Reactions of β-azolylenamines with sulfonyl azides as an approach to N-unsubstituted 1,2,3-triazoles and ethene-1,2-diamines

Article abstract of DOI:10.1002/ejoc.201402130

The reactions of β-azolylenamines 1 with sulfonyl azides 2 in acetonitrile furnished 1H-4-(azol-5-yl)-1,2,3-triazoles 3 in yields of 52-93%. β-Benzoylenaminones and β-nitroenamine of type 1 also reacted with tosyl azide to form the same type of products 3, proving the generality and efficiency of the method for the synthesis of N-unsubstituted 1,2,3-triazoles. On the other hand, the reactions of 3-(1-aryl-1,2,3-triazol-5-yl)enamines with tosyl azide in the absence of a solvent afforded a mixture of (E)-1-dimethylamino-2-tosylaminoethenes 5 and N,N-dimethyl-N′- tosylformamidine 6 in yields of 40-50 and 20%, respectively. The formation of a variety of compounds from the reactions of enamines 1 with sulfonyl azides 2 is rationalized by the various possible transformations of the intermediate 5-dimethylamino-1,2,3-triazolines 7.

Full text of DOI:10.1002/ejoc.201402130

Job/Unit: O42130
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FULL PAPER
DOI: 10.1002/ejoc.201402130
Reactions of β-Azolylenamines with Sulfonyl Azides as an Approach to
N-Unsubstituted 1,2,3-Triazoles and Ethene-1,2-diamines
Ilya Efimov,[a] Vasiliy Bakulev,*[a] Nikolai Beliaev,[a] Tetyana Beryozkina,[a]
Uwe Knippschild,[b] Johann Leban,[c] Fan Zhi-Jin,[d] Oleg Eltsov,[a] Pavel Slepukhin,[e]
Marina Ezhikova,[e] and Wim Dehaen[f]
Keywords: Nitrogen heterocycles / Enamines / Cycloaddition / Azides / Reaction mechanisms
The reactions of β-azolylenamines 1 with sulfonyl azides 2
in acetonitrile furnished 1H-4-(azol-5-yl)-1,2,3-triazoles 3 in
yields of 52–93%. β-Benzoylenaminones and β-nitroenamine
of type 1 also reacted with tosyl azide to form the same type
of products 3, proving the generality and efficiency of the
method for the synthesis of N-unsubstituted 1,2,3-triazoles.
On the other hand, the reactions of 3-(1-aryl-1,2,3-triazol-5-
yl)enamines with tosyl azide in the absence of a solvent af-
forded a mixture of (E)-1-dimethylamino-2-tosylaminoeth-
enes 5 and N,N-dimethyl-NЈ-tosylformamidine 6 in yields of
40–50 and 20%, respectively. The formation of a variety of
compounds from the reactions of enamines 1 with sulfonyl
azides 2 is rationalized by the various possible transforma-
tions of the intermediate 5-dimethylamino-1,2,3-triazolines 7.
azolylenamines and their cycloaddition reactions with az-
ides (Scheme 1). This methodology was unknown before
our preliminary reports were published.[6e,7] The reactions
of β-azolylenamines with aryl and alkyl azides were shown
to be a convenient, regioselective, and general method for
the preparation of 4-azolyl-1,2,3-triazoles in which these en-
amines are the synthetic equivalents of azolylalkynes.[6e]
Therefore we can characterize this reaction as a “click” re-
action. Although the reactions of enamines with alkynes
are known from the theoretical work of Jones and Houk[6a]
as HOMO (enamine)–LUMO (azide) controlled processes,
reports of experimental cycloaddition reactions between en-
amines and azides bearing a strong electron-withdrawing
substituent such as tosyl are not numerous[8] and totally
lacking for β-azolylenamines. To expand our approach to
4-azolyl-1,2,3-triazoles and to evaluate the feasibility of
using the cycloaddition reaction between β-azolylenamines
and sulfonyl azides for the synthesis of 1-sulfonyl-4-azolyl-
1,2,3-triazoles (potential precursors of azavinylcarbenes[9]),
we have investigated the reactions of sulfonyl azides 2a,b
with a series of β-azolylenamines 1a–j, enaminones 1k,l,
and N,N-dimethyl-2-nitroetheneamine 1m (Scheme 2).
