Synthesis of (3-indolylsulfanyl)alkanecarboxylic acids

Article abstract of DOI:10.1023/A:1022566202511

A method was developed for preparation of (3-indolylsulfanyl)alkanecarboxylic acids from 1H-, 1-methyl(benzyl)-, 2-methylindoles, thiourea, iodine, and halocarboxylic acids.

Full text of DOI:10.1023/A:1022566202511

Russian Journal of Organic Chemistry, Vol. 38, No. 11, 2002, pp. 1641 1646. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 11, 2002,
pp. 1697 1703.
Original Russian Text Copyright
2002 by Levkovskaya, Rudyakova, Mirskova.
Synthesis of (3-Indolylsulfanyl)alkanecarboxylic Acids
G. G. Levkovskaya, E. V. Rudyakova, and A. N. Mirskova
Faworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, 664033 Russia
Received June 27, 2001
Abstract A method was developed for preparation of (3-indolylsulfanyl)alkanecarboxylic acids from 1H-,
1-methyl(benzyl)-, 2-methylindoles, thiourea, iodine, and halocarboxylic acids.
(3-Indolylsulfanyl)alkanecarboxylic acids attract
interest as biologically active substances [1], semi-
products in pharmaceutical syntheses [2 4], and as
technically valuable products [5]. In extension of our
systematic studies aimed at preparation of biologically
active substances based on organylsulfanylalkane-
carboxylic acids [6], in particular, indolylsulfanyl-
acetic acid [7], we developed a preparative synthesis
of 1H-, 1- and 2-methyl(benzyl)-substituted (3-indol-
ylsulfanyl)alkanecarboxylic acids.
However the acids I VI were isolated in yields no
more than 40 50% (Table 1). Note that indolethiol is
very unstable and is easily oxidized with air oxygen
to di(3-indolyl) disulfide. Therefore the (3-indolyl-
sulfanyl)alkanecarboxylic acids obtained by condens-
ation of indolethiol with halocarboxylic acids contain-
ed this disulfide as impurity. The additional purific-
ation both of indolethiol under inert atmosphere and
of target products reduced the yield of the latter and
provided complications for the process as a whole.
Previously some representatives of this class com-
pounds were obtained by a traditional method utiliz-
ing reaction of indolethiols with halocarboxylic acids
or derivatives thereof [1 3]. Therewith this method
became widespread after development of 3-indolethiol
preparation from equimolar amounts of indole,
thiourea, and iodine [2]. But this method was unsuit-
able for preparative synthesis of 2-methylindole-3-
thiol for in the course of reaction between 2-methyl-
indole, thiourea, iodine, and potassium iodide formed
a complex mixture of products [8].
Aiming at developing a preparative procedure for
(3-indolylsulfanyl)alkanecarboxylic acids we studied a
reaction of monohalocarboxylic acids with S-(3-
indolyl)isothiuronium iodide [9, 10] used instead of
indolethiol. In a saturated alcoholic solution of alkali
this reaction afforded acids I VI. It should be men-
tioned however that here the yield of acids I VI also
was unstable and did not exceed 50%, and the pro-
ducts obtained also required additional purification.
To improve the yield and purity of the target pro-
ducts I VI we investigated how these parameter were
affected by the ratio of the initial reagents and by the
order of their introducing into the reaction.
By heating under inert atmosphere 3-indolethiol
obtained by the known method [2] with equimolar
amounts of bromo- or chloroalkanecarboxylic acids
in the presence of alcoholic alkalis we also prepared a
series of acids, both known and previously not de-
scribed, (I VI) (Tables 1, 2).
It was established that S-(3-indolyl)isothiuronium
iodide could be obtained only at simultaneous bring-
ing into reaction of thiourea and indole, and the stable
yield of the product is attainted at the reagents ratio
indole thiourea iodine of 1: 2: 1. This fact disagrees
with the previously assumed formation mechanism of
S-(3-indolyl)- and S-(2-pyrrolyl)isothiuronium salts
[9, 10]. According to this mechanism first thiourea is
oxidized by halogen to disulfide that again reacts with
halogen furnishing the corresponding sulfenyl halide.
