Synthesis of (1H-pyrrol-2-ylsulfanyl)alkanoic acids

Article abstract of DOI:10.1134/S1070428008100205

(1-Benzyl-1H-pyrrol-2-ylsulfanyl)acetic acid, 2- and 3-(1-benzyl-1H-pyrrol- 2-ylsulfanyl)propionic acids, 1,1′-[1,4-phenylenebis(methylene)]bis[(1H- pyrrol-2-ylsulfanyl)acetic acid], and 1,1′-(hexane-1,6-diyl)bis-[(1H- pyrrol-2-ylsulfanyl)acetic acid] were synthesized for the first time by reactions of 1-benzyl-1H-pyrrole, 1,1′-[1,4-phenylenebis(methylene)] bis(1H-pyrrole), and 1,1′-(hexane-1,6-diyl)bis(1H-pyrrole) with thiourea, iodine, and the corresponding halogen-substituted alkanoic acids. 1-(4-Nitrophenyl)-1H-pyrrole failed to react with thiourea and iodine.

Full text of DOI:10.1134/S1070428008100205

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 10, pp. 1517–1521. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © E.V. Rudyakova, A.N. Mirskova, G.G. Levkovskaya, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 10,
pp. 1539–1543.
Synthesis of (1H-Pyrrol-2-ylsulfanyl)alkanoic Acids
E. V. Rudyakova, A. N. Mirskova, and G. G. Levkovskaya
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: ggl@irioch.irk.ru
Received June 6, 2007
Abstract—(1-Benzyl-1H-pyrrol-2-ylsulfanyl)acetic acid, 2- and 3-(1-benzyl-1H-pyrrol-2-ylsulfanyl)propionic
acids, 1,1′-[1,4-phenylenebis(methylene)]bis[(1H-pyrrol-2-ylsulfanyl)acetic acid], and 1,1′-(hexane-1,6-diyl)bis-
[(1H-pyrrol-2-ylsulfanyl)acetic acid] were synthesized for the first time by reactions of 1-benzyl-1H-pyrrole,
1,1′-[1,4-phenylenebis(methylene)]bis(1H-pyrrole), and 1,1′-(hexane-1,6-diyl)bis(1H-pyrrole) with thiourea,
iodine, and the corresponding halogen-substituted alkanoic acids. 1-(4-Nitrophenyl)-1H-pyrrole failed to react
with thiourea and iodine.
DOI: 10.1134/S1070428008100205
Pyrrolyl-substituted carboxylic acids are widely
used as intermediate products and biologically active
substances [1]. Pyrrolylsulfanyl-substituted alkanoic
acids also attract strong interest from the practical
viewpoint since their closest analogs, hetaryl- and
indolylsulfanylalkanoic acids and hydroxyalkylammo-
nium salts derived therefrom are known to act as
growth stimulators toward microorganisms, herbicides,
and immunostimulatory, adaptogenic, and antiphlogis-
tic agents [2, 3]. Therefore, development of methods
for the preparation of pyrrolylsulfanylalkanoic acids is
an important problem. However, pyrrolethiols that
could be used as starting compounds for the synthesis
of pyrrolylsulfanyl-substituted alkanoic acids remain
so far almost inaccessible.
these involves initial oxidation of thiourea with halo-
gen to produce dithiobis(formimidamide), reaction of
the latter with the remaining halogen to give sulfenyl
halide, and electrophilic substitution of hydrogen in the
pyrrole ring. According to the second mechanism,
initial halogenation of pyrrole is followed by nucleo-
philic replacement of the halogen atom by thiourea or
its analogs. As shown in [5], preliminarily prepared
iodopyrrole failed to react with thiourea under analo-
gous conditions; therefore, the proposed mechanisms
for formation of pyrrolylisothiuronium salts [4, 5], as
well as of those derived from indole [6], via halo-
genation of hetarenes and subsequent reaction with
thiourea was not confirmed.
