Reaction of pyrrole anions with carbon disulfide. Synthesis of pyrrole-3-carbodithioates

Article abstract of DOI:10.1016/S0040-4020(00)00641-4

2,5-Disubstituted pyrroles react with carbon disulfide in the system KOH-DMSO with selective formation of pyrrole-3-carbodithioate anions from which pyrrole-3-carbodithioates were prepared by ethylation in 36-61% yield. From 2-methyl-5-phenyl(2-furyl- or

Full text of DOI:10.1016/S0040-4020(00)00641-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 7325–7329
Reaction of Pyrrole Anions with Carbon Disulfide.
Synthesis of Pyrrole-3-carbodithioates
a
a
a
Boris A. Trofimov,a, Lubov’ N. Sobenina, Al’bina I. Mikhaleva, Andrey P. Demenev,
*
Ol’ga A. Tarasova,a Igor’ A. Ushakovb and Sergey V. Zinchenkoa
aA.E. Favorsky Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, Russ-664033 Irkutsk, 1 Favorsky, Russia
bIrkutsk State Polytechnic University, Russ-664074, Irkutsk, 83 Lermontov, Russia
Received 20 April 2000; revised 4 July 2000; accepted 13 July 2000
Abstract—2,5-Disubstituted pyrroles react with carbon disulfide in the system KOH–DMSO with selective formation of pyrrole-3-carbo-
dithioate anions from which pyrrole-3-carbodithioates were prepared by ethylation in 36–61% yield. From 2-methyl-5-phenyl(2-furyl- or
2-thienyl)pyrroles only pyrrole-3-carbodithioates are formed, with no isomeric pyrrole-4-carbodithioates being present. The reaction
direction depends on pyrrole ring substitution: unsubstituted pyrrole selectively forms pyrrole-1-carbodithioate, whereas 2-methyl-, 2,3-
and 2,4-dimethylpyrroles give exclusively pyrrole-2-carbodithioates under the same conditions. ᭧ 2000 Elsevier Science Ltd. All rights
reserved.
Pyrroledithiocarboxylic acids and their derivatives are
related to a poorly understood class of synthetically and
biologically attractive pyrrole compounds, in particular, as
highly potent starting materials for constructing complex
pyrrole systems. Prior to our research in this field1,2 only
pyrrole-1-carbodithioates obtained by addition of pyrroles
to carbon disulfide in the presence of superbases were
known.3 The only described representative of pyrrole-2-
carbodithioates, ethyl pyrrole-2-dithiocarboxylate, was
synthesized via N-pyrrolylmagnesium bromide.4 The synth-
esis of a salt of 4,5-dimethyl-2-pyrroledithiocarboxylic acid
from the corresponding pyrrole and carbon disulfide in an
aqueous-alkaline medium (89% yield)5 proved to be irre-
producible.1
ate with carbon disulfide.6 This suggests that the pyrrole
anion could react with carbon disulfide exclusively via the
nitrogen atom on condition that the positions 2 and 5 are
substituted. Meanwhile, judging by the pyrrole anion reso-
nance structures, the electrophilic attack is quite possible to
be directed to the 3 and 4 positions as well (Scheme 1).
When the substituents are in positions 2 and 5, the attack
by a carbon disulfide molecule at positions 3 and 4 becomes
even more probable.
For the first time we managed to involve a series of 2,5-
disubstituted pyrroles (1a–f) into the reaction with carbon
disulfide in KOH–DMSO system. For comparison, 2-methyl-,
2,3- and 2,4-disubstituted pyrroles (1g–j) were studied
under the same conditions.
It turned out that in the superbase system KOH–DMSO,
pyrroles regioselectively add to carbon disulfide at the
position 2 to form pyrrole-2-carbodithioates; the only
exception is unsubstituted pyrrole, which reacts as before
at position 1 only, and 2-arylpyrroles affording some
amount (24–29%) of pyrrole-1-carbodithioates along with
the corresponding 2-isomers as major products (52–59%).1,2
Contrary to data3,6 and our expectations, under the con-
ditions examined, all the 2,5-disubstituted pyrroles react
with carbon disulfide in a regio-selective manner to give
ethyl pyrrole-3-carbodithioates (3a–f) in 36–61% yield
after EtI-ethylation of the salts (2a–f) (Scheme 2).7
The reaction was carried out at room temperature over 3 h.