The latter effects an electrophilic substitution of a
hydrogen atom in the heterocycle to form isothiuron-
ium salt. Basing on this scheme Harris [9, 10] recom-
mended to use the reagents in equimolar amounts.
The reaction between indoles, thiourea, and iodine
was formerly studied at the reagents ratio 1: 2: 1
respectively. In this case with 95% yield were isolated
Hlg = Cl, Br; n = 1, R = H, R = H (I), CH3 (II),
C2H5 (III), R = R = CH3 (IV); n = 2, R = R = H
(V), n= 3, R = R = H (VI).
1070-4280/02/3811-1641$27.00 2002 MAIK Nauka/Interperiodica

1642
LEVKOVSKAYA et al.
Table 1. Yields, melting points, and elemental analyses of 3-indolylsulfanylalkanecarboxylic acids (I IX)
Found, %
Calcd., %
Compd. Yield,
mp,
oC
Formula
a
no.
%
C
H
N
S
C
H
N
S
I
II
III
IV
V
VI
VII 89
VIII 84
84 (50) 110 [2]
62 (50) 95 98
69 (40) 78 80
62 (50) 101 103
53 (50) 130 132 [3]
60 (50) 65 68
57.54 4.47 6.72
59.74 4.79 6.53
61.97 5.38 5.90
60.74 7.79 5.53
59.81 4.88 6.23
61.44 5.38 5.83
59.84 4.87 6.46
68.71 5.06 4.74
59.70 5.03 6.41
15.38
14.32
13.30
13.22
14.52
13.51
14.41
10.71
14.53
C10H9NO2S
C11H11NO2S
C12H13NO2S
C12H13NO2S
C11H11NO2S
C12H13NO2S
C11H11NO2S
C17H15NO2S
C11H11NO2S
57.96 4.38
59.73 4.98
61.25 5.57
61.25 5.57
59.73 4.98
61.25 5.57
59.73 4.98
68.67 5.09
59.73 4.98
6.76 15.47
6.33 14.48
5.95 13.62
5.95 13.62
6.33 14.48
5.95 13.62
6.33 14.48
4.71 10.76
6.33 14.48
98 100
103 106
150 155
IX
69
a
Yields obtained by method a is given in parentheses.
Table 2. IR and 1H NMR spectra of 3-indolylsulfanylalkanecarboxylic acids (I IX)
1
IR spectra, , cm
Alk COOH
1H NMR spectra, , ppm (J, Hz)
CH2 CH3 SCH2 (SCH) NH (COOH)
Compd.
no.
NH
C=C
Het
I
II
3350 2900 1690
3420 2920, 1680
2960
3360 2900, 1680
2940
1500, 1540, 1600 7.18 m, 7.48 m, 7.57 s
1440, 1485, 1600 6.90 m, 7.28 m, 7.42 s
3.41 s
1.05 d (3.27 q)
(6.6)
11.44a
11.39a
III
IV
1550, 1590
7.18 m, 7.53 m, 7.69 s 1.70 m 0.96 t (3.29)
(7.1)
11.35a
11.52a
3410 2890, 1670
2920
1450, 1485, 1600 7.12 m, 7.42 d,
7.46 s, 7.63 d
1.42 s
1.36 s
2970
V
3350 2920, 1660
1440, 1485
1485, 1600
1500
7.11 m, 7.44 d (7.8), 2.44 t
7.52 d (2.5), 7.64 d (7.1)
2.82 t
2.69 t
11.39
(12.23)
VI
3350 2890, 1670
2910
7.10 m, 7.34 d,
7.55 s, 7.65 d
6.69 d (7.6), 7.11 t,
7.19 t, 7.38 d, 7.39 s
7.15 m, 7.47 d
(7.6), 7.75 s
2.39 m
1.17 s
11.41a
VIIb
VIIIc
IX
2900, 1690
2980
2900, 1690
2940
3.77 3.39 t
3.43 s
a
a
1460, 1500
1630
5.43 m
3375 2900, 1700
2950
7.06 m, 7.27 d (7.8),
7.50 d
2.47 3.25 s
11.25
(12.20)
a
Proton signal of COOH group not observed due to fast exchange with protons of water present in the solvent.
1H NMR spectrum registered in acetone-d6.
