Reactions of 2-alkoxypropenals with thiols in neutral and acid media

Article abstract of DOI:10.1023/A:1020893310626

Addition of thiols to 2-alkoxypropenal in neutral medium at 20°C in the absence of a catalyst occurs regioselectively, following the Markownikoff pattern. The resulting 2-alkoxy-2-R-thiopropanals are capable of undergoing spontaneous isomerization to 1-al

Full text of DOI:10.1023/A:1020893310626

Russian Journal of Organic Chemistry, Vol. 38, No. 7, 2002, pp. 970 976. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 7, 2002,
pp. 1012 1018.
Original Russian Text Copyright
2002 by Keiko, Funtikova, Stepanova, Chuvashev, Larina.
Dedicated to Full Member of the Russian Academy of Sciences
M.G. Voronkov on the 80th Anniversary of His Birth
Reactions of 2-Alkoxypropenals with Thiols
*
in Neutral and Acid Media
N. A. Keiko, E. A. Funtikova, L. G. Stepanova,
Yu. A. Chuvashev, and L. I. Larina
Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: keiko@irioch.irk.ru
Received May 4, 2001
Abstract Addition of thiols to 2-alkoxypropenal in neutral medium at 20 C in the absence of a catalyst
occurs regioselectively, following the Markownikoff pattern. The resulting 2-alkoxy-2-R-thiopropanals are
capable of undergoing spontaneous isomerization to 1-alkoxy-1-R-thiopropanones. The addition and iso-
merization processes are accelerated by heating to 60 C or in the presence of acid catalysts (TsOH, HCl).
The reaction is also accompanied by partial disproportionation of 2-oxopropanal O,S-acetals to give O,O- and
S,S-acetals.
Biochemical activity of , -unsaturated carbonyl
various conditions, in the present work we examined
compounds is explained by nucleophilic addition at their reactions in neutral and acid media at room tem-
the double bond of thiol groups of some enzymes, co-
enzymes, and mercapto amino acids [1]. Just that
reaction is responsible for biological activity of
acrylic compounds having an alkoxy group in the
perature and on heating. It is known that acrolein
reacts with methanethiol with heat evolution even in
the absence of a catalyst to afford 3-(methylthio)-
propanal in 94 99% yield [3]. Michael addition of
butanethiol [4] and benzenethiol [5] occurs also
readily. Unlike acrolein, the reaction of -ethoxy-
acrolein with butanethiol at 20 C is very slow, and
-position [2].
With the goal of establishing the regioselectivity
of the reaction of 2-alkoxypropenals with thiols under
Scheme 1.
I, R = Et (a), Me (b); II, R = Bu (a), CH2 CHCH (b), Ph (c), PhCH (d); III, R = Et, R = Bu (a), CH CHCH (b), Ph (c),
2
2
2
2
PhCH (d); R = Me, R = Bu (e), Ph (f); V, R = Bu (a), Ph (b); VI, R = Et, R = Bu (a), CH CHCH (b), Ph (c), PhCH (d);
2
2
2
2
R = Me, R = Ph (e).
____________
*
This study was financially supported by the Russian Founda-
tion for Basic Research (project no. 99-03-33057).
1
070-4280/02/3807-0970$27.00 2002 MAIK Nauka/Interperiodica

REACTIONS OF 2-ALKOXYPROPENALS WITH THIOLS
Reactions of 2-alkoxypropenals with thiols at 20 C
971
Composition of the reaction mixture,a mol %
Run
no.
