Reactions of aliphatic, aromatic, and heterocyclic aminothiols with diacetylene

Article abstract of DOI:10.1007/s11178-005-0078-1

Reactions of aliphatic, aromatic, and heterocyclic aminothiols with diacetylene in liquid ammonia or methanol furnished the corresponding aminoorganylsulfanylbutenynes of predominantly Z-configuration. 2004 MAIK "Nauka/Interperiodica".

Full text of DOI:10.1007/s11178-005-0078-1

Russian Journal of Organic Chemistry, Vol. 40, No. 11, 2004, pp. 1679 -1681. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 11,
2004, pp. 1725-1727.
Original Russian Text Copyright Ó 2004 by Volkov, Volkova.
Reactions of Aliphatic, Aromatic, and Heterocyclic Aminothiols
with Diacetylene
A.N. Volkov and K.A. Volkova
Faworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
Irkutsk, 664033 Russia
Received October 29, 2003
Abstract--Reactions of aliphatic, aromatic, and heterocyclic aminothiols with diacetylene in liquid ammonia or
methanol furnished the corresponding aminoorganylsulfanylbutenynes of predominantly Z-configuration.
Diacetylene opens up new fields for preparation ver-
satile unsaturated heteroatomic compounds with specific
characteristics [1, 2]. Reactions of diacetylene with thi-
ols and hydrogen sulfide in various media [3], in particu-
lar, in liquid ammonia [4], gave rise to enyne sulfides [5]
and thiophene [6].
Taking into account the presence of two reaction sites
in aminothiol molecules and the thiols ability to be oxi-
dized into disulfides it was presumable that the reaction
would give rise to several products. However the use of
mild conditions (liquid ammonia) prevented participation
in the reaction of the amino group and also disulfides for-
mation. The basic quality of ammonia favors thiolate ion
formation, and the high reactivity of the latter is ensured
by its weak solvation with the ammonia molecules. There-
fore the reaction begins by a nucleophilic attack of the
thiolate ion on the triple bond and affords the correspond-
ing enyne sulfides I–V that were isolated in high yields
(78–98%).
We report here on the study of nucleophilic addition of
1,2-aminothiols to diacetylene in liquid ammonia or in
methanol aimed at elucidation of the reaction direction
and at preparation of new biologically active compounds.
The combination in a single molecule of acid and base
properties makes it possible for the compound to exist in
a form of an internal salt (zwitter-ion). By changing the
+
pH of the medium the ammonium salt HSCH2CH2 NH3
The diacetylene reaction with the b-aminoethanethiol
in methanol in the presence of alkali also resulted in sul-
fide I but in a lower yield (52%).
–
+
can be converted through SCH2CH2 NH3 into a free
base SCH2CH2NH2 [7].
–
The nucleophilic ability of 1,2-aminothiols in reactions
with activated unsaturated compounds is well consistent
with the acidity of the mercapto and amino groups in
aminothiols [7].According to [8] at comparable values of
the medium pK and comparable spatial surrounding the
ꢀ
65
+65
B
,ꢁꢁꢁ9
5ꢀ ꢀ1+ &+ &+ ꢀꢁ,ꢂꢃꢀꢁ& + ꢂ 1&+ &+ ꢀꢁ,,ꢂꢃ
–
–
HS anions are 280 times more active than NH2 anions.
Therefore the proton elimination from the b-amino-
ethanethiol occurred exclusively from the SH groups. The
analysis of published data [9–12] revealed that sometimes
NH2 groups are involved, and cyclization also may hap-
pen. For instance, the reaction of a-acetylene ketones
with b-aminoethanethiol hydrochloride in methanol solu-
tion in the presence of sodium methylate resulted in
bis(acylvinylaminoethyl) disulfides, i.e., only amino group
was involved into the process. At excess initial ketone
(2:1) alongside the disulfides formed also 1,4-bis-
(acylvinyl)-1-thia-4-azabutanes [9].
