Thermal rearrangement of terf-butylsulfinamide

Article abstract of DOI:10.3762/bjoc.7.2

tert-Butylsulfinamides are unstable above room temperature, and in chlorinated solvents they undergo rearrangement to form the more stable N-(tert-butylthio)-tert-butylsulfonamide.

Full text of DOI:10.3762/bjoc.7.2

Thermal rearrangement of tert-butylsulfinamide
Veera Reddy Arava*1, Laxminarasimhulu Gorentla1
and Pramod Kumar Dubey2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 9–12.
1R&D Laboratories, SUVEN Life Sciences Ltd, #18, Phase III,
Jeedimetla, Hyderabad – 500 055, India and 2Department of
Chemistry, J.N.T. University, Hyderabad – 500 072, India
doi:10.3762/bjoc.7.2
Received: 30 September 2010
Accepted: 09 November 2010
Published: 04 January 2011
Email:
Veera Reddy Arava* - reddyvenis@rediffmail.com;
Laxminarasimhulu Gorentla - laxman164@rediffmail.com;
Pramod Kumar Dubey - pkdubeyjntu@yahoo.co.in
Associate Editor: J. Murphy
© 2011 Arava et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
chlorinated solvents; N-(tert-butylthio)-tert-butylsulfonamide;
tert-butylsulfinamide; thermal rearrangement
Abstract
tert-Butylsulfinamides are unstable above room temperature, and in chlorinated solvents they undergo rearrangement to form the
more stable N-(tert-butylthio)-tert-butylsulfonamide.
Introduction
Over the past decade, an ever increasing number of methods
based upon the chiral amine reagent tert-butylsulfinamide (1)
(Figure 1) has become one of the most extensively used syn-
thetic approaches for both the production and discovery of drug
candidates [1]. In particular, the tert-butylsulfinyl group showed
high levels of asymmetric induction in many processes. The
Figure 1: tert-Butylsulfinamide.
importance of these reagents (R and S) is evident by the number
of manufacturers (>75) and by the number of publications
(>400).
when sulfinamide 1 was reacted with an organic acid in the
presence of boric acid [3] to obtain an amide 2 (Scheme 1), no
amide was obtained, which was confirmed by IR and NMR
Results and Discussion
During our studies [2] on the industrial utilization of these two data, and the product was also devoid of an acid residue. The
reagents (R and S), we found an interesting observation, i.e., product appeared to be derived only from the reagent 1.
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Beilstein J. Org. Chem. 2011, 7, 9–12.
Scheme 1: Synthesis of acid amide.
From the spectral data, structure 3 was assigned to the product
shown in Figure 2. The structure of 3 was confirmed by chem-
ical synthesis (Scheme 2) and finally by XRD [4] (Figure 3).
Both tert-butylsulfanyl chloride 4 (Scheme 3) and tert-butylsul-
fonamide 5 (Scheme 4) were prepared by known procedures
[5,6].
Figure 3: ORTEP diagram of 3.
A possible mechanism for the proposed rearrangement is shown
in Scheme 5.
Scheme 3: Synthesis of tert-butylsulfanyl chloride.
Figure 2: N-(tert-butylthio)-tert-butylsulfonamide.
Scheme 4: Synthesis of tert-butylsulfonamide.
Scheme 2: Chemical synthesis of 3.
Scheme 5: Proposed mechanism for rearrangement.
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Beilstein J. Org. Chem. 2011, 7, 9–12.
Table 1: Screening of rearrangement conditions.
Entry
Reaction conditions
Reagent / condition Solvent
Yield (%)a
Starting
material
T (°C)
Time (h)
type
1
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(R)-isomer
(S)-isomer
(R)-isomer
-
-
toluene
o-xylene
ethylene dichloride
CHCl3
110
110
140
80
3
48
48
72
72
48
24
24
48
1
27
70
2
-
3
-
64
4
-
40 + 20c
25
5
-
65
6
-
boric acid (1.0 equiv)
boric acid (1.0 equiv)
boric acid (0.5 equiv)
MeSO3H
toluene
toluene (u/N2)
toluene
toluene
toluene
toluene
toluene
toluene
CHCl3
110
110
110
110
110
110
110
110
RT
70
7
65
8
65
9
60
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
tartaric acid
citric acid
24
24
24
2
38
16
p-TSA
38
sonication
34b
2b
sonication
DMF
RT
1
sonication
ethyl acetate
CHCl3
RT
1
5b
sonication + boric acid
sonication + p-TSA
-
RT
1
16b
23b
3
CHCl3
RT
0.5
144
144
144
48
40
24
48
0.5
toluene
CHCl3
RT
-
RT
21b
3b
-
MeOH
RT
benzoyl peroxide
TEMPO
toluene
toluene
toluene
toluene
DMF
110
RT - 110
110
110
150
60
9b
2,6-di-tert-butylphenol
-
75
70
MW 150 Watt
70
aIsolated yield, b% conversion in HPLC, crecovered starting material with SOR +5°
First it is assumed that the product is formed only by the de- butylphenol (entry 23) or with microwave irradiation (entry 25),
gradation of reagent 1. Further experiments, in the presence of complete consumption of starting material was observed. In
acids (entries 7 to 13, Table 1) or the absence of acids (entries 1 other cases (entries 4, 5, 11 and 12), 10 to 30% of the starting
to 6, Table 1), under sonication (entries 14 to 18) and with material was recovered without racemization.
microwave irradiation (entry 26), confirmed the assumption that
the reagent is thermally unstable. Also the rearrangement is Conclusion
likely not to proceed by a homolytic fission (radical) mecha- We found that both (R and S) tert-butanesulfinamides are
nism, because the rate of reaction is not affected either by unstable above room temperature and in chlorinated solvents.
benzoyl peroxide, by TEMPO a radical initiator (entries 22 and
23) or by a radical inhibitor 2,6-di-tert-butylphenol (entry 24). Experimental
See Supporting Information File 1 for full experimental data.
When the reagent 1 alone was subjected to thermal rearrange-
ment (entry 1), complete consumption of starting material was
Supporting Information
observed. Only 27% product was isolated and 73% of the ma-
terial was lost by vaporitation. When the reaction was carried
Supporting Information File 1
out in the presence of solvents such as toluene (entries 2, 6 and
24), o-xylene (entry 3), or solvents with reagents such as boric
acid (entries 7, 8 and 9), methanesulphonic acid (entry 10),
p-TSA (entry 13), benzoyl peroxide (entry 22), 2,6-di-tert-
Full experimental data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-2-S1.pdf]
11

Beilstein J. Org. Chem. 2011, 7, 9–12.
Acknowledgements
We wish to thank Prof. A. Srikrishna of IISc. (Bangalore) for
the X-ray analysis and the management of Suven for providing
excellent facilities.
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