Synthesis of functionalized unsymmetrical thiophene diols and their use in the synthesis of cis-21-monothia- and cis-21,23-dithiaporphyrin building blocks with two different functional groups

Article abstract of DOI:10.1055/s-2005-872245

A series of functionalized unsymmetrical thiophene diols were synthesized and used for the synthesis of cis-21-monothia and cis-21,23-dithiaporphyrin building blocks having two different functional groups at meso-positions. To show the use of the cis-thia

Full text of DOI:10.1055/s-2005-872245

LETTER
2199
Synthesis of Functionalized Unsymmetrical Thiophene Diols and Their Use in
the Synthesis of cis-21-Monothia- and cis-21,23-Dithiaporphyrin Building
Blocks with Two Different Functional Groups
Synthesis of
F
o
unctionalized
k
Unsymmet
k
a
ne
D
iols lingam Punidha, Mangalampalli Ravikanth*
Department of Chemistry, Indian Institute of Technology, Powai, Mumbai 400076, India
Fax +91(22)25767152; E-mail: ravikanth@chem.iitb.ac.in
Received 16 May 2005
unit.2 Interestingly, to the best of our knowledge, there is
no report on porphyrin arrays containing more than two
different types of porphyrin cores assembled by covalent
or non-covalent interactions. This may be due to the inac-
Abstract: A series of functionalized unsymmetrical thiophene
diols were synthesized and used for the synthesis of cis-21-mono-
thia and cis-21,23-dithiaporphyrin building blocks having two
different functional groups at meso-positions. To show the use of
the cis-thiaporphyrin building blocks with two different functional cessibility of the suitable porphyrin building blocks. In
groups, a porphyrin trimer comprised of N4, N3S and N2S2 por-
this paper, we report the synthesis of a series of new func-
phyrin sub-units was synthesized by using both covalent and non-
covalent interactions.
tionalized unsymmetrical thiophene diols and their use in
the synthesis of 21-monothia-and 21,23-dithiaporphyrin
building blocks containing two different functional
groups in a cis fashion. The use of cis-thiaporphyrin build-
Key words: functionalized unsymmetrical diols, cis-thiaporphyrin,
porphyrin trimer, covalent, non-covalent interactions
ing blocks was demonstrated by synthesizing the first por-
phyrin trimer comprised of three different porphyrin cores
(N2S2, N3S and N4 cores) assembled by using both cova-
lent and non-covalent bonds.
The thiophene mono-ols 1–3 were obtained2e by treating
one equivalent of thiophene with 1.2 equivalents of n-
BuLi followed by addition of 1.2 equivalents of function-
alized aryl aldehyde in THF at 0 °C (Scheme 1). The
crude compounds were purified by silica gel column chro-
matography using petroleum ether–ethyl acetate (8–10%)
and afforded 1–3 as white solids in 38–45% yields. To
prepare the unsymmetrical thiophene diols 4–9, the mono-
Porphyrin arrays containing two or more porphyrin sub-
units with different porphyrin cores connected covalently
or non-covalently are very interesting systems which may
have several applications in bioorganic and materials
chemistry.1 Recently we synthesized a series of unsym-
metrical porphyrin arrays containing two different por-
phyrin sub-units such as N2S2–N4, N3S–N4, N3O–N4,
N3S–N3O, etc. and observed an efficient energy transfer in
some of these systems from one porphyrin unit to another
porphyrin unit on selective excitation of one porphyrin
R
R
TMEDA, n-BuLi, THF, 0 °C
R'-CHO
n-BuLi, THF
R'
H
OH
H
S
S
H
R-CHO
OH
S
OH
R = Br
= I
: 1 (45%)
: 2 (38%)
R = Br
R = Br
R = I
;
;
R' =
I
: 4 (36%)
: 5 (32%)
NO2
= CCC(CH3)2OH : 3 (40%)
R' =
NO2
;
R' =
R' =
: 6 (30%)
: 7 38%)
R = CCC(CH3)2OH
;
Br
R' =
R' =
R = CCC(CH3)2OH
R = CCC(CH3)2OH
;
I
: 8 (32%)
: 9 (26%)
;
N
Scheme 1 Synthetic scheme for the preparation of functionalized unsymmetrical thiophene diols 4–9
SYNLETT 2005, No. 14, pp 2199–2203
0
2
.0
9
.2
0
0
5
Advanced online publication: 26.07.2005
DOI: 10.1055/s-2005-872245; Art ID: D13205ST
© Georg Thieme Verlag Stuttgart · New York

2200
S. Punidha, M. Ravikanth
LETTER
