J =

Eur. J. Org. Chem. 2008, 1884–1900

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1895

I. Gupta, R. Fröhlich, M. Ravikanth

4.5 Hz, 1 H), 6.89 (d, J = 4.5 Hz, 1 H), 7.09 (d, J = 4.2 Hz, 1 H), Diol 11: Treatment of the lithiated derivative of 15 (1.5 g,

FULL PAPER

7.22 (d, J = 4.8 Hz, 1 H), 7.27 (m, 7 H), 7.42 (m, 4 H), 7.52 (m, 4

H), 11.73 (br. s, 1 H), 12.87 (br. s, 1 H) ppm. ¹³C NMR (75 MHz,

CDCl₃): δ = 8.59, 21.38, 22.54, 29.76, 37.23, 43.21, 108.12, 121.19,

122.34, 123.03, 125.98, 128.53, 128.77, 128.86, 129.48, 130.59,

131.37, 131.98, 132.51, 134.69, 134.95, 135.31, 136.70, 136.96,

137.08, 137.18, 138.24, 138.66, 139.32, 140.19, 140.92, 146.92,

10.547 mmol) with an ice-cold solution of p-bromobenzaldehyde

(2.3 g, 12.656 mmol) in THF (30 mL) followed by silica gel column

chromatographic purification with petroleum ether/ethyl acetate

(65:35) yielded diol 11 as a brown oil in 60% yield (2.1 g). ¹H NMR

(300 MHz, CDCl₃, 25 °C, TMS): δ = 1.61 (s, 6 H), 2.09 (s, 2 H)

5.92 (s, 1 H), 6.69 (m, 1 H), 6.75 (m, 1 H), 7.31 (m, 2 H), 7.48 (m,

2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 14.19, 21.54, 31.94,

71.38, 71.71, 111.48, 121.54, 123.19, 125.32, 128.01, 131.56, 137.09,

146.19,

146.93,

152.79,

166.38 ppm.

UV/Vis:

λ_max

(εϫ10³Lmol^–1cm^–1) = 325 (23.13), 415 (30.87), 689 nm (18.28).

ES-MS: C₄₄H₃₈N₂S₂, calcd. av. mass: 658.9; obsd. m/z: 659.4 [M]⁺.

C₄₄H₃₈N₂S₂(658.9): calcd. C 80.20, H 5.81, N 4.25, S 9.73; found C

80.31, H 5.86, N 4.34, S 9.93.

141.94, 145.86, 154.57 ppm. IR (neat): ν = 3409 (OH), 3277

˜

(OH) cm^–1. ES-MS: C₁₄H₁₅BrO₂S, calcd. av. mass 327.2; obsd. m/z:

311 [M + 1 – 17]⁺(90%). C₁₄H₁₅BrO₂S (327.2): calcd. C 51.38, H

4.62, S 9.80; found C 50.96, H 4.28, S 9.74.

5-Methyl-5-phenyl-10,15,20-tri(p-tolyl)-21,23-dithiaphlorin

(8):

Diol 12: An ice-cold solution of p-(3-hydroxy-3-methylbut-1-ynyl)-

benzaldehyde (2.3 g, 12.180 mmol) in THF (30 mL) was treated

with the lithiated derivative of 15 (1.4 g, 10.125 mmol) followed by

silica gel column chromatographic purification with petroleum

ether/ethyl acetate (60:40) to afford pure diol 12 as a brown oil in

Condensation of 4 (0.4 g, 1.223 mmol) and 16-thiatripyrrane 5

(0.6 g, 1.223 mmol) under similar reaction conditions and purifica-

tion by silica gel column chromatography with petroleum ether/

ethyl acetate (95:5) afforded pure N₂S₂-phlorin 8 as a green solid

1

in 7% yield (0.07 g); m.p. Ͼ250 °C. H NMR (400 MHz, CDCl₃,

1

24% yield (0.8 g). H NMR (400 MHz, CDCl₃, 25 °C, TMS): δ =

25 °C, TMS): δ = 2.47 (m, 9 H, CH₃), 2.56 (s, 3 H), 6.54 (d, J =

3.6 Hz, 1 H), 6.63 (d, J = 3.6 Hz, 1 H), 6.83 (d, J = 7.6 Hz, 2 H),

6.89 (d, J = 4.8 Hz, 1 H), 7.03 (d, J = 7.2 Hz, 1 H), 7.09 (m, 2 H),

7.22 (d, J = 4.4 Hz, 1 H), 7.30 (m, 8 H), 7.41 (d, J = 3.6 Hz, 2 H),

7.48 (d, J = 5.6 Hz, 1 H), 7.56 (m, 5 H), 8.67 (s, 1 H), 9.69 (s, 1

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 21.35, 21.45, 29.37,

48.53, 109.57, 121.08, 123.25, 124.05, 126.51, 126.96, 128.15,

128.54, 128.84, 129.65, 130.64, 131.42, 132.11, 132.40, 134.54,

135.43, 136.04, 136.79, 136.98, 137.28, 138.32, 138.56, 140.79,

1.57 (m, 12 H, CH₃), 3.06 (br. s, 2 H), 5.88 (s, 1 H), 6.61 (d, J =

3.3 Hz, 1 H), 6.70 (d, J = 3.6 Hz, 1 H), 7.35 (m, 4 H) ppm. ¹³C

NMR (75 MHz, CDCl₃): δ = 14.16, 21.04, 21.51, 30.92, 31.42,

31.94, 60.53, 65.55, 71.28, 71.86, 81.88, 94.08, 111.28, 121.47,

123.17, 124.59, 125.23, 126.21, 126.53, 131.72, 137.11, 143.12,

145.84, 146.03, 146.55, 154.47 ppm. IR (neat): ν = 3386 (OH), 3277

˜

(OH) cm^–1. ES-MS: C₁₉H₂₂SO₃, calcd. av. mass 330.5; obsd. m/z:

313.2 [M – 17]⁺(90%) 330.2 [M]⁺(10%). C₁₉H₂₂O₃S (330.5): calcd.

C 69.06, H 6.71, S 9.70; found C 69.42, H 6.37, S 9.42.

141.37,

145.82,

148.72,

152.83 ppm.

UV/Vis:

λ_max

(εϫ10³Lmol^–1cm^–1) = 325 (26.82), 417 (37.70), 686 nm (21.81).

ES-MS: C₄₈H₃₈N₂S₂, calcd. av. mass: 706.9; obsd. m/z: 706.9 [M]⁺.

