N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-2,5-dienylideneamine as a mild and highly regioselective chlorinating reagent

Article abstract of DOI:10.1081/SCC-120002512

N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-2,5-dienylideneamine was used as a new, mild and highly regioselective chlorinating reagent in the chlorination of phenol and o-cresol in CCl₄, DMF and CH₃CN. The effects of C₂H₅OH, C₅H₅N, DMF and Et₃N on the regioselectivity in CCl₄ have also been examined.

Full text of DOI:10.1081/SCC-120002512

This article was downloaded by: [Stony Brook University]
On: 26 October 2014, At: 17:35
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
N-CHLORO-2,3,4,4,5,6-HEXACHLOROCYCLOHEXA-
2,5-DIENYLIDENEAMINE AS A MILD AND HIGHLY
REGIOSELECTIVE CHLORINATING REAGENT
a
b
a
M. Mamaghani , M. A. Zolfigol & M. Shojaei
a
Chemistry Department , Faculty of Science , Guilan University , P.O. Box 1914, Rasht,
Iran
b
Department of Chemistry , College of Science , Bu-Ali Sina University , Hamadan, Iran
Published online: 16 Aug 2006.
To cite this article: M. Mamaghani , M. A. Zolfigol & M. Shojaei (2002) N-CHLORO-2,3,4,4,5,6-HEXACHLOROCYCLOHEXA-
2,5-DIENYLIDENEAMINE AS A MILD AND HIGHLY REGIOSELECTIVE CHLORINATING REAGENT, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:5, 735-740, DOI: 10.1081/
SCC-120002512
To link to this article: http://dx.doi.org/10.1081/SCC-120002512
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 COMMUNICATIONS, 32(5), 735–740 (2002)
N-CHLORO-2,3,4,4,5,6-
HEXACHLOROCYCLOHEXA-
2
,5-DIENYLIDENEAMINE AS A MILD
AND HIGHLY REGIOSELECTIVE
CHLORINATING REAGENT
1
,
2
1
M. Mamaghani, * M. A. Zolfigol, and M. Shojaei
1
Chemistry Department, Faculty of Science, Guilan
University, P.O. Box 1914, Rasht, Iran
Department of Chemistry, College of Science,
Bu-Ali Sina University, Hamadan, Iran
2
ABSTRACT
N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-2,5-dienylidene-
amine was used as a new, mild and highly regioselective chlo-
rinating reagent in the chlorination of phenol and o-cresol in
CCl , DMF and CH CN. The effects of C H OH, C H N,
4
3
2
5
5
5
DMF and Et N on the regioselectivity in CCl have also
3
4
been examined.
Chlorinated aromatic compounds are very important synthetic inter-
1
mediates for the synthesis of herbicides, and bioactive compounds. The
reactivity of these products more often depends on the position of the chlo-
rine on the aromatic ring. The need for isomerically pure chloroaromatics
*
Corresponding author. Fax: (þ98) 1313220066; E-mail: M-chem41@cd.gu.ac.ir
35
7
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
7
36
MAMAGHANI, ZOLFIGOL, AND SHOJAEI
has led to investigations into more selective chlorinating agents. Reactions
2
using bulky chlorinating agents, N-chloro succinimide (NCS), chlorous
3
4
acid and S-chlorodimethylsulfonium chloride, or chlorination in the pres-
5
6
ence of oxides, zeolites and reactions making use of complexes between
7–9
1
0
substrate and chlorinating agents have been described in the literatures.
However, in a systematic studies Smith and his co-workers reported highly
selective chlorination of phenols, anisoles, anilines and the related com-
1
1–13
pounds with N-chloroamine systems.
co-workers have shown a good selectivity in the chlorination of phenol by
Recently Sheldon and his
1
4
sulfuryl chloride in the presence of amine catalysts.
In the research described in this report we wish to introduce N-chloro-
imine (3) as a new and highly regioselective chlorinating reagent for
the mono-chlorination of activated aromatic compounds. This reagent
1
5
was prepared more conveniently by iodine catalyzed rearrangement of
1
6
N,N,2,3,4,5,6-heptachloroaniline (2) in carbon tetrachloride in 75% yield
Scheme 1). The structure of chloroimine (3) was established by spectro-
scopic analysis and also by hydrolysis to known 2,3,4,4,5,6-hexachloro-
(
1
7
cyclohexa-2, 5-dienone (4).
Scheme 1.
Our studies focused on the chlorination of phenol and o-cresol by this
reagent in CCl , DMF and CH CN. Reaction of equimolar amount of
4
3
ꢀ
substrates and the reagent in CCl , DMF and CH CN at 25 C produced
3
4
the results presented in Table 1.