We previously studied [7] reactions of indole and
its substituted derivatives with thiourea and iodine and
found optimal conditions for the synthesis of S-in-
dolylisothiuronium iodides and their subsequent trans-
formation into the corresponding indolylsulfanyl-
alkanoic acids. In the same publication we also de-
scribed for the first time reactions of chloroacetic acid
with S-pyrrolylisothiuronium iodides generated in situ
from unsubstituted pyrrole and 1-methyl-1H-pyrrole,
thiourea, and iodine at a ratio of 1:2:1. The reactions
were carried out both with addition of hydrazine hy-
drate and without it. We found that addition of hydra-
zine hydrate (0.2 equiv with respect to initial hetarene)
at the stage of reaction of isothiuronium salts with
halocarboxylic acids ensures improved yield and purity
of the final products, presumably as a result of elimina-
With the goal of developing a synthetic route to
pyrrolylsulfanylalkanoic acids as promising biological-
ly active substances and intermediate products, we
continued our studies on reactions of pyrroles with
iodine and thiourea and of the isothiuronium iodides
thus obtained with halogen-substituted carboxylic
acids. It is known that ethyl 2,4-dimethyl-1H-pyrrole-
3-carboxylate reacts with an equivalent amount of
thiourea, imidazolidine-2-thione, and imidazole-2-thiol
in the presence of 1 equiv of bromine or potassium
triiodide to give the corresponding isothiuronium salts
in more than 75% yield; no sulfanyl-substituted pyr-
role was isolated upon alkaline decomposition of these
salts [4]. Two mechanisms were proposed for the
formation of S-pyrrolylisothiuronium salts. The first of
1517

RUDYAKOVA et al.
1518
Scheme 1.
NH2
·
S
S
S
NH2
· 2I– or
+ 2HI
+
I2 + KI
H2N
S
H2N
NH2
H2N
NH
NH2
A
B
NH
R
S
N
S
H
· HI +
+ HI + KI
NH2
H2N
NH2
R
N
H
tion of side oxidation of thiols and isothiuronium salts.
However, the yield of the corresponding (1H-pyrrol-2-
yl)sulfanylacetic acids (which were identified by the
IR and H NMR spectra) did not exceed 5–20%, and
we failed to separate them from unidentified impurities
by column chromatography.
thesized according to the procedure described previ-
ously for the synthesis of 1-methyl-1H-indole [8], i.e.,
by alkylation of pyrrole with benzyl chloride and
arylation with 4-fluoronitrobenzene in DMSO in the
presence of alkali. Unlike the original procedure, we
used considerably lower amounts of the solvent (by
a factor of 2 to 3) and alkali (by a factor of 1.5).
1,1′-(Hexane-1,6-diyl)bis(1H-pyrrole) (Ic) and
1,1′-[1,4-phenylenebis(methylene)]bis(1H-pyrrole)
(Id) were obtained under analogous conditions from
pyrrole and 1,6-dichlorohexane or 1,4-bis(chloro-
methyl)benzene, respectively. The yields of N-substi-
tuted pyrroles Ia–Id were 85–95% (Scheme 2).
1
We examined the effect of the reactant ratio and
order of their mixing on the yield of S-indolyliso-
thiuronium iodide and found that the use of 2 equiv of
thiourea rules out intermediate formation of sulfenyl
halide NH2C(=NH)SCl or 3-iodoindole. Our results
allowed us to propose two possible paths for the
formation of S-indolylisothiuronium salt: (1) through
intermediate of dithiobis(formimidamide) dihydro-
iodide A and its reaction in statu nascendi with indole
(it should be emphasized that preliminarily isolated
disulfide A is inactive as electrophile toward indole);
(2) via formation of radical species B and radical sub-
stitution of hydrogen in the indole ring (Scheme 1). At
the optimal reactant ratio, the entire amount of iodine
is consumed for the oxidation of thiourea.
Pyrroles Ia–Id were brought into reactions with
thiourea, potassium triiodide, and haloalkanoic acids
under the conditions reported in [7]. The reactions
were carried out in lower alcohols (methanol, ethanol,
or propan-2-ol), the ratio pyrrole–thiourea–iodine–po-
tassium iodide–haloalkanoic acid being 1:2:1:1:1.2.