C₄₈H₃₈N₂S₂(706.9): calcd. C 81.55, H 5.42, N 3.96, S 9.07; found C

81.83, H 5.71, N 3.48, S 9.46.

Diol 13: The lithiated derivative of 15 (0.8 g, 5.626 mmol) was

treated with an ice-cold solution of p-cyanobenzaldehyde (0.7 g,

6.751 mmol) in THF (25 mL), and purification of the crude com-

pound by silica gel column chromatography with petroleum ether/

ethyl acetate (65:35) afforded the desired diol 13 as a yellow solid

5,5-Dimethyl-10,15,20-tri(p-tolyl)-21-thiaphlorin (9): Samples of 2

(0.7 g, 2.477 mmol), p-tolylaldehyde (0.6 g, 0.6 mL, 4.954 mmol)

and pyrrole (0.5 g, 0.5 mL, 7.431 mmol) were condensed in CH₂Cl₂

(70 mL) under the mild acid catalysis conditions used for com-

pound 6. The crude compound was subjected to silica gel column

chromatography and the desired N₃S phlorin 9 was obtained with

petroleum ether/ethyl acetate (99:1) as a green solid in 3% yield

(0.04 g); m.p. Ͼ150 °C. ¹H NMR (500 MHz, CDCl₃, –50 °C,

TMS): δ = 1.79 (s, 6 H), 2.46 (m, 9 H), 6.45 (br. s, 1 H), 6.58 (s, 1

H), 6.98 (m, 4 H), 7.18 (br. s, 2 H), 7.31 (br. s, 5 H), 7.39 (s, 1 H),

7.43 (br. s, 1 H), 7.53 (br. s, 3 H), 7.62 (br. s, 2 H) ppm. UV/Vis:

λ_max(εϫ10³Lmol^–1cm^–1) = 323 (15.012), 413 (25.67), 672 nm

(14.26). ES-MS: C₄₃H₃₇N₃S, calcd. av. mass: 627.8; obsd. m/z:

627.9 [M]⁺. C₄₃H₃₇N₃S (627.8): calcd. C 82.26, H 5.94, N 6.69, S

5.11; found C 82.29, H 5.73, N 6.38, S 5.23.

1

in 52% yield (0.9 g); m.p. 78–80 °C. H NMR (300 MHz, CDCl₃,

25 °C, TMS): δ = 1.59 (s, 6 H, CH₃), 2.08 (s, 1 H), 3.03 (s, 1 H),

6.01 (s, 1 H), 6.73 (d, J = 3.6 Hz, 1 H), 6.76 (d, J = 3.6 Hz, 1 H),

7.55 (d, J = 8.4 Hz, 2 H), 7.63 (d, J = 8.4 Hz, 2 H) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 21.47, 31.94, 71.39, 71.45, 111.28, 111.72,

118.77, 121.58, 123.21, 124.99, 125.65, 126.87, 132.29, 136.95,

144.99, 145.435, 146.48, 148.14, 155.06 ppm. IR (KBr, film): ν =

˜

3414 (OH), 3272 (OH) cm^–1. ES-MS: C₁₅H₁₅NO₂S, calcd. av. mass

273.4; obsd. m/z: 273.2 [M]⁺(10%), 256.1 [M – 17]⁺(90%).

C₁₅H₁₅NO₂S (273.4): calcd. C 65.91, H 5.53, N 5.12, S 11.73; found

C 65.46, H 5.23, N 4.96, S 11.39.

Diol 14: The lithiated derivative of 15 was treated with an ice-cold

solution of m-nitrobenzaldehyde (2.6 g, 16.876 mmol) in THF

(40 mL) and the resulting crude compound was purified by silica

gel column chromatography with petroleum ether/ethyl acetate

(65:35) to give 14 as a brown oil in 62% yield (2.3 g). ¹H NMR

(400 MHz, CDCl₃, 25 °C, TMS): δ = 1.59 (s, 6 H, CH₃), 2.35 (br.

s, 1 H), 3.27 (br. s, 1 H), 6.05 (s, 1 H), 6.75 (m, 2 H), 7.52 (m, 1

H), 7.78 (d, J = 7.6 Hz, 1 H), 8.14 (d, J = 7.2 Hz, 1 H), 8.30 (s, 1

H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 21.40, 31.81, 60.56,

71.01, 71.31, 111.59, 121.11, 121.57, 124.93, 129.35, 132.42, 145.05,

Diol 10: The lithiated derivative of 15 (1.9 g, 13.359 mmol) was

treated with an ice-cold solution of p-iodobenzaldehyde (3.7 g,

16.031 mmol) in THF (35 mL), and the crude compound was puri-

fied by silica gel column chromatography with petroleum ether/

ethyl acetate (65:35). The solvent was removed in a rotary evapora-

tor to afford 10 as a white solid in 36% yield (1.8 g); m.p. 59–61 °C.

¹H NMR (400 MHz, CDCl₃, 25 °C, TMS): δ = 1.56 (s, 6 H), 2.76

(br. s, 2 H), 5.83 (s, 1 H), 6.43 (d, J = 3.6 Hz, 1 H), 6.71 (d, J =

3.6 Hz, 1 H), 7.13 (m, 2 H), 7.64 (m, 2 H) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 21.71, 32.15, 71.42, 71.84, 93.47, 121.45,

124.62, 128.12, 137.41, 142.55, 145.64, 154.46 ppm. IR (KBr, film):

145.32, 148.10, 154.91 ppm. IR (neat): ν = 3399 (OH), 3272

˜

(OH) cm^–1. ES-MS: C₁₄H₁₅NO₄S, calcd. av. mass 293.3; obsd. m/z:

276.1 [M – 17]⁺(90%). C₁₄H₁₅NO₄S (293.3): calcd. C 57.32, H

5.15, N 4.77, S 10.93; found C 56.91, H 4.98, N 4.49, S 10.86.

ν = 3445 (OH), 3272 (OH) cm^–1. ES-MS: C H IO S, calcd. av.

10-(p-Iodophenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21,23-dithiaphlorin

(16): Compound 10 (0.7 g, 1.871 mmol) and 16-thiatripyrrane 5

(0.8 g, 1.871 mmol) were condensed in CH₂Cl₂under mild acidic

catalysis conditions and the resulting crude compound was purified

˜

14 15

2

mass 374.2; obsd. m/z: 358.0 [M + 1 – 17]⁺(90%). C₁₄H₁₅IO₂S

(374.2): calcd. C 44.93, H 4.04, S 8.57; found C 44.59, H 4.25, S

8.19.

