Reactions of Thioacetamide Derivatives with Sulfonyl Azides: An Approach to Active-Methylene N-Sulfonylacetamidines

Article abstract of DOI:10.1002/ejoc.201500968

Reactions of functionalized [CN, CO₂Et, C(O)NHR, C(S)NR¹R²] derivatives of thiomalonic acid and 2-arylthioacetamides with sulfonyl azides were shown to give active-methylene N-sulfonylamidines in 62-98 yields. Various procedures for the reactions, including the use of pyridine, boiling ethanol, and water, or running the reactions in the absence of a base and solvent at 80 C, were carried out and compared. The solvent-free variant was the best in terms of yield, and also because it does not require the use of an excess of the toxic and hazardous azides. The reaction was shown to tolerate electron-withdrawing substituents such as carbonyl, cyano, and aryl groups at the C-2 position. The presence of alkyl and phenyl groups on the nitrogen atom of the thioacetamide fragment, and the presence of substituents on the sulfonyl group were also tolerated. Thus, an efficient solvent-free, catalyst-free, and base-free synthetic approach for the synthesis of N-sulfonylmalonacetamidines and 2-arylacetamidines was found. An efficient, solvent-free and base-free approach to active-methylene N-sulfonylacetamidines has been developed.

Full text of DOI:10.1002/ejoc.201500968

Job/Unit: O50968
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Date: 24-09-15 11:33:27
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FULL PAPER
DOI: 10.1002/ejoc.201500968
Reactions of Thioacetamide Derivatives with Sulfonyl Azides: An Approach to
Active-Methylene N-Sulfonylacetamidines
[
a]
[a]
[a]
[a]
[a]
Lidia Dianova, Vera Berseneva, Tetyana Beryozkina, Ilya Efimov, Maria Kosterina,
[a]
[a,b]
[a]
Oleg Eltsov, Wim Dehaen,
and Vasiliy Bakulev*
Keywords: Synthetic methods / Azides / Sulfonamides / Thioamides
Reactions of functionalized [CN, CO
NR R ] derivatives of thiomalonic acid and 2-arylthioacet-
amides with sulfonyl azides were shown to give active-meth-
2
Et, C(O)NHR, C(S)-
cess of the toxic and hazardous azides. The reaction was
shown to tolerate electron-withdrawing substituents such as
carbonyl, cyano, and aryl groups at the C-2 position. The
1
2
ylene N-sulfonylamidines in 62–98% yields. Various pro- presence of alkyl and phenyl groups on the nitrogen atom of
cedures for the reactions, including the use of pyridine, boil-
ing ethanol, and water, or running the reactions in the ab-
sence of a base and solvent at 80 °C, were carried out and
compared. The solvent-free variant was the best in terms of
yield, and also because it does not require the use of an ex-
the thioacetamide fragment, and the presence of substituents
on the sulfonyl group were also tolerated. Thus, an efficient
solvent-free, catalyst-free, and base-free synthetic approach
for the synthesis of N-sulfonylmalonacetamidines and 2-aryl-
acetamidines was found.
Introduction
Ir-catalyzed insertion of a sulfonyl imino group into C–H
bonds in reaction with sulfonyl azides has also been re-
ported.
We turned our attention to reactions of thioamides bear-
ing active methylene groups with sulfonyl azides. It is well
known that the reaction of thioamides of malonic and
cyanoacetic acids 1 with sulfonyl azides represents a good
Sulfonyl azides, mostly tosyl and mesyl azides, show a
wide range of reactivities, and are widely used in organic
[13]
[
1–3]
synthesis.
They serve as diazo-transfer agents, and allow
the synthesis of various types of diazo compounds from C–
H-acidic compounds,
[4,5]
[6]
of azides from amines, and of
N-unsubstituted 1,2,3-triazoles from enamines.[ They can
undergo cycloaddition reactions with acetylenes to give 1-
sulfonyl-1,2,3-triazoles, in which they are the source of the
sulfonyl triaza fragment.[ They can react with enamines to
form N-sulfonyl derivatives of diamino alkenes, and here
7]
method for the synthesis of 5-amino-1,2,3-thiadiazoles 2
[14,15]
(Scheme 1).
The reaction of mesyl and benzenesulfonyl
azides with thioacetamides 3, in which the methylene group
8]
is not activated, takes a different direction, leading to the
[16]
formation of acetamidines 4.
Recently, we discovered
[
7,9]
they serve as the source of the sulfonyl imino fragments.
In the last decade, two powerful synthetic methods were
developed based on metal-catalyzed processes for the gener-
that tosyl azide can react with N,N-disubstituted cyano-
[10–12]
ation of N-sulfonylazavinyl carbenoids
and N-sulf-
onyl-substituted ketenimines[ from acetylenes and sulfonyl
azides, followed by reaction with various nucleophilic rea-
gents to form a huge variety of different types of valuable
heterocyclic and organic compounds, such as amidines,
sulfonamides, azadienes, α-amino ketones, cyclopentadi-
enes, etc. Also in these reactions, sulfonyl azides provide the
sulfonyl imine fragments for the reaction products. Rh- and
3]
[
a] TOSLab of Ural Federal University named after the first
President of Russia B. N. Yeltsin,
1
9 Mira st., 620002 Yekaterinburg, Russia
E-mail: v.a.bakulev@urfu.ru
http://urfu.ru/en/home/faculties/hti/
[b] Molecular Design and Synthesis, Department of Chemistry,
KU Leuven,
Celestijnenlaan 200F, 3001 Leuven, Belgium
Supporting information and ORCID(s) from the author(s) for
this article are available on the WWW under http://dx.doi.org/
Scheme 1. Reactions of sulfonyl azides with thioacetamide deriva-
tives.
1
0.1002/ejoc.201500968.
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V. Bakulev et al.
