General and efficient synthesis of o-sulfonylhydroxylamine derivatives

Article abstract of DOI:10.1080/00397910903007111

A general and efficient synthetic route to O-sulfonylhydroxylamine derivatives is described. The approach involves acylation of hydroxylamine with benzyl chloroformate to give N-carbobenzoxy hydroxylamine, followed by sulfonation and hydrogenolysis to giv

Full text of DOI:10.1080/00397910903007111

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General and Efficient Synthesis of O-
Sulfonylhydroxylamine Derivatives
Liqiong Qin a , Zhiming Zhou a , Jia Wei a , Ting Yan a & Hongliang
Wen a
a School of Chemical Engineering and Environment, Beijing Institute
of Technology, Beijing, China
Version of record first published: 04 Feb 2010.
To cite this article: Liqiong Qin, Zhiming Zhou, Jia Wei, Ting Yan & Hongliang Wen (2010): General
and Efficient Synthesis of O-Sulfonylhydroxylamine Derivatives, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:5, 642-646
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Synthetic Communications1, 40: 642–646, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903007111
GENERAL AND EFFICIENT SYNTHESIS OF
O-SULFONYLHYDROXYLAMINE DERIVATIVES
Liqiong Qin, Zhiming Zhou, Jia Wei, Ting Yan, and
Hongliang Wen
School of Chemical Engineering and Environment, Beijing Institute of
Technology, Beijing, China
A general and efficient synthetic route to O-sulfonylhydroxylamine derivatives is described.
The approach involves acylation of hydroxylamine with benzyl chloroformate to give
N-carbobenzoxy hydroxylamine, followed by sulfonation and hydrogenolysis to give
products.
Keywords: Benzyl chloroformate; hydrogenolysis; O-sulfonylhydroxylamine derivatives; sulfonation
INTRODUCTION
Recently, O-sulfonylhydroxylamine derivatives have attracted considerable
attention in heterocyclic synthesis. O-Tosylhydroxylamine reacted with olefine to
give azidines stereospecifically in moderate to high yield.[1] It can also react with
1,5-diaryl-1,5-diazapenta-1,3-diene in spontaneous cyclization to give pyrazole
derivative.[2] As aminating regents, O-sulfonylhydroxylamine derivatives can react
with pyridine, quinoline, and isoquinoline to give corresponding N-imines,[3,4] which
are important intermediates in heterocyclic synthesis. Hajos et al. prepared a series of
pyrido[1,2-b]-as-triazinium salts by condensation a-dioxo regents with diamino-
pyridium salt, which resulted from aminating 2-aminopyridine with tosyl hydroxyl-
amine.[5] With the same strategy, [1,2,4]-triazole-[1,5-a]-quinoline and [1,2,4]-triazole
[5,1-a]-isoquinoline derivatives were also obtained.[6]
The traditional methods for synthesis of O-sulfonylhydroxylamine derivatives
involve masking the amine function, sulfonation, and deprotection.[1,7,8] In the
present communication, we describe
a general and efficient synthesis of
O-sulfonylhydroxylamine derivatives in which benzyl chloroformate is used to
protect the amine group.
The O-sulfonylhydroxylamine derivatives were synthesized via the general
route depicted in Scheme 1. Benzyl chloroformate reacted with hydroxylamine
in CH2Cl2=H2O at room temperature to give N-carbobenzoxy hydroxylamine,
Received March 12, 2009.
Address correspondence to Hongliang Wen, School of Chemical Engineering and Environment,
Beijing Institute of Technology, Zhongguancun South Street No. 5, Haidian District, Beijing 100081,
China. E-mail: hongliang_wen@hotmail.com
642