1896

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Eur. J. Org. Chem. 2008, 1884–1900

Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

by silica gel column chromatography with petroleum ether/ethyl

acetate (95:5) to afford the pure 21,23-dithiaphlorin 16 as a green

solid in 15% yield (0.2 g); m.p. Ͼ250 °C. ¹H NMR (300 MHz,

112.01, 118.82, 121.58, 128.83, 128.95, 130.92, 131.39, 131.61,

132.06, 132.88, 135.41, 136.44, 136.91, 137.21, 138.60, 140.30,

144.67 ppm. UV/Vis: λ_max(εϫ10³Lmol^–1cm^–1) = 314 (26.79), 415

CDCl₃, 25 °C, TMS): δ = 1.84 (s, 6 H), 2.44 (s, 6 H), 6.29 (br. s, 1 (34.36), 708 nm (23.69). ES-MS: C₄₃H₃₃N₃S₂, calcd. av. mass:

H), 6.52 (br. s, 1 H), 6.92 (d, J = 4.5 Hz, 1 H), 7.09 (br. s, 1 H), 655.9; obsd. m/z: 655.8 [M]⁺. C₄₃H₃₃N₃S₂(655.9): calcd. C 78.74,

7.18 (br. s, 1 H), 7.29 (m, 8 H), 7.47 (m, 5 H), 7.82 (m, 2 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 21.44, 21.48, 29.71, 29.84, 39.25,

95.01, 107.36, 121.56, 128.88, 128.99, 130.27, 131.47, 132.08,

134.18, 134.86, 135.10, 136.33, 136.33, 136.74, 137.13, 138.45,

139.59, 139.93, 140.47, 147.13, 147.89, 152.87 ppm. UV/Vis: λ_max

(εϫ10³Lmol^–1cm^–1) = 329 (31.17), 417 (37.23), 696 nm (24.07).

ES-MS: C₄₂H₃₃IN₂S₂, calcd. av. mass: 756.8; obsd. m/z: 757.2

[M]⁺. C₄₂H₃₃IN₂S₂(756.8): calcd. C 66.66, H 4.40, N 3.70, S 8.47;

found C 65.98, H 4.71, N 3.68, S 8.56.

H 5.07, N 6.41, S 9.78; found C 78.82, H 5.27, N 6.38, S 9.84.

5,5-Dimethyl-10-(m-nitrophenyl)-15,20-di(p-tolyl)-21,23-dithiaphlo-

rin (20): Samples of thiophenedimethanol 14 (0.4 g, 1.531 mmol)

and 16-thiatripyrrane 5 (0.6 g, 1.531 mmol) in CH₂Cl₂were con-

densed in the presence of catalytic amounts of trifluoroacetic acid

(0.2 g, 0.1 mL, 1.531 mmol). The crude mixture was purified by

silica gel column chromatography with petroleum ether/ethyl ace-

tate (90:10) and afforded pure 20 as a green solid in 5 % yield

(0.05 g); m.p. Ͼ150 °C. ¹H NMR (300 MHz, CDCl₃, –50 °C,

TMS): δ = 1.89 (s, 6 H), 2.51 (s, 6 H), 6.38 (s, 1 H), 6.68 (br. s, 2

H), 7.12 (d, J = 4.2 Hz, 1 H), 7.29 (m, 6 H), 7.51 (m, 3 H), 7.62

(d, J = 7.5 Hz, 2 H), 7.73 (m, 2 H), 7.99 (d, J = 7.2 Hz, 1 H), 8.42

(d, J = 7.5 Hz, 1 H), 7.64 (s, 1 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 14.16, 21.37, 21.42, 22.75, 29.61, 29.76, 31.99, 39.28,

121.69, 123.19, 126.71, 128.85, 128.97, 129.35, 129.64, 131.05,

10-(p-Bromophenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21,23-dithiaphlo-

rin (17): Samples of 11 (0.4 g, 1.222 mmol) and 16-thiatripyrrane

5 (0.5 g, 1.222 mmol) were condensed in CH₂Cl₂(40 mL) under

porphyrin forming conditions. The crude compound was purified

by silica gel column chromatography with petroleum ether/ethyl

acetate (94:6) and afforded 17 as green solid in 16% yield (0.14 g);

m.p. Ͼ250 °C. ¹H NMR (300 MHz, CDCl₃, –50 °C, TMS): δ = 131.42, 132.07, 134.17, 135.42, 135.78, 136.49, 136.98, 137.58,

1.87 (s, 6 H), 2.50 (s, 6 H), 6.34 (br. s, 1 H), 6.62 (br. s, 1 H), 6.79

(br. s, 1 H), 7.07 (d, J = 4.5 Hz, 1 H), 7.19 (d, J = 4.5 Hz, 2 H),

138.12, 137.20, 138.12, 138.58, 139.53, 140.37, 141.68, 146.78,

148.07, 148.79 ppm. UV/Vis: λ_max(ε ϫ 10³L mol^–1cm^–1) = 314

7.29 (m, 5 H), 7.49 (m, 3 H), 7.59 (m, 3 H), 7.67 (m, 3 H), 11.89 (27.77), 407 (36.71), 705 nm (24.19). ES-MS: C₄₂H₃₃N₃O₂S₂, calcd.

(s, 1 H), 13.17 (s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

21.44, 21.71, 29.84, 39.25, 107.30, 121.56, 123.20, 128.89, 129.00,

130.26, 131.16, 131.47, 132.08, 133.16, 133.97, 134.88,

135.10,136.33, 136.74, 137.16, 137.19, 138.46, 138.98, 139.99,

140.48 ppm. UV/Vis: λ_max(εϫ10³Lmol^–1cm^–1) = 327 (30.50), 416

(39.84), 694 nm (23.95). ES-MS: C₄₂H₃₃BrN₂S₂, calcd. av. mass:

709.8; obsd. m/z: 709.2 [M]⁺. C₄₂H₃₃BrN₂S₂(709.8): calcd. C 71.07,

H 4.69, N 3.95, S 9.04; found C 71.41, H 4.91, N 3.88, S 9.16.

av. mass: 675.9; obsd. m/z: 676.3 [M]⁺. C₄₂H₃₃N₃O₂S₂(675.9):

calcd. C 74.64, H 4.92, N 6.22, S 9.49; found C 784.71, H 4.83, N

6.34, S 9.72.