FULL PAPER
thiocetamide 5 in the presence of triethylamine to give 4- noacetamidine 10a. All our attempts to improve this proto-
tosylamidino-1,2,3-thiadiazoles 6 and 7; in this reaction it col failed. Luckily, we found that cyanothioacetamide 8a
acts as the source of both diazo and sulfonyl imino reacted smoothly with an equimolar amount of tosyl azide
[
17]
groups.
and sulfonyl imino fragments in reactions of thioamides midine 10a in 97% yield (Scheme 2). Encouraged by this
with sulfonyl azides. result, we expanded the reaction to a variety of sulfonyl
Thus, sulfonyl azides could be donors of diazo (9b) in the absence of solvent at 80 °C to form cyanoaceta-
In contrast to similar reactions in the presence of bases, azides 9, and to primary, secondary, and tertiary thioamides
the reactions of thioamides bearing an active methylene of cyanoacetic acid, functionalized derivatives of thiocarb-
group with sulfonyl azides have, to the best of our knowl- amoyl acetic acid, mono- and dithioamides of malonic acid,
edge, never been studied under base-free conditions. To de- and thioamides of arylacetic acid 8a–8m (Figure 1). We
velop a new and efficient approach to functionalized deriva- found that the reaction tolerates electron-withdrawing sub-
tives of N-sulfonylacetamidines 10, a detailed study of the stituents such as carbonyl, cyano, and aryl groups at the C-
reactions of thiomalonamides and 2-arylthioacetamides 8 2 position, and also tolerates the introduction of alkyl
with arylsulfonyl and mesyl azides 9 under various condi- groups and phenyl substituents onto the nitrogen atom of
tions was carried out.
the thioacetamides. Indeed, a small series of N-sulfonyl
cyanoacetamidines 10A were prepared in 80–97% isolated
yields. We also demonstrated that sulfonyl azides such as
tosyl, mesyl, 4-fluorophenyl, 2,4-dimethylphenyl, and
Results and Discussion
Two papers, apart from ours,[17] have been published on benzothiadiazolylsulfonyl azides 9a–9e readily react with 2-
the reactions of thioamides with sulfonyl azides. The first arylthioacetamides 8f–8h and functionalized derivatives of
report, from O. V. Zelenskaya et al., deals with the prepara- thiocarbamoyl acetic acid 8i–8m to form amidines 10B–10D
tion of sulfonyl amidines by the reaction of thioamides with in 62–98% yields. Interestingly, both substituted and unsub-
tosyl azide under relatively harsh conditions: heating at 90– stituted thioamide groups of malondithioamides 7k–7m re-
00 °C in pyridine for 5 h.[ Conversely, M. Aswad et al. act with tosyl azide to form bis-acetamidines 10q–10s. All
18]
1
found that thioamides of acetic and benzoic acids 3 and our attempts to induce 4-nitrophenyl and 1-methyl-4-nitro-
cyclic thioamides react with benzenesulfonyl and mesyl az- imidazol-5-yl azides into reaction with thioamides 8 failed.
ides under very mild conditions in ethanol or other organic Working with tosyl azide and other sulfonyl azides at 80 °C
solvents, or even in water, under catalyst-free conditions, can be considered safe, certainly on the scale we worked on,
to form the corresponding amidines (i.e., 4) in very good but at temperatures above 120 °C, rapid decomposition may
[
16]
yields.
Based on literature data on the reaction of occur, so we advise against working at such high tempera-
[14–18]
thioamides with azides,
apart from amidines, various tures or on a scale where the reaction energy could not be
heterocyclic compounds could be formed as a result of the effectively dissipated. The elimination of dinitrogen results
reactions of malonic acid thioamides and 2-arylthioacetam- in the formation of amidines 10, as evidenced by the pres-
–1
–1
ides 8 with sulfonyl azides 9 (Figure 1). This complicates ence of cyano (2254 cm ) and carbonyl (1740 cm ) stretch-
the development of a selective and efficient method for a ing in the IR spectra. Mass spectral data and further NMR
base-catalyzed preparation of N-sulfonylacetamidines of sectroscopic data were all in good agreement with the struc-
type 10. We started our experiments by studying the reac- tures of compounds 10: proton signals typical for the meth-
tion of tosyl azide (9b) with cyanothioacetamide 8a ylene group at δ = 3.80–4.32 ppm, and for the cyclic amines
1
(
Scheme 2). Thioamide 8a was found to be unreactive when at δ = 1.14–4.01 ppm in the H NMR spectra; carbon sig-
we used ethanol at room temperature, under the conditions nals at δ = 18.8–51.1 ppm (CH ) and at δ = 154.9–
2
[
17]
13
15
of Aswad. We also found that the reaction of thioamide 168.5 ppm (C=NTs) in the C NMR spectra; two N sig-
8
a with tosyl azide in pyridine, according to Zelenskaya et nals due to the nitrogen atoms of the amidine fragment at
[18]
1
15
al., led to an oily brown residue containing traces of cya- δ = 121.5 and 123.5 ppm derived from H, N HMBC spec-
Figure 1. Structures of starting thioamides 8 and azides 9.
2
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Reactions of Thioacetamide Derivatives with Sulfonyl Azides
Scheme 2. Reactions of thioamides 8a–8m with sulfonyl azides 9a–9e.
tra. Final proof of the structures of amidines 10, and the tons bound to Me and CH , we can conclude that N-mono-
2
connectivity of the methylene, cyano, and sulfonyl groups subsituted amidines 10q and 10r also exist in tautomeric
1
and nitrogen atoms, came from 2D HSQC data and HMBC form II. Interestingly, in the H NMR spectra of amidines
1
13
1
15
H, C and H, N spectra. The HSQC spectrum of amid- 10c and 10o–10r, which contain an NH group, the NH
2
ine 10a showed cross-peaks for all of the carbon and protons appear as two singlets. This fact could be interpre-
hydrogen atoms of each of the C–H bonds. The HMBC ted in favor of tautomer III. Alternatively, this can be ex-
spectrum of amidine 10a showed cross-peaks between the plained by the nonequivalence of the protons of the amino
proton signals of the methylene group at δ = 4.31 ppm and group, as we can see in the NMR spectra of thioamide 8k.
1
15
the carbon of the cyano group at δ = 113.1 ppm and the The 2D HSQC and HMBC H, N spectra of compound
carbon of the amidine group at δ = 154.9 ppm, and also 10p give evidence that the two hydrogen atoms are directly
between the signals of the morpholine OCH fragment at δ connected to the same nitrogen atom, as expected for tauto-
2
=
3.63 and 3.69 ppm and the amidine carbon atom signal mer II (see Supporting Information). Thus, all unsubsti-
at δ = 154.9 ppm. Remarkably, cross-peaks between the tuted, monosubstituted, and disubstituted N-sulfonyl amid-
methylene signals at δ = 4.31 ppm and both nitrogen atoms ines 10 exist in tautomeric form II. A plausible mechanism
of the amidine fragment at δ = 121.5 and 123.5 ppm were for the formation of amidines 10 is presented in Scheme 4.