O-SULFONYLHYDROXYLAMINE DERIVATIVES
643
Scheme 1. Synthesis of O-sulfonylhydroxylamine derivatives.
which could be used for the next step without further purification. N-
Carbobenzoxyhydroxylamine was converted into O-sulfonyl hydroxamic esters
by treatment with various sulfonyl chlorides. The high reactivity of both enabled
their complete conversion after the addition of sulfonyl chlorides. O-Sulfonyl hydro-
xamic esters were deprotected by hydrolysis with hydrogen and Pd-C to furnish
almost quantitative products of O-sulfonylhydroxylamine derivatives. In compari-
son with other methods, O-sulfonylhydroxylamine derivatives prepared by this
method are more stable and can be kept at low temperature for several days with
no decomposition.
EXPERIMENTAL
Melting points were determined on an XT4A microscopic digital melting-point
apparatus and are uncorrected. 1H NMR spectra were recorded on Varian Inova 400
spectrometer in CDCl3 or dimethylsulfoxide (DMSO-d6) (with tetramathylsilane as
internal standard). Infrared (IR) spectra were recorded on a Nicolet Fourier trans-
form (FT)–IR 5700 spectrophotometer using KBr pellets. Mass spectra (MS) were
recorded on a Thermo Scientific LTQ Orbitrap XLM mass spectronmeter.
N-Carbobenzoxyhydroxylamine (3)
Hydroxylamine hydrochloride (3.2 g, 0.046 mol) was added to a solution of 6.5 g
(0.06 mol) Na2CO3 in 20 ml H2O with continuous stirring. Subsequently, 6.82 g
(0.04 mol) benzyl chloroformate in 15 ml CH2Cl2 were added slowly. The mixture
was stirred at room temperature for 4 h, after which the reaction mixture was acidified
with concentrated hydrochloric acid. The reaction mixture was then extracted with
CH2Cl2, and CH2Cl2 solution was dried and concentrated under reduced pressure
to give the crude product, which was recrystallized with ether and hexane to afford
N-carbobenzoxyhydroxylamine. Mp 62–64ꢀC (lit. 65–70), yield: 83.6%. IR (KBr)
1
3373, 3300, 1703, 1502, 1398, 1288, 1119 cmꢁ1. H NMR (CDCl3, 400 MHz) d 5.19
(s, 2H), 6.70 (s, 1H), 7.21 (s, 1H), 7.36 (s,5H). ESI-MS: 190 (M þ Na)þ.
Sulfonation of N-Carbobenzoxyhydroxylamine (2)
A solution of 2.8 mmol substituted sulfonyl chloride in 4 ml THF was added
dropwise to a solution of 3 mmol N-carbobenzoxyhydroxylamine and 3.2 mmol

644
L. QIN ET AL.
triethylamine in 8 ml tetrahydrofuran (THF) at a temperature of ꢁ15ꢀC. After
addition, the reaction mixture was kept at this temperature for 0.5 h. After that,
the precipitate triethylamine hydrochloride was filtered off, and the filtrate was
concentrated under vacuum to give crude products. The crude material was purified
by flash chromatography on silica gel.
Selected Data
O-p-Toluenesulfonyl benzyloxyhydroxamate (4a). Flash chromatography
gave white solid, mp 120–123ꢀC. Yield: 82.5%. IR (KBr) 3138, 2938, 1759, 1732,
1595, 1484, 1365, 1261, 1198, 1181, 1077 cmꢁ1 1H NMR (CDCl3, 400 MHz) d
.
2.431 (s, 3H), 5.035 (s, 2H), 7.190–7.213 (m, 2H), 7.260 (d, 2H), 7.335–7.357 (m,
3H), 7.754 (s, 1H), 7.830 (d, 2H). ESI-MS: 344 (M þ Na)þ.
O-Benzenesulfonyl benzyloxyhydroxamate (4b). Flash chromatography
gave pale yellow solid, mp 65–68ꢀC. Yield: 89.9%. IR (KBr) 3284, 1749, 1451,
1
1384, 1239, 1187, 1174, 1071 cmꢁ1. H NMR (CDCl3, 400 MHz) d 5.036 (s, 2H),
7.194–7.218 (m, 2H), 7.342–7.359 (m, 3H), 7.478–7.517 (m, 2H), 7.664–7.681 (m,
1H), 7.795 (s, 1H), 7.959–7.983 (m, 2H). ESI-MS: 330 (M þ Na)þ.
O-Methanesulfonyl benzyloxyhydroxamate (4c). Flash chromatography
gave white solid, mp 85–87ꢀC. Yield: 73.2%. IR (KBr) 3237, 2941, 1740, 1490,
1
1455, 1361, 1247, 1150, 1100 cmꢁ1. H NMR (CDCl3, 400 MHz) d 3.171 (s, 3H),
5.270 (s, 2H), 7.380–7.396 (m, 5H), 8.024 (s, 1H). ESI-MS: 268 (M þ Na)þ.
O-3,4-Difluorobenzenesulfonyl benzyloxyhydroxamate (4d). Flash chro-
matography gave pale yellow oil. Yield: 78.8%. IR (KBr) 3284, 1770, 1603, 1510,
1457, 1379, 1281, 1245, 1184, 1119, 1063 cmꢁ1 1H NMR (CDCl3, 400 MHz) d
.
5.043 (s, 2H), 7.170–7.210 (m, 3H), 7.335–7.362 (m, 3H), 7.770–7.773 (m, 1H),
7.752–7.797 (m, 1H), 8.329 (s, 1H). ESI-MS: 366 (M þ Na)þ.
O-p-Trifluoromethylbenzenesulfonyl benzyloxyhydroxamate (4e). Flash
chromatography gave pale yellow solid, mp 57–59ꢀC. Yield: 73.4%. IR (KBr) 3302,
1766, 1498, 1433, 1407, 1376, 1328, 1243, 1193, 1066, 1016 cmꢁ1. 1H NMR (CDCl3,
400 MHz) d 5.020 (s, 2H), 7.173–7.199 (m, 2H), 7.342–7.36 (m, 3H), 7.706 (d, 2H),
7.955 (s, 1H), 8.066 (d, 2H). ESI-MS: 398 (M þ Na)þ.
O-m-Fluorobenzenesulfonyl benzyloxyhydroxamate (4f). Flash chroma-
tography gave pale yellow solid, mp 76–77ꢀC. Yield: 84.2%. IR (KBr) 3285, 1774,
1
1594, 1478, 1459, 1430, 1378, 1309, 1244, 1223, 1186, 1083, 1059 cmꢁ1. H NMR
(CDCl3, 400 MHz) d 5.052 (s, 2H), 7.198–7.221 (m, 2H), 7.343–7.359 (m, 4H),
7.431–7.484 (m, 1H), 7.669 (d, 1H), 7.759 (d, 1H), 7.902 (s, 1H). ESI-MS: 348
(M þ Na)þ.
O-2,5-Difluorobenzenesulfonyl benzyloxyhydroxamate (4g). Flash chro-
matography gave pale yellow oil. Yield: 66.8%. IR (KBr) 3307, 1775, 1494, 1458,
1423, 1382, 1241, 1256, 1201, 1185, 1059 cmꢁ1 1H NMR (CDCl3, 400 MHz) d
.
5.073 (s, 2H), 7.018–7.072 (m, 1H). ESI-MS: 366 (M þ Na)þ.