ols 1–3 were treated with 2.5 equivalents of correspond- phyrin building blocks 11–16 were characterized by all
ing functionalized aryl aldehyde in THF at 0 °C under spectroscopic techniques.5
similar reaction conditions2f (Scheme 1). Purification by
silica gel column gave 4–9 in 26–36% yields. The other
To show the applicability of cis-thiaporphyrin building
blocks, we synthesized the first example of porphyrin tri-
mer 20 having three different porphyrin cores (N4, N3S
and N2S2) using porphyrin building block 16 containing 4-
precursor 16-thiatripyrrane 10 was synthesized by follow-
ing the literature procedure.3
The required cis-21-monothiaporphyrins 11, 12 and cis- ethynylphenyl and 4-pyridyl functional groups at the
21,23-dithiaporphyrins 13–15 containing two different meso-positions (Scheme 3). The other required porphy-
functional groups at the meso-positions were synthesized rins, N3S porphyrin having mono iodophenyl functional
as shown in Scheme 2. The cis-21-monothiaporphyrins group at the meso-position 17 and RuTPP(CO)(EtOH)
11 and 12 were synthesized by condensing one equivalent (19) were synthesized by following the literature meth-
of 5 and 8, respectively, with two equivalents of p-tolual- ods.2e,6 The N2S2–N3S porphyrin dimer 18 was synthe-
dehyde and three equivalents of pyrrole under standard sized by following the coupling conditions developed by
porphyrin-forming conditions.4 The crude porphyrinic Lindsey and co-workers.7 Coupling of 16 and 17 in tolu-
mixture was subjected twice to silica gel column chroma- ene–triethylamine at 35 °C in the presence of catalytic
tography and afforded pure 11 and 12 in 8–9% yields. The amount of Pd2(dba)3/AsPh3 followed by silica gel column
cis-21,23-dithiaporphyrins 13, 14 and 15 were synthe- chromatographic purification afforded pure dimer 18 in
sized by condensing one equivalent of diol 4, 7 and 9, re- 62% yield (Scheme 3). The dimer 18 was characterized by
spectively, with known 16-thiatripyrrane3 10 under all spectroscopic techniques. In the 1H NMR spectrum of
similar acid-catalyzed porphyrin-forming conditions. Pu- dimer 18, the resonances corresponding to both the por-
rification by column chromatography on silica afforded phyrinic sub-units and the bridging group are present with
pure 13–15 in 8–13% yields. The deprotection of ethyne minor differences in the chemical shift positions of the
group of 15 to afford 16 was carried out by treating 15 protons compared to their respective monomeric porphy-
with KOH in benzene–methanol at 80 °C. The cis-thiapor- rins 16 and 17, respectively, indicating that the porphyrin
R'
R
H
OH
H
S
(a)
(b)
OH
H3C
CH3
CHO
+
S
H+
DDQ
H+
DDQ
NH
HN
10
N
H
R'
R'
S
N
S
S
N
R
R
CH3
CH3
N
N
HN
CH3
CH3
NO2
:
R =
R =
R =
11 (8%)
12 (9%)
Br ; R' =
Br ; R' =
; R' =
I
: 13 (13%)
R =
R =
Br ; R' =
:
OH
14 (11%)
15 (8%)
:
R' =
OH
I ;
N
N
:
OH
C6H6, CH3OH
KOH
R =
; R' =
:
H
16 (88%)
Scheme 2 Synthetic scheme for the preparation of cis-21-monothia (a) and cis-21,23-dithiaporphyrin (b) building blocks with different
functional groups 11–16
Synlett 2005, No. 14, 2199–2203 © Thieme Stuttgart · New York

LETTER
Synthesis of Functionalized Unsymmetrical Thiophene Diols
2201
CH3
CH3
CH3
S
Pd2(dba)3/AsPh3
N
S
S
N
S
N
H3C
+
I
16
CH3
CH3
N
N
HN
N HN
toluene/TEA, 35 °C
18
(62%)
N
CH3
CH3
17
toluene
reflux
CO
N
N
N
Ru
N
EtOH
19
CH3
CH3
S
N
S
S
N
H3C
CH3
N
N
HN
N
CH3
N
Ru
N
N
N
20
(48%)
CO
Scheme 3 Synthetic scheme for the preparation of porphyrin trimer 20 comprised of three different porphyrin sub-units
sub-units in the dimer 18 interact very weakly. The ES- imum upfield shifts were observed for the 2,6- and 3,5-
MS mass spectrum of dimer 18 showed a strong M+ ion pyridyl protons of N2S2 porphyrin sub-unit of trimer 20
peak. The absorption spectrum of 18 showed absorption implying the coordination of pyridyl group with central
peaks corresponds to both N2S2 and N3S porphyrin sub- ruthenium ion of RuTPP unit. The absorption spectrum of
units and exhibited five Q-bands and a single broad Soret 20 also showed very interesting features compared to
band.
