One-pot synthesis of N-alkyl sulfonyl hydrazones by dialkyl acetylenedicarboxylate-mediated reaction of trialkylphosphites with sulfonyl hydrazones

Article abstract of DOI:10.1080/00397911.2013.786088

Stable derivatives of N-alkyl sulfonyl hydrazone were obtained in excellent yields from the reaction between electron-deficient acetylenic ester compounds and sulfonyl hydrazones in the presence of trialkylphosphites in dichloromethan at room temperature.

Full text of DOI:10.1080/00397911.2013.786088

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One-Pot Synthesis of N-Alkyl
Sulfonyl Hydrazones by Dialkyl
Acetylenedicarboxylate-Mediated
Reaction of Trialkylphosphites with
Sulfonyl Hydrazones
Seyed Abolghasem Hashemi a
a Chemistry Department , Islamic Azad University, Bushehr Branch ,
Bushehr , Iran
Published online: 05 Sep 2013.
To cite this article: Seyed Abolghasem Hashemi (2013) One-Pot Synthesis of N-Alkyl Sulfonyl
Hydrazones by Dialkyl Acetylenedicarboxylate-Mediated Reaction of Trialkylphosphites with Sulfonyl
Hydrazones, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 43:24, 3352-3356
To link to this article: http://dx.doi.org/10.1080/00397911.2013.786088
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Synthetic Communications1, 43: 3352–3356, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.786088
ONE-POT SYNTHESIS OF N-ALKYL SULFONYL
HYDRAZONES BY DIALKYL
ACETYLENEDICARBOXYLATE-MEDIATED REACTION
OF TRIALKYLPHOSPHITES WITH SULFONYL
HYDRAZONES
Seyed Abolghasem Hashemi
Chemistry Department, Islamic Azad University, Bushehr Branch,
Bushehr, Iran
GRAPHICAL ABSTRACT
Abstract Stable derivatives of N-alkyl sulfonyl hydrazone were obtained in excellent yields
from the reaction between electron-deficient acetylenic ester compounds and sulfonyl hydra-
zones in the presence of trialkylphosphites in dichloromethan at room temperature.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Dialkyl acetylenedicarboxylate; N-alkyl sulfonyl hydrazone; sulfonyl hydra-
zone; trialkylphosphite
INTRODUCTION
The synthesis of sulfones has drawn much attention over the years because
sulfones constitute useful building blocks in natural products and pharmaceutical
compounds.[1–3] On the other hand, sulfonyl hydrazones exhibit interesting chemical
properties and are useful intermediates in organic synthesis.[4–7] In this context,
N-alkylated hydrazones are of interest because they have various applications
in organic synthesis as useful precursors.[8–12] In accordance with that, interest in
the development of new methods for their preparation continues unabated.
Commonly, N-alkylation is achieved using alkyl halide, a base, and a phase-transfer
catalyst.[13–15] Recently, acid-catalyzed reaction of tosylhydrazones can achieve N-
alkylation of tosylhydrazones.[16] Of the previously reported methods of N-alkyl-
Received September 14, 2012.
Address correspondence to Seyed Abolghasem Hashemi, Chemistry Department, Islamic Azad
University, Bushehr Branch, P. O. Box 7519619555, Bushehr, Iran. E-mail: abolghasem.hashemy@
gmail.com
3352

N-ALKYL SULFONYL HYDRAZONES
3353
Scheme 1. Synthesis of N-alkyl sulfonyl hydrazones via one-pot reaction of sulfonyl hydrazone,
trialkylphosphite, and dialkyl acetylenedicarboxylate.
ation of hydrazones, the reaction of tosylhydrazone as nucleophile in the Mitsunobu
reaction is one of the most attractive routes because of its simplicity and the great
diversity of alcohols.[17,18]
In the context of our interest in multicomponent reactions,[19] we observed the
formation of N-alkyl sulfonyl hydrazones in good yield when sulfonyl hydrazones
were reacted with zwitterion derived from trialkylphosphite and dialkyl acetylenedi-
carboxylate (Scheme 1). Under optimized conditions, studies on the development of
substrate scope were then carried out. Various substituted sulfonyl hydrazones,
which were prepared from ketones, arylbenzealdehydes, and relative sulfonyl hydra-
zides, were used as substrate. This method was proven to be general and efficient for
preparing aranesulfonyl hydrazones.
RESULTS AND DISCUSSION
The products were separated by chromatography on a silica-gel column and
supported by spectroscopic data. In the infrared (IR) spectrum of 3a the vibrational
stretching of the sulfonamide group was observed at 1353 and 1161 cmꢀ1 as two
strong absorptions. The methyl proton of tosyl resonated as sharp singlet at 2.41
while the proton of the N-Me displayed at 3.24 ppm. The hydrogen of imine bond
appeared as a singlet at 7.52 ppm. The aromatic proton signals were visible as four
doublets at d 7.30, 7.79 (J ¼ 8.80 Hz) and d 7.36, 7.59 (J ¼ 6.80 Hz). In the 100.6-
MHZ 13C NMR spectrum (CDCl3), the peaks at d ¼ 141 and 33.2 were discernible

