One-pot oxidation of alanine and its ethyl ester with a mild oxidant 4′-methylazobenzene-2-sulfenyl bromide

Article abstract of DOI:10.1080/00397911.2010.515361

One-pot oxidation of alanine and its ethyl ester with a mild oxidant 4′-methylazobenzene-2-sulfenyl bromide is described. Using a nonreactively water-soluble electrophilic species, 4′-methylazobenzene-2-sulfenyl bromide, with L-alanine and its ethyl ester (in 3:1 molar proportions) in aqueous solution at room temperature, the corresponding sulfenimines are prepared. On hydrolysis in acidic medium at room temperature, these sulfenimines give ethanal and pyruvic acid respectively. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.515361

This article was downloaded by: [130.108.121.217]
On: 06 October 2014, At: 06:28
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
One-Pot Oxidation of Alanine and Its
Ethyl Ester with a Mild Oxidant 4′-
Methylazobenzene-2-sulfenyl Bromide
Pranjit Barman a , Saibal Kanti Bhattacharjee b & Tirtha
Bhattacharjee a
a Department of Chemistry , National Institute of Technology ,
Silchar , Assam , India
b Department of Chemistry , Gauhati University , Guwahati , Assam ,
India
Published online: 29 Jun 2011.
To cite this article: Pranjit Barman , Saibal Kanti Bhattacharjee & Tirtha Bhattacharjee (2011) One-
Pot Oxidation of Alanine and Its Ethyl Ester with a Mild Oxidant 4′-Methylazobenzene-2-sulfenyl
Bromide, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 41:19, 2870-2875, DOI: 10.1080/00397911.2010.515361
To link to this article: http://dx.doi.org/10.1080/00397911.2010.515361
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,

systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 2870–2875, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.515361
ONE-POT OXIDATION OF ALANINE AND ITS
ETHYL ESTER WITH A MILD OXIDANT
4’-METHYLAZOBENZENE-2-SULFENYL BROMIDE
Pranjit Barman,1 Saibal Kanti Bhattacharjee,2 and
Tirtha Bhattacharjee1
1Department of Chemistry, National Institute of Technology,
Silchar, Assam, India
2Department of Chemistry, Gauhati University, Guwahati, Assam, India
GRAPHICAL ABSTRACT
Abstract One-pot oxidation of alanine and its ethyl ester with
a mild oxidant
40-methylazobenzene-2-sulfenyl bromide is described. Using a nonreactively water-soluble
electrophilic species, 40-methylazobenzene-2-sulfenyl bromide, with L-alanine and its ethyl
ester (in 3:1 molar proportions) in aqueous solution at room temperature, the correspond-
ing sulfenimines are prepared. On hydrolysis in acidic medium at room temperature, these
sulfenimines give ethanal and pyruvic acid respectively.
Keywords Alanine; aqueous medium; oxidation; sulfenimine
INTRODUCTION
Oxidation of a-amino acids plays an important role in biochemistry.
Sulfenylation of the amino group with electrophilic bivalent organosulfur com-
pounds, such as sulfenyl halides[1] and sulfenyl thiocyanates, and related compounds,
such as thiolsulfonates,[2] have been reported. Such reactions in practice provide
the best method of synthesizing sulphur–nitrogen bonds[3] in sulfenamides.[4,5]
Received May 7, 2010.
Address correspondence to Tirtha Bhattacharjee, Department of Chemistry, National Institute of
Technology, Silchar, Assam 788010, India. E-mail: Tirtha_07@yahoo.com
2870

OXIDATION OF ALANINE AND ITS ESTER
2871
Preparations of thiooximes or sulfenimines by reaction between sulfenamides
and various carbonyl compounds were also reported.[6] These sulfenamides and
sulfenimines[7] have versatile utility in synthetic organic chemistry.[8]
In this article, the results on the studies of oxidation[9] of alanine and its ethyl
ester by sulfenylation reaction are presented. 40-Methylazobenzene-2-sulfenyl bro-
mide 1a belongs to a class of nonreactive water- and alcohol-soluble sulfenyl
bromide.[10] The unusual stability of the sulfur–bromine bond of this sulfenyl
bromide in these solvents can be attributed to the existence of strong ortho
azo-sulfur interaction 1b in the molecule of this compound.[11] Ultraviolet (UV)
and visible spectra of the compound shows no azo p-pꢀ transition band, which
supports this view.
However, in spite of the presence of a strong ortho azo-sulfur interaction in the
molecule, its sulfenylating ability has not been totally sacrificed. This electrophilic
mild bivalent organosulfur reagent takes part in many electrophilic reactions[12] with
various carbon-centered and hetero atom–centered nucleophiles to give a wide range
of organosulfur compounds.
As 40-methylazobenzene-2-sulfenyl bromide is nonreactively soluble in alcohol
with sulfenylating properties, so we have used this species for the sulfenylation of
alanine and its ethyl ester in aqueous solution at room temperature, and oxidized
products ethanal and pyruvic acid respectively were obtained.
RESULTS AND DISCUSSION
When L-alanine 2 is subjected to a reaction with 40-methylazobenzene-2-sulfe-
nyl bromide 1a in 1:3 molar proportion in the presence of an acid scavenger such as
triethylamine, a sulfenimine of acetaldehyde 3 is obtained. The corresponding disul-
fide 4 is obtained as the other product. The organic base triethylamine used in the
reaction enhances the reaction in two ways: by breaking the zwitterionic nature of
the amino acid and by increasing the reactivity of the sulfenyl group of the sulfenyl
bromide 1a. Formation of the sulfenimine 3 can be rationalized as base-promoted
a-decarboxylative elimination reaction of the exhaustively sulfenylated alanine
(Scheme 1).
When ethyl ester of alanine 5 is subjected to the sulfenylation reaction under
similar conditions, the sulfenimine of ethyl pyruvate 6 is obtained along with the dis-
ulfide 4 as a product. The formation of the sulfenimine takes place by a base-induced