Initial
compounds
Solvent
(catalyst, mol %)
Time,
days
IIIa IIIf
IV
Va, Vb
VIa VIe
VII
1
2
3
4
5
6
7
Ia+ IIa
Ia+ IIb
Ib+ IIa
Ia+ IIc
Ib+ IIc
Ia+ IId
IIIc
IIIa
IIIa
IIIc
IIIc
5
4
17
7
17
5
55
3 h
5 h
3 h
3 h
1
75
53
50
100
33
77
10
5
7
22
10
11
30
40
50
40
71
70
57
42
b
b
b
b
b
78
54
11
16
40
25
49
14
6
1
1
1
1
2
c
8
9
CDCl3
CDCl3
CDCl3
c
c
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
c
10
IIIa
IIIc
(TsOH, 1)
(TsOH, 1)
(HCl, 1)
14
4
6
1
2
10
18
14
80
20
b
Ia+ IIa
Ia+ IIa
Ia+ IIa
Ia+ IIc
Ia+ IIa
Ia+ IIc
VII+ IIc
VII+ IIa
20
(TsOH, 1)
6
6
42
10
d
Et O (TsOH, 0.5)
2
(TsOH, 5)
5
7
7
5
5
20
11
19
60
67
35
70
80
e
e
Et O (TsOH, 5)
22
2
Et O (TsOH, 5)
46
2
29
14
a
b
c
d
e
1
According to the H NMR data.
According to the GC MS data.
At 60 C.
Compound VIII, 10 mol %, was identified by GC MS.
Reactant ratio I:II = 1:1.5.
almost no change could be observed over the first
4 h [6]. Therefore, in the previous studies the
2-phenylthiopropanal (IIIc) is formed in quantitative
yield (run no. 4). On storage, the latter gradually
undergoes isomerization to 1-ethoxy-1-phenylthio-2-
propanone (VIc) (run no. 7). Another minor iso-
merization product is 1,1-bis(phenylthio)-2-propanone
(Vb); presumably, it appears as a result of dispropor-
tionation of monothioacetal (VIc). After storage of
this mixture for 2 months at room temperature, the
ratio IIIc:VIc:Vb became 8:1:1. One more dis-
proportionation product, acetal VII, was difficult to
2
mixture was heated (90 C, 11 h), and 2-butylthio-2-
ethoxypropanal was then isolated in 30% yield.
1
We now performed H NMR monitoring of the
reactions of 2-alkoxypropenals with thiols at 20 C.
Even at that temperature and in the absence of a catal-
yst the addition follows the Markownikoff rule, and
the yields of 2-alkoxy-2-R-thiopropanals III attain
5
0 100% in several days (see table, run nos. 1 6;
1
Scheme 1).
detect by H NMR spectroscopy, but it was identified
by GC MS. The formation of acetals Va, Vb, and
VIc prompted us to investigate their origin and deter-
mine the sequence and the rate of thiol attack on
particular reaction centers of the substrate. Com-
pounds Va, Vb, and VIc are structurally related to
2-oxopropenal thioacetals which play an important
role in biochemical transformations of the glyoxalase
enzymatic system in cells of all living bodies [7].
Examination of the product mixtures by GC MS
showed that in the reaction of 2-ethoxypropenal (Ia)
with butanethiol (IIa), apart from the major adduct
IIIa, products of its disproportionation, 2,2-bis-
(butylthio)propanal (IV) and 1,1-bis(butylthio)-2-pro-
panone (Va), were formed (run no. 1). The addition
of benzenethiol to 2-ethoxypropenal at 20 C in the
absence of a catalyst is regioselective, and 2-ethoxy-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

9
72
KEIKO et al.
A possible way of formation of dithioacetals V via
The rate of isomerization of sulfur-containing com-
pounds sometimes depends on the solvent nature [8].
Therefore, we specially examined thermal isomeriza-
tion of S,O-acetal IIIc in the absence of a solvent
thioacetalization of initial aldehyde I and subsequent
hydrolysis of the vinyloxy group with liberated water
was ruled out, for the reactions were carried out in
the absence of acids. Moreover, in none of the experi- (run no. 11). After heating for 3 h at 60 C, the ratio
ments intermediate product having a vinyloxy group
was detected.
IIIc:VIc:Vb was equal to 1:4:5. In this case the
degree of isomerization of monothioacetal IIIc is
We have found that heating of pure monothioacetal
slightly lower than in CDCl (cf. run no. 10), as
3
IIIa in CDCl results in its spontaneous isomerization
follows from the fact that a small amount of initial
compounds IIIc remains unchanged; the degree of
disproportionation of S,O-acetal VIc is twice as high.
It should be emphasized that both reactions occur in
the absence of a solvent and catalyst.