1&+ &+ ꢀꢁ,,,ꢂꢃ 2
Rꢄ1+ & + ꢀꢁ9ꢂꢅ
1&+ &+ꢀꢁ,9ꢂꢃ
2
&+
In the IR spectra of compounds I–V appear the ab-
–1
sorption bands of the triple bond at 2060–2100 cm and
–1
of ºCH group at 3250–3290 cm . To the vibrations of
S–C=C and C–S bonds belong the absorption bands at
–1
–1
1550–1600 cm and 690–710 cm respectively. The fol-
1
lowing resonances were observed in the H NMR spec-
1070-4280/04/4011-1679Ó2004 MAIK “Nauka/Interperiodica”

VOLKOV,VOLKOVA
1680
tra of compounds I–V recorded in CD3OD, d, ppm: 3.17–
3.75 d (ºCH, 4JHH ~2.3 Hz), 5.33–5.16 q (=CHCº, 3JHH
~10 Hz), 6.39–6.76 d (=CHS, 3JHH ~10 Hz). Enyne sul-
fides III–V were obtained as Z-isomers, and sulfides I
and II as mixtures of Z- and E-isomers in a ratio 3:1 and
6:1 respectively. The lack of stereospecificity in addition
of b-aminoethanethiol and b-(N,N-diethylamino-
ethanethiol to diacetylene is in agreement with the for-
merly obtained data on the partial deviation from the rule
of the trans-nucleophilic thiol addition to diacetylene oc-
curring in liquid ammonia [4]. In the 13C NMR spectrum
of sulfide I were found the signals belonging to the Z-
and E-isomers (CDCl3), d, ppm: 78.30 and 76.81 (–Cº),
84.85 and 82.09 (ºCH), 103.92 and 104.05 (=CHCº),
141.30 and 140.25 (=CHS), 41.75 and 40.74 (CH2N),
37.46 and 36.04 (CH2S) respectively.
hydrochloride in 100 ml of liquid NH3 was added at stir-
ring a solution of 2 g (40 mmol) of diacetylene in 50 ml of
liquid NH3. The mixture was stirred for 3 h at –33°C,
NH3 was evaporated, the residue was extracted with ethyl
ether, dried on MgSO4, and dilstilled.Yield 0.53 g (77.8%),
–1
bp 92–95°C (2 mm Hg), nD20 1.5724. IR spectrum, cm :
3350, 3280, 3020, 2080, 1655, 1550, 1410, 1370, 1330,
1
1210, 1065, 1010, 960, 830, 770, 700, 640. H NMR spec-
trum, d, ppm: (Z, CDCl3) – 3.35 d (1H, ºCH), 5.44 q (1H,
=CHCº), 6.51 d (1H, =CHS), 2.86 m (2H, CH2N), 2.79
m (2H, CH2S); (Z, CD3OD) – 3.75 d (1H, ºCH), 5.58 q
(1H, =CHCº), 6.76 d (1H, =CHS); (Z, DMSO-d6)
– 4.28 d (1H, ºCH), 5.52 q (1H, =CHCº), 6.85 d (1H,
=CHS), 2.79 m (2H, CH2N), 2.73 m (2H, CH2S), 1.97 br
(2H, NH2); (E, CD3OD) – 3.68 d (1H, ºCH), 5.47 q (1H,
=CHCº), 6.68 d (1H, =CHS); (E, DMSO-d6) – 3.84 d
(1H, ºCH), 5.56 q (1H, =CHCº), 6.93 d (1H, =CHS),
2.82 m (2H, CH2N), 2.70 m (2H, CH2S). Found, %:
C 57.01; H 7.02; N 10.73; S 24.97. C6H9NS. Calculated,
%: C 56.68; H 7.09; N 11.02; S 25.19.
The presence of amino group in sulfide I may lead to
intramolecular cyclization into a 1,3-thiazole. However
the heating of sulfide I in dioxane (90°C, 10 h) did not
result in the cyclization. The reaction of sulfide I with
acetic acid afforded 2-(but-1-en-3-yn-1-ylsulfanyl)-
ethylammonium acetate (VI), mp 105–106°C.
Note that the acetylene proton in the 1H NMR spec-
trum of compound I is the most shielded (3.35 ppm) in
CDCl3 solution and the least shielded (4.28 ppm) in
DMSO-d6 environment.The downfield shift of the acety-
lene proton (~1 ppm) is presumably caused by formation
of a relatively strong associate of the enyne compound
with DMSO-d6.
(b) To a solution of 0.91 g (8 mmol) of b-amino-
ethanethiol in 35 ml of methanol was added 0.32 g
(70 mmol) of NaOH, 3.61 g (72 mmol) of diacetylene
was passed through, and the reaction mixture was stirred
for 3 h and then distilled. Yield 0.45 g.
