New method for the preparation of N-chloroamines by oxidative N-halogenation of amines using oxone-KCl

Article abstract of DOI:10.1080/00397911.2017.1418890

A mild and efficient method for preparation of N-chloroamines by oxidative N-halogenation of primary/secondary amines using oxone-KCl is described.

Full text of DOI:10.1080/00397911.2017.1418890

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
New method for the preparation of N-
chloroamines by oxidative N-halogenation of
amines using oxone-KCl
Vinodkumar Sriramoju, Srinivas Kurva & Sridhar Madabhushi
To cite this article: Vinodkumar Sriramoju, Srinivas Kurva & Sridhar Madabhushi (2018): New
method for the preparation of N-chloroamines by oxidative N-halogenation of amines using oxone-
KCl, Synthetic Communications, DOI: 10.1080/00397911.2017.1418890
To link to this article: https://doi.org/10.1080/00397911.2017.1418890
View supplementary material
Published online: 09 Feb 2018.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

SYNTHETIC COMMUNICATIONS®
https://doi.org/10.1080/00397911.2017.1418890
New method for the preparation of N-chloroamines by
oxidative N-halogenation of amines using oxone-KCl
Vinodkumar Sriramoju , Srinivas Kurva , and Sridhar Madabhushi
Fluoroorganics Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India
ABSTRACT
ARTICLE HISTORY
Received 23 October 2017
A mild and efficient method for preparation of N-chloroamines by
oxidative N-halogenation of primary/secondary amines using oxone-
KCl is described.
KEYWORDS
Amines; N-chloroamines;
oxidative N-halogenation;
oxone-KCl
GRAPHICAL ABSTRACT
Introduction
N-chloroamines are important intermediates in organic synthesis for preparation
[
1]
[1a]
[2]
[3]
of nitriles,
chloroimines,
diazirines,
diazene N-oxides,
aroyliminoselenyl-
[
4]
[5]
[6]
chlorides, nitramides and aminoketones. N-chloroamines are also studied as
cross-coupling partners for Buchwald-Hartwig type electrophilic amination reactions.[7,8]
In literature, several methods were known for preparation of N-chloroamines by oxidative
[
1a]
N-halogenation using reagents such as m-chloroperbenzoic acid-FeCl ,
isocyanuric
3
[
1b]
0
0
[1c]
[1d]
[6]
chloride,
N,N,N ,N -tetrachlorobenzene-1,3-disulfonamide,
Ca(OCl)2,
Cl -H O,
2
2
[
9]
[10]
N-chlorosuccinimide (NCS) and t-BuOCl.
Oxone is a mild, inexpensive solid oxidant and widely used in organic synthesis. Oxone
efficiently promotes oxidative halogenation reactions in the presence of a halide source in
aqueous organic medium such as acetonitrile–water, acetone–water, methanol–water, etc.
Some of the important oxidative halogenation reactions reported in literature using oxone-
[
11]
MX system are (i) nuclear chlorination of aromatic compounds,
(ii) transformation of
[
12]
[13]
alkynes into a,a-dihaloketones,
(iii) alkynyl silanes into a,a,a-trihaloketones,
(iv) alkenes into halohydrins,
[
14]
[15]
(iv) thiols into sulfonyl halides
(v) oximes into
[
16]
hydroximoyl chlorides
etc.
In literature, studies on transformation of amines into N-chloroamines by reaction with
oxone and a halide are so far not known. Here, we report for the first time, a mild and
efficient method for preparation of N-chloroamines in high yields (61–95%) from a variety
CONTACT Sridhar Madabhushi
smiict@gmail.com
Fluoroorganics Division, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
©
2018 Taylor & Francis