Introduction
The chemistry of 1,2,3-triazoles has received increased
interest after the copper-catalyzed alkyne to azides cycliza-
tion reaction was discovered, a reaction often associated
with the concept of “click chemistry”.[1] Many interesting
1,2,3-triazole derivatives that may act as bioconjugates,[2]
chemosensors,[3] ligands,[4] or anion receptors[5] became eas-
ily available as a result of what is often called the “click
reaction”. In turn, it led to an increase in the use of 1,2,3-
triazoles in medicine, materials chemistry, analytical chem-
istry, and organic synthesis. Cycloaddition reactions of en-
amines and 1,3-dicarbonyl compounds with azides present
a promising but less studied approach to 1,2,3-triazoles.[6]
We have turned our attention to the self-condensation of β-
[a] TOS Laboratory of Ural Federal University named after the
first President of Russia B. N. Yeltsin,
19 Mira st., 620002 Ekaterinburg, Russia
E-mail: v.a.bakulev@urfu.ru,
http://urfu.ru/en/home/faculties/hti/
[b] Klinik für Allgemein- und Viszeralchirurgie Zentrum für
Chirurgie Universitätsklinikum Ulm,
23 Albert-Einstein-Allee, 89081 Ulm, Germany
[c] Gert Lubec Proteomics Laboratory, Medicinal University of
Vienna,
14 Lazarettgasse, 1090 Vienna, Austria
[d] State Key Laboratory of Elemento-Organic Chemistry Nankai
University,
300071 Tianjin, China
[e] I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of
the Russian Academy of Science,
20 S. Kovalevskaya st., 620990 Ekaterinburg, Russia
[f] Molecular Design and Synthesis, Department of Chemistry,
KU Leuven,
Celestijnenlaan 200F, 3001 Leuven, Belgium
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402130.
Scheme 1. Self-condensation and cycloaddition reactions of en-
amines 1.
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Scheme 2. Synthesis of 4-substituted 1H-1,2,3-triazoles.
5-H with C-4 and with both β-nitrogen atoms, confirming
unambiguously the presence of the 1,2,3-triazole fragment
Results and Discussion
We found that the reactions of β-azolylenamines 1a–j in 3a.
with tosyl azide 2a and of 1a,l with mesyl azide 2b in or-
N-Unsubstituted 1,2,3-triazoles 3 were obtained from re-
ganic solvents such as acetonitrile afforded N-unsubstituted actions of enamines 1 bearing 1,2,3-thiadiazole, 1,2,3-tri-
4-azolyl-1,2,3-triazoles 3a–j in yields of 52–93% instead of azole, isoxazole, and 1,2,4-oxadiazole rings. Moreover, en-
the expected 1-sulfonyl-1,2,3-triazoles. This reaction was ac- aminones 1l,m and β-nitroenamine 1n also reacted readily
companied by the formation of N,N-dimethylsulfon- with tosyl azide to form the corresponding 1H-1,2,3-tri-
ylamides 4; tosylamide 4 (R2 = Ts) was isolated and iden- azoles 3l–n in yields of 50–71%. The NMR spectra and
1
tified by H NMR spectroscopy and by comparison of its melting points of triazoles 3l,n are very similar to the data
melting point with data found in the literature.[10] The reported for these compounds prepared by an independent
method of choice included the use of acetonitrile as solvent method.[11] N-Unsubstituted 1,2,3-triazoles possess many
at room temperature followed by the extraction of triazoles interesting biological properties.[12] However, in contrast to
3a–j with chloroform from the aqueous solutions of the re- 1,4-disubstituted 1,2,3-triazoles, access to 1H-1,2,3-triazoles
action products. The use of other solvents and bases low- is not well developed and includes the reactions of alkynes
ered the yields of the target products and resulted in the and haloalkenes with sodium azide, which has its limita-
formation of tar-like mixtures. The structures of triazoles tions for the synthesis of azolyl-1H-1,2,3-triazoles because
3a–j were confirmed by a combination of 1H and 13C NMR of the poor availability of azolylalkynes and -alkenes.[13]
spectroscopy, including 2D HSQC and HMBC (1H–13C Probably for this reason, heterocyclic systems of 1H-1,2,3-
and 1H–15N), and mass spectrometry, which gave good triazoles conjugated to other azoles are very poorly repre-
1
agreement with the proposed structures. The H and 13C sented in the literature,[14] and a general and efficient
NMR spectra of compounds 3a–j exhibit signals in the method for their preparation has not yet been developed.