1
15
observed in the H, N HMBC spectrum of compound 10a. We propose the formation of intermediate thiatriazolines 11
Acetamidines 10 bearing electron-withdrawing groups as the result of a 1,3-dipolar cycloaddition reaction between
can exist as a mixture of possible tautomeric forms I–III the azido group of the sulfonyl azides and the C=S bond
1
(
Scheme 3). Form I was rejected based on the H NMR of thioamides 7. Thiatriazolines are known to be produced
1
[19,20]
spectra. The H NMR spectra of all compounds 10 contain by the reaction of azides with N-tosyl isothiocyanates.
singlet signals due to the protons of the methylene group; They are proposed intermediates in reaction of mono- and
N,N-disubstituted amidines 10a, 10b, and 10e–10n do not dithioacids with sulfonyl azides to form N-sulfonylamides
[
20]
[16]
contain NH proton signals, confirming their existence in and thioamides.
Aswad et al.
proposed a stepwise
1
form II. Because the H NMR spectra of N-methyl- (10q) mechanism for the formation of thiatriazolines based on the
and N-benzyl-acetamidines (10r) show signals for NH pro- evidence of the increased rate of the reaction of thioamides
Scheme 3. Tautomerism in N-sulfonylacetamidines.
Scheme 4. Plausible mechanism of the formation of amidines 10.
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V. Bakulev et al.
FULL PAPER
with mesyl and benzenesulfonyl azides in polar solvents. In been shown to take place in either ethanol or water at re-
any case, elimination of dinitrogen and sulfur from thiatria- flux, or under solvent-free conditions at 80 °C, to form N-
zoline 11 finalizes the formation of amidines 10; this degra- sulfonylacetamidines and N-sulfonylmalonamidines in good
dation process is typical for 1,2,3,4-thiatriazoles.[
19]
yields. The solvent-free procedure is the best in terms of
We also found that sulfonylacetamidines 10 can be pre- yield; it is also more environmentally friendly and safer be-
pared by the reaction of thioamides 8f, 8j, and 8m with cause it requires only an equimolar amount of the toxic
azide 9b in either boiling ethanol or water. But for the reac- azides, rather than the five-fold excess required in solvents.
tion to go to completion, 5 equiv. of azide 9b was required, The reaction has a wide scope. Obviously, the reaction has
probably because of hydrolysis of the latter compound un- a rather general character with respect to the thioamides,
der these conditions. The synthesis of amidines 10f, 10j, and and is limited to sulfonyl azides. Thus, an efficient, solvent-
10m in the absence of a solvent has some advantages over free and catalyst-free method to prepare functionalized de-
the reactions in ethanol and water in terms of yield and rivatives of N-sulfonylmalonacetamidines and 2-arylaceta-
reaction time, and also as a lower amount of hazardous midines has been developed.
azides 9b was required (see Table 1).
Table 1. Comparative studies of the reaction of thioamides 8f, 8j,
and 8m with azide 9b.
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded at 400
Product
Yield [%][a]
Yield [%][b]
Yield [%][c]
and 100 MHz, respectively, with a Bruker DRX 400 instrument in
[D ]DMSO or CDCl . SiMe was used as an internal reference, and
6 3 4
1
1
1
0f
83
92
86
61
65
58
79
82
84
0j
0m
δ values are given in ppm. The mass spectra of 8m and 10a–10s
were obtained (EI, 70 eV) with a Shimadzu GC–MS-QP2010 Ultra
spectrometer with direct introduction of the sample into the ion
source. The mass spectrum of compound 10a was recorded with a
Bruker Daltonics instrument using electrospray ionization. IR
spectra were recorded with a Bruker Alpha FTIR spectrometer
[
a] In the absence of solvent at 80 °C for 0.5 h. [b] Reflux in anhy-
drous EtOH with 9b (5 mol) for 20–30 h. [c] Reflux in boiling water
with 9b (5 mol) for 20 h.
Thus, we have developed an efficient and environmen-
2
1
tally friendly approach to highly C- and N -substituted N -
sulfonylacetamidines. Amidines are found in many biolo-
(
ZnSe ATR accessory). Microanalysis was carried out with a
CHNS/O Perkin–Elmer 2400 II elemental analyzer. Reactions were
gically active natural products,[ and have been identified monitored by TLC (Silyfol® on aluminium foil plates), eluting with
21]
as important pharmacophores.[ Recently, amidines con- CHCl
22]
3 3
/hexane (9:1), CHCl /benzene (7:1), EtOAc/hexane (1:3), or
taining sulfonyl groups were identified as osteoclast differ- EtOAc/hexane (1:6). TLC plates were visualized under UV light.
entiation inhibitors.[
23]
Melting points were determined with a Stuart SMP-10 apparatus.
Unlike amidines in general, N-sulf-
onylacetamidines bearing electron-withdrawing groups on
the carbon atom are represented in the literature only by a thioamides 8e–8h,[ and dithioamides 8k–8m[30] were prepared ac-
[28]
thioamides 8c, 8i, and 8j,[15,28]
Thiomalonamides 8a, 8b, and 8d,
29]
very few examples, and their chemical properties have been cording to known procedures. Azides 9a–9e were bought from com-
[
24–26]
poorly studied.
As they have both nucleophilic and mercial suppliers.
electrophilic functionalities, they are promising chemical
reagents for organic synthesis.
3
-(Piperidin-1-yl)-3-thioxopropanethioamide (8m): The compound
was obtained by analogy[30] from 2-(piperidin-1-yl)-2-thioxoaceto-
Our preliminary experiments with reaction of amidine nitrile.[ Yellow needles (35%), m.p. 119–121 °C. H NMR ([D ]-
29]
1
6
1
0o with methyl 2,4-dioxovalerate (12) in ethanol solution DMSO): δ = 1.66–1.69 (m, 6 H, CH
2
), 3.85–3.78 (m, 2 H, CH
), 4.20–4.17 (m, 2 H, CH ), 8.90 (s, 1 H, NH),
]DMSO): δ = 23.3, 25.0,
6.1, 50.7, 51.7, 57.6, 192.0, 200.0 ppm. IR: ν˜ = 3266 (NH), 3140
2
),
4
9
2
.14 (s, 2 H, CH
2
2
at room temperature in the presence of triethylamine have
shown that both the amine and methylene groups can be
involved in a cyclization process to form pyrrolo[3,4-c]pyr-
idine 13 in 69% yield (Scheme 5). This reaction is similar
to the earlier reported reaction of unsubstituted carbamoyl-
1
3
.53 (s, 1 H, NH) ppm. C NMR ([D
6
–
1
+
(
6
NH) cm . MS (EI): m/z (%) = 202 [M] (18), 142 (17), 91 (100),
0 (30). C (202.34): calcd. C 47.49, H 6.97, N 13.84; found
8 14 2 2
H N S
C 47.88, H 7.34, N 13.57.