3
into thermodynamically more stable 1-butylthio-1-
ethoxy-2-propanone (VIa). Partial disproportionation
of the latter gives rise to dithioacetal Va and 1,1-di-
ethoxy-2-propanone (VII) (run no. 8, Scheme 2).
The isomerization of individual S,O-acetals III in
the presence of catalytic amounts of acids occurs even
more readily than on heating. By the action of
p-toluenesulfonic acid (1 mol %) acetals IIIa and IIIc
are converted into acetals VI, V, and VII in 24 h at
Scheme 2.
20 C (run nos. 12 and 13). Here, the major products
are O,S-acetals VIa and VIc. The ratio VIa:Va:VII
is 5:1:1. The ratio of 1-ethoxy-1-phenylthio-2-pro-
panone (VIc) to products of its isomerization Vb and
VII is equal to 14:1:1, the fraction of diphenyl di-
sulfide reaching 10% (run no. 13).
In order to accelerate the Markownikoff addition of
butanethiol (IIa) to 2-ethoxypropenal (Ia), a catalytic
amount of hydrochloric acid (1 mol %) was added to
an equimolar mixture of the reactants (run. no. 14).
1
The reaction was exothermic. According to the H
NMR data, after 48 h, the molar ratio IIIa:VIa:Va
was 1:3:1. These data indicate that hydrochloric acid
not only accelerates primary addition at the double
bond but also strongly favors isomerization of
2-butylthio-2-ethoxypropanal (IIIa) into 1-butylthio-
1-ethoxy-2-propanone (VIa) whose disproportionation
yields dithioacetal (Va). On the other hand, the latter
can also be formed (in the presence of an acid) via
direct thioacetalization of the initial aldehyde and
hydrolysis of the vinyloxy group.
Further heating of the reaction mixture leads to
complete transformation of monothioacetal IIIa to
dithioacetals VIa and Va at a ratio of 1:1 (run no. 9).
Analogous reaction sequence was observed on heating
of pure monothioacetal IIIc having an aromatic
group (run no. 10, Scheme 3).
Scheme 3.
p-Toluenesulfonic acid as catalyst acts somewhat
differently. Addition of a catalytic amount (1 mol %)
of TsOH to an equimolar mixture of reactants Ia and
IIa leads to formation of O,S-acetal IIIa which
undergoes (during the process; 6 days, 20 C) both
isomerization to monothioacetal VIa and appreciable
disproportionation to 2,2-bis(butylthio)propanal (IV)
and 2,2-diethoxypropanal (VIII) (Scheme 4, run
no. 15). No formation of compounds IV was observed
for aromatic derivatives.
In the reactions with arenethiols considerable
amounts (8 30%) of diaryl disulfides are formed as
a result of thermally induced radical decomposition
of aryl thioacetals and subsequent combination of
ArS radicals.
The reaction between compounds Ia and IIa in
diethyl ether, catalyzed by TsOH (run no. 16), is more
selective. Here, monothioacetal IIIa is formed in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

REACTIONS OF 2-ALKOXYPROPENALS WITH THIOLS
973
Scheme 4.
8
0% yield; in addition, disproportionation products
Our results convincingly showed that O,S-acetals
III derived from 2-oxopropanal are capable of under-
going spontaneous isomerization into O,S-acetals VI.
The transformation is accelerated by heating or adding
an acid catalyst.
Some examples of deacetalization of ketone acetals
with other ketones are known, but these reactions
occur intermolecularly in the presence of acids [9].
Removal of monothioacetal protection from -dicar-
bonyl compounds having a ketone and an aldehyde
group (which exchange RS and RO groups) has not
been reported. However, the reaction of 2-chloro-2-
phenylthio aldehydes with methanol is known to give
IV and 2,2-diethoxypropanal (VIII) were detected.
The addition of benzenethiol (IIc) to an equimolar
amount of 2-ethoxypropenal was carried out in the
presence of 5 mol % of TsOH. After 5 days, a mixture
of acetals IIIc, VIc, and Vb was obtained (run
no. 17). The yield of semithioacetal VIc may be raised
to 70% by performing the reaction for 3 h at 50 C.