range 8.3–8.8 and 132.6–134.2 ppm corresponding to 5-H Although the formation of unsubstituted 1,2,3-triazoles
and C-4, respectively, confirming that all the products from the reactions of enamines 1 with sulfonyl azides is a
belong to the same class of compounds. The signals of general process, we found that the use of a nonpolar solvent
C-4 and C-5 corresponding to the 1,2,3-thiadiazole ring of such as hexane or 1,4-dioxane or the absence of solvent
the product 3a and those of C-4, C-3, and C-5 of the dramatically changed the direction of the reactions of tria-
isoxazole ring of products 3b–f in the 13C NMR zolylenamines 1i–k with tosyl azide; the novel (E)-triazoly-
spectra are very similar to those observed for ethyl 5-[1-(4- lethene-1,2-diamines 5a–c and amidine 6 were formed in
chlorophenyl)-1H-1,2,3-triazol-4-yl]-1,2,3-thiadiazole-4- yields of 40–50 and 20%, respectively (Scheme 3). The reac-
carboxylate and ethyl 5-[1-(4-nitrophenyl)-1H-1,2,3-triazol- tion of enamine 1i with tosyl azide in dioxane was found to
4-yl]-3-phenylisoxazole-4-carboxylate, respectively, de- form, in addition to compounds 5a and 6, unsubstituted
1
scribed previously.[6e] Furthermore, the 2D HMBC H–13C triazole 3i in 5% yield. The study of the scope and limita-
and 1H–15N spectra of compound 3a contain cross-peaks of tion of the reactions of enamines with sulfonyl azides for
2
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Approach to N-Unsubstituted Triazoles and Ethenediamines
the synthesis of diaminoalkenes of type 5 is in progress. the first step in all the reactions is the formation of nonaro-
Diamines 5a–c are less soluble in 1,4-dioxane and were eas- matic 4,5-dihydro-1,2,3-triazolines 7. This type of process is
ily separated from amidine 6 by filtration. Amidine 6 was well documented.[6c,16] Scheme 4 illustrates the formation of
separated from the remaining diamines 5a–c and tar-like different kinds of follow-up products depending on the spe-
products by column chromatography on silica gel. The reac- cific modes [A, B, C (I, II), and D] of stabilization of triazol-
tions of triazolylenamines 1i–k with tosyl azide represent a ines 7. Thus, the elimination of dialkylamine leads to 1,4-
rare example of an enamine transformation to diaminoalk- disubstituted 1,2,3-triazole 8 as described by us recently.[6e]
enes, reported recently by Contini and Erba for the reac- Somewhat similar eliminations of HCN, HHal, RSO2H,
tions of morpholinoenamines with sulfonyl azides.[8a] The and HNO2 from intermediate triazolines to afford aromatic
structures of diamines 5a–c were reliably confirmed by the 1,2,3-triazoles are also known.[6f,17] The elimination of N,N-
combination of 1H and 13C NMR spectroscopy, HMBC dimethyltosylamide 4 followed by a 1,5-hydrogen shift in
(H–C, H–N), LCMS, and finally by X-ray diffraction analy- the intermediate 4H-triazolines is an unknown mechanism
sis performed on a single crystal of 5c (see Figure 1). In for the formation of 1,2,3-triazoles of type 3, described here
contrast to the results of Contini and Erba,[8a] diamines of for the reactions of enamines 1 with sulfonyl azides 2 (R =
type 5, as shown by the X-ray analysis, exist in the E iso- Ts, Ms). The formation of amidine 6 is proposed here to
meric form. Amidine 6 has very similar NMR spectra to proceed as a retro 1,3-dipolar cycloaddition reaction of in-
the reported compound prepared by the reaction of tosyl termediate triazoline 7 by analogy with the work of Contini
azide with DEAD in the presence of triethylamine.[15]
and Erba for the reaction of tosyl azide with β-alkylenami-
nes.[8a] The second product, (5-ethyl-4-ethoxycarbonyl-
1,2,3-triazol-5-yl)diazomethane, is not isolated probably be-
cause of its fast degradation. The pathway triazoline 7Ǟ
acetamidine 6 was also recently used by Xu et al. to explain
the formation of acetamidines in the reaction of tosyl azide
with triethylamine and diethyl azodicarboxylate.[15] Because
of the formation of a mixture of 1,2-diaminoethene 5 with
amidine 6 in the reactions of β-(1,2,3-triazol-5-yl)enamines
with TsN3, we assume that the formation of 5 also started
from intermediate triazoline 7. The concerted mechanism
proposed by Contini and Erba[8a] for the transformation of
morpholino-dihydrotriazolines into azacycloalkenemono-
sulfonyl diamines looks hardly possible for the reactions of
enamines of type 1 involving the shift of a dialkylamino
group, which should have a higher activation barrier than
Scheme 3. Reactions of enamines 1i–k with tosyl azide.
Figure 1. Structure of compound 5c.
Discussion of the Reaction Mechanisms
The mechanism proposed for the reactions of enamines
1 with alkyl, aryl, benzyl, and sulfonyl azides 2 to yield
compounds 3–5 and 8 are summarized in Scheme 4. Clearly, Scheme 4. Mechanisms for the reactions of enamines 1 with azides 2.
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V. Bakulev et al.