10-(p-Iodophenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21-thiaphlorin (21):

Condensation of 10 (0.5 g, 1.344 mmol), p-tolylaldehyde (0.3 g,

0.3 mL, 2.688 mmol) and pyrrole (0.3 g, 0.3 mL, 4.032 mmol) in

CH₂Cl₂(50 mL) under mild acid catalysis conditions gave a crude

mixture of compounds. The crude mixture was purified by silica

gel column chromatography with petroleum ether/ethyl acetate

10-[p-(3-Hydroxy-2-methylbut-1-ynyl)phenyl]-5,5-dimethyl-15,20-di-

(p-tolyl)-21,23-dithiaphlorin (18): Samples of 12 (0.3 g, 0.908 mmol) (99:1) and afforded pure 21 as a green solid (0.09 g, 9%); m.p.

1

and 16-thiatripyrrane 5 (0.4 g, 0.908 mmol) were condensed in

CH₂Cl₂under similar porphyrin forming conditions. The resulting

crude product was purified by silica gel column chromatography

with petroleum ether/ethyl acetate (70:30) and afforded pure 18 as

a green solid in 21% yield (0.14 g); m.p. Ͼ250 °C. ¹H NMR

Ͼ250 °C. H NMR (300 MHz, CDCl₃, –50 °C, TMS): δ = 1.81 (s,

6 H), 2.49 (s, 6 H), 6.49 (m, 1 H), 6.62 (m, 1 H), 6.87 (m, 1 H),

6.97 (br. s, 3 H), 7.25 (m, 6 H), 7.54 (m, 6 H), 7.79 (m, 2 H), 9.85

(s, 1 H), 11.77 (s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

21.34, 21.38, 28.63, 29.76, 38.56, 93.02, 106.95, 114.69, 121.20,

(300 MHz, CDCl₃, –50 °C, TMS): δ = 1.66 (s, 6 H), 1.87 (s, 6 H), 126.42, 127.65, 127.86, 128.48, 129.06, 129.17, 132.50, 132.54,

2.49 (br. s, 6 H), 6.34 (br. s, 1 H), 6.62 (br. s, 1 H), 6.85 (br. s, 1 133.25, 133.50, 134.23, 134.84, 135.49, 135.71, 136.59, 137.55,

H), 7.07 (d, J = 4.5 Hz, 1 H), 7.18 (br. s, 1 H), 7.32 (m, 5 H), 7.46

137.69, 137.81, 138.25, 140.06, 142.03, 142.95, 144.99, 150.65,

(m, 3 H), 7.59 (m, 7 H), 11.82 (br. s, 1 H), 13.07 (br. s, 1 H) ppm.

165.18 ppm. UV/Vis: λ_max(εϫ10³Lmol^–1cm^–1) = 337 (41.03), 416

¹³C NMR (100 MHz, CDCl₃): δ = 21.43, 21.47, 29.71, 29.83, 31.47, (78.70), 671 nm (50.77). ES-MS: C₄₂H₃₄IN₃S, calcd. av. mass:

31.66, 39.25, 65.84, 76.86, 77.18, 77.49, 82.09, 95.47, 107.33,

121.55, 121.71, 123.05, 123.13, 128.88, 128.99, 129.61, 130.16,

131.16, 131.47, 132.07, 132.12, 132.47, 134.94, 135.07, 135.40,

136.37, 136.76, 137.15, 137.19, 138.43, 140.05, 140.46 ppm. UV/

Vis: λ_max(εϫ10³Lmol^–1cm^–1) = 342 (29.23), 412 (31.81), 697 nm

(21.29). ES-MS: C₄₇H₄₀N₂S₂, calcd. av. mass: 713.1; obsd. m/z:

713.4 [M]⁺. C₄₇H₄₀N₂S₂(713.1): calcd. C 79.18, H 5.65, N 3.93, S

9.00; found C 79.38, H 5.71, N 4.38, S 9.06.

739.7; obsd. m/z: 740.2 [M]⁺. C₄₂H₃₄IN₃S (739.7): calcd. C 68.20,

H 4.63, N 5.68, S 4.33; found C 68.41, H 4.71, N 5.38, S 4.83.

10-(p-Bromophenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21-thiaphlorin

(22): Samples of 11 (0.8 g, 2.445 mmol), p-tolylaldehyde (0.6 g,

0.6 mL, 4.889 mmol) and pyrrole (0.5 g, 0.5 mL, 7.335 mmol) were

condensed in CH₂Cl₂(80 mL) under acid catalysis conditions. Af-

ter standard workup, the crude mixture was subjected to silica gel

column chromatography with ether/ethyl acetate (98:2) and af-

forded pure 22 as a green solid in 6% yield (0.09 g); m.p. Ͼ250 °C.

¹H NMR (300 MHz, CDCl₃, –50 °C, TMS): δ = 1.82 (s, 6 H), 2.46

(s, 6 H), 6.48 (br. s, 1 H), 6.62 (br. s, 1 H), 6.83 (m, 1 H), 6.98 (m,

3 H), 7.30 (m, 6 H), 7.56 (m, 8 H), 9.86 (s, 1 H), 11.81 (s, 1 H),

12.04 (s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 14.18, 21.38,

10-(p-Cyanophenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21,23-dithiaphlo-

rin (19): Condensation of 13 (0.33 g, 1.222 mmol) and 16-thiatri-

pyrrane 5 (0.5 g, 1.222 mmol) in CH₂Cl₂under acid catalysis condi-

tions and purification of the resulting crude product by silica gel

column chromatography afforded 19 as a green solid in 12% yield

(0.09 g); m.p. Ͼ250 °C. ¹H NMR (300 MHz, CDCl₃, 25 °C, TMS): 28.63, 29.77, 38.57, 106.96, 109.77, 114.64, 121.21, 121.52, 126.43,

δ = 1.85 (s, 6 H), 2.46 (s, 6 H), 6.34 (d, J = 3.6 Hz, 1 H), 6.72 (d, 127.68, 127.87, 128.48, 129.14, 131.59, 132.51, 133.19, 133.27,

J = 3.6 Hz, 1 H), 6.96 (d, J = 4.2 Hz, 1 H), 7.11 (m, 2 H), 7.29 (m, 134.24, 134.87, 135.40, 135.73, 136.59, 137.71, 137.82, 138.26,

6 H), 7.43 (d, J = 7.5 Hz, 2 H), 7.51 (m, 3 H), 7.76 (m, 4 H) ppm.

139.48, 142.14, 142.94, 145.06, 150.64, 165.19 ppm. UV/Vis: λ_max

¹³C NMR (75 MHz, CDCl₃): δ = 21.38, 29.59, 29.75, 39.243,

(εϫ10³Lmol^–1cm^–1) = 334 (30.03), 416 (56.12), 669 nm (33.71).