From 1-benzyl-1H-pyrrole (Ia) and chloroacetic and
2-chloropropionic acids we obtained, respectively,
(1-benzyl-1H-pyrrol-2-ylsulfanyl)acetic and 2-(1-ben-
zyl-1H-pyrrol-2-ylsulfanyl)propionic acids II and III
in 59–68% yield (Scheme 3). 2-(1-Benzyl-1H-pyrrol-
2-ylsulfanyl)butanoic acid (IV) and 2-(1-benzyl-1H-
pyrrol-2-ylsulfanyl)propionic acid (III) were also
formed with a fairly good yield, but they were con-
taminated with unidentified impurities which we failed
to separate by recrystallization or chromatography.
The present work continues our studies on reactions
of 1-substituted pyrroles with iodine, thiourea, and
halocarboxylic acids. Initial pyrroles Ia–Id were syn-
Scheme 2.
Hlg–Y
N
Y
Thus, the presence of a benzyl group on the pyrrole
nitrogen atom ensures chemoselective reactions of
compound Ia with thiourea and iodine at a ratio of
1:2:1 and subsequent reactions with halocarboxylic
acids to obtain α-(1-benzyl-1H-pyrrol-2-ylsulfanyl)-
substituted acetic and propionic acids II and III.
Presumably, the benzyl group on the pyrrole nitrogen
atom stabilizes both transition states and intermediate
Ia, Ib
N
H
Z
1/2ZHlg2
N
N
Ic, Id
Hlg = Cl, Y = PhCH2 (a); Hlg = F, Y = 4-O2NC6H4 (b);
Hlg = Cl, Z = (CH2)6 (c), p-CH2C6H4CH2 (d).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

SYNTHESIS OF α-(1H-PYRROL-2-YLSULFANYL)ALKANOIC ACIDS
1519
Scheme 3.
HN
(1) Hlg–X–COOH, NaOH
S
(2) HCl
X
NH2
· HI
COOH
+
2
+
KI3
S
S
–NH2C(S)NH2
N
N
N
H2N
NH2
CH2Ph
CH2Ph
CH2Ph
Ia
II–V
II, X = CH2; III, X = CH(Me); IV, X = CH(Et); V, X = CH2CH2; Hlg = Cl, Br.
Scheme 4.
HN
NH
NH2 H2N
S
S
S
N
X
N
+
4
+
KI3
· 2HI
N
X
N
H2N
NH2
HO
Ic, Id
(1) ClCH2COOH, NaOH
(2) HCl
S
S
OH
O
O
N
X
N
–NH2C(S)NH2
VI, VII
VI, X = (CH2)4; VII, X = p-C6H4.
2-(1-benzyl-1H-pyrrol-2-ylsulfanyl)butanoic acid (IV)
isothiuronium salts, and the process is also favored by
high reactivity of halogen atom in the α-position of
acetic and propionic acids. Lower selectivity in the
reactions with 2-bromobutanoic and 3-bromopropionic
acids is likely to be related to steric hindrances in the
first case and weak electrophilicity of the β-carbon
atom in the latter.
showed a complex pattern in the 1H NMR spectrum.
Thus we were the first to obtain a series of 1H-pyr-
rol-2-ylsulfanyl-substituted alkanoic acids by reactions
of 1-substituted pyrroles with iodine, thiourea, and
chloroacetic and 2-chloropropionic acids. These com-
pounds attract interest as potential biologically active
substances and intermediate products for their pre-
paration.
Electron-withdrawing substituents on the pyrrole
nitrogen atom reduce nucleophilicity of the pyrrole
ring, thus preventing formation of isothiuronium salts.
1-(4-Nitrophenyl)-1H-pyrrole (Ib) failed to react with
thiourea and potassium triiodide even on prolonged
heating (3 h at 68–70°C) and was recovered from the
reaction mixture (75%) together with a small amount
of tars. Using bridged bis-pyrroles Ic and Id as initial
compounds we obtained 59–73% of bis-pyrrolylsul-
fanylacetic acids VI and VII, respectively (Scheme 4).