[
27]
acetamidines.
General Procedures for the Preparation N-Sulfonylamidines 10a–10s
General Procedure A: A mixture of the corresponding thiomalon-
amide 8 (1.0 equiv.) and azide 9 (1.0 equiv.) was heated at 80 °C for
Conclusions
Reactions of diversely substituted thioacetamides with 0.5–1 h. The reaction mixture was cooled, and ethanol was added.
The precipitate was collected by filtration, and purified by flash
aryl- and heteroarylsulfonyl azides and mesyl azide have
chromatography on silica gel (60–120) using EtOAc/hexane mix-
tures. To achieve better separation, the composition of the eluent
was gradually changed from 1:6 to 1:2, EtOAc/hexane.
N-(2-Cyano-1-morpholinoethylidene)-4-methylbenzenesulfonamide
1
(
10a): Colorless powder (97%), m.p. 125–127 °C. H NMR ([D
6
]-
), 4.47 (s,
), 7.36 (d, J = 8.0 Hz, 2 H, ArH), 7.73 (d, J = 8.0 Hz, 2
DMSO): δ = 2.37 (s, 3 H, CH
H, CH
H, ArH) ppm. C NMR ([D
65.8, 114.6, 126.3, 130.0, 140.7, 142.9, 156.1 ppm. IR: ν˜ = 2255
3 2
), 3.60–3.68 (m, 8 H, CH
2
2
1
3
Scheme 5. Reaction of amidine 10o with methyl 2,4-dioxovalerate
12).
6
]DMSO): δ = 19.3, 21.4, 45.7, 47.7,
(
4
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Reactions of Thioacetamide Derivatives with Sulfonyl Azides
–
1
+
(
8
CN) cm . MS (EI): m/z (%) = 307 [M] (2), 152 (100), 91 (46), NMR ([D
6
]DMSO): δ = 3.30–3.35 (m, 2 H, CH
), 3.47–3.49 (m, 2 H, CH ), 3.64–3.66 (m, 2 H, CH
(s, 2 H, CH ), 7.20–7.29 (m, 5 H, ArH), 7.74–7.77 (m, 1 H, ArH),
.18–8.21 (m, 2 H, ArH) ppm. C NMR (CDCl
47.1, 66.1, 125.5, 127.2, 127.8, 128.1, 129.0, 129.1, 133.6, 135.0,
50.0, 155.6, 165.5 ppm. MS (EI): m/z (%) = 402 [M]+ (10), 338
13), 135 (53), 86 (100). C18 (402.49): calcd. C 53.71, H
.51, N 13.92; found C 53.42, H 4.45, N 13.71.
2
), 3.41–3.43 (m, 2
+
6 (46). MS (ESI): m/z = 308 [M + H] . C14
calcd. C 54.72, H 5.53, N 13.68; found C 54.56, H 5.69, N 13.47.
H
17
N
3
O
3
S (307.37):
H, CH
2
2
2
), 4.58
2
1
3
8
3
): δ = 37.2, 45.3,
N-[2-Cyano-1-(pyrrolidin-1-yl)ethylidene]-4-methylbenzenesulfon-
amide (10b): Colorless powder (80%), m.p. 118–120 °C. H NMR
1
1
(
4
(
[D
CH
8.0 Hz, 2 H, CH
ArH), 7.70 (d, J = 8.0 Hz, 2 H, ArH) ppm. C NMR ([D
DMSO): δ = 20.2, 21.5, 24.1, 25.8, 48.3, 49.7, 112.9, 126.4, 129.4,
6
]DMSO): δ = 1.89–1.94 (m, 2 H, CH
), 2.40 (s, 3 H, CH ), 3.45 (t, J = 8.0 Hz, 2 H, CH
), 4.30 (s, 2 H, CH ), 7.30 (d, J = 8.0 Hz, 2 H,
2
), 1.97–2.04 (m, 2 H,
18 4 3 2
H N O S
2
3
2
), 3.68 (t, J
=
2
2
1
3
6
]-
N-[2-(4-Chlorophenyl)-1-morpholinoethylidene]methanesulfonamide
1
(10i): Colorless powder (85%), m.p. 127–129 °C. H NMR ([D ]-
DMSO): δ = 2.97 (s, 3 H, CH ), 3.30–3.40 (m, 4 H, CH ), 3.57–
6
–1
1
(
(
40.2, 142.7, 153.3 ppm. IR: ν˜ = 2254 (CN) cm . MS (EI): m/z
%) = 291 [M]+ (5), 136 (48), 91 (48), 70 (100). C14
291.37): calcd. C 57.71, H 5.88, N 14.42; found C 57.51, H 5.61,
3
2
H
17
N
3
O
2
S
2 2 2
3.60 (m, 2 H, CH ), 3.67–3.75 (m, 2 H, CH ), 4.39 (s, 2 H, CH ),
7.31 (d, J = 8.0 Hz, 2 H, ArH), 7.40 (d, J = 8.0 Hz, 2 H, ArH)
1
3
N, 14.23.
6
ppm. C NMR ([D ]DMSO): δ = 35.0, 43.4, 44.4, 46.5, 66.0,
1
29.0, 131.0, 131.3, 134.0, 164.2 ppm. MS (EI): m/z (%) = 316
2
-Cyano-NЈ-tosylacetimidamide (10c): Colorless powder (92 %),
+
1
2 3
[M] (25), 150 (100), 125 (44), 79 (21). C13H17ClN O S (316.80):
calcd. C 49.29, H 5.41, N 8.84; found C 49.49, H 5.64, N 9.03.
m.p. 128–130 °C. H NMR ([D
6
]DMSO): δ = 2.38 (s, 3 H, CH
3
),
3
8
.80 (s, 2 H, CH
.0 Hz, 2 H, ArH), 8.13 (s, 1 H, NH), 8.86 (s, 1 H, NH) ppm.