Eur. J. Org. Chem. 2008, 1884–1900

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1897

I. Gupta, R. Fröhlich, M. Ravikanth

FULL PAPER

ES-MS: C₄₂H₃₄BrN₃S, calcd. av. mass: 692.7; obsd. m/z: 692.4

[M]⁺. C₄₂H₃₄BrN₃S (692.7): calcd. C 72.82, H 4.95, N 6.07, S 4.63;

found C 72.79, H 4.87, N 6.18, S 4.81.

with desired dimer was collected by elution with petroleum ether/

dichloromethane (60:40). The solution was concentrated in vacuo,

the resulting crude mixture dimer with small amounts of un-

changed monomers was dissolved in dichloromethane (3 mL), and

a dry slurry was prepared by adding neutral alumina powder. The

slurry was loaded onto a neutral alumina column packed with pe-

troleum ether. The small amounts of porphyrin and phlorin mono-

mers were removed first with petroleum ether/ethyl acetate (98:2)

and the desired dyad 25 was then collected with petroleum ether/

dichloromethane (96:4). Concentration of the solution gave 25 as

a violet solid in 35% yield (20 mg). ¹H NMR (300 MHz, CDCl₃,

–50 °C, TMS): δ = 1.87 (m, 24 H), 2.47 (s, 6 H), 2.65 (s, 9 H), 6.37

(br. s, 1 H), 6.65 (br. s, 1 H), 6.73 (br. s, 1 H), 6.89 (m, 2 H), 7.17

(m, 3 H), 7.28–7.65 (m, 14 H), 7.83 (m, 4 H), 7.99 (d, J = 7.5 Hz,

2 H), 8.25 (d, J = 7.2 Hz, 2 H), 8.71 (s, 4 H), 8.77 (m, 2 H), 8.88

(br. s, 2 H), 11.47 (br. s, 1 H), 13.05 (br. s, 1 H) ppm. UV/Vis:

λ_max(εϫ10⁴Lmol^–1cm^–1) = 422 (59.82), 513 (7.22), 551 (2.53), 592

(0.98), 698 nm (1.81). ES-MS: C₉₇H₇₈N₆S₂Zn, calcd. av. mass:

1457.2; obsd. m/z: 1457.5 [M]⁺.

10-(p-Cyanophenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21-thiaphlorin

(23): Samples of 13 (0.4 g, 1.536 mmol), p-tolylaldehyde (0.4 g,

0.4 mL, 3.071 mmol) and pyrrole (0.3 g, 0.3 mL, 4.608 mmol) were

condensed in CH₂Cl₂(40 mL) under acid catalysis conditions and

the resulting crude mixture was purified by silica gel column

chromatography with petroleum ether/ethyl acetate (98:2) to afford

23 as a green solid (0.05 g, 5 %); m.p. Ͼ250 °C. ¹H NMR

(300 MHz, CDCl₃, –50 °C, TMS): δ = 1.82 (s, 6 H), 2.47 (s, 6 H),

6.55 (d, J = 3.9 Hz, 1 H), 6.85 (d, J = 4.8 Hz, 1 H), 6.89 (d, J =

3.9 Hz, 2 H), 7.09 (d, J = 3.9 Hz, 1 H), 7.15 (d, J = 5.7 Hz, 1 H),

7.26 (m, 6 H), 7.46 (m, 4 H), 7.71 (d, J = 8.1 Hz, 2 H), 7.79 (d, J =

5.7 Hz, 2 H), 9.96 (s, 1 H), 11.32 (s, 1 H) ppm. ¹³C NMR (75 MHz,

CDCl₃): δ = 21.39, 26.98, 28.59, 29.76, 38.56, 107.18, 109.83,

111.28, 112.93, 119.27, 121.27, 127.02, 127.90, 128.52, 129.12,

129.90, 129.99, 131.89, 132.11, 132.38, 132.50, 134.17, 134.45,

134.66, 135.93, 136.67, 136.82, 137.38, 137.98, 138.03, 141.02,

1 4 4 . 1 2 , 1 4 5 . 0 7 , 1 5 0 . 7 0 , 1 6 5 . 2 3 p p m . U V / V i s : λ _{m a x}

(εϫ10³Lmol^–1cm^–1) = 340 (24.06), 424 (57.75), 671 nm (41.37).

ES-MS: C₄₃H₃₄N₄S, calcd. av. mass: 638.8; obsd. m/z: 639.2 [M]⁺.

C₄₃H₃₄N₄S (638.8): calcd. C 80.85, H 5.36, N 8.77, S 5.02; found

C 80.94, H 5.72, N 8.38, S 5.16.

21,23-Dithiaphlorin-N₄Porphyrin Dyad 26: Dyad 25 (18.0 mg,

12.8 µmol) was dissolved in dichloromethane (30 mL) in a 100 mL

round-bottomed flask. Trifluoroacetic acid (1 mL) was added to

this solution, and the reaction mixture was allowed to stir at room

temperature for 12 h. The demetallation was confirmed by TLC

analysis and absorption spectroscopy. The solution was diluted

with CH₂Cl₂, washed thoroughly with sodium hydrogen carbonate

and dried with sodium sulfate. The solvent was removed in a rotary

5,5-Dimethyl-10-(m-nitrophenyl)-15,20-di(p-tolyl)-21-thiaphlorin

(24): Condensation of 14 (1 g, 3.827 mmol), p-tolylaldehyde (0.9 g,

0.9 mL, 7.654 mmol) and pyrrole (0.8 g, 0.8 mL, 11.481 mmol) in

CH₂Cl₂(100 mL) under acid catalysis conditions and purification

of the resulting crude mixture by silica gel column chromatography

with petroleum ether/ethyl acetate (97:3) afforded 24 as a green

solid (0.07 g, 3 %); m.p. Ͼ250 °C. ¹H NMR (500 MHz, CDCl₃,

–50 °C, TMS): δ = 1.80 (s, 6 H), 2.47 (m, 6 H), 6.54 (s, 1 H), 6.60

(s, 1 H), 6.94 (m, 2 H), 6.99 (s, 1 H), 7.18 (d, J = 3.9 Hz, 1 H),

7.25 (m, 2 H), 7.31 (d, J = 7.4 Hz, 1 H), 7.36 (m, 2 H), 7.48 (br. s,

3 H), 7.57 (br. s, 1 H), 7.65 (m, 1 H), 7.73 (br. s, 1 H), 8.04 (d, J

= 7.4 Hz, 1 H), 8.22 (d, J = 8 Hz, 1 H), 8.61 (s, 1 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 19.22, 21.38, 27.78, 28.62, 38.57,