In order to increase the yield of dithioacetals Va and
Vb, the reactions of 2-ethoxypropenal with butane-
thiol and benzenethiol were carried out at a substrate-
to-reagent molar ratio of 1:1.5 with a considerable
amount of the catalyst (TsOH, 5 mol %) in diethyl
ether at 20 C (reaction time 7 days; runs nos. 18 and
1
-methoxy-1-phenylthio-2-alkanones rather than the
expected ketone acetals [10]. It should be noted
that the above reaction occurred in the presence of
an equimolar amount of hydrogen chloride, i.e., under
conditions of acid catalysis.
1
9). However, no significant increase in the product
yield was attained. This result indirectly indicates that
dithioacetals Va and Vb are not formed by direct
condensation at the aldehyde group with subsequent
hydrolysis of the vinyloxygroup. Presumably, these
products appear as a result of some reaction sequence
Analysis of the transformations of ketone O,S-
acetals III to O,S-acetals VI led us to conclude that
the mechanism of catalytic effect of acids involves
intermolecular transfer of RO and RS fragment
between the reacting centers (isomerization and dis-
proportionation). Also, we can presume that in the
absence of a catalyst the isomerization of -formyl-
ketone monothioacetals into -oxoaldehyde mono-
thioacetals occurs intramolecularly.
The high yields of O,S-acetals III and VI and also
dithioacetals V suggest that some experimental condi-
tions can be utilized in preparative syntheses of such
compounds. Previously, some of these were obtained
from -alkyl(aryl)thio- -chloromethylketones [10, 11]
or could be obtained from 2,2-dichloropropanal [12]
or, probably, by methylation of enamines derived
from bis(ethylthio)acetaldehyde [13].
(see Schemes 2 and 3) which inhibits the effect of
excess reagent on the formation of dithioacetal V.
The structure of compounds VIa and VIc was
proved by independent synthesis from 1,1-diethoxy-
2
-propanone (VII) and the corresponding thiols
(Scheme 5). The yields of mixed acetals VIa and VIc
attain 70 80% (runs nos. 20 and 21) when the reac-
tions were carried out at room temperature in the
presence of 4- molecular sieves as catalyst and
ethanol acceptor.
Scheme 5.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
DPX-400 spectrometer (400 MHz) in CDCl using
3
HMDS as internal reference. The IR spectra were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

9
74
KEIKO et al.
measured on a Specord 75IR instrument. Gas chro-
matographic mass spectrometric analysis was per-
formed on an HP 5971A mass-selective detector
Heat evolution was observed, and the mixture was
kept at 20 C.
f. (Run no. 16). Butanethiol, 3.81 g (4.54 ml,
(
70 eV) coupled with an HP 5890 chromatograph;
4
2.4 mmol), p-toluenesulfonic acid, 0.04 g
0.5 mol %) in 2 ml of ether, and freshly calcined
molecular sieves, 3 g, were added to a solution
Ultra-2 column (5% of phenylmethylsilicone), injector
temperature 250 C, oven temperature 70 280 C (at
(
4
-
20 deg/min), carrier gas helium.
of 4.24 g (42.4 mmol) of 2-ethoxypropenal (Ia) in
31 ml of ether. Heat evolution was observed, and the
mixture was kept for 6 days at 20 C.
Reaction of 2-ethoxypropenal (Ia) with benzene-
thiol in the presence of p-toluenesulfonic acid.
A mixture of 0.485 g (4.85 mmol) of aldehyde Ia,
Reaction of 2-ethoxypropenal (Ia) with butane-
thiol (IIa). a. (See table, run no. 1). Butanethiol,
.436 g (4.85 mmol), was added to 0.48 g (4.85 mmol)
0
of 2-ethoxypropenal stabilized by 0.001 g of hydro-
quinone. The mixture was kept for 5 days at 20 C,
and the substrate disappearance was monitored by
0
.5 ml (4.85 mmol) of benzenethiol, 0.04 g (5 mol %)
1
H NMR spectroscopy.
of TsOH, and 2 g of 4- molecular sieves was kept
for 5 days at 20 C (run no. 17). When the same mix-
ture containing 0.001 g of hydroquinone instead of
4- molecular sieves was heated for 3 h at 50 C, the
yield of semithioacetal VIc was 70% (according to
b. (Run nos. 8 and 9). A half of the reaction mix-
ture obtained as described in a was diluted with
a twofold volume of CDCl , and the mixture was
3
refluxed for 3 h.