]DMSO): δ = 20.9, 26.1, 115.8, 126.3, 130.1, 139.7,
2
), 7.37 (d, J = 8.0 Hz, 2 H, ArH), 7.75 (d, J =
1
3
C
N-[2-(4-Chlorophenyl)-1-morpholinoethylidene]-4-methylbenzene-
sulfonamide (10j): Colorless powder (92%), m.p. 130–132 °C.
NMR ([D ]DMSO): δ = 2.36 (s, 3 H, CH ), 3.30–3.37 (m, 4 H,
6 3
1
NMR ([D
6
H
–1
143.2, 154.9 ppm. IR: ν˜ = 2254 (CN) cm . MS (EI): m/z (%) =
2
37 [M]+ (19), 155 (36), 91 (100), 65 (28). C10
11 3 2
H N O
S (237.28): CH ), 3.56–3.58 (m, 2 H, CH ), 3.67–3.70 (m, 2 H, CH ), 4.43 (s,
2
2
2
calcd. C 50.62, H 4.67, N 17.71; found C 50.43, H 4.61, N 17.97.
2 H, CH ), 7.22 (d, J = 8.0 Hz, 2 H, ArH), 7.30 (d, J = 8.0 Hz, 2
2
H, ArH), 7.38 (d, J = 8.0 Hz, 2 H, ArH), 7.69 (d, J = 8.0 Hz, 2 H,
N-(4-Chlorophenyl)-2-cyano-NЈ-tosylacetimidamide (10d): Pale yel-
1
3
1
ArH) ppm. C NMR ([D
6
]DMSO): δ = 21.6, 35.2, 45.2, 47.3, 66.0,
low powder (85%), m.p. 132–134 °C. H NMR ([D
6
]DMSO): δ =
1
26.3, 129.1, 129.7, 130.3, 131.8, 134.0, 141.6, 142.3, 164.8 ppm.
2
7
1
1
.39 (s, 3 H, CH
3 2
), 4.20 (s, 2 H, CH ), 7.38–7.46 (m, 4 H, ArH),
+
MS: m/z (%) = 393 [M] (2), 155 (79), 91 (100), 86 (66).
21ClN S (392.90): calcd. C 58.08, H 5.39, N 7.13; found C
7.87, H 5.20, N 7.09.
.57 (d, J = 8.0 Hz, 2 H, ArH), 7.78 (d, J = 8.0 Hz, 2 H, ArH),
0.92 (s, 1 H, NH) ppm. 1 C NMR ([D
3
C
5
19
H
2 3
O
6
]DMSO): δ = 20.7, 22.7,
14.8, 123.3, 125.9, 128.9, 129.5, 136.2, 139.6, 142.8, 153.7 ppm.
–1
+
IR: ν˜ = 2254 (CN) cm . MS (EI): m/z (%) = 347 [M] (7), 155
33), 91 (100), 65 (28). C16 14ClN S (347.82): calcd. C 55.25, H
.06, N 12.08; found C 55.12, H 3.86, N 12.17.
N-[2-(4-Chlorophenyl)-1-morpholinoethylidene]-2,4-dimethyl-
(
4
H
3 2
O
benzenesulfonamide (10k): Colorless powder (68 %), m.p. 120–
1
1
CH
22 °C. H NMR (CDCl
3
): δ = 2.36 (s, 3 H, CH
), 3.60–3.70 (m, 2 H, CH
3.85 (m, 2 H, CH ), 4.41 (s, 2 H, CH ), 7.02 (d, J = 8.0 Hz, 2 H,
3
), 2.70 (s, 3 H,
), 3.30–3.42 (m, 4 H, CH
2
2
), 3.70–
N-(1-Morpholino-2-phenylethylidene)methanesulfonamide (10e):
3
1
Colorless powder (60%), m.p. 85–88 °C. H NMR ([D
2.96 (s, 3 H, CH ), 3.23–3.41 (m, 4 H, CH ), 3.55–3.65 (m, 2 H,
CH ), 3.67–3.75 (m, 2 H, CH ), 4.39 (s, 2 H, CH ), 7.21–7.31 (m,
H, ArH), 7.34 (d, J = 8.0 Hz, 2 H, ArH) ppm. C NMR ([D
DMSO): δ = 36.3, 44.0, 44.9, 47.0, 66.0, 126.9, 128.5, 129.0, 135.3,
6
]DMSO): δ
2
2
ArH), 7.10 (d, J = 8.0 Hz, 2 H, ArH), 7.28 (d, J = 8.0 Hz, 2 H,
=
3
2
1
3
ArH), 7.88 (d, J = 8.0 Hz, 2 H, ArH) ppm. C NMR (CDCl
= 20.6, 21.3, 36.3, 45.0, 47.0, 66.3, 126.3, 127.8, 129.3, 129.4, 132.7,
32.9, 133.1, 137.0, 138.8, 142.5, 164.5 ppm. MS (EI): m/z (%) =
3
): δ
2
2
2
1
3
3
6
]-
1
+
+
20 23 2 3
407 [M] (8), 169 (89), 105 (100), 86 (83). C H ClN O S (406.93):
1
65.0 ppm. MS (EI): m/z (%) = 282 [M] (24), 116 (100), 86 (91),
9 (50). C13 S (282.36): calcd. C 55.30, H 6.43, N 9.92;
calcd. C 59.03, H 5.70, N 6.88; found C 59.28, H 5.42, N 7.07.
7
18 2 3
H N O
found C 55.59, H 6.69, N 9.73.
N-[2-(4-Chlorophenyl)-1-morpholinoethylidene]-4-fluorobenzene-
1
4
-Methyl-N-(1-morpholino-2-phenylethylidene)benzenesulfonamide
sulfonamide (10l): Colorless powder (98%), m.p. 164–166 °C.