1

evaporator to afford 26 as a violet solid in 69% yield (12 mg). H

NMR (300 MHz, CDCl₃, –50 °C, TMS): δ = –2.74 (s, 2 H), 1.87

(m, 24 H), 2.51 (s, 6 H), 2.66 (s, 9 H), 6.38 (br. s, 1 H), 6.65 (br. s,

1 H), 6.84 (br. s, 1 H), 7.14 (d, J = 3.9 Hz, 1 H), 7.24–7.46 or 7.35

(m, 14 H), 7.53 (m, 3 H), 7.66 (m, 5 H), 7.83 (m, 4 H), 8.01 (d, J

= 7.8 Hz, 2 H), 8.46 (d, J = 7.8 Hz, 2 H), 8.78 (m, 8 H), 9.84 (br.

s, 1 H), 11.64 (br. s, 1 H) ppm. UV/Vis: λ_max(εϫ10⁴Lmol^–1cm^–1)

= 419 (42.18), 516 (2.15), 550 (1.16), 594 (1.08), 649 (1.53), 698 nm

(1.61). ES-MS: C₉₇H₈₀N₆S₂, calcd. av. mass: 1393.9; obsd. m/z:

1394.8 [M]⁺.

71.85, 107.18, 110.87, 112.23, 121.58, 125.97, 126.82, 127.89, 4-[5,10,15-Tri(p-octyloxyphenyl)-21-thia-20-porphinyl]-4Ј-[5,5-di-

128.51, 128.90, 129.27, 130.09, 130.97, 132.53, 134.21, 134.56, methyl-10,15-di(p-tolyl)-21,23-dithia-20-phlorinyl]diphenylethyne

135.91, 136.78, 137.32, 138.03, 141.39, 142.32, 144.39, 148.69, (27): Samples of 21,23-dithiaphlorin 16 (30.0 mg, 39.6 µmol) and

150.65, 165.26, 167.73 ppm. UV/Vis: λ_max(εϫ10³Lmol^–1cm^–1) =

342 (24.58), 419 (58.54), 664 nm (31.59). ES-MS: C₄₂H₃₄N₄SO₂,

calcd. av. mass: 658.8; obsd. m/z: 659.4 [M]⁺. C₄₂H₃₄N₄O₂S (658.8):

calcd. C 76.57, H 5.20, N 8.50, S 4.87; found C 76.49, H 5.61, N

8.38, S 4.91.

5,10,15-tris(p-octyloxyphenyl)-20-(p-ethynylphenyl)-21-thiaporphy-

rin (49.4 mg, 47.5 µmol) were dissolved in dry toluene/triethyl-

amine (5:1, 40 mL) in a 100 mL round-bottomed flask, and nitro-

gen purging was carried out for 15 min. The coupling was initiated

by adding AsPh₃(14.3 mg, 46.8 µmol) and Pd₂(dba)₃(5.4 mg,

5.9 µmol) and the reaction mixture was stirred at 50 °C for 24 h.

After standard workup, the crude reaction mixture was passed

through two neutral alumina columns and the desired dyad 27 was

collected with petroleum ether/ethyl acetate (90:10). Concentration

of the solution in a rotary evaporator under reduced pressure gave

N₂S₂phlorin-N₃S porphyrin dyad 27 as a violet solid in 48% yield

21,23-Dithiaphlorin-ZnN₄Porphyrin Dyad 25: A solution of 21,23-

dithiaphlorin 16 (30.0 mg, 39.6 µmol) and 5,10,15-tri(mesityl)-20-

(ethynylphenyl)porphyrinzinc(II) (39.0 mg, 47.5 µmol) were dis-

solved in dry toluene/triethylamine (5:1, 30 mL) in a 50 mL round-

bottomed flask. The flask was fitted with a reflux condenser, and

a gas inlet tube was inserted through the top of the condenser into

the solution for nitrogen purging. The reaction vessel was placed

in an oil bath preheated to 50 °C. Nitrogen purging was carried

out for 15 min. AsPh₃(14.3 mg, 46.8 µmol) and Pd₂(dba)₃(5.4 mg,

5.9 µmol) were added to this solution and the reaction mixture was

stirred under nitrogen at 50 °C for 24 h. TLC analysis of the reac-

tion mixture showed the disappearance of spots corresponding to

starting materials and the appearance of a new spot corresponding

to dimer. The solvents were removed in vacuo, the crude compound

was passed through a small silica column with petroleum ether/

dichloromethane (80:20) to remove the excess of AsPh₃, and the

crude mixture of small amounts of monomeric porphyrins along

1

(32 mg). H NMR (300 MHz, CDCl₃, –50 °C, TMS): δ = –2.76 (s,

1 H), 0.97 (br. s, 9 H), 1.23–1.57 (m, 30 H), 1.93 (br. s, 12 H), 2.48

(m, 6 H), 4.13 (br. s, 6 H), 6.14 (br. s, 1 H), 6.35 (br. s, 1 H), 6.63

(br. s, 1), 6.84 (br. s, 1 H), 6.99 (br. s, 1 H), 7.29 (m, 13 H), 7.69

(m, 10 H, Ar), 8.12 (m, 6 H), 8.31 (br. s, 2 H), 8.68 (m, 4 H), 8.98

(br. s, 2 H), 9.86 (s, 2 H), 11.83 (s, 1 H), 13.09 (s, 1 H) ppm. UV/

Vis: λ_max(εϫ10⁴Lmol^–1cm^–1) = 435 (35.14), 520 (2.42), 557 (1.77),

628 (1.59), 864 nm (2.75). ES-MS: C₁₁₂H₁₀₉N₅O₃S₃, calcd. av.

mass: 1669.3; obsd. m/z: 1669.8 [M]⁺.