2
V. SRIRAMOJU ET AL.
Scheme 1. Synthesis of N-chloroamines using oxone-KCl.
of primary and secondary amines by oxidative N-halogenation using oxone-KCl at ambient
temperature in acetonitrile-water (2:1) as shown in Scheme 1.
In this study, initially we found that benzylamine 1a reacts efficiently with oxone-KCl in
aqueous acetonitrile at ambient temperature producing N,N-dichlorobenzylamine 2a,
which was obtained 2a in maximum yield (95%) when 1a was reacted with two equivalents
of oxone-KCl in acetonitrile–water (2:1) medium as shown in Table 1.
Next, we found that the present reaction proceeds well also with a variety of
primary aralkyl amines 1a–1k, alkyl amines 1l–1o and secondary alkyl amines 1p–1r,
which were reacted with oxone-KCl in acetonitrile–water (2:1) medium at ambient
temperature to obtain the corresponding N,N-dichloroamines 2a–2o in 61–95% yields
and N-chloroamines 2p–2r in 84–88% yields.
In literature, it is reported that activated arenes such as anisoles and phenols undergo
[
11a]
regioselective ring chlorination with oxone-KCl in acetonitrile.
In the present study,
when aralkyl amines 1a–1k, which have electron releasing and electron withdrawing
groups on the aromatic ring, were reacted with oxone-KCl in aqueous acetonitrile, aralkyl
amines 1a–1i were found to produce exclusively N-chlorinated products 2a–2i in 85–95%
yields. However, under similar reaction conditions, 3-methoxybenzylamine 1j and
4
-methoxybenzylamine 1k behaved differently as they underwent simultaneously ring
chlorination as well as N-chlorination producing N,N-dichloro-1-(2-chloro-5-methoxyphe-
nyl)methanamine 2j and N,N-dichloro-1-(3-chloro-4-methoxyphenyl)methanamine 2k in
6
3 and 61% yields respectively (Table 2). Here, it appears that oxidative N-chlorination
proceeds possibly through radical reaction pathway involving chlorine radicals (Cl·), which
are generated by the homolytic fission of the in situ generated hypochlorous acid (HOCl)
and ring chlorination proceeds through electrophilic chlorination pathway by reaction of
Table 1. Screening of solvents for N-chlorination of benzylamine 1a using oxone-KCl.
a
Entry
Oxone (equi)
KCl (equi)
Solvent
Reaction time (min)
%Yield
1
2
3
4
5
6
7
8
1
1
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
CN þ H
2
2
2
2
2
O (2:1)
25
25
25
60
60
60
60
60
48
60
95
40
30
15
10
10
1.5
2
1.5
2
CN þ H
CN þ H
CN þ H
CN þ H
CN
O (2:1)
O (2:1)
O (2:1)
O (2:1)
2
2
2
2
2
2
2
2
CHCl
THF
3
2
2
a
Isolated yields.

SYNTHETIC COMMUNICATIONS®
3
Table 2. N-chlorination of various primary and secondary amines.
a
Entry
a
Amine 1
N-chloroamine 2
Time (min)
25
%Yield
95
b
c
40
40
85
85
d
e
25
35
86
89
f
30
40
90
88
g
h
20
87
i
j
30
30
91
63
k
30
61
l
25
30
30
90
85
87
m
n
o
45
84
p
q
35
45
88
84
(Continued)

4
V. SRIRAMOJU ET AL.
Table 2. Continued.
a
Entry
r
Amine 1
N-chloroamine 2
Time (min)
20
%Yield
85
s
t
–
–
–
60
60
60
NR
NR
NR
u
v
30
35
65
45
w
x
25
51
a
Isolated yields.
1
13
All products gave satisfactory H & C NMR, IR and mass spectral data.
NR, no reaction.
in situ generated chlorine with an activated arene such as methoxylated benzene as shown
in Scheme 2. Though chlorine is not a good electrophile, substrates 1j and 1k showed
remarkable reactivity and underwent electrophilic ring chlorination with chlorine. It could
Scheme 2. Plausible mechanism for N-chlorination and ring chlorination reactions.