2872
P. BARMAN, S. K. BHATTACHARJEE, AND T. BHATTACHARJEE
Scheme 1. Oxidation of alanine by 40-methylazobenzene-2-sulfenyl bromide.
a-deprotonative elimination reaction of the exhaustively sulfenylated ethylester of
alanine (Scheme 2).
Sulfenimines 3 and 6 on acidic hydrolysis give acetaldehyde and pyruvic acid
respectively along with the disulfide as the product. Formation of these products
can be rationalized as per Scheme 3.
Acetaldehyde and pyruvic acid were isolated and identified as their 2,4-
dinitrophenylhydrazones.
Because the reactions are carried out in an aqueous medium at room tem-
perature (27 ꢁC), 40-methylazobenzene-2-sulfenyl bromide 1a provides a reagent
for oxidation of amines and a-amino acids to carbonyl compounds under quite mild
conditions.
Scheme 2. Oxidation of ethyl ester of alanine by 40-methylazobenzene-2-sulfenyl bromide.

OXIDATION OF ALANINE AND ITS ESTER
2873
Scheme 3. Hydrolysis of sulfenimine 3.
CONCLUSION
In brief, we are able to establish the fact that L-alanine and its ethyl ester can
be oxidized with this mild electrophilic sulfenylating species, 40-methylazobenzene-
2-sulfenyl bromide, in an aqueous medium at room temperature. Because the
conditions maintained during the reactions are mild and workup is quite simple, this
sulfenyl bromide 1a shows promise as a mild oxidant of a-amino acids to the
corresponding carbonyl compounds.
EXPERIMENTAL
Melting points were recorded on a Reico melting-point apparatus. Infrared
(IR) spectra were recorded on Perkin-Elmer 73633 Fourier transform (FT)–IR spec-
1
trometer as KBr pellets. H NMR spectra were recorded on Varian 400-MHz FT
NMR spectrometer, using tetramethylsilane (TMS) as internal standard and CDCl3
as solvent. All the chemicals used are from Merck.
Reaction of Alanine and Its Ethyl Ester with 4’-Methylazobenzene-
2-sulfenyl Bromide
A solution of the sulfenyl bromide (1.23 g, 4.02 mmol) in absolute ethanol
(30 mL) was added to a well-stirred solution of alanine or its ethyl ester (1.34 mmol)