Proton signals of C6H5, , ppm: 7.22 m, 7.29 m.
b
c
the corresponding bis(3-indolyl) disulfides. It was
sulfides. The route to isothiuronium salts presumed
in [11] was found to be wrong for it was demonstrat-
ed in [10] that iodopyrrol prepared by independent
procedure did not react with thiourea under similar
conditions.
presumed that the disulfides arose from a succession
of reactions: indole halogenation, conversion of
3-iodoindoles under the action of thiourea into iso-
thiuronium salts that provided thiols by decomposi-
tion in alkaline medium. Finally the thiols were
oxidized by iodine excess or oxygen yieldingthe di-
We established that carrying out the reaction
between indole, thiourea, and iodine taken in the ratio
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 11 2002

SYNTHESIS OF (3-INDOLYLSULFANYL)ALKANECARBOXYLIC ACIDS
1: 2: 1 respectively under inert atmosphere furnished
1643
not a disulfide but isothiuronium iodide in a quantit-
ative yield. Therewith the reaction time was shorter
and in the reaction mixture lacked excessive iodine
that could have decreased the yield of the target
product by oxidizing the heterocycle and the iso-
thiuronium salt.
The published data [9 11] and our own experi-
ments suggest two possible routes of indolyliso-
thiuronium salt formation. Firstly, it may be presum-
ed that arising disulfide cation (A) reacts with indole
in statu nascendi. It should be reminded that the
preliminary prepared disulfide (A) is incapable of
electrophilic substitution in the indole ring. Secondly,
the substitution in the indole ring may be effected by
the primarily formed thiyl radical (B).
Hlg = Cl, Br; n = 1, R = R = H, X = CH3, Y= H
(VII), X = C6H5CH2, Y = H (VIII), X = H, Y =
CH3 (IX).
We also established that addition of hydrazine
hydrate from 20 mol% with respect to indole up to
an equimolar amount at the stage of reaction between
isothiuronium salts and halocarboxylic acids increas-
ed the yield and purity of the target products ap-
parently due to suppression of the side oxidation
processes occurring with indolethiol and isothiuron-
ium salts.
The reactions were carried out in methanol,
ethanol, or 2-propanol. The purity of acids obtained
by the developed procedure without additional
purification was estimated by potentiometric titration
of their methanol solutions with a solution of sodium
methylate; the determined purity was 99%.
The acids I IX synthesized are crystalline com-
pounds with a specific odor, of cream color, well
soluble in alcohol, DMSO, insoluble in water, stable
at storage. The structure of compounds synthesized
1
was proved by IR and H NMR spectroscopy, the
composition was confirmed by elemental analysis and
potentiometric titration (Tables 1, 2).
Thus the lower yield of target products at the
equimolar reagents ratio is due to the mechanism of
indolylthiuronium salt formation involving successive
bringing into reaction of the original and recovered
thiourea.
IR spectra of acids I IX contain weak absorption
1
bands at 1400 1600 cm corresponding to vibrations
1
of the heterocycle, strong bands at 1670 1700 cm
of C=O vibrations. In the spectra of compounds
We demonstrated that the (3-indolyl)isothiuronium
iodides treated without preliminary isolation with
monohalocarboxylic acids in the presence of alkali
afforded in high and reproducible yields indolyl-
sulfanylalkanecarboxylic acids I X of high purity. It
was especially feasible that this process allowed
preparation both derivatives of 1-methyl(benzyl)indo-
lethiols and 2-methylindolethiol. This is obviously a
very attractive possibility taking into account that the
2-methylindole-3-thiol is excessively unstable and has
not been previously isolated [8].
I VI, IX appear the absorption bands of the NH
bonds vibrations at 3350 1420 cm .
1
1
In the H NMR spectra of acids I IX alongside
the proton signals from the indole moiety (6.90
7.69 ppm) appear singlets from NH protons (in com-
pounds I VI, IX), and the signals with the character-
istic splitting from the protons attached to carbon
chains (Table 2). For instance, in the 1H NMR
spectrum of acid II is present a doublet from the
protons of a methyl group and a quartet from the
methine proton. In the spectrum of compound III the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 11 2002

1644
LEVKOVSKAYA et al.
methyl group signal appears as a triplet, and the ethyl
group of this compound gives rise to a triplet of the
methyl group and a multiplet from the methylene
spectra of the compounds appear the signals of
protons from pyrrole rings, OH groups, and SCH2 of
the expected intensity. At the same time in the spectra
was observed unidentified singlet at 1.5 ppm.