H
[
27]
6 3
NMR ([D ]DMSO): δ = 3.37 (br. s, 4 H, CH ), 3.59 (br. s, 2 H,
CH ), 3.71 (br. s, 2 H, CH ), 4.44 (s, 2 H, CH ), 7.21 (d, J = 8.0 Hz,
2 2 2
(
10f):
Colorless powder (83 %), m.p. 153–155 °C (ref. 148–
1
1
50 °C). H NMR ([D
), 3.54–3.56 (m, 2 H, CH
.44 (s, 2 H, CH ), 7.20–7.26 (m, 3 H, ArH), 7.29–7.34 (m, 4 H,
6
]DMSO): δ = 2.35 (s, 3 H, CH
3
), 3.28–3.35
(m, 4 H, CH
2
2
), 3.67–3.70 (m, 2 H, CH
2
), 2 H, ArH); 7.30–7.40 (m, 4 H, ArH), 7.87 (d, J = 8.0 Hz, 2 H,
1
3
4
2
6
ArH) ppm. C NMR ([D ]DMSO): δ = 35.6, 45.0, 47.6, 66.1,
1
3
116.2, 116.4, 129.1, 129.2, 130.3, 130.2, 132.0, 140.8, 162.9, 164.9,
ArH), 7.70 (d, J = 8.0 Hz, 2 H, ArH) ppm. C NMR ([D
DMSO): δ = 21.4, 36.0, 45.2, 47.3, 66.0, 126.3, 127.0, 128.4, 129.1,
6
]-
165.4 ppm. MS (EI): m/z (%) = 396 [M]+ (11), 159 (47), 150 (100),
1
2 3
29.7, 135.1, 141.7, 142.2, 165.4 ppm. MS (EI): m/z (%) = 358 95 (91). C18H18ClFN O S (396.86): calcd. C 54.48, H 4.57, N, 7.06;
+
found C 54.58, H 4.49, N 6.82.
[M] (4), 155 (61), 91 (100), 86 (87). C19
22 2 3
H N O S (358.45): calcd.
C 63.66, H 6.19, N 7.82; found C 63.45, H 6.09, N 7.60.
N-[2-(4-Chlorophenyl)-1-(piperidin-1-yl)ethylidene]-4-methylbenz-
enesulfonamide (10m): Yellow powder (86%), m.p. 125–127 °C. H
1
4
-Fluoro-N-(1-morpholino-2-phenylethylidene)benzenesulfonamide
1
(10g): Colorless powder (62%), m.p. 130–133 °C. H NMR ([D
6
]-
), 3.26–3.29 (m, 2 H, CH
CH ), 7.11 (d, J = 8.0 Hz, 2 H, ArH), 7.20–7.26 (m, 4 H, ArH),
6
7.80 (d, J = 8.0 Hz, 2 H, ArH) ppm. C NMR ([D ]DMSO): δ =
NMR (CDCl
3
): δ = 1.53–1.60 (m, 6 H, CH
2
), 2.39 (s, 3 H, CH
3
),
DMSO): δ = 3.32–3.34 (m, 4 H, CH
2
), 3.50–3.62 (m, 2 H, CH
2
2
), 3.72–3.77 (m, 2 H, CH
2
), 4.38 (s, 2 H,
3
.66–3.72 (m, 2 H, CH
2
), 4.44 (s, 2 H, CH
2
), 7.13–7.41 (m, 7 H,
]DMSO): δ =
5.5, 44.8, 46.8, 66.5, 115.7, 115.9, 126.7, 127.8, 128.6, 128.7, 134.3,
40.3, 162.3, 164.8, 164.9 ppm. MS (EI): m/z (%) = 362 [M]+ (3),
59 (47), 116 (86), 86 (100). C18
9.65, H 5.28, N 7.73; found C 59.42, H 5.59, N 7.91.
2
ArH), 7.80–7.90 (m, 2 H, ArH) ppm. 13C NMR ([D
13
6
3
1
1
5
20.8, 23.1, 24.8, 35.0, 45.3, 47.3, 125.6, 128.4, 129.1, 131.0, 141.3,
141.5, 166.5 ppm. MS (EI): m/z (%) = 390 [M]+ (2), 155 (25), 91
H
2 3
19FN O
2 2
S (362.42): calcd. C (52), 84 (100). C20H23ClN O S (390.93): calcd. C 61.45, H 5.93, N
7.17; found C 61.58, H 5.69, N 6.92.
N-(1-Morpholino-2-phenylethylidene)benzo[c][1,2,5]thiadiazole-4-
N-[2-(4-Methoxyphenyl)-1-(4-methylpiperazin-1-yl)ethylidene]-
4-methylbenzenesulfonamide (10n): Yellow powder (79%), m.p. 103–
1
sulfonamide (10h): Colorless powder (55%), m.p. 123–126 °C.
H
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O50968
/KAP1
Date: 24-09-15 11:33:27
Pages: 8
V. Bakulev et al.
FULL PAPER
1
1
2
CH
CH
05 °C. H NMR ([D
6
]DMSO): δ = 2.02 (t, J = 4.0 Hz, 2 H, CH
), 2.27 (t, J = 4.0 Hz, 2 H, CH
), 3.34 (t, J = 4.0 Hz, 2 H, CH ), 3.66 (t, J = 4.0 Hz, 2 H,
), 3.74 (s, 3 H, OCH ), 4.29 (s, 2 H, CH ), 6.82 (d, J = 8.0 Hz,
2
),
C
22
H
28
N
4
O
4
S
2
(476.61): calcd. C 55.44, H 5.92, N 11.76; found C
.11 (s, 3 H, N-CH
3
2
), 2.38 (s, 3 H, 55.49, H 6.26, N 11.62.
3
2
General Procedure B: A solution of the corresponding thiomalon-
amide 8e–8g (1.0 equiv.) and tosyl azide (9b; 5.0 equiv.) in anhy-
drous EtOH was heated at reflux for 20–30 h. The reaction mixture
was concentrated in vacuo to dryness, and the residue was purified
by flash chromatography on silica gel (60–120) using EtOAc/hexane
mixtures. To achieve better separation, the composition of the elu-
ent was gradually changed from 1:6 to 1:2, EtOAc/hexane.
2
3
2
2
H, ArH), 7.11 (d, J = 8.0 Hz, 2 H, ArH), 7.27 (d, J = 8.0 Hz, 2
1
3
H, ArH), 7.66 (d, J = 8.0 Hz, 2 H, ArH) ppm. C NMR ([D
DMSO): δ = 26.2, 39.7, 49.7, 51.1, 51.8, 59.0, 60.1, 119.6, 131.3,
6
]-
1
4
31.9, 134.4, 146.7, 147.7, 163.1, 170.1 ppm. MS (EI): m/z (%) =
01 [M]+ (4), 246 (60), 91 (61), 70 (100). C21
S (401.52):
27 3 3
H N O
calcd. C 62.82, H 6.78, N, 10.47; found C 62.68, H 6.56, N 10.77.