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrometer from samples prepared as KBr pellets or
1
thin films. The H NMR spectra were measured on
a Bruker DPX-400 spectrometer (400.13 MHz); the
1H–1H coupling constants were determined with
an accuracy of ±0.1 Hz.
The IR spectra of acids II–VII contained absorp-
tion bands belonging to vibrations of the carboxy
groups, pyrrole rings, and alkyl groups. Pyrrolylsul-
fanylacetic acids II, VI, and VII displayed in the
1H NMR spectra signals from protons in positions 3–5
of the pyrrole ring, OH group, and SCH2 fragment
with an intensity ratio corresponding to the assumed
structures. In the 1H NMR spectrum of acid III signals
from protons in the CH3CH and OH groups were
present. Molecule III possesses a chiral center; there-
fore, double sets of signals from the SCH2 protons and
protons in the pyrrole ring are observed. Likewise,
General procedure for N-alkylation of pyrrole.
Pyrrole, 6.70 g (0.1 mol), was added to a solution of
12 g (0.3 mol) of sodium hydroxide in 50 ml of
DMSO, the mixture was stirred for 20–30 min and
cooled to 10–15°C, and the corresponding halogen
derivative [0.05 mol of 1,6-dichlorohexane, 0.05 mol
of 1,4-bis(chloromethyl)benzene, or 0.1 mol of benzyl
chloride or 4-fluoronitrobenzene] was slowly added.
The mixture was stirred for 3 h at 20–22°C and poured
into 200 ml of ice water, and the precipitate was
filtered off, washed with water, and dried (liquid prod-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

RUDYAKOVA et al.
1520
ucts were extracted into diethyl ether, the extract was
dried and evaporated, and the residue was distilled
under reduced pressure).
of the corresponding haloalkanoic acid in 5 ml of
water were slowly added, and the mixture was heated
for 2 h on a boiling water bath. When the reaction was
complete, the alcohol was evaporated, the precipitate
was dissolved in water on heating to 50°C, the solution
was treated with activated charcoal (0.5–1 h) and fil-
tered, the filtrate was acidified with 10% hydrochloric
acid until complete precipitation (pH 1–2), the mixture
was kept for at least 12 h at 5°C, and the precipitate
was filtered off or separated by decanting, purified by
reprecipitation from 5% alkali, and dried in a vacuum
desiccator over P2O5.
1-Benzyl-1H-pyrrole (Ia). Yield 13.4 g (85%),
bp 134–135°C (15 mm); published data [9]: bp 245–
1
247°C, 137–139°C (27 mm). H NMR spectrum
(DMSO-d6), δ, ppm: 5.22 s (2H, CH2), 6.42 br.s (2H,
3-H, 4-H), 6.87 br.s (2H, 2-H, 5-H), 7.31 d and 7.49 m
(5H, C6H5).
1-(4-Nitrophenyl)-1H-pyrrole (Ib). Yield 15.0 g
(80%) (from 6.70 g of pyrrole and 14.11 g of 4-fluoro-
nitrobenzene), mp 186–187°C; published data [10]:
mp 181°C. IR spectrum, ν, cm–1: 3140, 3075 (=CH);
(1-Benzyl-1H-pyrrol-2-ylsulfanyl)acetic acid (II)
was obtained using 15.72 g (0.1 mol) of 1-benzyl-1H-
pyrrole (Ia), 15.22 g (0.2 mol) of thiourea, 25.38 g
(0.1 mol) of iodine, 16.60 g (0.1 mol) of potassium
iodide, 5.00 g (0.1 mol) of hydrazine hydrate, 20.00 g
(0.5 mol) of NaOH, and 11.40 g (0.12 mol) of chloro-
acetic acid. Yield 16.83 g (68%), mp 88–92°C. IR
spectrum, ν, cm–1: 3100, 3050, 3010 (=CH); 2980,
2900 (C–H); 1700 (C=O); 1500 (C=C). 1H NMR spec-
trum (CDCl3), δ, ppm: 3.05 s (2H, SCH2), 5.24 s (2H,
NCH2), 6.15 t (1H, 4-H, J = 3.1 Hz), 6.50 m (1H, 3-H,
J = 1.7 Hz), 6.80 d (1H, 5-H, J = 1.7 Hz), 7.04 m and
7.25 m (5H, Harom), 11.11 s (1H, OH). Found, %:
C 63.25; H 5.32; N 5.62; S 13.00. C13H13NO2S. Cal-
culated, %: C 63.14; H 5.30; N 5.66; S 12.96.