FULL PAPER
the shift of an aromatic azolyl radical.[8b] Therefore we pro-
pose that the second step for the formation of compounds
5 involves the elimination of dinitrogen from triazolines 7
to form aziridines 9. Precedents for this kind of reaction
have been published elsewhere.[18] In its turn, aziridine 9
could undergo transformation to the final reaction products
by the pathways I or II shown in Scheme 4. Both of them
include aziridine ring-opening to form either zwitterion 10
or carbene 12. Notably, a rearrangement is required for the
formation of diamines 5 in which the dimethylamino group
and triazolyl moiety are connected to the same carbon, in
contrast to enamine 1 and aziridine 9 in which they are
connected to adjacent carbon atoms. Mechanism I involves
an azole1,2-shift whereas mechanism II involves three steps,
1) elimination of dimethylamine, 2) ring-opening of inter-
mediate antiaromatic azirine 11 to form carbene 12 (the lat-
ter can also be formed directly from aziridine by concerted
elimination of dimethylamine and rupture of the C–N
bond), and 3) insertion of dimethylamine into the carbene.
Both generate the same product (13), which in turn,
through a 1,3-hydrogen shift, affords the final products 5.
Methyl 3-Phenyl-5-(1H-1,2,3-triazol-4-yl)isoxazole-4-carboxylate
(3b): Colorless solid; yield 0.180 g (63%); m.p. 168–170 °C; Rf =
0.47 (EtOAc/hexane, 1:1). IR: ν = 766, 1232, 1327, 1541, 1718 cm–1.
˜
1H NMR: δ = 7.44–7.55 (m, 3 H, Ar-H), 7.61 (m, 2 H, Ar-H), 8.60
(br. s, 1 H, 5-H), 15.71 (br. s, 1 H, NH) ppm. 13C NMR: δ = 52.1
(OCH3), 108.8 (br. s, C-4), 125.8 (br. s, C-5Ј), 127.5 (C-i, Ph), 128.3
(C-m, Ph), 128.8 (C-o, Ph), 130.1 (C-p, Ph), 133.7 (br. s, C-4Ј), 161.3
(C=O), 162.1 (C-3), 164.5 (C-5) ppm. MS (EI): m/z = 270 [M]+.
C14H12N4O3 (284.27): calcd. C 59.15, H 4.25, N 19.71; found C
59.09, H 4.29, N 19.77.
Ethyl 3-(4-Chlorophenyl)-5-(1H-1,2,3-triazol-4-yl)isoxazole-4-carb-
oxylate (3c): Colorless solid; yield 0.262 g (82%); m.p. 180–182 °C;
R = 0.41 (EtOAc/hexane, 1:1). IR: ν = 832, 1132, 1313, 1416,
˜
f
1719 cm–1. 1H NMR: δ = 1.11 (t, J = 7.1 Hz, 3 H, OCH2CH3),
4.22 (d, J = 7.1 Hz, 2 H, OCH2CH3), 7.60 (m, 2 H, Ar-H), 7.70
(m, 2 H, Ar-H), 8.77 (s, 1 H, 5Ј-H), 15.96 (br. s, 1 H, NH) ppm.
13C NMR: δ = 13.5 (OCH2CH3), 61.2 (OCH2CH3), 108.1 (C-4),
126.6 (C-i, Ar), 128.3 (C-m, Ar), 129.7 (br. s, C-5Ј), 130.9 (C-o,
Ar), 133.6 (br. s, C-4Ј), 134.0 (C-p, Ar), 160.6 (C=O), 161.4 (C-3),
164.8 (C-5) ppm. MS (EI): m/z = 318 [M]+. C14H11ClN4O3
(318.72): calcd. C 52.76, H 3.48, N 17.58; found C 52.70, H 3.43,
N 17.48.
Ethyl 3-(3,4-Dichlorophenyl)-5-(1H-1,2,3-triazol-4-yl)isoxazole-4-
carboxylate (3d): Colorless solid; yield 0.247 g (70%); m.p. 188–
190 °C; Rf = 0.51 (EtOAc/hexane, 1:1). H NMR: δ = 1.11 (t, J =
1
Conclusions
7.1 Hz, 3 H, OCH2CH3), 4.21 (d, J = 7.1 Hz, 2 H, OCH2CH3),
7.66 (dd, J = 8.4, 1.8 Hz, 1 H, Ar-H), 7.79 (d, J = 8.4 Hz, 1 H, Ar-
H), 7.99 (d, J = 1.8 Hz, 1 H, Ar-H), 8.77 (s, 1 H, 5Ј-H), 15.94 (br.
s, 1 H, NH) ppm. 13C NMR: δ = 13.9, 61.6, 108.5, 127.8, 128.9,
129.9, 130.9, 131.5, 131.8, 133.5, 134.0, 160.8, 161.0, 165.6 ppm.