1
group. The HNMR spectra of acids VI and VII
contain multiplets belonging to CH2 and CH3 groups.
Note that the H NMR spectrum of acid IV contains
two singlets from methyl groups evidencing that the
rotation is hindered in the fragment SC(CH3)2COOH
of the molecule.
Thus we developed preparative procedures for syn-
thesis of a number of (3-indolylsulfanyl)alkanecarb-
oxylic acids. It was shown that addition to the reac-
tion mixture of hydrazine hydrate in equimolar to
indole amount improved the yield and purity of the
final products apparently by excluding the side oxida-
tion processes involving indole, indolethiol, and
isothiuronium salts.
1
The signal from protons in the groups SCH2C(O)
and SCHRC(O) in the spectra of acids I III, VII IX
is shifted downfield by 0.4 0.7 ppm as compared
with that of the protons in the SCH2 group in the
spectra of acids V, VI.
EXPERIMENTAL
1
It should also be noted that in the H NMR spectra
IR spectra were recorded on spectrophotometer
Specord IR 75 from samples pelletized with KBr.
1H NMR spectra were recorded on spectrometers
Bruker DPX-400 (400 MHz) and Jeol FX-90 Q
(90 MHz) from solutions in DMSO-d6, internal
reference HMDS.
of compounds I III is present a signal from the
proton in the 2 position of the indole ring, and it is
sometimes split with a coupling constant of 2 Hz. In
1
the H NMR spectrum of compound IX this signal is
lacking; only signals from the benzene part of the
indole moiety are observed with the characteristic
splittings (Table 2), and also appear the proton
resonances from the alkyl part of the molecule.
The potentiometric titration was performed on
ionomer EA-74. Initial monohalocarboxylic acids
used in the study were purified by distillation.
Ethanol was dried with calcium oxide. Isothiuronium
disulfide diiodide (A) and 3-indolethiol were obtained
by published methods [2, 9. 10]. Initial 1-methyl and
1-benzylindoles were prepared by known procedures
[12, 13].
The procedure described in this paper was also
applied to preparation of (2-pyrrolylsulfanyl)acetic
acid. It was already mentioned in [10] that 3,5-di-
methyl-4-ethoxycarbonylpyrrole also afforded the
corresponding (2-pyrrolyl)isothiuronium salt when
reacted with thiourea and iodine.
(3-Indolylsulfanyl)acetic acid (I). (a) To a dis-
persion of 14.9 g of 3-indolethiol in 25 ml of
anhydrous ethanol at stirring was added under nitro-
gen or argon atmosphere a solution of 13 g of KOH
in 100 ml of ethanol and a solution of 11.3 g (20%
excess) of monochloroacetic acid in 50 ml of ethanol.
The reaction mixture was boiled on a water bath
while stirring under inert atmosphere for 3 h, then
it was cooled, the alcohol was distilled off. The
separated precipitate was dissolved in 150 ml of
water, the solution was acidified with HCl till pH 2 4
and maintained at 5 C for 12 h for total precipitation
of the product. Then the precipitate was filtered off
and dried. We obtained 10.3 g (50%) of acid I.
The reaction of 1H- and 1-methylpyrrole with
thiourea and iodine at the respective reagents ratio
1: 2: 1 under conditions we developed followed by
treatment with monochloroacetic acid in the presence
or absence of hydrazine hydrate furnished (2-pyr-
rolylsulfanyl)acetic acids that however contained
1
unidentified impurity as shown by IR and H NMR
spectra.
(b) To a solution of 11.7 g (0.1 mol) of indole and
7.6 g (0.1 mol) of thiourea in 200 ml of methanol at
stirring and bubbling nitrogen or argon was added by
portions a solution of 25 g (0.1 mol) of iodine and
17 g (0.1 mol) of KI in 50 ml of water maintaining
the temperature of the reaction mixture below 40 C.