General Procedure C: A suspension of the corresponding thio-
malonamide 8e–8g (1.0 equiv.) and tosyl azide (9b; 5.0 equiv.) was
heated at reflux in H O for 10–20 h. The solvent was removed in
2
vacuo, and the residue was purified by flash chromatography on
silica gel (60–120) using EtOAc/hexane mixtures. To achieve better
separation, the composition of the eluent was gradually changed
from 1:6 to 1:2, EtOAc/hexane.
3
-Amino-N-o-tolyl-3-(tosylimino)propanamide (10o): Colorless pow-
1
der (81%), m.p. 153–155 °C. H NMR ([D
H, CH ), 2.36 (s, 3 H, CH ), 3.46 (s, 2 H, CH
ArH), 7.18–7.21 (m, 3 H, ArH), 7.73 (d, J = 8.0 Hz, 2 H, ArH),
6
]DMSO): δ = 2.15 (s, 3
3
3
2
), 7.0–7.15 (m, 3 H,
1
3
8.16 (s, 1 H, NH), 8.73 (s, 1 H, NH), 9.47 (s, 1 H, NH) ppm.
C
6
NMR ([D ]DMSO): δ = 16.2, 21.4, 43.9, 125.2, 125.8, 126.4, 129.6,
1
30.8, 132.1, 136.4, 140.4, 142.6, 164.4, 165.3 ppm. IR: ν˜ = 3429
–1
(NH), 3325 (NH), 3239 (NH), 1670 (C=O) cm . MS (EI): m/z (%)
4
-Methyl-N-[6-methyl-1,3-dioxo-2-o-tolyl-2,3-dihydro-1H-pyrrolo-
+
=
19 3 3
345 [M] (3), 147 (63), 106 (89), 91 (100). C17H N O S (345.42):
[3,4-c]pyridin-4(5H)-ylidene]benzenesulfonamide (13): Methyl 2,4-di-
calcd. C 59.11, H 5.54, N 12.17; found C 59.22, H 5.64, N 12.37.
oxovalerate (12; 0.53 g, 3.6 mmol) and triethylamine (0.5 mL,
3.6 mmol) were added to a suspension of malonamidine 10o
(1.24 g, 3.6 mmol) in ethanol (5 mL). The reaction mixture was
Ethyl 3-Amino-3-(tosylimino)propanoate (10p): Colorless powder
1
(90%), m.p. 122–124 °C. H NMR (CDCl
3
): δ = 1.27 (t, J = 8.0 Hz,
), 3.37 (s, 2 H, CH
), 7.29 (d, J = 8.0 Hz, 2 H, ArH), 7.74 (br. s, 1 pound 12 was collected by filtration, and washed with ethanol and
3
8
H, CH
3
), 2.42 (s, 3 H, CH
3
2
), 4.20 (q, J = stirred at room temperature for 3 h. The yellow precipitate of com-
.0 Hz, 2 H, CH
2
1
H, NH), 7.82 (d, J = 8.0 Hz, 2 H, ArH), 8.17 (br. s, 1 H, NH)
ppm. 13C NMR (CDCl
): δ = 13.8, 21.9, 40.1, 62.0, 126.5, 129.3,
38.8, 143.1, 161.6, 168.7 ppm. IR: ν˜ = 3386 (NH), 3305 (NH), CH
hexane. Colorless powder (71 %), m.p. 173–175 °C. H NMR
(CDCl ): δ = 2.15 (s, 3 H, CH ), 2.43 (s, 3 H, CH ), 2.63 (s, 3 H,
), 7.15 (d, J = 4.0 Hz, 1 H, ArH), 7.24 (s, 1 H, =CH), 7.31–
740 (C=O) cm . MS (EI): m/z (%) = 284 [M] (14), 155 (18), 91 7.37 (m, 5 H, ArH), 7.15 (d, J = 4.0 Hz, 2 H, ArH), 8.69 (s, 1 H,
3
3
3
3
1
1
3
–1
+
1
3
(100), 65 (25). C12
H
16
N
2
O
4
S (284.33): calcd. C 50.69, H 5.67, N
3
NH) ppm. C NMR (CDCl ): δ = 17.8, 21.6, 25.4, 106.7, 111.5,
9
.85; found C 50.43, H 5.61, N 9.96.
126.9, 128.5, 129.1, 129.7, 131.4, 136.4, 136.6, 142.6, 144.6, 147.0,
165.6, 166.8, 167.3 ppm. MS (EI): m/z (%) = 421 [M]+ (3), 356
1
1
3
N -Methyl-NЈ ,NЈ -ditosylmalonimidamide (10q): Colorless powder
1
19 3 4
(100), 266 (35), 91 (58). C22H N O S (421.47): calcd. C 62.69, H
(
87%), m.p. 214–216 °C. H NMR ([D
CH ), 2.37 (s, 3 H, CH ), 2.68 (d, J = 4.0 Hz, 3 H, CH
H, CH ), 7.25 (d, J = 8.0 Hz, 2 H, ArH), 7.29 (d, J = 8.0 Hz, 2
H, ArH), 7.62 (d, J = 8.0 Hz, 2 H, ArH), 7.69 (d, J = 8.0 Hz, 2 H,
ArH), 7.97 (s, 1 H, NH ), 8.63 (s, 1 H, NH ), 8.69 (q, J = 4.0 Hz,
H, NH) ppm. 13C NMR ([D
]DMSO): δ = 21.1, 28.4, 125.8,
29.0, 139.8, 141.2, 142.0, 161.2, 163.6 ppm. MS (EI): m/z (%) =
57 [M – Ts]+ (30), 155 (30), 91 (100), 65 (28). C18
6
]DMSO): δ = 2.35 (s, 3 H,
4.54, N 9.97; found C 62.28, H 4.25, N 10.19.
3
3
3
), 3.73 (s,
2
2
Acknowledgments
2
2
1
1
3
6
This project was supported by the Russian Scientific Foundation
15-13-10031).
(
H
22
N
4
O
4
S
2
(422.52): calcd. C 51.17, H 5.25, N 13.26; found C 50.92, H 5.27,
N 13.03.
1
[1] B. A. Shainyan, L. L. Tolstikova, Chem. Rev. 2013, 113, 699–
1
3
733.
N -Benzyl-NЈ ,NЈ -ditosylmalonimidamide (10r): Colorless powder
[
[
[
2] H. Quast, S. Ivanova, E.-M. Peters, K. Peters, Eur. J. Org.
Chem. 2000, 122, 1577–1587.