1
the H NMR data).
c. (Run no. 12). p-Toluenesulfonic acid, 0.004 g
(
1 mol %), and hydroquinone, 0.001 g, were added to
Reaction of 2-ethoxypropenal (Ia) with excess
thiols. Butanethiol, 2.91 mmol (run no. 18), or ben-
zenethiol (run no. 19), p-toluenesulfonic acid,
a half of the reaction mixture obtained in run no. 1.
The mixture was kept for 24 h at room temperature.
0
.0025 g (5 mol %), and hydroquinone, 0.001 g, were
Reaction of 2-ethoxypropenal (Ia) with benzene-
thiol (IIc) (run no. 4). Hydroquinone, 0.001 g, and
benzenethiol, 0.53 g (4.85 mmol), were added to
added to a solution of 0.2 g (1.94 mmol) of compound
Ia in 2 ml of ether.
0
7
9
.45 g (4.85 mmol) of 2-etoxypropenal (Ia). After
days, the yield of acetal IIIc was quantitative; purity
5.5% (GC MS).
Reaction of 1,1-diethoxy-2-propanone (VII) with
thiols. Benzenethiol, 4.85 mmol (run no. 20), or
butanethiol (run no. 21), and 4- molecular sieves,
3
g, were added to 0.7 g (4.85 mmol) of acetal VII.
Thermal decomposition of 2-ethoxy-2-(phenyl-
thio)propanal (IIIc). A mixture of 0.5 ml of acetal
Below are given the propeties of the compounds
prepared.
IIIc and 1 ml of CDCl was refluxed for 3 h, the
3
1
composition of the mixture being monitored by H
2
-Butylthio-2-ethoxypropanal (IIIa) was obtained
NMR spectroscopy (run no. 10). Taking into account
that chloroform can contain traces of HCl which
catalyzes the isomerization, pure acetal IIIc was also
heated for 3 h (without a solvent; run no. 11).
Isomerization of 2-ethoxy-2-(phenylthio)pro-
panal by the action of p-toluenesulfonic acid (run
no. 13). p-Toluenesulfonic acid, 0.008 g (1 mol %),
and hydroquinone, 0.001 g, were added to 0.5 ml of
acetal IIIc.
Reaction of 2-ethoxypropenal with butanethiol
in the presence of acids. d. (Run no. 14). Butane-
thiol, 0.87 g (1.04 ml, 9.7 mmol), and concentrated
hydrochloric acid, 1 drop (1 mol %), were added to
in run no. 16 by neutralization of the catalyst with
potassium carbonate, removal of the solvent, and
vacuum distillation. Yield 4.48 g (56%), bp 67 C
20
1
(
1 mm), nD = 1.4640. H NMR spectrum, , ppm:
3
0.88 t (3H, CH in Bu, J = 7.3 Hz), 1.26 t (3H, CH
3
3
in Et), 1.35 m (2H, CH CH in Bu), 1.45 m (2H,
2
3
SCH CH ), 1.53 s (3H, CH CO), 2.35 t (2H, SCH ,
2
2
3
2
3
2
J = 7.35 Hz), 3.55 d.q and 3.77 d.q (2H, OCH ,
2
3
J = 9.09, J = 7.04 Hz), 9.07 s (1H, CHO). Mass
spectrum, m/z (I , %): 190 (1) M , 161 (100) [M
+
rel
+
+
+
CHO] , 133 (45) [M Bu] , 101 (14) [M SBu] , 73
1
(46), 59 (24). 43 (78). IR spectrum (film), , cm :
2955 s, 2925 s, 2870, 2820, 1725 v.s (C O), 1445,
1380, 1200, 1145 1155, 1100, 1070, 1045 s. Found,
%: C 57.60; H 9.70; S 16.48. C H O S. Calculated,
0.97 g (9.7 mmol) of 2-ethoxypropenal (Ia). The
mixture spontaneously warmed up to 50 C and was
kept at 20 C.