MS (EI): m/z = 352 [M]+. C14H10Cl2N4O3 (353.16): calcd. C 47.61,
H 2.85, N 15.86; found C 47.69, H 2.78, N 15.80.
A general and efficient method for the synthesis of N-
unsubstituted 1,2,3-triazoles based on the reactions of en-
amines with sulfonyl azides has been developed. The forma-
tion of various products from the reactions of enamines 1
with sulfonyl azides 2 led to the proposal of several path-
ways for the subsequent reactions of intermediates 5-amino-
1,2,3-triazolines 7. These reactions lead to 1H-1,2,3-tri-
azoles 3 by elimination of N,N-dimethylsulfonylamides 4,
(E)-1-triazolyl-1-dimethylamino-2-tosylaminoethenes 5 by
the elimination of dinitrogen, and N,N-dimethyl-NЈ-sulfon-
ylamidoformamidine 6 by a retro 1,3-dipolar cycloaddition.
Methyl 3-Cyclohexyl-5-(1H-1,2,3-triazol-4-yl)isoxazole-4-carboxyl-
ate (3e): Colorless solid; yield 0.247 g (70%); m.p. 160–162 °C; Rf
= 0.44 (EtOAc/hexane, 1:1). IR: ν = 792, 1104, 1543, 1617, 1723,
˜
2854, 2940 cm–1. 1H NMR: δ = 1.25–1.42 (m, 3 H, cyclohexyl-
H), 1.43–1.53 (m, 2 H, cyclohexyl-H), 1.70 (d, J = 12.1 Hz, 1 H,
cyclohexyl-H), 1.79 (d, J = 12.1 Hz, 2 H, cyclohexyl-H), 1.98 (d, J
= 11.5 Hz, 2 H, cyclohexyl-H), 3.04–3.22 (m, 1 H, cyclohexyl-H),
3.84 (s, 3 H, OCH3), 8.66 (s, 1 H, 5Ј-H); 15.86 (br. s, 1 H, NH) ppm.
13C NMR: δ = 25.5, 25.8, 31.0, 35.4, 52.0 (OCH3), 107.1 (C-4),
133.9 (C-4Ј), 161.5 (C=O), 164.1 (C-3), 167.1 (C-5) ppm. MS (EI):
m/z = 276 [M]+. C13H16N4O3 (276.29): calcd. C 56.51, H 5.84, N
20.28; found C 56.58, H 5.81, N 20.22.
Experimental Section
The enamines 1a–l were prepared by a method reported in the lite-
rature.[6e]
General Procedure for the Preparation of Methyl 5-(1H-1,2,3-Tri-
azol-4-yl)-1,2,3-thiadiazole-4-carboxylate (3a): A mixture of en-
amine 1a (0.228 g, 1.0 mmol) and tosyl azide 2b (0.592 g, 3.0 mmol)
in CH3CN (5 mL) was stirred at room temperature for 12 h. The
reaction mixture was then diluted with 5% aq. Na2CO3 (20 mL)
and extracted with chloroform. Concentrated hydrochloric acid
was added to the aqueous layer until pH 5 and the mixture ex-
tracted with EtOAc (2ϫ 20 mL). The combined organic layers were
dried with Na2SO4 and solvent was removed under reduced pres-
sure to furnish 3a as a colorless solid, yield 0.200 g (88%); m.p.
3-Phenyl-5-(1H-1,2,3-triazol-4-yl)isoxazole-4-carbonitrile (3f): Col-
orless solid; yield 0.120 g (52%); m.p. 189–190 °C; Rf = 0.48
(EtOAc/hexane, 1:1). 1H NMR: δ = 7.63–7.64 (m, 3 H, Ar-H),
7.91–7.94 (m, 2 H, Ar-H), 8.49 (s, 1 H, 5-H) ppm. 13C NMR: δ =
85.0 (C-4), 112.8 (CN), 126.6 (C-i, Ar), 127.8 (C-o, Ar), 129.9 (C-
m, Ar), 130.6 (C-5Ј), 131.8 (C-p, Ar), 132.2 (C-4Ј), 161.7 (C-3),
171.2 (C-5) ppm. MS (EI): m/z = 237 [M]+. C12H7N5O (237.22):
calcd. C 60.87, H 3.05, N 29.60; found C 60.76, H 2.97, N 29.52.