[5,10,15-Tri(p-tolyl)-21-thia-20-porphinyl]-4Ј-[5,5-dimethyl-10,15-

di(p-tolyl)-21,23-dithia-20-phlorinyl]phenylethyne (28): AsPh₃

1898

www.eurjoc.org

Eur. J. Org. Chem. 2008, 1884–1900

Anion Binding in Thiaphlorins and Thiaphlorin–Porphyrin Dyads

(14.6 mg, 47.5 µmol) and Pd₂(dba)₃(5.4 mg, 5.9 µmol) were added

under nitrogen, to initiate coupling, to a solution of N₂S₂phlorin

16 (30.0 mg, 39.6 µmol) and 5,10,15-tritolyl-20-ethynyl-21-thiapor-

phyrin (27.1 mg, 43.6 µmol) in dry toluene/triethylamine (5:1,

30 mL) in a 50 mL round-bottomed flask. The reaction mixture

was stirred at 50 °C for 24 h. Column chromatographic purification

on neutral alumina with petroleum ether/ethyl acetate (94:6) gave

pound 31 and a very faint spot corresponding to starting phlorin

16. The solvent was removed in vacuo, the crude compound was

dissolved in dichloromethane (3 mL), and a dry slurry was pre-

pared by adding neutral alumina powder followed by removal of

traces of solvent under high vacuum. The slurry was loaded onto

a neutral alumina column packed with petroleum ether. The small

amount of unchanged phlorin 16 was removed first with petroleum

ether/ethyl acetate (98:2) and the desired phlorin 31 was collected

1

the pure dyad 28 as a green solid in 20% yield (10 mg). H NMR

(300 MHz, CDCl₃, –50 °C, TMS): δ = –2.32 (s, 1 H), 1.81 (m, 6 with petroleum ether/ethyl acetate (96:4). Concentration of the

H), 2.53 (m, 9 H), 2.75 (s, 6 H), 6.19 (br. s, 1 H), 6.45 (br. s, 1 H), solution gave 31 as a green solid in 65% yield (0.6 g); m.p. Ͼ250 °C.

6.70 (br. s, 2 H), 6.94–7.29 (m, 8 H), 7.59–7.70 (m, 14 H), 8.14 (m,

¹H NMR (300 MHz, CDCl₃, –50 °C, TMS): δ = 0.30 (m, 9 H,

8 H), 8.65 (m, 3 H), 8.91 (br. s, 1 H), 9.41 (br. s, 1 H), 9.93 (br. s,

CH₃), 1.87 (s, 6 H), 2.49 (s, 6 H), 6.34 (s, 1 H), 6.61 (s, 1 H), 6.82

1 H), 10.40 (br. s, 1 H), 12.01 (br. s, 1 H), 13.14 (br. s, 1 H) ppm. (s, 1 H), 7.07 (br. s, 1 H), 7.19 (s, 1 H), 7.34 (m, 3 H), 7.48 (m, 4

UV/Vis: λ_max(εϫ10³Lmol^–1cm^–1) = 445 (86.54), 517 (2.23), 553 H), 7.61 (m, 8 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 21.47,

(1.98), 698 nm (7.47). ES-MS: C₈₅H₆₃N₅S₃, calcd. av. mass: 1250.6; 21.51, 29.75, 32.01, 39.28, 96.11, 104.99, 121.60, 123.51, 128.90,

obsd. m/z: 1250.6 [M]⁺.

129.02, 130.19, 131.51, 132.10, 132.47, 134.96, 135.09, 136.42,

136.79, 137.17, 137.23, 138.45, 140.08, 140.29, 146.07, 146.90,

147.81, 153.06 ppm. UV/Vis: λ_max(ε ϫ 10³L mol^–1cm^–1) = 345

(31.22), 436 (35.68), 550 (sh), 696 nm (21.35). ES-MS:

Dyad 29: Coupling of 21-thiaphlorin 21 (40.0 mg, 54.1 µmol) and

5,10,15-tri(mesityl)-20-(4-ethynylphenyl)porphyrinzinc(II)

(54.0 mg, 64.9 µmol) in dry toluene/triethylamine (5:1, 40 mL) was

carried out under nitrogen in the presence of AsPh₃(19.9 mg,

64.9 µmol) and Pd₂(dba)₃(7.4 mg, 8.1 µmol) at 50 °C for 24 h. Af-

ter workup, the crude compound was subjected twice to alumina

column chromatographic purification, and the pure dyad 29 was

collected with petroleum ether/ethyl acetate (98:2). Removal of sol-

vent by rotary evaporation under reduced pressure afforded dyad

29 as a violet solid in 33% yield (26 mg). ¹H NMR (500 MHz,

CDCl₃, –50 °C, TMS): δ = 1.82 (m, 24 H), 2.48 (m, 6 H), 2.63 (s,

9 H), 6.59 (m, 3 H), 6.99 (s, 3 H), 7.27 (m, 10 H), 7.51 (m, 6 H),

7.79 (m, 4 H), 7.96 (s, 2 H), 8.24 (s, 2 H), 8.70 (s, 4 H), 8.77 (s, 2

H), 8.89 (s, 2 H), 9.83 (s, 1 H), 11.73 (s, 1 H), 11.94 (s, 1 H) ppm.

UV/Vis: λ_max(εϫ10⁴Lmol^–1cm^–1) = 422 (78.24), 515 (1.49), 552

(4.17), 593 (sh), 681 nm (4.81). ES-MS: C₉₇H₇₉N₇SZn, calcd. av.

mass: 1440.2; obsd. m/z: 1440.6 [M]⁺.

C

₄₇H₄₂N₂S₂Si, calcd. av. mass: 727.1; obsd. m/z: 727.3 [M]⁺.

C₄₇H₄₂N₂S₂Si (727.1): calcd. C 77.64, H 5.82, N 3.85, S 8.82; found

C 77.32, H 5.71, N 3.68, S 8.56.

10-(p-Ethynylphenyl)-5,5-dimethyl-15,20-di(p-tolyl)-21,23-dithia-

phlorin (32): A sample of 21,23-dithiaphlorin 31 (90 mg,

0.124 mmol) in dry and distilled THF (30 mL) was placed in a

100 mL round-bottomed flask fitted with a reflux condenser, and

a calcium chloride guard tube was placed on top of the condenser.