9
18
2
%: C 56.80; H 9.53; S 16.85.
e. (Run no. 15). Butanethiol, 0.87 g (1.04 ml,
.7 mmol), p-toluenesulfonic acid, 0.016 g (1 mol %),
and freshly calcined 4- molecular sieves, 3 g, were
added to 0.97 g (9.7 mmol) of 2-ethoxypropenal (Ia).
2-Allylthio-2-ethoxypropanal (IIIb) (run no. 2).
1
3
9
H NMR spectrum, , ppm: 1.27 t (3H, CH in Et,
3
J = 7.0 Hz), 1.53 s (3H, CH ), 3.06 d.d (2H, SCH ,
3
2
2
J = 6.5 Hz), 3.58 d.q and 3.80 d.q (2H, OCH , J =
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

REACTIONS OF 2-ALKOXYPROPENALS WITH THIOLS
975
3
3
9
5
.0, J = 7.0 Hz), 5.06 d (1H, CH , J = 9.6 Hz),
1.63 s (3H, CH ), 2.5 m (2H, SCH ), 9.05 s (1H,
3 2
2
3
+
.16 d (1H, CH , J = 16.8 Hz), 5.58 d.d.t (1H,
CH , J = 16.8, J = 9.6, J = 6.5 Hz), 9.12 s (1H,
CHO). Mass spectrum, m/z (I , %): 145 (88) [M
CHO] , 129 (2) [M OEt] , 117 (3), 101 (15) [M
SCH2 CH CH ] , 75 (32), 73 (71) [SCH
CH CH ] , 59 (18) (CH CS), 45 (62) [OEt] , 43
100) [CH CO] .
-Ethoxy-2-(phenylthio)propanal (IIIc) was
isolated by vacuum distillation of the reaction mixture
obtained in run no. 4. bp 120 124 C (3 mm), n
.5560. H NMR spectrum, , ppm: 1.28 t (3H,
CHO). Mass spectrum, m/z (I , %): 234 (1) M , 205
2
rel
+
3
3
3
(
4
100) [M CHO] , 149 (11), 103 (7), 93 (10), 59 (74),
+
1 (30), 29 (42) [CHO] .
rel
+
+
1,1-Bis(butylthio)-2-propanone (Va) (run no. 9).
+
1
H NMR spectrum, , ppm: 0.9 t (6H, CH in Bu),
2
2
3
+
+
2
3
1.4 m (4H, SCH CH CH ), 1.53 m (4H, SCH CH ),
2
2
2
2
2
+
(
3
2.35 s (3H, CH ), 2.35 m (4H, CH S), 5.28 s (1H,
3 2
SCHS). Mass spectrum, m/z (I , %): 234 (1) M , 205
rel
(2) [M CHO] , 191 (100), 135 (27), 89 (6) [SBu] ,
+
2
+
+
2
2
=
79 (21), 43 (81), 41 (37).
D
1
1
1
,1-Bis(phenylthio)-2-propanone (Vb) (run
3
1
OCH CH , J = 7.0 Hz), 1.55 s (3H, CH CO), 3.7 d.q
2
3
3
no. 11). H NMR spectrum, , ppm: 2.35 s (3H, CH ),
2
3
3
(
1H, OCH , J = 7.3, J = 7.0 Hz), 4.05 d.q (1H,
2
5.45 s (1H, SCHS), 7.29 m and 7.44 m (10H, Ph).
2
3
OCH , J = 7.3, J = 7.0 Hz), 7.29 m (3H, p-H, m-H),
+
2
Mass spectrum, m/z (I , %): 231 (41) [M CH CO] ,
3
rel
3
7
.43 d (2H, o-H, J = 8.0 Hz), 9.17 s (1H, CHO).