Then 20% solution of NaOH was added to pH 9 and
a solution of 11.28 g (0.12 mol) of monochloroacetic
acid. The pH of the reaction mixture was maintained
X = CH3 (X), H (XI).
In the IR spectra of acids X, XI are present the
absorption bands corresponding to vibrations of C=O
bonds, pyrrole ring, and alkyl groups. In the 1HNMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 11 2002

SYNTHESIS OF (3-INDOLYLSULFANYL)ALKANECARBOXYLIC ACIDS
1645
no lower than 9 by adding 20% solution of NaOH.
The reaction mixture was heated to boiling for 2 4 h.
Then the alcohol was distilled off, the residue was
dissolved in water at heating, activated carbon was
added, and the mixture was left standing for 0.5 1 h.
The solution was filtered and acidified with HCl to
pH 2 4 and then was kept at 20 25 C no less than
12 h to wait for complete precipitation and crystalliz-
ation of the product. The precipitated acid was filter-
ed off and dried. We obtained 10.4 g (51%) of acid I.
3-(3-Indolylsulfanyl)propanoic acid (V). (a) Ac-
cording to procedure (a) described for acid I from
14.9 g of 3-indolethiol and 18.3 g (0.12 mol) of
3-bromopropanoic acid was obtained 11.05 g of acid
V. (b) According to procedure (c) used for acid I
from 11.7 g (0.1 mol) of indole, 15.2 g (0.2 mol) of
thiourea, 25 g (0.1 mol) of iodine, 17 g (0.1 mol) of
potassium iodide, and 18.3 g (0.12 mol) of 3-bromo-
propanoic acid was obtained 11.71 g of acid V.
4-(3-Indolylsulfanyl)butanoic acid (VI). (a)
According to procedure (a) described for acid I from
14.9 g of 3-indolethiol and 16.7 g (0.12 mol of
4-chlorobutanoic acid or 20.04 g (0.12 mol) of
4-bromobutanoic acid was obtained 12.23 g of acid
VI. (b) According to procedure (c) used for acid I
from 11.7 g (0.1 mol) of indole, 15.2 g (0.2 mol) of
thiourea, 25 g (0.1 mol) of iodine, 17 g (0.1 mol) of
potassium iodide, and 20.04 g (0.12 mol) of 4-bromo-
butanoic acid was obtained 14.12 g of acid VI.
(c) To a solution of 11.7 g (0.1 mol) of indole and
15.2 g (0.2 mol) of thiourea in 200 ml of methanol at
stirring and bubbling nitrogen or argon was added by
portions a solution of 25 g (0.1 mol) of iodine and
17 g (0.1 mol) of KI in 50 ml of water maintaining
the temperature of the reaction mixture below 40 C.
Then 20% solution of NaOH was added to pH 9 and
a solution of 11.3 g (0.12 mol) of monochloroacetic
acid. The further procedure was the same as describ-
ed under (b). We obtained 17.41 g (84%) of com-
pound I of 99.1% purity as estimated by potentio-
metric titration of the acid methanol solution with
sodium methylate.
(1-Methylindol-3-ylsulfanyl)acetic acid (VII) was
prepared in the same way as compound IX from
13.1 g (0.1 mol) of 1-methylindole, 15.2 g (0.2 mol)
of thiourea, 25 g (0.1 mol) of iodine, 17 g (0.1 mol)
of potassium iodide, and 11.34 g (0.12 mol) of mono-
chloroacetic acid. Yield of acid VII 19.7 g.
2-(3-Indolylsulfanyl)propanoic acid (II). (a) Ac-
cording to procedure (a) described for acid I from
1.49 g of 3-indolethiol and 1.30 g (0.012 mol) of
2-chloropropanoic acid or 1.83 g (0.012 mol) of
2-bromopropanoic acid was obtained 1.11 g of acid II.
(b) According to procedure (c) used for acid I from
11.7 g (0.1 mol) of indole, 15.2 g (0.2 mol) of
thiourea, 25 g (0.1 mol) of iodine, 17 g (0.1 mol) of
potassium iodide, and 18.3 g (0.12 mol) of 2-bromo-
propanoic acid was obtained 13.77 g of acid II.