The pyrrole–KOH–carbon disulfide molar ratio was 1:2:2.
The intermediate salts were EtI ethylated without isolation
(room temperature, 2 h). Under the same conditions the
pyrroles (1g–j) without substituents in position 5 reacted
In the literature there are no data concerning the synthesis of
pyrrole-3-carbodithioates from pyrroles and carbon disul-
fide in the presence of superbases. It is known that in the
presence of potassium metal 2,5-dimethylpyrrole in toluene
selectively forms the corresponding pyrrole-1-carbodithio-
Keywords: pyrrole anions; carbon disulfide; pyrrole-3-carbodithioates;
regioselectivity.
Scheme 1.
* Corresponding author. Fax: ϩ7-39-60-46; e-mail: admin@irioch.irk.ru
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00641-4

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B. A. Trofimov et al. / Tetrahedron 56 (2000) 7325–7329
Scheme 2.
in the same manner to form ethyl pyrrole-2-carbodithioates
(3g–j) in 46–62% yield (Scheme 3).
either pyrrole-1- or, quite possible in this case, pyrrole-4-
carbodithioates (4d–f) (Scheme 4).
In no case we could fix formation of isomeric pyrrolecarbo-
dithioates (all the reaction mixtures were analyzed by H
NMR spectroscopy prior to isolation of products on alu-
minum oxide). The reaction mixtures always contain
diethyldisulfide (up to 12% per ethyl iodide taken) as a
side product formed as the result of ethylation and oxidation
of the products of carbon disulfide alkaline hydrolysis.
The formation of isomers (4d–f) seems to be sterically
hindered by either hydrogen atom in the phenyl radical
o-position or lone electron pairs of heteroatoms (O, S).
The choice between alternative structures—pyrrole-3- and
pyrrole-4-carbodithioates for compounds (3d–f), was made
on the basis of 1H NMR data.
1
It should be noted that in contrast to pyrroles (1a–d), which
react with carbon disulfide completely (no the pyrroles
recovered), the conversion of pyrroles (1e) and (1f) is 81
and 79%, respectively.
Comparing the results with those obtained previously for
unsubstituted pyrrole, which gives only pyrrole-1-carbo-
dithioate,2,3 we come to an unexpected conclusion that the
introduction of a single methyl substituent into the pyrrole
ring position 2 is enough to change the direction of carbon
disulfide attack on the multidentate pyrrole anion.
Thus, the reaction of 2,5-substituted pyrroles with carbon
disulfide in KOH–DMSO system is of general character.
The reaction involves pyrroles with alkyl substituents as
well as those annelated with saturated aliphatic rings or
linked with aryl and hetaryl substituents. In all cases
pyrrole-3-carbodithioates are selectively formed.
Earlier we have shown that 2-aryl- and 2-aryl-3-alkyl-
pyrroles react with carbon disulfide under the same con-
ditions to form a mixture of pyrrole-1- and pyrrole-2-
carbodithioates.1,2 However, the anions of 2-methyl-5-
aryl-(hetaryl)pyrroles (1d–f) add to carbon disulfide selec-
tively with the formation of only pyrrole-3-carbodithioates
(3d–f): in the reaction mixture there are not even traces of
The structure of compounds is supported by elemental
analysis, IR, 1H and 13C NMR spectroscopy. The IR spectra
of the pyrroles (3a–j) are characterized by the presence of
Scheme 3.

B. A. Trofimov et al. / Tetrahedron 56 (2000) 7325–7329
7327
Scheme 4.
intense bands in the 3300–3400 cmϪ1 region, corresponding
to the NH group vibrations. In the 1H NMR spectra of all the
pyrroles (3a–j) there are quartets (SCH2) and triplets (Me)
of the SEt group in the 3.40–3.32 and 1.40–1.34 ppm
region, respectively. The pyrrole proton signals in
compounds (3a, d–h) in the ortho-position to the C(S)SEt
group are in the 7.04–6.48 ppm range. The pyrrole protons
in compounds (3g, i, j) in the meta-position to the C(S)SEt
group resonate in the 6.02–5.92 ppm range. These protons
The methyl group proton cross peak through three bonds
to a quaternary carbon in the pyrrole ring position 3 is
indicative of the presence of carbodithioate group in the
above position.