dimer 18 and also as compared to the corresponding mo-
nomeric porphyrins.
The dimer 18 was treated with 1.2 equivalents of
RuTPP(CO)(EtOH) (19) in toluene at refluxing tempera- In conclusion, we synthesized a series of functionalized
ture for four hours.2d The TLC analysis indicated the dis- unsymmetrical thiophene diols and used them for the syn-
appearance of starting materials and the formation of the thesis of cis-21-monothia-and cis-21,23-dithiaporphyrin
required trimer 20. The crude compound was purified by building blocks containing two different functional
simple silica gel column chromatography and afforded the groups. The application of cis-thiaporphyrin building
pure trimer 20 in 48% yield. The trimer 20 was highly sol- blocks was demonstrated by synthesizing the first exam-
uble in most of the organic solvents and was characterized ple of novel trimer composed of three different porphyrin
by NMR, ES-MS, and absorption spectroscopy. In the 1H sub-units assembled via covalent and non-covalent inter-
NMR spectrum, the trimer 20 showed signals correspond- actions. The synthetic strategy presented in this paper will
ing to all three porphyrin sub-units. The N3S porphyrin be extended in our laboratory to synthesize several novel
and RuTPP porphyrin sub-units showed minor changes in heteroporphyrins based systems.
the chemical shifts of various protons compared to their
corresponding monomers 17 and 19, respectively. How-
ever, the protons of N2S2 porphyrin sub-unit experienced
Acknowledgment
MR thanks DST and CSIR, Government of India for supporting the
project and SP thanks CSIR for fellowship.
large upfield shifts compared to corresponding monomer-
ic porphyrin 16 because of RuTPP ring current. The max-
Synlett 2005, No. 14, 2199–2203 © Thieme Stuttgart · New York

2202
S. Punidha, M. Ravikanth
LETTER
H, s, CH3), 7.52 (2 H, d, J = 7.8 Hz, aryl), 7.62 (4 H, d,
References
J = 8.0 Hz, aryl), 7.98 (2 H, d, J = 7.8 Hz, aryl), 8.11 (4 H,
d, J = 8.0 Hz, aryl), 8.20 (2 H, d, J = 7.8 Hz, 3,5-pyridyl),
8.54 (1 H, m, b-pyrrole), 8.64 (1 H, d, J = 4.6 Hz, b-pyrrole),
8.72 (1 H, d, J = 4.6 Hz, b-pyrrole), 8.78–8.81 (1 H, m, b-
pyrrole), 9.14 (2 H, br s, 2,6-pyridyl), 9.54 (1 H, d, J = 4.4
Hz, b-thiophene), 9.72 (1 H, d, J = 4.4 Hz, b-thiophene),
9.76 (2 H, s, b-thiophene) ppm. 13C NMR (100 MHz,
CDCl3): d = 22.56, 22.68, 31.06, 31.49, 128.03, 129.49,
133.61, 134.71, 134.93, 135.14, 135.73, 136.13, 138.02,
146.90, 147.61, 148.53, 148.68, 149.75, 150.87, 155.11,
156.63, 157.01 ppm. ES-MS: m/z calcd for C50H37N3OS2:
759.96; found: 760.31 (100%) [M+]. UV/Vis (in toluene,
lmax/nm, e/mol–1 dm3 cm–1): 437 (292652), 515 (26193), 549
(9062), 634 (2073), 697 (5030).