(1-Benzylindol-3-ylsulfanyl)acetic acid (VIII)
was prepared in the same way as compound IX from
20.7 g (0.1 mol) of 1-benzylindole, 15.2 g (0.2 mol)
of thiourea, 25 g (0.1 mol) of iodine, 17 g (0.1 mol)
of potassium iodide, and 11.34 g (0.12 mol) of
monochloroacetic acid. Yield of acid VIII 25 g.
(2-Methylindol-3-ylsulfanyl)acetic acid (IX). To
a solution of 3.93 g (0.03 mol) of 2-methylindole and
4.57 g (0.06 mol) of thiourea in 30 ml of methanol at
stirring under argon was added dropwise a solution
of 7.62 g (0.03 mol) of iodine and 4.98 g (0.03 mol)
of potassium iodide in 25 ml of water maintaining the
temperature of the reaction mixture below 30 C. The
reaction mixture was kept at 30 40 C for 3 h, then
was added dropwise 1.5 g (0.03 mol) of hydrazine
hydrate and then slowly was added a solution of 6 g
of sodium hydroxide in 30 ml of water and 2.97 g of
monochloroacetic acid in 5 ml of alcohol. The mix-
ture was heated on boiling water bath for 2 h, then
cooled, and the solvent was distilled off in a vacuum.
The separated precipitate was dissolved in 50 ml of
1% solution of NaOH, the solution was heated with
activated carbon to 60 C for 30 min, filtered, and
acidified with concn. HCl till it no more get turbid at
addition of the next portion of the acid. The mixture
was maintained at 5 C for 12 h. We obtained 4.5 g
of acid IX.
2-(3-Indolylsulfanyl)butanoic acid (III). (a) Ac-
cording to procedure (a) described for acid I from
1.49 g of 3-indolethiol and 2.0 g (0.012 mol) of
2-bromobutanoic acid was obtained 0.94 g of acid
III. (b) According to procedure (c) used for acid I
from 11.7 g (0.1 mol) of indole, 15.2 g (0.2 mol) of
thiourea, 25 g (0.1 mol) of iodine, 17 g (0.1 mol) of
potassium iodide, and 20.4 g (0.12 mol) of 2-bromo-
butanoic acid was obtained 16.23 g of acid III.
2-(3-Indolylsulfanyl)-2-methylpropanoic
acid
(IV). (a) According to procedure (a) described for
acid I from 14.9 g of 3-indolethiol and 20.4 g
(0.12 mol) of 2-bromo-2-methylpropanoic acid was
obtained 11.75 g of acid IV. (b) According to proce-
dure (c) used for acid I from 11.7 g (0.1 mol) of
indole, 15.2 g (0.2 mol) of thiourea, 25 g (0.1 mol)
of iodine, 17 g (0.1 mol) of potassium iodide, and
20.4 g (0.12 mol) of 2-bromo-2-methylpropanoic acid
was obtained 15.29 g of acid IV.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 11 2002

1646
LEVKOVSKAYA et al.
2. Bourdais, J. and Lorre, A., Eur. J. Med. Chem.-
(1-Methylpyrrol-2-ylsulfanyl)acetic acid (X) was
Chim. Ther., 1974, vol. 9, no. 3, pp. 269 273;
Chem. Abstr., 1975, vol. 82, 31199.
3. Harris, R.L.N. and Geissler, A.E., Austral. J. Plant.
Physiol., 1977, vol. 4, no. 2, p. 235; Chem. Abstr.,
1977, vol. 87, 79499.
prepared in the same way as compound IX from
4.05 g (0.05 mol) of 1-methylpyrrole, 7.6 g (0.1 mol)
of thiourea, 12.5 g (0.05 mol) of iodine, 8.5 g
(0.05 mol) of potassium iodide, and 5.7 g (0.06 mol)
of monochloroacetic acid. We obtained 6.35 g of acid
X with an impurity of unestablished structure, mp
4. US Patent 4059583, 1977; Ref. Zh. Khim., 1978,
14O 115P.
1
67 C. IR spectrum, , cm : 1700 (COOH), 1520
5. Levkovskaya, G.G., Mirskova, A.N., and Bel,ko-
va, O.N., Zh. Prikl. Khim., 1996, vol. 69, no. 12,
pp. 2034 2037.