Mild conditions of dithiocarbonization, availability of the
initial compounds and possibility of structural variations,
good preparative yields and high selectivity of the reaction
makes the developed synthesis of hardly accessible pyrrole-
3-carbodithioates a rather promising process for broad
application in the chemistry of pyrroles.
are characterized by a far spin–spin coupling (JNH
–
ˆ
H-3
2.40–3.50 Hz) transmitted through a W-shaped fragment.
The NH group protons in pyrrole-3-carbodithioates (3a–f)
manifest themselves as a broad singlet in the 8.68–7.79 ppm
region, whereas those in pyrrole-2-carbodithioates (3g–j)
are observed in the 9.68–9.34 ppm range. The methyl
group singlet in a position neighbouring to the C(S)SEt
group in (3a–f, i, j) is shifted by 0.2–0.4 ppm downfield
and observed in the 2.67–2.37 ppm range.
Experimental
IR Spectra were recorded on a Bruker IFS 25 instrument
(KBr pellets). 1H and 13C NMR spectra were run on a Bruker
DPX 400 spectrometer (250.13 and 101.61 MHz, respec-
tively, HMDS, chloroform). Analysis of the reaction
mixtures and purity control of the products were carried
out by TLC on Silufole UV-254. The products were
separated by column chromatography (Al2O3, hexane).
Dimeric homonuclear 1H–1H Noesy spectra of pyrroles
(3d–f) point to interaction of the NH proton with methyl
group and the H-4 proton with benzene and furan ring ortho-
protons in compounds (3d) and (3e). This allows the
C(S)SEt group position to be uniquely identified. The inter-
action of the NH proton with both the methyl group and the
thiophene ring H-3 proton, which is observed for the pyrrole
(3f), bears witness to the predominant anti-orientation of
heterocycles in contrast the syn-orientation of furan analo-
gue (3e). The absence of cross peak of methyl group with
pyrrole ring proton H-3 provides further evidence for the
presence of C(S)SEt group in this position (Scheme 5).
Synthesis of pyrrolecarbodithioates (3a–j) (routine
procedure)
Pyrrole (10 mmol) and KOH (1.12 g, 20 mmol) are stirred
for 0.5 h in 20 ml of DMSO, then carbon disulfide (1.52 g,
20 mmol) is added. The reaction mixture is allowed to stand
3 h at room temperature, after addition of ethyl iodide
(1.56 g, 10 mmol) the resultant mixture is stirred for 2 h,
diluted with water and extracted with ether. The residue is
fractionated by column chromatography. The isolated
products are diethyldisulfide (10–12% yield basing on
The structure of compound (3f) was also proved by 13C
NMR spectroscopy. The signals were assigned using
dimeric heteronuclear techniques HSQC8 and HMBC.9
Scheme 5.

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B. A. Trofimov et al. / Tetrahedron 56 (2000) 7325–7329
ethyl iodide), unreacted pyrrole (in the case of pyrroles (3e)
and (3f)) and pyrrolecarbodithioates.
1237, 1194, 1146, 1014, 985, 834, 792, 682, 657,
587 cmϪ1; dH (250.13 MHz, CDCl3) 8.40 (1H, br s, NH),
7.17 (1H, dd, Jˆ5.0, 1.2 Hz, H-5 of thiophene), 7.04 (1H,
dd, Jˆ3.5, 1.2 Hz, H-3 of thiophene), 7.00 (1H, dd, Jˆ4.9,
3.5 Hz, H-4 of thiophene), 6.93 (1H, d, Jˆ3.0 Hz, H-4),
3.32 (2H, q, Jˆ7.4 Hz, SCH2), 2.65 (3H, s, Me-2), 1.36
(3H, t, Jˆ7.4 Hz, Me); dC (101.61 MHz, CDCl3) 217.6,
135.0, 134.6, 130.5, 127.8, 124.4, 123.7, 121.8, 106.0,
29.5, 16.4, 13.00.
Ethyl 2,5-dimethylpyrrole-3-carbodithioate (3a). 52%,
purity 95% (NMR date), yellow crystals, mp 60ЊC;
[Found: C, 54.03; H, 6.34; N, 6.67; S, 31.71. C9H13NS2
requires C, 54.23; H, 6.57; N, 7.03; S, 32.17%]; nmax(KBr)
3266, 2964, 2921, 2869, 1595, 1502, 1449, 1416, 1367,
1327, 1242, 1192, 1126, 1017, 988, 826, 711, 678,
508 cmϪ1; dH (250.13 MHz, CDCl3) 8.17 (1H, br s, NH),
6.48 (1H, d, Jˆ2.8 Hz, H-4), 3.33 (2H, q, Jˆ7.4 Hz, SCH2),
2.58 (3H, s, Me-2), 2.19 (3H, s, Me-5), 1.37 (3H, t,
Jˆ7.4 Hz, Me).