1
1600, 1595 (C=C); 1500, 1330 (NO2). H NMR spec-
trum (DMSO-d6), δ, ppm: 6.32 br.s (2H, 3-H, 4-H),
7.52 br.s (2H, 2-H, 5-H), 7.80 d and 8.22 d (4H, C6H4,
AA′BB′ system, J = 8.8 Hz). 13C NMR spectrum, δC,
ppm: 112.20, 119.21, 119.47, 125.39, 144.25, 144.76.
Found, %: C 63.27; H 4.23; N 14.81. C10H8N2O2. Cal-
culated, %: C 63.83; H 4.28; N 14.89.
1,1′-(Hexane-1,6-diyl)bis(1H-pyrrole) (Ic). Yield
6.47 g (60%) (from 6.70 g of pyrrole and 7.75 g of
1,6-dichlorohexane), bp 102–105°C (3 mm). IR spec-
trum, ν, cm–1: 3145, 3075 (=CH), 1600, 1595 (C=C).
1H NMR spectrum (CDCl3), δ, ppm: 1.20 m (4H,
CH2), 1.65 m (4H, CH2), 3.73 t (4H, CH2), 6.07 br.s
(4H, 3-H, 4-H), 6.54 s (4H, 2-H, 5-H). Found, %:
C 77.20; H 9.30; N 12.92. C14H20N2. Calculated, %:
C 77.73; H 9.32; N 12.95.
2-(1-Benzyl-1H-pyrrol-2-ylsulfanyl)propionic
acid (III) was obtained using 15.72 g (0.1 mol) of
1-benzy-1H-pyrrole (Ia), 15.22 g (0.2 mol) of thiourea,
25.38 g (0.1 mol) of iodine, 16.60 g (0.1 mol) of potas-
sium iodide, 5.00 g (0.1 mol) of hydrazine hydrate,
20.00 g (0.5 mol) of sodium hydroxide, and 13.02 g
(0.12 mol) of 2-chloropropionic acid. Yield 17.23 g
(66%), tarry substance. IR spectrum, ν, cm–1: 3010
(=CH); 2920, 2980 (C–H); 1700 (C=O); 1440, 1500,
1,1′-[1,4-Phenylenebis(methylene)]bis(1H-pyr-
role) (Id). Yield 8.12 g (69%) [from 6.70 g of pyrrole
and 8.75 g of 1,4-bis(chloromethyl)benzene], mp 118–
120°C; published data [11]: mp 117–118°C. IR spec-
trum, ν, cm–1: 3110, 3090, 3050 (=CH); 2920 (CH);
1
1500 (C=C). H NMR spectrum (CDCl3), δ, ppm:
1
5.08 s (4H, CH2), 6.23 s (4H, 3-H, 4-H), 6.57 s (4H,
2-H, 5-H), 6.97 s (4H, Harom). Found, %: C 81.75;
H 6.92; N 11.86. C16H16N2. Calculated, %: C 81.32;
H 6.82; N 11.85.
1600 (C=C). H NMR spectrum (CDCl3), δ, ppm:
1.34 d (3H, CH3, J = 7.1 Hz), 3.27 q (1H, SCH, J =
7.1 Hz), 5.25 d.d (2H, NCH2, J = 5.4 Hz), 6.15 m (1H,
4-H, J = 3.7, 2.9, 1.0 Hz), 6.50 m (1H, 3-H), 6.80 m
(1H, 5-H), 7.31 m and 7.08 m (5H, Harom), 10.70 s (1H,
OH). Found, %: C 64.30; H 5.81; N 5.34; S 12.28.