186–188 °C; R = 0.43 (EtOAc/hexane, 1:1). IR: ν = 832, 1201,
˜
f
3-Phenyl-5-(1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazole (3g): Colorless
solid; yield 0.198 g (93%); m.p. 210–212 °C; Rf = 0.40 (EtOAc/hex-
1297, 1502, 1724, 2869, 3169 cm–1. 1H NMR: δ = 4.01 (s, 3 H,
OCH3), 8.76 (s, 1 H, 5Ј-H), 15.81 (br. s, 1 H, NH) ppm. 13C NMR:
δ = 52.4 (OCH3), 127.4 (C-5Ј is not decoupled), 134.0 (C-4Ј),
146.4 (C-5), 152.0 (C-4), 160.3 ppm. MS (ESI): m/z = 211.017 [M
+ H]+. C7H7N5O2S: C 37.33, H 3.13, N 31.09, S 14.24; found C
37.41, H 3.08, N 31.01, S 14.29.
ane, 1:1). IR: ν = 1237, 1304, 1373, 1440, 1524, 1641, 2921,
˜
1
3149 cm–1. H NMR: δ = 7.54–7.69 (m, 3 H, Ar-H), 8.00–8.17 (m,
2 H, Ar-H), 8.96 (br. s, 1 H, 5-H), 16.13 (br. s, 1 H, NH) ppm. 13
C
NMR: δ = 125.9 (C-i, Ph), 127.1 (C-o, Ph), 129.3 (C-m, Ph), 130.1
(C-5Ј), 131.7 (C-p, Ph), 132.6 (C-4Ј), 168.1 (C-3), 169.4 (C-5) ppm.
MS (EI): m/z = 213 [M]+. C10H7N5O (213.20): calcd. C 56.34, H
3.31, N 32.85; found C 56.39, H 3.26, N 32.80.
Compounds 3b–n were obtained following the procedure for the
preparation of 3a from the corresponding enamines and tosyl azide.
4
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Approach to N-Unsubstituted Triazoles and Ethenediamines
3-(3-Fluoro-4-methylphenyl)-5-(1H-1,2,3-triazol-4-yl)-1,2,4-oxadi-
azole (3h): Colorless solid; yield 0.167 g (68%); m.p. 258–259 °C;
C21H22FN5O4S (459.49): calcd. C 54.89, H 4.83, N 15.24, S 6.98;
found C 54.82, H 4.89, N 15.19, S 6.93.
R = 0.49 (EtOAc/hexane, 1:1). IR: ν = 814, 835, 1084, 1508, 1720,
˜
f
Compounds 5b,c were obtained following the procedure used for
the preparation of 5a from the corresponding enamines and TsN3.
3304 cm–1. H NMR: δ = 2.32–2.39 (m, 3 H, CH3), 7.43 (s, 1 H,
1
Ar-H), 7.72 (m, 1 H, Ar-H), 7.77–7.87 (m, 1 H, Ar-H), 8.66 (s, 1
H, 5-H), 15.93 (br. s, 1 H, NH) ppm. 13C NMR: δ = 14.7 (CH3),
113.8, 123.4, 125.8, 128.9, 132.9, 133.1, 161.2, 167.6, 170.0 ppm.
MS (EI): m/z = 245 [M]+. C11H8FN5O (245.22): calcd. C 53.88, H
3.29, N 28.56; found C 53.78, H 3.23, N 28.51.
Methyl 1-(4-Chlorophenyl)-5-[(E)-1-(dimethylamino)-2-(4-methyl-
phenylsulfonamido)ethenyl]-1H-1,2,3-triazole-4-carboxylate (5b):
Colorless solid; yield 0.200 g (42%); m.p. 194–195 °C; Rf = 0.35
(EtOAc/hexane, 1:1). IR: ν = 1057, 1122, 1225, 1341, 1729,
˜
1
3236 cm–1. H NMR: δ = 2.31 (s, 6 H, NMe2), 2.45 (s, 3 H, CH3),
Methyl 3Ј-(4-Fluorophenyl)-1H,3ЈH-4,4Ј-bi-1,2,3-triazole-5Ј-carb-
oxylate (3i): Compound 3i was obtained following the procedure
used for the preparation of 3a, but MsN3 was used instead of TsN3.
Colorless solid; yield 0.187 g (65%); m.p. 125–127 °C; Rf = 0.45
3.79 (s, 3 H, OCH3), 5.49 (d, J = 9.1 Hz, 1 H, CH), 7.07 (m, 2 H,
Ar-H), 7.27–7.37 (m, 6 H, Ar-H), 7.56 (m, 2 H, Ar-H), 9.09 (d, J
= 9.1 Hz, 1 H, CH) ppm. 13C NMR: δ = 21.5, 41.0, 52.2, 109.3,
124.9, 125.9, 126.8, 129.6, 130.1, 134.6, 134.7, 134.9, 137.8, 139.3,
143.3, 160.7 ppm. C21H22ClN5O4S (475.95): calcd. C 52.99, H 4.66,
N 14.71, S 6.74; found C 52.89, H 4.62, N 14.78, S 6.65.