SYNTHETIC COMMUNICATIONS®
5
be due to the presence of high activating methoxy functionality on the aromatic rings of
these substrates.[17]
In our study, aryl amines such as aniline 1s, 3-nitroaniline 1t and 4-methoxyaniline 1u
were found to be unreactive with oxone-KCl under the reaction conditions. However, their
acetanilide derivatives, i.e., 1v–1x were found to be reactive under similar conditions and
[
11a]
formed exclusively ring chlorination products,
i.e., N-(2,4-dichlorophenyl)acetamide
2
v, N-(2-chloro-5-nitrophenyl)acetamide 2w and N-(2,5-dichloro-4-methoxyphenyl)-
acetamide 2x in 65, 45, and 51% yields respectively.
Conclusion
In conclusion, this work describes an efficient method for preparation of N-chloroamines
from a variety of primary and secondary amines by oxidative N-chlorination under mild
conditions using oxone-KCl.
Experimental section
Typical procedure for the synthesis of N,N-dichlorobenzylamine (2a): In a 50 mL round
bottom flask, benzylamine 1a (0.5 g, 4.67 mmol), oxone (2.9 g, 9.35 mmol), NaCl (0.55 g,
9
.35 mmol) and acetonitrile-water (2:1, 10 mL) were taken and stirred at room temperature
for 25 min. After completion of the reaction (TLC), the reaction mixture was extracted
with ethyl acetate (3 � 10 mL) and the combined organic layer was washed with brine
(
1 � 10 mL), dried over anhydrous Na SO and concentrated under reduced pressure.
2
4
Purification of the crude product by normal column chromatography (silica gel 60–120
mesh, n-hexane) furnished N,N-dichlorobenzylamine 2a as yellow liquid (0.78 g, 95%).
1
The characterization data obtained for 2a is as follows: H NMR (300 MHz, CDCl ):
3
1
3
δ ¼ 7.39–7.36 (m, 5H), 4.67 (s, 2H);
C NMR (75 MHz, CDCl ): δ ¼ 134.84,
3
1
5
30.02, 129.18, 128.51, 78.83; IR (neat): υ 3035, 2923, 2853, 1496, 1455, 1218, 771, 700,
91 cm ; GC-MS: C H Cl N: m/z 175[M] ; HRMS: 174.99546 (calcd. 174.99555).
−1
þ
7
7
2
Acknowledgment
Authors Vinodkumar Sriramoju, Srinivas Kurva are thankful to UGC, New Delhi for the award of
Senior Research Fellowship.
ORCID
Vinodkumar Sriramoju
http://orcid.org/0000-0002-2303-6693
Srinivas Kurva
http://orcid.org/0000-0001-9665-9093
Sridhar Madabhushi
http://orcid.org/0000-0001-7279-7846
References
[
1] (a) Liu, J.; Xu, J.; Ren, J.; Zeng, B. Chem. Lett. 2014, 43, 190–192; (b) De Luca, L.; Giacomelli, G.
Synlett 2004, 12, 2180–2184; (c) Ghorbani-Vaghei, R.; Veisi, H. Synthesis 2009, 2009, 945–950;
(
d) Roberts, J. T.; Rittberg, B. R.; Kovacic, P. J. Org. Chem. 1981, 46, 4111–4115.
[
[
[
2] Martinu, T.; Dailey, W. P. J. Org. Chem. 2006, 71, 5012–5015.
3] Nelson, V.; Serianz, A.; Kovacic, P. J. Org. Chem. 1976, 41, 1751–1754.
4] (a) Derkach, N. Y.; Lyapina, T. V.; Levchenko, E. S. Zh. Org. Khim. 1980, 16, 33–39;
(
b) Zibarev, A. V.; Dolenko, G. N.; Krupoder, S. A.; Mazalov, L. N.; Poleshchuk, O. Kh.; Furin,

6
V. SRIRAMOJU ET AL.
G. G.; Yakobson, G. G. Zh. Org. Khim. 1980, 16, 390–398; (c) Derkach, N. Y. Zh. Org. Khim.
1
984, 20, 2377–2383.
[
[
[
[
[
5] Smart, G. N. R.; Wright, G. F. Can. J. Res. 1948, 26B, 284; Chem. Abstr. 1948, 42, 5844a.
6] Baumgarten, H. E.; Bower, F. A. J. Am. Chem. Soc. 1954, 76, 4561–4564.
7] Qian, X.; Yu, Z.; Auffrant, A.; Gosmini, C. Chem. Eur. J. 2013, 19, 6225–6229.
8] Yin, Z.; Wang, Z.; Li, W.; Wu, X. Eur. J. Org. Chem. 2017, 2017, 1769–1772.
9] Guillemin, J. C.; Denis, J. M. Synthesis 1985, 1985, 1131–1133.
[
10] Zimmer, H.; Audrieth, L. F. J. Am. Chem. Soc. 1954, 76, 3856–3857; (b) Alt, G. H.; Knowles,
W. S. Org. Syn. Coll. 1965, 45, 16–19.
11] Narender, N.; Srinivasu, P.; Kulkarni, S. J.; Raghavan, K. V. Synth. Commun. 2002, 32, 279–286;
[
(
b) Narender, N.; Mohan, K. V. V. K.; Srinivasu, P.; Kulkarni, S. J.; Raghavan, K. V. Indian J.
Chem. 2004, 43B, 1335–1338.
[
12] Sridhar, M.; Raveendra, J.; Reddy, M. K. K.; Reddy, G. K.; Sairam, V. V. Tetrahedron Lett. 2013,
5
4, 3993–3996.
[
[
[
[
[
13] Vinodkumar, S.; Raveendra, J.; Srinivas, K.; Sridhar, M. Chem. Lett. 2017, 46, 560–562.
14] Sridhar, M.; Raveendra, J.; Vinodkumar, S.; Rajpal, S. Green Chem. 2014, 16, 3125–3131.
15] Macharla, A. K.; Nappunni, R. C.; Nama, N. Tetrahedron Lett. 2012, 53, 1401–1405.
16] Kim, J. N.; Ryu, E. K. J. Org. Chem. 1992, 57, 6649–6650.
17] Hirano, M.; Yakabe, S.; Monobe, H.; Morimoto, T. Can. J. Chem. 1997, 75, 1905–1912.