2-(But-1-en-3-yn-1-ylsulfanyl)ethyldiethylamine
(II) was prepared similarly from 2.54 g (19 mmol)
b-(N,N-diethylamino)ethanethiol in 50 ml of liquid NH3
and 1.6 g (3.2 mmol) of diacetylene in 50 ml of liquid
NH3 at –33°C within 5 h. Yield 3.42 g (98%), bp 83–
In the case of o-aminothiophenol the formation of
sulfide V was less predictable for the thiophenols (pKa
7–8) formed stronger ammonium salts with ammonia.
However the structure of sulfide V is unambiguously
–1
84°C (2 mm Hg), nD20 1.5260. IR spectrum, cm : 3310,
3270, 2100, 1500, 1460, 1385, 1310, 1300, 1200, 1150, 1115,
1
1070, 1040, 1020, 1000, 960, 915, 840, 790. H NMR
1
confirmed by its H NMR spectrum (d, ppm) where
spectrum, d, ppm: (Z, CCl4) – 3.17 d (1H, ºCH), 5.33 q
(1H, =CHCº), 6.50 d (1H, =CHS), 2.56 m (2H, CH2N),
2.42 m (2H, CH2S), 0.93 t (3H, CH3); (E, CCl4) – 3.09 d
(1H, ºCH), 5.07 q (1H, =CHCº), 6.67 d (1H, =CHS).
Found, %: C 65.20; H 9.44; N 7.63; S 17.60. C10H17NS.
Calculated, %: C 65.54; H 9.35; N 7.64; S 17.46.
appear signals of NH2 protons(4.08), and also of olefin
3
protons (5.49 q and 6.74 d, J HH ~10 Hz) corresponding
to Z-isomer.
EXPERIMENTAL
N-[2-(But-1-en-3-yn-1-ylsulfanyl)ethyl]-
morpholine (III) was prepared similarly from 1.74 g
(12 mmol) of 2-(morpholino)ethanethiol in 4 ml of CH3OH
and 100 ml of liquid NH3, and 1.15 g (23 mmol) of
diacetylene in 50 ml of liquid NH3. The mixture was stirred
for 5 h at –33°C. Yield 2.03 g (87%), bp 118°C (3 mm
1H NMR spectra of compounds I–V were registered
from solutions in CDCl3 on spectrometer Bruker DPX-
400 (400 MHz), 1H and 13C NMR spectra of compound
I were taken on spectrometer Bruker DPX-250 (250.1
and 62.4 MHz), internal reference HMDS. IR spectra
were recorded on spectrometer Specord 751R from thin
films.
Hg), nD20 1.5540. IR spectrum, cm : 3290, 3040, 2095,
–1
1690, 1600, 1580, 1450, 1370, 1330, 1275, 1200, 1120, 1010,
910, 870, 750, 690. 1H NMR spectrum, d, ppm: (Z,
CD3OD) – 3.25 d (1H, ºCH), 5.88 q (1H, =CHCº),
2-(But-1-en-3-yn-1-ylsulfanyl)ethylamine (I). (a)
To a solution of 0.56 g (4.9 mmol) of b-aminoethanethiol
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 40 No. 11 2004

REACTIONS OFALIPHATIC,AROMATIC,AND HETEROCYCLICAMINOTHIOLS
1681
6.70 d (1H, =CHS), 2.82 t (2H, CH2N), 2.47 m (2H, CH2S),
3.68 t (2H, CH2O). Found, %: C 60.69; H 7.69; N 7.36;
S 15.83. C10H15NOS. Calculated, % : C 60.89; H 7.67;
N 7.10; S 16.16.
1280, 1240, 1120, 1030, 1000, 970, 920, 890, 740, 690,
640, 620. H NMR spectrum, d, ppm: (Z, DMSO-d6) –
1
4.32 d (1H, ºCH), 5.55 q (1H, =CHCº), 6.87 d (1H,
=CHS), 2.89 m (2H, CH2N), 2.81 m (2H, CH2S), 1.80 s
(3H, CH3), 6.00 (3H, NH30). 13C NMR spectrum, d, ppm
: (Z, DMSO-d6) – 80.62. (–Cº), 88.08 (HCº), 103.65
(=CH–Cº), 142.63 (=CH–S), 41.34 (NCH2), 34.15
(SCH2), 22.62 (CH3CO).