C14H15NO2S. Calculated, %: C 64.34; H 5.79; N 5.36;
S 12.27.
General procedure for the synthesis of (1H-pyr-
rol-2-ylsulfanyl)alkanoic acids. Substituted pyrrole
Ia, Ic, or Id, 0.1 mol, and thiourea, 15.20 g (0.2 mol),
were dissolved in 30 ml of alcohol, and a solution of
25.38 g (0.1 mol) of iodine and 16.60 g (0.1 mol) of
potassium iodide in 50 ml of 50% alcohol was added
in portions under argon at such a rate that the tempera-
ture did not exceed 40°C. The mixture was kept for 3 h
at 30–40°C, 5.00 g (0.1 mol) of hydrazine hydrate was
added, a solution of 20.00 g (0.5 mol) of sodium
hydroxide in 30 ml of water and a solution of 0.12 mol
2-(1-Benzyl-1H-pyrrol-2-ylsulfanyl)butanoic
acid (IV) was obtained using 15.72 g (0.1 mol) of
1-benzyl-1H-pyrrole (Ia), 15.22 g (0.2 mol) of thio-
urea, 25.38 g (0.1 mol) of iodine, 16.60 g (0.1 mol) of
potassium iodide, 5.00 g (0.1 mol) of hydrazine hy-
drate, 20.00 g (0.5 mol) of sodium hydroxide, and
20.04 g (0.12 mol) of 2-bromobutanoic acid. We
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

SYNTHESIS OF α-(1H-PYRROL-2-YLSULFANYL)ALKANOIC ACIDS
1521
isolated 16.80 g of a tarry material containing 70% of
compound IV (yield 43%). IR spectrum, ν, cm–1: 3100
(=CH); 2920, 2980 (C–H); 1700 (C=O); 1500 (C=C).
1H NMR spectrum (CDCl3), δ, ppm: 0.91 t (3H, CH3),
1.63 m and 1.75 m (2H, CH2), 2.99 m (1H, SCH),
5.21 d.d (2H, NCH2), 6.15 d (1H, 3-H), 6.50 m (1H,
4-H), 6.80 br.s (1H, 5-H), 7.31 m and 7.08 m (5H,
Harom), 9.4 br.s (1H, OH). Found, %: C 64.30; H 5.81;
N 5.34; S 12.28. C14H15NO2S. Calculated, %: C 64.34;
H 5.79; N 5.36; S 12.27.
(71%), mp 80–84°C. IR spectrum, ν, cm–1: 3100
(=C–H); 2950, 2900 (C–H); 1700 (C=O); 1490 (C=C).
1H NMR spectrum (CDCl3), δ, ppm: 3.21 s (4H,
SCH2), 5.23 s (4H, NCH2), 6.08 t (2H, 4-H), 6.35 br.s
(2H, 3-H), 7.01 br.s (2H, 5-H), 7.03 s (4H, Harom),
10.80 s (2H, OH). Found, %: C 57.68; H 4.86; N 6.77;
S 15.42. C20H20N2O4S2. Calculated, %: C 57.67;
H 4.84; N 6.73; S 15.39.
REFERENCES
3-(1-Benzyl-1H-pyrrol-2-ylsulfanyl)propionic
acid (V) was obtained using 15.72 g (0.1 mol) of
1-benzyl-1H-pyrrole (Ia), 15.22 g (0.2 mol) of thio-
urea, 25.38 g (0.1 mol) of iodine, 16.60 g (0.1 mol) of
potassium iodide, 5.00 g (0.1 mol) of hydrazine
hydrate, 20.00 g (0.5 mol) of sodium hydroxide, and
18.36 g (0.12 mol) of 3-bromopropionic acid. We
isolated 15.40 g (59%) of a tarry material containing
70% of compound V (yield 41%). IR spectrum, ν,
cm–1: 3100 (=CH); 2980, 2940 (C–H); 1700 (C=O);
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1
1500 (C=C). H NMR spectrum (CDCl3), δ, ppm:
2.19 t (2H, CH2), 3.27 q (1H, SCH), 5.20 s (2H,
NCH2), 6.14 t (1H, 3-H), 6.53 m (1H, 4-H), 6.89 br.s
(1H, 5-H), 7.10 m and 7.30 m (5H, Harom), 11.35 s (1H,
OH). Found, %: C 64.30; H 5.81; N 5.34; S 12.28.