Tetrabutylammonium fluoride (53.8 µL of a ca. 1  solution in

THF) was added, and the reaction mixture was allowed to stir at

room temperature for 12 h. After this period, TLC analysis of the

crude reaction mixture showed the formation of a new green spot

along with the trace amount of starting compound 31. The solvents

were removed in vacuo and the crude compound was subjected to

neutral alumina column with elution with petroleum ether. The

small amount of unchanged phlorin 31 was removed first with pe-

troleum ether/ethyl acetate (96:4) and the desired 21,23-dithiaphlo-

rin 32 was then collected with petroleum ether/ethyl acetate (94:6).

Concentration of the solution gave 32 as green solid in 64 %

yield (0.5 g); m.p. Ͼ250 °C. ¹H NMR (300 MHz, CDCl₃, –50 °C,

TMS): δ = 1.87 (s, 6 H), 2.49 (s, 6 H), 3.27 (s, 1 H), 6.34 (s, 1 H),

6.61 (s, 1 H), 6.89 (br. s, 1 H), 7.06 (s, 1 H), 7.18 (s, 1 H), 7.31 (m,

3 H), 7.49–7.66 or 7.58 (m, 12 H) ppm. UV/Vis: λ_{m a x}

(εϫ10³Lmol^–1cm^–1) = 334 (32.33), 418 (36.49), 697 nm (20.89).

ES-MS: C₄₄H₃₄N₂S₂, calcd. av. mass: 654.9; obsd. m/z: 655.3 [M]⁺.

C₄₄H₃₄N₂S₂(654.9): calcd. C 80.70, H 5.23, N 4.28, S 9.79; found C

80.43, H 4.98, N 4.62, S 9.56.

4-[5,10,15-Trimesityl-20-porphinyl]-4Ј-[5,5-dimethyl-10,15-di(p-

tolyl)-21-thia-20-phlorinyl]diphenylethyne (30): Trifluoroacetic acid

(1 mL) was added to a solution of dyad 29 (30.0 mg, 20.8 µmol)

dissolved in dichloromethane (30 mL) in a 50 mL round-bottomed

flask, and the reaction mixture was allowed to stir at room tem-

perature for 12 h. The solution was poured into water and washed

thoroughly with sodium hydrogen carbonate. The solution was

dried with anhydrous sodium sulfate and evaporated in a rotary

evaporator to afford dyad 30 as a violet solid in 70% yield (20 mg).

¹H NMR (500 MHz, CDCl₃, –50 °C, TMS): δ = –2.73 (s, 2 H),

1.88 (m, 24 H), 2.53 (m, 6 H), 2.68 (s, 9 H), 6.67 (br. s, 2 H), 7.04

(br. s, 4 H), 7.32 (m, 10 H), 7.58 (br. s, 6 H), 7.85 (br. s, 4 H), 8.01

(br. s, 2 H), 8.28 (br. s, 2 H), 8.80 (m, 8 H), 9.93 (s, 1 H) ppm. UV/

Vis: λ_max(εϫ10⁴Lmol^–1cm^–1) = 419 (52.99), 516 (2.58), 553 (1.59),

598 (2.09), 653 (3.56), 680 nm (4.15). ES-MS: C₉₇H₈₁N₇S, calcd.

av. mass: 1376.7; obsd. m/z: 1376.7 [M]⁺).

4,4Ј-Bis[5,5-dimethyl-10,15-di(p-tolyl)-21,23-dithia-20-phlorinyl]di-

phenylethyne (33): Coupling of 21.23-dithiaphlorin 16 (34.0 mg,

44.9 µmol) with 21,23-dithiaphlorin 32 (35.3 mg, 53.9 µmol) in dry

toluene/triethylamine (5:1, 50 mL) in the presence of AsPh₃

(16.5 mg, 53.8 µmol) and Pd₂(dba)₃(6.2 mg, 6.7 µmol) at 50 °C un-

der nitrogen for 30 h, followed by standard workup, gave a crude

mixture of the desired compound along with unreacted monomers.

Column chromatographic purification of the crude mixture on neu-

tral alumina with petroleum ether/ethyl acetate 92:8) afforded pure

33 as a green solid in 24% yield (14 mg). ¹H NMR (300 MHz,

CDCl₃, –50 °C, TMS): δ = 1.88 (br. s, 12 H), 2.49 (m, 12 H), 6.35

(br. s, 2 H), 6.63 (br. s, 2 H), 6.81 (br. s, 2 H), 7.09 (br. s, 2 H),

7.20 (br. s, 2 H), 7.34 (m, 6 H), 7.44–7.64 (m, 16 H), 7.75 (br.

s, 8 H), 11.89 (s, 1 H), 13.09 (s, 1 H) ppm. UV/Vis: λ_max

(εϫ10³Lmol^–1cm^–1) = 394 (8.72), 435 (10.18), 517 (sh), 552 (1.42),

704 nm (5.61). ES-MS: C₈₆H₆₆N₄S₄, calcd. av. mass: 1283.7; obsd.

m/z: 1284.9 [M]⁺.

5,5-Dimethyl-10-{p-[2-(trimethylsilyl)ethynyl]phenyl}-15,20-di(p-

tolyl)-21,23-dithiaphlorin (31): A solution of N₂S₂phlorin 16

(90.0 mg, 118.9 µmol) was dissolved in dry toluene/triethylamine

(5:1, 30 mL) in a 100 mL round-bottomed flask. The flask was fit-

ted with a reflux condenser and a gas inlet tube was inserted

through the top of the condenser into the solution for nitrogen

purging. The reaction vessel was placed in an oil bath preheated to

50 °C. Nitrogen purging was carried out for 15 min, and (trimethyl-

silyl)acetylene (26.9 mg, 31.3 µL, 142.7 µmol) was added slowly by

syringe. AsPh₃(43.7 mg, 142.7 µmol) and Pd₂(dba)₃(16.3 mg,

17.8 µmol) were added to initiate the coupling and the reaction

mixture was stirred at 50 °C for 24 h. TLC analysis of the reaction

mixture showed a new spot corresponding to the desired com-

Eur. J. Org. Chem. 2008, 1884–1900

www.eurjoc.org

1899

I. Gupta, R. Fröhlich, M. Ravikanth

FULL PAPER

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Published Online: February 27, 2008

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Synthesis and anion-binding studies of thiaphlorins and covalently linked thiaphlorin-porphyrin dyads

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