Porphyrin 16: sample of porphyrin 15 (0.05 g, 0.07 mmol)
was dissolved in benzene–MeOH (3:1, 40 mL) taken in a
100-mL round-bottomed flask and excess KOH (0.20 g) was
added to it. The reaction mixture was refluxed at 80 °C using
a Dean–Stark apparatus. The excess solvent was removed
under vacuum and the crude compound was subjected to
silica gel column chromatography using PE–CH2Cl2 (5:95)
to afford the pure desired porphyrin 16 as a purple solid
(0.04 g, 88%). 1H NMR (400 MHz, CDCl3): d = 2.70 (6 H,
s, CH3), 3.32 (1 H, s, CH), 7.50 (2 H, d, J = 7.8 Hz, aryl),
7.62 (4 H, d, J = 8.0 Hz, aryl), 7.96 (2 H, d, J = 7.8 Hz, aryl),
8.14 (4 H, d, J = 8.0 Hz, aryl), 8.20 (2 H, d, J = 7.8 Hz, 3,5-
pyridyl), 8.56 (1 H, d, J = 4.5 Hz, b-pyrrole), 8.64 (1 H, d,
J = 4.6 Hz, b-pyrrole), 8.72 (1 H, d, J = 4.6 Hz, b-pyrrole),
8.80 (1 H, d, J = 4.5 Hz, b-pyrrole), 9.11 (2 H, br s, 2,6-
pyridyl), 9.58 (1 H, d, J = 4.4 Hz, b-thiophene), 9.68 (1 H, d,
J = 4.4 Hz, b-thiophene), 9.76 (2 H, s, b-thiophene) ppm. 13C
NMR (100 MHz, CDCl3) d = 21.61, 31.07, 31.49, 121.95,
128.31, 131.29, 132.54, 134.18, 134.55, 134.92, 135.75,
135.93, 138.32, 141.98, 147.52, 147.80, 148.92, 150.98,
155.95, 156.54, 156.60, 160.02 ppm. ES-MS: m/z calcd for
C47H31N3S2: 701.90; found: 702.22 (100%) [M+]. UV/Vis
(in toluene, lmax/nm, e/mol–1 dm3 cm–1): 436 (262893), 515
(24005), 549 (8393), 634 (1845), 697 (4601).
Dimer 18: A solution of 16 (0.02 g, 0.03 mmol) and 17 (0.02
g, 0.03 mmol) in dry toluene–Et3N (3:1, 30 mL) was purged
with nitrogen for 10 min. The coupling was initiated by
adding AsPh3 (0.01 g, 0.03 mmol) followed by Pd2(dba)3
(0.01 g, 0.01 mmol) and the reaction mixture was then stirred
at 40 °C for 12 h. After work-up, the crude compound was
subjected to silica gel column chromatography and the
desired dimer 18 was collected with PE–CH2Cl2 (15:85)
mixture as a violet solid (0.02 g, 64%). 1H NMR (400 MHz,
CDCl3): d = –2.71 (1 H, br s, NH), 2.70 (9 H, s, CH3), 2.73
(6 H, s, CH3), 7.53 (4 H, d, J = 7.6 Hz, aryl), 7.61 (8 H, d,
J = 7.6 Hz, aryl), 7.96 (2 H, d, J = 8.0 Hz, aryl), 8.06 (4 H,
d, J = 7.6 Hz, aryl), 8.12 (10 H, m, aryl), 8.17 (2 H, m, 3,5-
pyridyl), 8.62 (4 H, m, b-pyrrole), 8.68 (3 H, m, b-pyrrole),
8.73 (1 H, d, J = 5.6 Hz, b-pyrrole), 8.94 (2 H, m, b-pyrrole),
9.03 (2 H, br m, 2,6-pyridyl), 9.58 (1 H, d, J = 5.2 Hz, b-
thiophene), 9.67 (1 H, d, J = 5.2 Hz, b-thiophene), 9.72 (3 H,
m, b-thiophene), 9.76 (1 H, d, J = 5.2 Hz, b-thiophene) ppm.