C14H15NO2S. Calculated, %: C 64.34; H 5.79; N 5.36;
S 12.27.
2,2′-[Hexane-1,6-diylbis(1H-pyrrole-1,2-diyl)]di-
acetic acid (VI) was obtained using 10.81 g (0.05 mol)
of 1,1′-(hexane-1,6-diyl)bis(1H-pyrrole) (Ic), 15.22 g
(0.2 mol) of thiourea, 25.38 g (0.1 mol) of iodine,
16.60 g (0.1 mol) of potassium iodide, 5.00 g (0.1 mol)
of hydrazine hydrate, 20.00 g (0.5 mol) of sodium
hydroxide, and 11.40 g (0.12 mol) of chloroacetic acid.
Yield 14.46 g (73%), decomposes above 180°C. IR
spectrum, ν, cm–1: 2900, 2950 (C–H); 1700 (C=O);
4. Harris, R.L.N., Tetrahedron Lett., 1968, vol. 9, p. 4045.
5. Woodbridge, R.G. and Dougherty, G., J. Am. Chem.
Soc., 1950, vol. 72, p. 4320.
1
6. Harris, R.L.N., Tetrahedron Lett., 1969, vol. 10,
1410, 1490 (C=C). H NMR spectrum (CDCl3), δ,
p. 4465.
ppm: 1.34 br.s (4H, CH2), 1.75 br.s (4H, CH2), 3.35 s
(4H, SCH2), 4.04 t (4H, NCH2), 6.15 br.s (2H, 4-H),
6.47 br.s (2H, 3-H), 6.82 br.s (2H, 5-H), 10.97 s (2H,
OH). Found, %: C 54.47; H 6.07; N 7.09; S 16.19.
C18H24N2O4S2. Calculated, %: C 54.52; H 6.10;
N 7.06; S 16.17.
7. Levkovskaya, G.G., Rudyakova, E.V., and Mirsko-
va, A.N., Russ. J. Org. Chem., 2002, vol. 38, p. 1641.
8. Pozharskii, A.F., Anisimova, V.A., and Tsupak, E.B.,
Prakticheskie raboty po khimii geterotsiklov (Labora-
tory Works on the Chemistry of Heterocycles), Rostov-
on-Don: Rostov. Gos. Univ., 1988, p. 22.
2,2′-[1,4-Phenylenebis(methylene-1H-pyrrole-
1,2-diyl)]diacetic acid (VII) was obtained using
11.81 g (0.05 mol) of 1,1′-[1,4-phenylenebis(methyl-
ene)]bis(1H-pyrrole) (Id), 15.22 g (0.2 mol) of thio-
urea, 25.38 g (0.1 mol) of iodine, 16.60 g (0.1 mol) of
potassium iodide, 5.00 g (0.1 mol) of hydrazine
hydrate, 20.00 g (0.5 mol) of sodium hydroxide, and
11.40 g (0.12 mol) of chloroacetic acid. Yield 14.80 g
9. Beilsteins Handbuch der organischen Chemie, vol. H20,
p. 164.
10. Dhont, J. and Wibaut, J.P., Recl. Trav. Chim. Pays–Bas,
1943, vol. 62, p. 177; Chem. Abstr., 1944, vol. 38,
p. 2336.
11. Norman, D.S. and Sanborn, N.Y., US Patent
no. 2488336, 1949; Chem. Abstr., 1950, vol. 44,
p. 1544e.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008