2874
P. BARMAN, S. K. BHATTACHARJEE, AND T. BHATTACHARJEE
and triethylamine (0.3 mL) in absolute ethanol (10 mL). The mixture was stirred
magnetically (6 h) and then was kept at room temperature (27 ꢁC) for 48 h in the case
of alanine and 72 h in the case of ethyl ester of alanine, during which the solution was
occasionally swirled and shaken. On removal of the solvent under reduced pressure,
a pasty residue was obtained, which was dissolved in a benzene–chloroform mixture
(40:60) and chromatographed on a column of alumina. Two major zones were
obtained, which were eluted with benzene. The first elute in either case gave the dis-
ulfide, obtained as red crystals, in 60% yield, melted at 197–198 ꢁC, and the second
elute gave the sulfenimines 3 and 6 respectively.
Sulfenimine of Acetaldehyde (3)
Pale yellow crystals, mp 101 ꢁC, yield 0.45 g, 50%; IR (KBr) (nmax=cmꢂ1): 2893
=
(CH3), 1591 (N N), 3050 (S-N), 1572.9 (C N), 761 (C-S). Anal. calcd. for
=
C15H15N3S (269.36): C, 66.9; H, 5.58; N, 15.0%. Found: C, 67.20; H, 6.00; N,
1
15.3%. H NMR (CDCl3, 400 MHz) d: 2.19 (3H, s), 7.1 (2H, d), 7.45 (2H, d), 7.56
(1H, d), 7.29 (1H, t), 7.67 (1H, t), 7.53 (1H, d), 8.06 (1H, q), 2.06 (3H, d).
Sulfenimine of Pyruvic Acid (6)
Dull yellow crystals, mp 112 ꢁC, yield 0.45 g, 45%; IR (KBr) (nmax=cmꢂ1): 2891
=
=
=
(CH3), 1591 (N N), 3050 (S-N), 1572 (C N), 761 (C-S), 1730 (C O). Anal. calcd. for
C18H19N3O2S (341.43): C, 63.3; H, 5.57; N, 12.3%. Found: C, 63.2; H, 6.02; N, 12.0%.
1H NMR (CDCl3, 400 MHz) d: 2.19 (3H, s), 7.1 (2H, d), 7.45 (2H, d), 7.56 (1H, d),
7.29 (1H, t), 7.68 (1H, t), 7.54 (1H, d), 2.11 (3H, s), 4.23 (2H, q), 1.22 (3H, t).
Hydrolysis of Sulfenimines
Hydrochloric acid (1 mL, 1.2 mmol) in a 1:1 water–ethanol solution was added to
a well-stirred solution of the sulfanimines 3 or 6 (1.2 mmol) in ethanol (10 mL). The
mixture was stirred magnetically (60 min) at 45–50ꢁC on a warm water bath. On cool-
ing the solution to room temperature (27 ꢁC), the disulfide was precipitated, filtered
off, washed, dried, and crystallized from a benzene–ethanol mixture (mixed mp:
197–198 ꢁC). A solution of 2,4-dinitrophenylhydrazine hydrochloride (5 mL, 1.2 mmol)
in ethanol was added to the filtrate and washings collected in a small conical flask, and
the mixture was warmed on a water bath with scratching of the sides of the container
(20 min). Then the solution was concentrated under reduced pressure and allowed to
stand at room temperature (2 h). Slowly, crystals of 2,4-dinitrophenylhydrazone
appeared. The precipitate was filtered off, washed with a little dilute alcohol, and dried.
2,4-Dinitrophenylhydrazone of acetaldehyde was obtained as orange crystals (0.05 g)
from rectified spirit and melted at 161–163 ꢁC, and 2,4-dinitrophenylhydrazone of
pyruvic acid was obtained as yellow crystals (0.04 g) and melted at 218–220ꢁC.
ACKNOWLEDGMENTS
We thank the director of NIT, Silchar, for laboratory facilities and the Council
of Scientific and Industrial Research, New Delhi, for the award of a junior research
fellowship to T. B.

OXIDATION OF ALANINE AND ITS ESTER
2875
REFERENCES
1. Billman, J. H.; O’Mahony, E. The use of o-nitrobenzenesulfenyl chloride in the identifi-
cation of amines. J. Am. Chem. Soc. 1939, 61, 2340–2341.
2. Dunbar, J. E.; Rogers, J. H. Reactions of thiolsulfonates with amines. J. Org. Chem. 1966,
31, 2842–2846.
3. Davis, F. A.; Friedman, A. J.; Kluger, E. W. Chemistry of the sulfur–nitrogen bond, VIII:
N-Alkylidenesulfinamides. J. Am. Chem. Soc. 1974, 96, 5000–5001.
4. Major, R. T.; Peterson, L. H. Aliphatic sulfenamides. J. Am. Chem. Soc. 1956, 78,
6181–6182.
5. Behforouz, M.; Kerwood, J. E. Alkyl and aryl sulfenimides. J. Org. Chem. 1969,
34, 51–55.
6. Davis, F. A.; Slegeir, W. A. R.; Evans, S.; Schwartz, A.; Goff, D. L.; Palmer, R.
Chemistry of the sulphur–nitrogen bond, VI: Convenient one-step synthesis of
sulfenimines (S-aryl thiooximes). J. Org. Chem. 1973, 38, 2809–2813.
7. Burnett, D. A.; Hart, D. J.; Liu, J. b-Lactams from esters and sulfenimines: A new route
to monobactams. J. Org. Chem. 1986, 51, 1929–1930.
8. Davis, F. A. Adventures in sulfur–nitrogen chemistry. J. Org. Chem. 2006, 71, 8993–9003.
`
9. Armesto, X. L.; Canle, L. M.; Fernandez, M. I.; Garca, M. V.; Santaballa, J. A. First
steps in the oxidation of sulfur-containing amino acids by hypohalogenation: Very fast
generation of intermediate sulfenyl halides and halosulfonium cations. Tetrahedron
2000, 56, 1103–1109.
10. Karmakar, S.; Talukdar, A. N.; Barman, P.; Bhattacharjee, S. K. Crystal and molecular
structure of 20-chloroazobenzene-2-sulphenylbromide (C12H8BrClN2S). Indian J. Pure
App. Phy. 2001, 39, 357–360.
11. Karmakar, S.; Patowary, K.; Barman, P.; Hazarika, D.; Bhattacharjee, S. K. 40-
Methylazobenzene-2-sulphenylcyanide. Acta. Crystallogr. 2004, E60, o179–180.
12. Chaudhuri, A.; Bhattacharjee, S. K.; Dasgupta, S. K. Reaction of 2-p-tolylazonaphtha-
lene-1-sulphenyl bromide with resorcinol tautomer. Curr. Sci. India 1980, 49, 859–860.