(C=C). 1H NMR spectrum, , ppm: 3.02 s (3H,
NCH3), 3.25 s (2H, SCH2), 6.08 d (1H, pyrrole, J
3.4 Hz), 6.31 d (1H, pyrrole, J 3.4 Hz), 7.33 br
(1H, pyrrole) (in the spectrum is present a signal at
1.56 ppm corresponding to 3H). Found, %: C 48.50;
H 5.91; N 7.11; S 14.89. C7H9NO2S. Calculated, %:
C 49.11; H 5.30; N 8.18; S 18.73.
6. Levkovskaya, G.G., Mirskova, A.N., Kali-
khman, I.D., and Voronkov, M.G., Zh. Org. Khim.,
1984, vol. 20, no. 3, pp. 634 638; Nefedova, T.V.,
Kazimirovskaya, V.B., Levkovskaya, G.G., Bryuz-
gin, A.A., Guseva, S.A., Mirskova, A.N., and
Voronkov, M.G., Khim.-Farm. Zh., 1986, no. 3,
pp. 291 295; Nefedova, T.V., Kubatiev, A.L., Ka-
zimirovskaya, V.B., Chernyakhovskaya, B.I., Mir-
skova, A.N., Guseva, S.A., Levkovskaya, G.G., and
Voronkov, M.G., Khim.-Farm. Zh., 1988, no. 10,
pp. 1197 1203.
7. RF Patent 2086239, 1997; Byull. Izobr., 1997, no. 22;
RF Patent 2080861, 1997; Byull. Izobr., 1997, no. 16;
RF Patent 2108100, 1998; Byull. Izobr., 1998, no. 10,
p. 153.
8. Hino, T., Endo, M., and Nakagava, M., Chem.
Pharm. Bull., 1974, vol. 22, no. 11, p. 2728.
9. Harris, R.L.N., Tetrahedron Lett., 1969, no. 51,
pp. 4465 4467.
(2-Pyrrolylsulfanyl)acetic acid (XI) was prepared
in the same way as compound IX from 6.7 g (0.1mol)
of pyrrole, 15.2 g (0.2 mol) of thiourea, 25 g
(0.1 mol) of iodine, 17 g (0.1 mol) of potassium
iodide, and 11.5 g (0.12 mol) of monochloroacetic
acid. Yield of acid XI 2.85 g with an impurity of
unestablished structure, mp 140 142 C. IR spectrum,
1
, cm : 3350 (NH), 1690 (COOH), 1620, 1550
1
(C=C). HNMR, , ppm: 3.48br(2H, SCH2), 6.11 br
(2H, pyrrole), 6.75 br (1H, pyrrole), 10.64 br.s. (1H,
NH), 11.22 br.s (1H, OH) ((in the spectrum is present
a signal at 1.52 ppm corresponding to 3H) Found, %:
C 44.45; H 4.89; N 7.81; S 19.00. C6H7NO2S.
Calculated, %: C 45.85; H 4.49; N 8.91; S 20.40.
10. Harris, R.L.N., Tetrahedron Lett., 1968, no. 37,
pp. 4045 4047.
Similar results were obtained at addition in the
course of the process of hydrazine hydrate in amount
equimolar to pyrrole.
11. Woodbridge, R.G. and Dougherty, G., J. Am. Chem.
Soc., 1950, vol. 72, no. 9, pp. 4320 4321.
12. Suvorov, N.N., Smushkevich, Yu.I., Velezheva, V.S.,
Rozhkov, V.S., and Simakov, S.V., Khim. Getero-
tsikl. Soed., 1976, no. 2, pp. 191 193.
13. Pozharskii, A.F., Anisimova, V.A., and Tsupak, E.B.,
Prakticheskie raboty po khimii geterotsiklov
(Practicum on Chemistry of Heterocycles), Rostov:
PGU, 1988, p. 22.
REFERENCES
1. Nagargjan, K., Aryav, P., Partasarathy, T.N.,
Shenou, S., Shah, R.K., and Kulkarni, J.S., Ind. J.
Chem. Sect. B, 1981, vol. 20, pp. 672 679; Chem.
Abstr., vol. 96, 142615k.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 11 2002