(EtOAc/hexane, 1:1). IR: ν = 834, 1088, 1510, 1726, 2127,
˜
1
3108 cm–1. H NMR: δ = 3.89 (s, 3 H, OCH3), 7.30 (m, 2 H, Ar-
H), 7.49 (m, 2 H, Ar-H), 8.22 (br. s, 1 H, 5-H), 15.33 (br. s, 1 H,
NH) ppm. MS (EI): m/z = 288 [M]+. C12H9FN6O2 (288.24): calcd.
C 50.00, H 3.15, N 29.16; found C 50.10, H 3.10, N 29.21.
Methyl 5-[(E)-1-(Dimethylamino)-2-(4-methylphenylsulfonamido)-
ethenyl]-1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (5c): Col-
orless solid; yield 0.238 g (49 %); m.p. 219–221 °C; Rf = 0.28
Methyl 3Ј-(4-Chlorophenyl)-1H,3ЈH-4,4Ј-bi-1,2,3-triazole-5Ј-carb-
oxylate (3j): Colorless solid; yield 0.203 g (67%); m.p. 131–133 °C;
(EtOAc/hexane, 1:1). IR: ν = 1082, 1144, 1279, 1622, 1731, 2853,
˜
1
2923 cm–1. H NMR: δ = 2.31 (s, 6 H, NMe2), 2.37 (s, 3 H, CH3),
R = 0.48 (EtOAc/hexane, 1:1). IR: ν = 825, 1002, 1078, 1223, 1494,
˜
f
3.78 (s, 3 H, OCH3), 5.54 (d, J = 9.1 Hz, 1 H, CH), 7.33 (m, 2 H,
Ar-H), 7.56 (m, 2 H, Ar-H), 7.59–7.67 (m, 2 H, Ar-H), 8.15–8.26
(m, 2 H, Ar-H), 9.16 (d, J = 9.1 Hz, 1 H, CH) ppm. 13C NMR: δ
= 20.8 (CH3), 40.1 (NMe2), 51.9 (OCH3), 109.3 (C-2), 124.0 (C-1),
124.4 (C-m, Ar), 124.6 (C-o, Ar), 126.4 (C-o, Ts), 129.6 (C-m, Ts),
134.4 (C-5, triazole), 137.3 (C-i, Ts); 139.2 (C-4, triazole), 140.2 (C-
i, Ar), 142.9 (C-p, Ts), 147.3 (C-p, Ar), 160.0 (C=O) ppm. MS (EI):
m/z = 486 [M]+. C21H22N6O6S (486.50): calcd. C 51.84, H 4.56, N
17.27, S 6.59; found C 51.91, H 4.51, N 17.22, S 6.53.
1727, 2921, 3168 cm–1. 1H NMR: δ = 3.89 (s, 3 H, OCH3), 7.40
(m, 2 H, Ar-H), 7.50 (m, 2 H, Ar-H), 8.25 (br. s, 1 H, 5-H), 15.35
(br. s, 1 H, NH) ppm. MS (EI): m/z = 304 [M]+. C12H9ClN6O2
(304.70): calcd. C 47.30, H 2.98, N 27.58; found C 47.38, H 2.92,
N 27.50.
4-Benzoyl-1H-1,2,3-triazole (3l): Colorless solid; yield 0.105 g
(61%); m.p. 121–123 °C (ref.[11b] 122 °C). 1H NMR: δ = 7.54 (m, 2
H, Ar-H), 7.64 (m, 1 H, Ar-H), 8.27 (m, 2 H, Ar-H), 8.44 (br. s, 1
H, 5-H), 15.58 (br. s, 1 H, NH) ppm. The NMR spectrum of 3k is
similar to that published previously.[11b]
N-[(E)-(Dimethylamino)methylidene]-4-methylphenylsulfonamide
(6): After isolation of 5a, the residue was evaporated under vacuum
and the crude mass was purified by column chromatography
(AcOEt/hexane, 1:1) to afford sulfonamide 6 as a colorless solid,
yield 0.045 g (20%), m.p. 134–135 °C (ref.[19] 134–136); Rf = 0.2
(4-Fluorophenyl)(1H-1,2,3-triazol-4-yl)methanone (3m): Colorless
solid; yield 0.140 g (71%); m.p. 179–181 °C. IR: ν = 768, 1241,
˜
1598, 1659, 3120 cm–1. 1H NMR: δ = 7.43 (m, 2 H, Ar-H), 8.38
(m, 2 H, Ar-H), 8.69 (br. s, 1 H, 5-H), 13.81 (br. s, 1 H, NH) ppm.