Ethyl 5-methylpyrrole-2-carbodithioate (3g). 46%,
yellow crystals, mp 36ЊC; [Found: C, 50.96; H, 5.82; N,
7.89; S, 34.18. C8H11NS2 requires C, 51.58; H, 5.98; N,
7.56; S, 34.61%]; nmax(KBr) 3327, 2968, 2926, 2861,
1552, 1483, 1444, 1379, 1366, 1279, 1242, 1208, 1063,
1050, 1031, 1009, 976, 820, 779, 767, 684, 650, 615, 489,
431 cmϪ1; dH (250.13 MHz, CDCl3) 9.38 (1H, br s, NH),
6.99 (1H, dd, Jˆ3.5 Hz, H-3), 6.02 (1H, dd, Jˆ3.5 Hz,
H-4), 3.35 (2H, q, Jˆ7.4 Hz, SCH2), 2.27 (3H, s, Me-5),
1.36 (3H, t, Jˆ7.4 Hz, Me).
Ethyl 2,4,5-trimethylpyrrole-3-carbodithioate (3b). 43%,
yellow crystals, mp 38ЊC; [Found: C, 56.64; H, 6.84; N,
7.11; S, 29.55. C10H15NS2 requires C, 56.29; H, 7.09; N,
6.56; S, 30.06%]; nmax(KBr) 3387, 2957, 2922, 2852,
1597, 1503, 1447, 1424, 1399, 1380, 1322, 1244, 1118,
1064, 1042, 996, 978, 965, 810, 774, 634, 577, 546 cmϪ1
;
dH (250.13 MHz, CDCl3) 7.88 (1H, br s, NH), 3.30 (2H, q,
Jˆ7.4 Hz, SCH2), 2.37 (3H, s, Me-2), 2.14 (3H, s, Me-4),
2.04 (3H, s, Me-5), 1.35 (3H, t, Jˆ7.4 Hz, Me).
Ethyl 4,5-dimethylpyrrole-2-carbodithioate (3h). 51%,
yellow crystals, mp 80ЊC; [Found: C, 54.03; H, 6.34; N,
6.67; S, 31.71. C9H13NS2 requires C, 54.23; H, 6.57; N,
7.03; S, 32.17%]; nmax(KBr) 3337, 2916, 2865, 2830,
1555, 1512, 1450, 1442, 1424, 1356, 1220, 1195, 1160,
1130, 1009, 976, 840, 830, 720, 680, 640, 500 cmϪ1; dH
(250.13 MHz, CDCl3) 9.34 (1H, br s, NH), 6.86 (1H, d,
Jˆ2.56 Hz, H-3), 3.35 (2H, q, Jˆ7.4 Hz, SCH2), 2.17
(3H, s, Me-5), 1.98 (3H, s, Me-4), 1.34 (3H, t, Jˆ7.4 Hz,
Me).
Ethyl 2-methyl-4,5,6,7-tetrahydroindole-3-carbodithio-
ate (3c). 36%, yellow crystals, mp 60ЊC; [Found: C,
59.85; H, 7.01; N, 5.31; S, 26.32. C12H17NS2 requires C,
60.20; H, 7.16; N, 5.58; S, 26.79%]; nmax(KBr), 3320,
2952, 2926, 2851, 1607, 1458, 1437, 1406, 1376, 1320,
1246, 1118, 1016, 990, 943, 890, 845, 776, 650 cmϪ1; dH
(250.13 MHz, CDCl3) 7.79 (1H, br s, NH), 3.31 (2H, q,
Jˆ7.4 Hz, SCH2), 2.77 (2H, m, CH2-7), 2.49 (3H, s,
Me-2), 2.44 (2H, m, CH2-4), 1.75 (4H, m, CH2-5,6), 1.34
(3H, t, Jˆ7.4 Hz, Me).