N-[2-(But-1-en-3-yn-1-ylsulfanyl)propyl]-
morpholine (IV) was prepared similarly from 4.63 g
(29 mmol) of 1-morpholinopropane-2-thiol in 100 ml of
liquid NH3 and 4.38 g (88 mmol) of diacetylene in 70 ml
of liquid NH3. Yield 5.93 g (97%), bp 145–149°C (1 mm
–1
Hg), nD20 1.6695. IR spectrum, cm : 3250, 3050, 2060,
REFERENCES
1560, 1450, 1350, 1310, 1300, 1200, 1100, 1060, 1040, 1020,
1000, 960, 850, 790, 775, 700. 1H NMR spectrum, d,
ppm: (Z, CDCl3) – 3.40 d (1H, ºCH), 5.49 q (1H, =CHCº),
6.74 d (1H, =CHS), 2.95 d (2H, CH2N), 2.44 m (2H,
CH2S), 3.66 t (2H, CH2O), 1.34 d (3H, CH3). Found, %:
C 62.69; H 8.39; N 6.93; S 15.07. C11H17NOS. Calculated,
%: C 62.54; H 8.11; N 6.63; S 15.15.
1. Maretina, I. A., and Trofimov, B. A., Usp. Khim., 2000,
vol. 69, p. 642.
2. Maretina, I.A. and Trofimov, B.A., Adv. Heterocyclic Chem.,
2000, vol. 82, p. 157.
3. Volkov, A. N., Volkova, K. A., and Trofimov, B. A., Sulfur
Rep., 2001, vol. 22, p. 277.
4. Volkov, A. N., Volkova, K. A., Levanova, E. P., and Trofi-
mov, B.A., Izv. Akad. Nauk SSSR, Ser. Khim., 1981, p. 831.
5. Volkov, A.N., Volkova, K. A., Levanova, E. P., and Trofi-
mov, B.A., Zh. Org. Khim. , 1982, vol. 18, p. 2049.
6. Voronkov, M. G., Trofimov, B.A., Kryuchkov, V. V.,Amoso-
va, S. V., Skvortsov,Yu. M., Volkov,A. N., Mal’kina,A. G.,
and Mushii, R. Ya., Khim. Geterotsikl. Soed., 1981, p. 1694.
7. Rachinskii, F. Yu., and Slavachevskaya, N. N., Khimiya
aminothiolov (Chemistry of Aminothiols), Moscow:
Khimiya, 1965, 295 p.
8. Friedman, M., Cavins, J. F., and Wall, J. S., J. Am. Chem.
Soc., 1965, vol. 87, p. 3672.
9. Glotova, T.E., Nakhmanovich, A.S., Skvortsova, G.G.,
Komarova, T. N., Kalikhman, I.D., and Voronkov, M.G., Zh.
Org. Khim., 1981, vol. 17, p. 749.
2-(But-1-en-3-yn-1-ylsulfanyl)aniline (V) was pre-
pared similarly from 3.21 g (24 mmol) of o-amino-
thiophenol in 50 ml of liquid NH3 and 1.51 g (30 mmol) of
diacetylene in 50 ml of liquid NH3. Yield 3.5 g (79 %), bp
–1
116°C (1 mm Hg) IR spectrum, cm : 3460, 3365, 3280,
3040, 3015, 2100, 1610, 1565, 1555, 1480, 1445, 1330,
1
1310, 1250, 1160, 1080, 1030, 970, 800, 770, 720. H
NMR spectrum, d, ppm: (Z, CCl4) – 3.26 d (1H, ºCH),
5.43 q (1H, =CHC?), 6.39 d (1H, =CHS), 7.12 m (4H,
C6H4), 4.08 br (2H, NH2). Found, %: C 68.80; H 5.37; N
7.87; S 17.90. C10H9NS. Calculated, %: C 68.56; H 5.18;
N 8.00; S 18.27.
2-(But-1-en-3-yn-1-ylsulfanyl)ethylammonium
acetate (VI). To a solution of 0.25 g (1.97 mmol) of
compound I in 10 ml of dioxane was added dropwise
0.12 g (2 mmol) of acetic acid; the mixture was main-
tained for 15 min at 25–30°C, and dioxane was evapo-
10. Mushkalo, L. K. and Lanovaya, Z. I., Ukr. Khim. Zh., 1955,
vol. 21, p. 631.
11. Volkov,A. N. and Volkova, K.A., Izv. Akad. Nauk SSSR, Ser.
Khim., 1988, p. 2860.
12. Nakhmanovich,A. S., Glotova, T. E., and Skvortsova, G. G.,
Khim. Geterotsikl. Soed., 1986, p. 280.
–1
rated. Yield 0.33 g (89.6%). IR spectrum, cm : 3440,
3170, 3050, 2080, 1630, 1560 sh, 1520, 1450, 1390, 1330,
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 40 No. 11 2004