1
(
82%), m.p. 170–172 °C. H NMR ([D
CH ), 2.36 (s, 3 H, CH ), 3.80 (s, 2 H, CH
H, CH ), 7.15–7.35 (m, 9 H, ArH), 7.55 (d, J = 8.0 Hz, 2 H,
ArH), 7.70 (d, J = 8.0 Hz, 2 H, ArH), 7.99 (s, 1 H, NH), 8.71 (s,
6
]DMSO): δ = 2.34 (s, 3 H,
3
3
2
), 4.38 (d, J = 4.0 Hz,
3] S. H. Kim, S. H. Park, J. H. Choi, S. Chang, Chem. Asian J.
2
2
2011, 6, 2618–2634.
4] M. Regitz, H. Schwall, Justus Liebigs Ann. Chem. 1969, 728,
H, NH), 9.15 (t, J = 4.0 Hz, 1 H, NH) ppm. 1 C NMR ([D
DMSO): δ = 20.8, 20.9, 44.7, 125.7, 126.0, 126.9, 127.5, 128.1,
28.9, 129.0, 137.0, 139.8, 141.1, 141.4, 142.0, 160.8, 163.6 ppm.
3
1
6
]-
99–107.
[5] E. F. Dankova, V. A. Bakulev, D. P. Krut’ko, Chem. Heterocycl.
Compd. 1991, 27, 607–613.
[6] J. Waser, H. Nambu, E. M. Carreira, J. Am. Chem. Soc. 2005,
1
+
MS (EI): m/z (%) = 343 [M – Ts] (48), 155 (30), 106 (35), 91 (100).
(498.62): calcd. C 57.81, H 5.26, N 11.24; found C
1
27, 8294–8295.
24 26 4 4 2
C H N O S
[
7] I. Efimov, V. Bakulev, N. Beliaev, T. Beryozkina, U. Knipp-
schild, J. Leban, Z.-J. Fan, O. Eltsov, P. Slepukhin, M. Ezhi-
kova, W. Dehaen, Eur. J. Org. Chem. 2014, 17, 3684–3689.
57.68, H 5.11, N 11.15.
3
-(Piperidin-1-yl)-NЈ-tosyl-3-(tosylimino)propanimidamide (10s):
1
Colorless powder (88%), m.p. 195–197 °C. H NMR ([D
6
]DMSO): [8] E. J. Yoo, M. Ahlquist, S. H. Kim, I. Bae, V. V. Fokin, K. B.
Sharpless, S. Chang, Angew. Chem. Int. Ed. 2007, 46, 1730–
δ = 1.44–1.60 (m, 6 H, CH
2
), 2.40 (s, 3 H, CH
), 3.50–3.62 (m, 2 H, CH
2
), 7.22 (d, J = 8.0 Hz, 2 H, ArH), 7.28 (d, J = 8.0 Hz, 2 H,
3
), 2.42 (s, 3 H, CH
3
),
1
733; Angew. Chem. 2007, 119, 1760–1763.
3
CH
.25–3.40 (m, 2 H, CH
2
2
), 4.10 (s, 2 H,
[
[
9] A. Contini, E. Erba, RSC Adv. 2012, 2, 10652–10660.
10] H. M. L. Davies, J. S. Alford, Chem. Soc. Rev. 2014, 43, 5151–
ArH), 7.63 (d, J = 8.0 Hz, 2 H, ArH), 7.68 (d, J = 8.0 Hz, 2 H,
5162.
ArH), 7.95 (s, 1 H, NH), 8.67 (br. s, 1 H, NH) ppm. 13C NMR
[
11] V. Bakulev, W. Dehaen, T. Beryozkina, Top. Heterocycl. Chem.
(CDCl
3
): δ = 21.5, 21.5, 23.9, 25.4, 39.8, 47.1, 48.8, 126.2, 126.6,
2015, 40, 1–50.
129.3, 129.5, 138.8, 140.1, 142.7, 143.4, 156.6, 161.7 ppm. MS (EI):
[12] B. Chattopadhyay, V. Gevorgyan, Angew. Chem. Int. Ed. 2012,
51, 862–872; Angew. Chem. 2012, 124, 886–896.
+
m/z (%) = 231 [M – Ts] (25), 155 (20), 91 (69), 84 (100).
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50968
/KAP1
Date: 24-09-15 11:33:27
Pages: 8
Reactions of Thioacetamide Derivatives with Sulfonyl Azides
[
[
[
[
[
[
[
[
13] D. Lee, Y. Kim, S. Chang, J. Org. Chem. 2013, 78, 11102–
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V. S. Petrosyan, Tetrahedron 1989, 45, 7329–7340.
16] M. Aswad, J. Chiba, T. Tomohiro, Y. Hatanaka, Chem. Com-
mun. 2013, 49, 10242–10244.
17] L. N. Dianova, V. S. Berseneva, O. S. El’tsov, Z.-J. Fan, V. A.
Bakulev, Chem. Heterocycl. Compd. 2014, 7, 972–978.
18] O. V. Zelenskaya, V. A. Kozinskii, A. V. Nazarenko, A. P. Ran-
skii, Russ. J. Appl. Chem. 1984, 57, 1071–1072.
[24] P. S. Lobanov, D. V. Dar’in, Chem. Heterocycl. Compd. 2013,
49, 507–528.
1
[
25] E. J. Yoo, I. Bae, S. H. Cho, H. Han, S. Chang, Org. Lett. 2006,
, 1347–1350.
8
[26] J. Motoyoshiya, A. Teranishi, R. Mikoshiba, I. Yamamoto, H.
Gotoh, J. Enda, Y. Ohshiro, T. Agawa, J. Org. Chem. 1980, 45,
5385–5387.
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Job/Unit: O50968
/KAP1
Date: 24-09-15 11:33:27
Pages: 8
V. Bakulev et al.
FULL PAPER
Sulfonyl Azides
An efficient, solvent-free and base-free ap-
proach to active-methylene N-sulfonylacet-
amidines has been developed.
L. Dianova, V. Berseneva, T. Beryozkina,
I. Efimov, M. Kosterina, O. Eltsov,
W. Dehaen, V. Bakulev* .................... 1–8
Reactions of Thioacetamide Derivatives
with Sulfonyl Azides: An Approach to Ac-
tive-Methylene N-Sulfonylacetamidines
Keywords: Synthetic methods / Azides /
Sulfonamides / Thioamides
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0