ES-MS: m/z calcd for C94H63N6S3: 1373.76; found: 1373.57
(52%) [M+]. UV/Vis (in toluene, lmax/nm, e/mol–1 dm3 cm–1):
433 (484803), 515 (41725), 549 (13604), 624 (3694), 680
(5357), 696 (4918).
(1) (a) Burrell, A. K.; Officer, D. L.; Plieger, P. G.; Reid, D. C.
W. Chem. Rev. 2001, 101, 2751. (b) Aratani, N.; Osuka, A.
Bull. Chem. Soc. Jpn. 2001, 74, 1361. (c) Suslick, K. S.;
Rakow, N. A.; Kosal, M. E.; Chou, J.-H. J. Porphyrins
Phthalocyanines 2000, 4, 407. (d) Hunter, C. A.; Sarson, L.
D. Angew. Chem., Int. Ed. Engl. 1994, 33, 2313. (e) Chi,
X.; Guerin, A. J.; Haycock, R. A.; Hunter, C. A.; Sarso, L.
D. J. Chem. Soc., Chem. Commun. 1995, 2567. (f) Hunter,
C. A.; Shannon, R. J. Chem. Commun. 1996, 1361.
(g) Haycock, R. A.; Yartsev, A.; Michelsen, U.; Sundstrom,
V.; Hunter, C. A. Angew. Chem. Int. Ed. 2000, 39, 3616.
(h) Harriman, A.; Magda, D. A.; Sessler, J. L. J. Chem. Soc.,
Chem. Commun. 1991, 345. (i) Sessler, J. L.; Wang, B.;
Harriman, A. J. Am. Chem. Soc. 1995, 117, 704. (j) Kral,
V.; Springs, S. L.; Sessler, J. L. J. Am. Chem. Soc. 1995, 117,
8881. (k) Biemans, H. A. M.; Rowan, A. E.; Verhoeven, A.;
Vanoppen, P.; Latterini, L.; Foekama, J.; Schenning, A. P.
H. J.; Meijer, E. W.; De Shryver, F. C.; Nolte, R. J. M. J. Am.
Chem. Soc. 1998, 120, 11054. (l) Lensen, M. C.;
Castriciano, M.; Coumans, R. G. E.; Foekama, J.; Rowan, R.
E.; Scolaro, L. M.; Nolte, R. J. M. Tetrahedron Lett. 2002,
43, 9351.
(2) (a) Ravikanth, M. Tetrahedron Lett. 2000, 41, 3709.
(b) Kumaresan, D.; Agarwal, N.; Ravikanth, M. J. Chem.
Soc., Perkin Trans. 1 2001, 1644. (c) Santra, S.;
Kumaresan, D.; Agarwal, N.; Ravikanth, M. Tetrahedron
2003, 59, 2353. (d) Punidha, S.; Ravikanth, M. Tetrahedron
2004, 60, 8437. (e) Gupta, I.; Ravikanth, M. J. Org. Chem.
2004, 69, 6796. (f) Punidha, S.; Agarwal, N.; Ravikanth, M.
Eur. J. Org. Chem. 2005, 2500.
(3) (a) Sridevi, B.; Narayanan, S. J.; Srinivasan, A.; Reddy, M.
V.; Chandrashekar, T. K. J. Porphyrins Phthalocyanines
1998, 2, 69. (b) Heo, P.-Y.; Lee, C. H. Bull. Korean Chem.
Soc. 1996, 17, 515.
(4) (a) Adler, A. D.; Longo, F. R.; Finarelli, J. D.; Goldmacher,
J.; Assour, J.; Korsakoff, L. J. Org. Chem. 1967, 32, 476.
(b) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P.
C.; Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827.
(5) Experimental Procedure and Spectroscopic Data for
Selected Compounds.