C NMR spectrum (CDCl3), , ppm: 15.06 (CH ),
9.44 (CH ), 58.81 (CH ), 128.92 (C ), 128.87 (C ),
35.42 (C ), 193.47 (CHO). Mass spectrum, m/z
I , %): 210 (1) M , 181 (100) [M CHO] , 165 (2)
M OEt] , 153 (8), 137 (3), 123 (6), 110 (50)
HSPh] , 109 (66) [SPh] , 101 (34) [M SPh] , 73
100), 65 (43), 45 (67) [OEt] , 43 (70). Found, %:
C 62.64; H 6.3; S 15.66. C H O S. Calculated, %:
C 62.83; H 6.71; S 15.25.
-Benzylthio-2-ethoxypropanal (IIId) (run no. 6).
H NMR spectrum, , ppm: 1.24 t (3H, CH in Et,
J = 7.0 Hz), 1.54 s (3H, CH ), 3.71 d.q and 3.78 d.q
2H, OCH , J = 9.0, J = 7.0 Hz), 7.24 m (5H, Ph),
.09 s (1H, CHO). Mass spectrum, m/z (I , %): 195
49) [M CHO] , 179 (1) [M OEt] , 167 [M
CHOC H ] (1), 123 (3) [M SCH Ph] , 108 (1), 101
3) [M SCH Ph] , 91 (100) [PhCH ] , 77 (9) [Ph] ,
3 (27), 59 (7), 45 (44) [C H ] .
-Butylthio-2-methoxypropanal (IIIe) (run
no. 13). H NMR spectrum, , ppm: 0.88 t (3H, CH3
in Bu), 1.39 m (2H, CH CH ), 1.50 s (3H, CH ),
.55 m (2H, CH CH S), 2.53 m (2H, SCH ), 3.40 s
3H, OCH ), 9.06 s (1H, CHO). Mass spectrum, m/z
I , %): 147 (100) [M CHO] , 91 (73), 87 (32), 73
3), 59 (93), 43 (47).
-Methoxy-2-(phenylthio)propanal (IIIf) (run
no. 5). H NMR spectrum, , ppm: 1.56 s (3H, CH ),
.59 s (3H, OCH ), 7.28 m and 7.41 m (5H, Ph),
.15 s (1H, CHO). Mass spectrum, m/z (I , %):
+
+
1
65 (28) [M SPh] , 121 (46), 109 (41) [SPh] , 77
1
3
+
+
+
C
3
(31) [Ph] , 43 (100) [CH CO] , 28 (87) [CO] .
p
o
3
1
1
(
[
[
(
3 2
m
1-Butylthio-1-ethoxy-2-propanone (VIa) was
obtained as described above in e (run no. 15) from
2.75 g (27.5 mmol) of 2-ethoxypropenal. The mixture
was neutralized by passing it through a layer of potas-
sium carbonate. The product was isolated by vacuum
distillation. Yield 1.25 g (23%), bp 75 C (3 mm),
+
+
rel
+
+
+
+
+
1
1
14
2
20
D
1
n
= 1.4510. H NMR spectrum, , ppm: 0.84 t (3H,
CH in Bu, J = 7.3 Hz), 1.21 t (3H, CH in Et, J =
3
3
2
3
7
1
.0 Hz), 1.33 m (2H, CH CH in Bu, J = 7.5 Hz),
1
3
2 3
3
.48 m (2H, SCH CH ), 2.21 s (3H, CH CO), 2.45 m
2
2
3
2
3
(
2H, SCH ), 3.45 d.q and 3.84 d.q (2H, OCH , J =
2
3
2
2
(
9
(
3
2
9
.0, J = 7.0 Hz), 4.80 s (1H, CH). Mass spectrum,
+
+
rel
m/z (I , %): 190 (1) M , 147 (69) [M CH CO] , 119
+
+
rel
3
+
(48) [M CH CO C H ] , 101 (2), 91 (6), 73 (19),
+
+
3 2 4
+
+
2
5
2
57 (39), 43 (100) [CH CO] , 29 (58) [Et] , 27 (50).
+
+
+
3
(
7
2 2
Found, %: C 56.62; H 9.52; S 16.11. C H O S. Cal-
+
9
18
2
2 5
culated, %: C 56.84; H 9.47; S 16.85.