3354
S. A. HASHEMI
Scheme 2. Proposed mechanism for the synthesis of N-alkyl sulfonyl hydrazones.
and due to the imine and N-methyl carbon, respectively. All other signals were also
in good agreement with the proposed structure. Finally, the structure was confirmed
by elemental analysis and mass spectra.
The following mechanistic postulate may be invoked to rationalize the reaction
(Scheme 2). It is conceivable that the phosphite reacts with acetylenic ester to form
the zwitterion 4 and subsequent protonation of the reactive 1:1 adduct by sulfonyl
hydrazone 2. Then the intermediate 6 with a hydrogenic bond reacts with sulfonyl
hydrazone ion 5 by elimination of dimethyl acetylenedicarboxylate (DMAD) and
dialkylphosphonate.
In conclusion, we have uncovered a novel, clean, and efficient synthesis of
N-alkyl sulfonyl hydrazone by dialkyl actylenedicarboxylate–mediated reaction of
trialkylphosphites with sulfonyl hydrazones. The mild experimental conditions used
in this reaction are especially noteworthy.
EXPERIMENTAL
Trialkylphosphite and dialkyl actylenedicarboxylate were obtained commer-
cially and used without further purification. Compounds 2 were prepared accord-
ing to Ref. 20. Instruments used were as follows: mp, Electrothermal-9100
apparatus; IR spectra, Shimadzu-IR-460 spectrometer (n in cmꢀ1), 1H and
ꢀ
13CNMR spectra, Bruker DRX-400 Avance instrument at 400.1 and 100.6 MHz,
resp. (d in ppm, J in Hz); MS, Finnigan-MAT-8430EI-MS mass spectrometer at
70 eV in m=z (rel. %); and elemental analyses, Vario EL III CHNO elemental
analyzer.
General Procedure for Preparation of N-Alkyl Sulfonyl
Hydrazones (3a–3l)
A solution of dialkyl acetylenedicarboxylate (1 mmol) in 2 mL dry CH2Cl2 was
added dropwise to a magnetically stirred solution of trialkylphosphite 1 (1 mmol) and
sulfonyl hydrazone 2 (1 mmol) in 4 mL dry CH2Cl2 at room temperature over 10 min.
The reaction mixture stirred for 10 h. The solvent was removed under reduced

N-ALKYL SULFONYL HYDRAZONES
3355
pressure, and the residue was separated by silica-gel (Merck 230–240 mesh) column
chromatography using hexane–ethyl acetate mixture as eluent.
N’1-[(4-Chlorophenyl)methylene]-N1,4-dimethyl-1-
benzenesulfonohydrazide (3a)
White powder, mp: 152 ꢁC, yield: 0.27 g (85%). IR (KBr): 2932, 1559, 1468,
1353, 1161, 1093, 929, 819, 676, 547. 1H NMR (400.1 MHz, CDCl3): dH ¼ 2.41
(3H, s, Me), 3.24 (3H, s, NMe), 7.30 (2H, d, J ¼ 8.8 Hz, 2CH), 7.36 (2H, d,
J ¼ 6.8 Hz, 2CH), 7.52 (1H, s, CH), 7.59 (2H, d, J ¼ 6.8 Hz, 2CH), 7.79 (2H, d,
J ¼ 8.8 Hz, 2CH). 13C NMR (100.6 MHz, CDCl3): dC ¼ 21.5 (Me), 33.2 (NMe),
128.1 (2CH), 128.3 (2CH), 128.9 (2CH), 129.5 (2CH), 132.7 (C), 133.4 (C), 135.7
(C), 141.8 (CH), 144.2 (C). EI-MS: 322 (Mþ, 5), 277 (20), 167 (100), 152 (25), 132
(30), 111 (25), 84 (85), 65 (32). Anal. calc. for C15H15ClN2O2S (322.80): C, 55.81;
H, 4.68; N, 8.68. Found: C, 55.81; H, 4.50; N, 8.31.
Supplementary Material
1
Full experimental details and H and 13C NMR spectra can be found via the
Supplementary Content section of this article’s Web page.
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