Diol 9: the thiophene mono-ol 3 (1.00 g, 3.67 mmol),
tetramethylethylenediamine (1.39 mL, 9.18 mmol) and n-
BuLi (5.74 mL of ca. 15% solution in hexane) were added
successively to freshly distilled dry Et2O (30 mL) in a 250-
mL three-necked round-bottomed flask and stirred for 15
min under nitrogen atmosphere at 0 °C. An ice-cold solution
of 4-pyridine carboxaldehyde (0.87 mL, 9.18 mmol) in dry
THF (30 mL) was added to it. The mixture was stirred for 15
min and ice-cold NH4Cl (50 mL, ca. 1 M) was added to
quench the reaction. After standard work up, the crude
compound was purified by silica gel column
chromatography using CH2Cl2–MeOH (95:5) and diol 4
obtained as a yellow oily liquid (0.40 g, 29%). 1H NMR (400
MHz, CDCl3): d = 0.92 (6 H, s, CH3), 4.00 (3 H, br s, OH),
5.99–6.15 (2 H, m, CHOH), 6.82–6.86 (2 H, m, thiophene),
7.42–7.44 (2 H, m, aryl), 7.70 (2 H, d, J = 7.8 Hz, pyridyl),
8.03–8.06 (2 H, m, aryl), 8.30 (2 H, br s, pyridyl) ppm. ES-
MS: m/z calcd for C22H21NO3S: 379.48; found: 378.09
(100%) [M+ – H]. Anal. Calcd: C, 69.63; H, 5.58; N, 3.69.
Found: C, 69.74; H, 5.51; N, 3.74.
Trimer 20: The dimer 18 (0.02 g, 0.02 mmol) was dissolved
in 30 mL of toluene in a two-necked 100-mL round-
bottomed flask and was purged with N2 for 10 min.
RuTPP(CO)(EtOH) (19; 0.019 g, 0.02 mmol) was then
added and the solution was refluxed with stirring for 4 h. The
crude compound was purified by silica gel column
Porphyrin 15: condensation of diol 9 (0.45 g, 1.19 mmol)
with 10 (0.50 g, 1.19 mmol) in propionic acid (125 mL) at
refluxing temperature for 2 h followed by standard work up
and chromatography on silica using CH2Cl2–MeOH (96:4)
gave the desired porphyrin 15 as a purple solid (0.07 g, 8%).
1H NMR (400 MHz, CDCl3): d = 0.94 (6 H, s, CH3), 2.69 (6
Synlett 2005, No. 14, 2199–2203 © Thieme Stuttgart · New York

LETTER
Synthesis of Functionalized Unsymmetrical Thiophene Diols
2203
chromatography using PE–CH2Cl2 (50:50) mixture as an
thiophene), 9.57 (1 H, dd, J = 5.2 Hz, b-thiophene), 9.83 (2
H, m, b-thiophene) ppm. ES-MS: m/z calcd for
eluent and afforded trimer 20 as a purple solid (0.01 g, 35%).
1H NMR (400 MHz, CDCl3): d = –2.61 (1 H, br s, NH), 1.64
(2 H, d, J = 3.2 Hz, 2,6-pyridyl), 2.68 (6 H, s, CH3), 2.70 (9
H, s, CH3), 6.08 (2 H, d, J = 3.2 Hz, 3,5-pyridyl), 7.10 (1 H,
d, J = 4.4 Hz, b-pyrrole), 7.56 (18 H, m, aryl), 7.63 (4 H, d,
J = 7.8 Hz, aryl), 7.71 (10 H, m, aryl), 7.91 (4 H, t, J = 7.4
Hz, aryl), 8.04 (8 H, m, aryl), 8.14 (4 H, d, J = 7.8 Hz, aryl),
8.19 (1 H, m, b-pyrrole), 8.33 (1 H, m, b-thiophene), 8.57 (2
H, m, b-pyrrole), 8.63 (2 H, m, b-pyrrole), 8.74 (8 H, s, b-
pyrrole of TPP), 8.90 (4 H, m, b-pyrrole), 9.29 (2 H, m, b-
C
139H92N10OS3Ru: 2115.57; found: 2115.79 (23%). UV/Vis
(in toluene, lmax/nm, e/mol–1 dm3 cm–1): 412 (302417), 432
(527038), 516 (35230), 549 (17975), 626 (bs), 683 (6228),
698 (5204).
(6) Collman, J. P.; Barnes, C. E.; Brothers, P. J.; Collins, T. J.;
Ozawa, T.; Gallucci, J. C.; Ibers, J. A. J. Am. Chem. Soc.
1984, 106, 5151.
(7) Wagner, R. W.; Johnson, T. E.; Li, F.; Lindsey, J. S. J. Org.
Chem. 1995, 60, 5266.
Synlett 2005, No. 14, 2199–2203 © Thieme Stuttgart · New York