13C NMR: δ = 115.7, 132.5, 133.4, 133.7, 145.9, 165.5, 184.4 ppm.
MS (EI): m/z = 191 [M]+. C9H6FN3O (191.16): calcd. C 56.55, H
3.16, N 21.98; found C 56.45, H 3.11, N 21.91.
1
(AcOEt/hexane, 1:1). H NMR: δ = 2.40 (s, 3 H, CH3), 2.95 (s, 3
H, CH3), 3.17 (s, 3 H, CH3), 7.27 (m, 2 H, Ar-H), 7.62 (m, 2 H,
Ar-H), 8.16 (s, 1 H, CH) ppm. MS (ESI): m/z = 227.085 [M + H]+.
The NMR spectrum of 6 is similar to that published previously.[21]
4-Nitro-1H-1,2,3-triazole (3n): Colorless solid; yield 0.57 g (50%);
m.p. 158–159 °C (ref.[19] 160–161 °C); Rf = 0.35 (EtOAc/C2H5OH,
X-ray Crystallography: CCDC-979571 (for 5c) contains the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
10:1). IR: ν = 827, 1226, 1391, 1543, 3161, 3240 cm–1. 1H NMR: δ
˜
= 8.89 (s, 1 H, 5-H), 16.18 (br. s, 1 H, NH) ppm. 13C NMR: δ =
125.5, 153.5 ppm. The NMR spectra of 3n are similar to those
published previously.[20]
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, 1H and 13C NMR and HRMS spectra
for all key intermediates and final products, X-ray crystal data for
compound 5c.
General Procedure for the Preparation of Methyl 5-[(E)-1-(Dimeth-
ylamino)-2-(4-methylphenylsulfonamido)ethenyl]-1-(4-fluorophenyl)-
1H-1,2,3-triazole-4-carboxylate (5a): A mixture of enamine 1i
(0.290 g, 1.0 mmol) and TsN3 (0.591 g, 3.0 mmol) was kept at room
temperature for 1 h. CH3CN was added to the reaction mixture
and the precipitate was filtered off and washed with CH3CN
(2 mL). Triazole 5a was obtained as a colorless solid. Yield 0.188 g
Acknowledgments
I. E. and V. B. thank the Russian Foundation for Basic Research
(14-03-01033) and the Russian Scientific Foundation, and F. Z.-J.
thanks the National Natural Science Foundation of China
(21372132), and the International Science & Technology Coopera-
tion Program of China (2014DFR41030) for financial support.
(41%); m.p. 211–213 °C; R = 0.32 (EtOAc/hexane, 1:1). IR: ν =
˜
f
762, 1172, 1189, 1335, 1473, 1641, 3073, 3163, 3211 cm–1 1H
.
NMR: δ = 2.29 (s, 6 H, NMe2), 2.44 (s, 3 H, CH3), 3.78 (s, 3 H,
OCH3), 5.49 (d, J = 9.1 Hz, 1 H, CH), 7.07 (m, 2 H, Ar-H), 7.21–
7.46 (m, 4 H, Ar-H), 7.56 (m, 2 H, Ar-H), 9.08 (d, J = 9.1 Hz, 1
H, CH) ppm. 13C NMR: δ = 20.9 (CH3), 39.9 (NMe2), 51.7 (OMe),
108.8 (C-2), 115.9 (C-m, Ar), 124.5 (C-1), 126.2 (C-o, Ar), 126.3
(C- o, Ts), 129.6 (C-m, Ts), 132.0 (C-i, Ar), 134.4 (C-5, triazol),
137.3 (C-i, Ts), 138.7 (C-4, triazol), 142.9 (p-C-Ts), 160.3 (C=O),
162.1 (C-p, Ar) ppm. MS (ESI): m/z = 460.144 [M + H]+.
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Pages: 7
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Published Online: ᭿
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Approach to N-Unsubstituted Triazoles and Ethenediamines
Synthesis of Azoles
This paper deals with reactions of β-azol-
ylenamines with sulfonyl azides. Variation
of the reaction conditions leads to different
products
I. Efimov, V. Bakulev,* N. Beliaev,
T. Beryozkina, U. Knippschild, J. Leban,
F. Zhi-Jin, O. Eltsov, P. Slepukhin,
M. Ezhikova, W. Dehaen .................. 1–7
Reactions of β-Azolylenamines with Sul-
fonyl Azides as an Approach to N-Unsub-
stituted 1,2,3-Triazoles and Ethene-1,2-di-
amines
Keywords: Nitrogen heterocycles / En-
amines / Cycloaddition / Azides / Reaction
mechanisms
Eur. J. Org. Chem. 0000, 0–0
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7