O-SULFONYLHYDROXYLAMINE DERIVATIVES
645
Hydrogenolysis of O-Sulfonyl Hydroxamic Esters
Substituted O-sulfonyl hydroxamic esters 5a–g (1.5 mmol) and 0.5 g 10% Pd-C
were dissolved in 8 ml absolute methanol at room temperature. A gentle stream of
hydrogen was passed through the reaction mixture; the reaction proceeded for about
0.5 h. After the hydrolysis was completed (as monitored by thin-layer chromato-
graphy), the catalyst was removed by filtration through celite, and the filtrate was
concentrated to give products with no workup.
Selected Data
O-p-Tolenesulfonylhydroxylamine (5a). White solid, mp 200ꢀC (Dec).
Yield: 98%. IR (KBr) 3426, 3179, 3070, 1599, 1457, 1163, 1127, 1036, 1010 cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz) d 2.287 (s, 3H), 7.115 (d, 2H), 7.472 (d, 2H).
ESI-MS: 171 (M-NH2)ꢁ.
O-Benzenesulfonylhydroxylamine (5b). White solid, mp 195ꢀC (Dec).
Yield: 100%. IR (KBr) 3424, 3187, 3065, 1445, 1222, 1189, 1131, 1041, 1019 cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz) d 7.315 (m, 3H), 7.59 (m, 2H). ESI-MS: 157
(M-NH2)ꢁ.
O-Methanesulfonylhydroxylamine (5c). White solid, mp 177–179ꢀC (Dec).
1
Yield: 100%. IR (KBr) 3183, 3103, 1436, 1404, 1345, 1326, 1192, 1049 cmꢁ1. H
NMR (DMSO-d6, 400 MHz) d 2.312 (s, 3H). ESI-MS: 95 (M-NH2)ꢁ.
O-3,4-Difluorobenzenesulfonylhydroxylamine (5d). White solid, mp
178ꢀC (Dec). Yield: 98%. IR (KBr) 3408, 3243, 3089, 1644, 1611, 1516, 1417,
1
1282, 1259, 1231, 1106 cmꢁ1. H NMR (DMSO-d6, 400 MHz) d 7.374–7.489 (m,
3H). ESI-MS: 193 (M-NH2)ꢁ.
O-p-Trifluoromethylbenzenesulfonylamine (5e). White solid, mp >
300ꢀC. Yield: 99%. IR (KBr) 3437, 1669, 1434, 1406, 1331, 1225, 1202, 1173,
1
1131, 1065, 1051 cmꢁ1. H NMR (DMSO-d6, 400 MHz) d 7.661 (d, 2H), 7.748 (d,
2H). ESI-MS: 225 (M-NH2)ꢁ.
O-m-Fluorobenzenesulfonylamine (5f). White solid, mp 230ꢀC (Dec).
Yield: 96%. IR (KBr) 3424, 3189, 3069, 1680, 1655, 1589, 1476, 1427, 1272, 1223,
1
1179, 1107, 1075, 1060, 1039 cmꢁ1. H NMR (DMSO-d6, 400 MHz) d 7.138–7.180
(m, 1H), 7.280–7.306 (m, 1H), 7.358–7.441 (m, 2H). ESI-MS: 175 (M-NH2)ꢁ.
O-2,5-Difluorobenzenesulfonylamine (5g). White solid, mp 238ꢀC (Dec).
Yield: 100%. IR (KBr) 3438, 3203, 3079, 1672, 1640, 1598, 1481, 1434, 1408, 1251,
1
1213, 1192, 1120, 1083, 1032 cmꢁ1. H NMR (DMSO-d6, 400 MHz) d 7.195–7.271
(m, 2H), 7.337–7.372 (m, 1H). ESI-MS: 193 (M-NH2)ꢁ.
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