Ethyl 3,5-dimethylpyrrole-2-carbodithioate (3i). 48%,
yellow crystals, mp 96ЊC; [Found: C, 53.73; H, 6.18; N,
6.68; S, 31.63. C9H13NS2 requires C, 54.23; H, 6.57; N,
7.03; S, 32.17%]; nmax(KBr) 3307, 2966, 2927, 2865,
1553, 1469, 1418, 1371, 1240, 1190, 1144, 1022, 985,
974, 879, 821, 718, 682, 509, 469 cmϪ1; dH (250.13 MHz,
CDCl3) 9.68 (1H, br s, NH), 5.92 (1H, d, Jˆ2.40 Hz, H-3),
3.40 (2H, q, Jˆ7.4 Hz, SCH2), 2.45 (3H, s, Me-3), 2.23 (3H,
s, Me-5), 1.39 (3H, t, Jˆ7.4 Hz, Me).
Ethyl 2-methyl-5-phenylpyrrole-3-carbodithioate (3d).
61%, orange crystals, mp 108ЊC; [Found: C, 64.11; H,
5.65; N, 5.08; S, 24.10. C14H15NS2 requires C, 64.32; H,
5.78; N, 5.36; S, 24.53%]; nmax(KBr) 3297, 2971, 2928,
2875, 1605, 1587, 1567, 1511, 1488, 1458, 1416, 1251,
1210, 1149, 1070, 1007, 985, 933, 901, 842, 790, 752,
707, 690, 637, 550, 493 cmϪ1; dH (250.13 MHz, CDCl3)
8.45 (1H, br s, NH), 7.45, 7.35, 7.23 (5H, m, Ph), 7.04
(1H, d, Jˆ2.9 Hz, H-4), 3.33 (2H, q, Jˆ7.4 Hz, SCH2),
2.67 (3H, s, Me-2), 1.36 (3H, t, Jˆ7.4 Hz, Me).
Ethyl 5-(tert-butyl)-3-methylpyrrole-2-carbodithioate (3j).
62%, yellow crystals, mp 105ЊC; [Found: C, 59.34; H, 7.54;
N, 5.43; S, 26.13. C12H19NS2 requires C, 59.70; H, 7.93; N,
5.80; S, 26.56%]; nmax(KBr) 3386, 2963, 2926, 2868, 1546,
1484, 1462, 1425, 1398, 1375, 1366, 1326, 1264, 1248,
1190, 1118, 1046, 1026, 1003, 989, 970, 881, 819, 802,
744, 709, 689, 678, 610, 537, 493, 478 cmϪ1; dH
(250.13 MHz, CDCl3) 9.59 (1H, s, NH), 5.95 (1H, d,
Jˆ2.99 Hz, H-4), 3.38 (2H, q, Jˆ7.4 Hz, SCH2), 2.48
(3H, s, Me-3), 1.40 (3H, t, Jˆ7.4 Hz, Me), 1.34 (9H, s,
t-Bu).
Ethyl 2-methyl-5-(2-furyl)pyrrole-3-carbodithioate (3e).
44%, orange crystals, mp 52ЊC; [Found: C, 56.75; H, 4.81;
N, 4.89; S, 25.11. C12H13NOS2 requires C, 57.34; H, 5.21;
N, 5.57; S, 25.51%]; nmax(KBr) 3407, 3270, 2965, 2924,
2861, 1625, 1545, 1510, 1454, 1419, 1369, 1331, 1231,
1203, 1007, 985, 960, 884, 837, 780, 725, 684, 588,
500 cmϪ1; dH (250.13 MHz, CDCl3) 8.68 (1H, br s, NH),
7.59 (1H, d, Jˆ1.2 Hz, H-5 of furane), 6.96 (1H, d,
Jˆ2.7 Hz, H-4), 6.45 (2H, m, Jˆ3.5, 1.6 Hz, H-3 and H-4
of furane), 3.32 (2H, q, Jˆ7.4 Hz, SCH2), 2.66 (3H, s,
Me-2), 1.36 (3H, t, Jˆ7.4 Hz, Me).
References
Ethyl
2-methyl-5-(2-thienyl)pyrrole-3-carbodithioate
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4.81; N, 4.79; S, 35.41. C12H13NS3 requires C, 53.89; H,
4.90; N, 5.24; S, 35.97%]; nmax(KBr) 3367, 3112, 3064,
2965, 2923, 2868, 1598, 1521, 1458, 1419, 1365, 1338,

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