2
1
-Ethoxy-1-phenylthio-2-propanone (VIc) was
1
obtained by keeping the reaction mixture from run
no. 17 for 3 h at 50 C, neutralization of the catalyst
2
3
3
1
2 2 2
(
K CO ), and vacuum distillation. A considerable
2 3
(
(
(
3
amount of diphenyl disulfide was formed during dis-
+
20
1
rel
tillation. bp 120 C (2 mm), nD = 1.5515. H NMR
3
spectrum, , ppm: 1.29 t (3H, OCH CH , J =
2
3
2
7
.0 Hz), 2.07 s (3H, CH CO), 3.54 d.q (1H, OCH ,
3 2
1
2
3
2
3
J = 7.3 Hz, J = 7.0 Hz), 4.05 d.q (1H, OCH , J =
7.3, J = 7.0 Hz), 5.03 s (1H, OCHS), 7.29 m and
2
3
3
9
1
[
(
(
3
rel
7.44 m (5H, Ph). Mass spectrum, m/z (I , %): 210 (4)
rel
+
+
+
+
96 (27) [M] , 167 (16) [M CHO] , 152 (1)
PhSCOMe] , 135 (100) [M CHO MeOH], 123
60), 110 (74) [PhSH] , 109 (60) [PhS] , 91 (12), 77
16), 65 (25), 59 (11), 45 (35), 39 (12).
M , 167 (100) [M CH CO] , 139 (84) [M CH CO
3 3
+
+
+
+
C H ] , 111 (65), 109 (40) [SPh] , 77 (41) [Ph] ,
2 4
73 (26), 45 (69) [OEt] , 43 (85). Found, %: C 62.45;
H 7.18; S 15.68. C H O S. Calculated, %: S 62.83;
+
+
+
1
1
14
2
H 6.71; S 15.25.
2
,2-Bis(butylthio)propanal (IV) (run no. 1).
1
H NMR spectrum, , ppm: 0.89 t (6H, CH in Bu),
.4 m (2H, SCH CH CH ), 1.55 m (2H, SCH CH ),
1,1-Diethoxy-2-propanone (VII) (run no. 12).
3
1
3
1
H NMR spectrum, , ppm: 1.24 t (6H, 2CH , J =
2
2
2
2
2
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

9
7
76
KEIKO et al.
.0 Hz), 2.18 s (3H, CH CO), 3.69 q and 3.56 q (4H,
4. Griffith, O.W. and Meister, A., J. Biol. Chem., 1979,
3
2
3
AB system, 2OCH , J = 9.5, J = 7.0 Hz), 4.52 s
vol. 254, no. 16, pp. 7558 7560.
2
(
1H, CH). Mass spectrum, m/z (I , %): 103 (24)
rel
5. Cossy, J. and Pete, J.-P., Bull. Soc. Chim. Fr., 1988,
+
+
[M MeCO] , 75 (31) [M MeCO C H ] , 73 (29),
2 4
no. 6, pp. 989 994.
4
7 (100), 45 (42), 43 (89). The spectra of acetal VII
6
7
.
.
Keiko, N.A., Stepanova, L.G., Kalikhman, I.D., and
Voronkov, M.G., Izv. Akad. Nauk SSSR, Ser. Khim.,
were identical to those reported in [14]. Compounds
VIb, VId, and VIe (runs nos. 2, 5, and 6, respec-
tively), by analogy with O,S-acetals VIa and VIb
were identified by the appearance of singlets in the
1
986, no. 3, pp. 722 724.
Hall, S.S., Doweyko, L.M., Doweyko, A.M., and
Zelenovski, J.S.R., J. Med. Chem., 1977, vol. 20,
no. 10, pp. 1239 1242.
regions 2.07 2.21 (CH CO) and 4.8 5.03 ppm
3
[CH(OR)(SR)] with an intensity ratio of 3:1.
8
9
.
.
Grigor’eva, N.Y., Tsiklauri, P.G., and Buevich, A.V.,
Mendeleev Commun., 1998, no. 2, pp. 76 77.
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.
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1
1
0. Duhamel, L., Chauvin, J., and Messier, A., Tetra-
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002