ORDER
REPRINTS
CHLORINATING REAGENT
737
Our results show that DMF and CH CN produce a very impressing
3
regioselectivity and the reagent is para selective. The effect of DMF as a
co-solvent was examined on the regioselectivity of chlorination in CCl and
4
the results are given in Table 2. In the chlorination of phenol and o-cresol,
the best regioselectivity is observed by using a 3 : 1 mixture of DMF/CCl
4
ꢀ
at 0 C which furnish a p/o ratio of 70.4 and 89.9, respectively.
In this study it is believed that the hydrogen bonding between the
reagent and the substrate play a crucial role on the rate and the regioselec-
tivity of the reaction. This was clarified by studying the chlorination of
anisole with the chloroimine reagent (3) in DMF at room temperature.
After 48 h only a trace of monochlorinated products could be detected
Table 1. Chlorination of Phenol and o-Cresol by the N-Chloroimine Reagent (3)
a,b
Temperature
ꢀ
Time
(h)
Para
(%)
Ortho
(%)
Yield
(%)
Solvent
CCl
DMF
Substrate
( C)
p/o
4
phenol
o-cresol
phenol
o-cresol
phenol
o-cresol
25
25
25
25
25
25
24
30
24
30
24
30
55
45
1.22
0.84
9.63
9.41
22.25
9.86
80
85
90
82
78
70
45.7
90.6
90.4
95.7
90.8
54.3
9.4
9.6
4.3
9.2
3
CH CN
a
All products were analysed by comparison with authentic samples (GC analysis).
Isolated yield.
b
Table 2. Chlorination of Phenol and o-Cresol by the Chloroimine Reagent (3)
Solvent DMF%
in CCl
Temperature
ꢀ
Time
(h)
Para
(%)
Ortho
(%)
4
Substrate
( C)
p/o
1
2
5
7
7
0
5
0
5
5
phenol
o-cresol
phenol
o-cresol
phenol
o-cresol
phenol
o-cresol
phenol
o-cresol
25
25
25
25
25
25
25
25
0
24
30
24
30
24
30
24
30
24
30
71
292.4
64.935.1
72.8
71.6
84.6
89.9
88.2
90.1
98.6
98.9
1.85
27.2
28.4
15.4
10.1
11.8
9.9
2.67
2.52
5.5
8.95
7.47
9.10
1.4
1.1
70.4
89.9
0

ORDER
REPRINTS
7
38
MAMAGHANI, ZOLFIGOL, AND SHOJAEI
Table 3. Chlorination of Phenol and o-Cresol in CCl
a
Co-solvents
4
in the Presence of the
Temperature
ꢀ
Time
(h)
Para
(%)
Ortho
(%)
Co-solvent
C H OH
Substrate
( C)
p/o
phenol
o-cresol
phenol
o-cresol
phenol
o-cresol
phenol
o-cresol
0
0
0
0
0
0
0
0
24
30
24
30
24
30
24
30
54.3
89.8
96.3
78.8
98.6
98.9
7.7
45.7
10.2
3.7
21.2
1.4
1.1
92.3
76.3
1.19
8.80
26.02
3.71
70.42
89.90
0.08
2
5
C
H
5 5
N
DMF
Et
3
N
23.7
0.31
a
4
Co-solvent to CCl ratio 3 : 1.
with almost no regioselectivity. We also studied the effects of C H OH,
2
5
C H N and Et N as co-solvents on the chlorination in CCl (Table 3).
4
5
5
3
The results presented in Table 3 show that DMF is the best solvent for
para selectivity in this study. Surprisingly we observed a reverse regioselec-
tivity when Et N was used as a co-solvent. Full investigations of amines
3
effects on the selectivity in the chlorination by the chloroimine reagent (3)
are under way.
Finally we conclude N-chloro-2,3,4,4,5,6-hexachlorocyclohexa-2,5-
dienylidene amine as a mild and excellent regioselective reagent for the
chlorination of phenols is promising. In addition pentachloroaniline (1)
produced during the chlorination reaction (see Experimental) can be
recycled and used repeatedly for the preparation of the reagent. Since the
stereoselective chlorination of non-conjugate heterocyclic alkanes is our
1
8
main interest, therefore we also believe that this reagent is a very good
candidate for this purpose.
EXPERIMENTAL
General: Melting points were measured with Electro Thermal and are
uncorrected. IR spectra were determined on Shimadzo IR-470 spectrometer.
1
3
C NMR spectra were recorded on a Brucker AC, FT-NMR (80 MHz)
in (CD ) CO with Me Si as internal standard. TLC was carried out on
3
2
4
Merk Kieselgel 60H, F254. GC was conducted on a Unicam 4600 and
Perkin-Elemer 990, using SE30 and OV225 columns. All solvents used
were dried and distilled according to standard procedures.

ORDER
REPRINTS
CHLORINATING REAGENT
739
Preparation of N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-
,5-dienylideneamine (3)
2
To a magnetically stirred solution of N,N,2,3,4,5,6-heptachloro-
aniline (4.00 g, 11.9mmol) in carbon tetrachloride (70 ml), a small crystal of
iodine was added. The mixture was stirred under dry Argon gas for 20 h at
room temperature, during which time the progress of the reaction was checked
by IR spectroscopy. After complete disappearance of the aromatic ring vibra-
tion, the solvent was evaporated in vacuo to give N-chloro-2,3,4,4,5,6-hexa-
chlorocyclohexa-2,5-dienylideneamine (3.0 g, 8.9mmol) as yellow powder in
ꢀ
À1
7
5% yield, m.p. 68 C; IR (KBr), 1590, 1540, 1115, 765, 725, 680, 610 cm
;
1
3
C NMR (CD COCD ) d ppm, 153, 143.3, 136.4, 130.8, 12.6, 81.1. Anal.
3
3
calcd for C Cl N: C, 21.6; Cl, 74.2; N, 4.2. Found, C, 21.9; Cl, 74; N, 4.2%.
6
7
Hydrolysis of N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-
,5-dienylideneamine (3)
2
A magnetically stirred mixture of N-chloro-2,3,4,4,5,6-hexachloro-
cyclohexa-2,5-dienylideneamine (0.30 g, 0.89mmol) hydrochloric acid
(
1
2 M, 5 ml) and carbontetrachloride (2 ml) was heated under reflux for
0 h. The progress of the reaction was monitored by TLC (EtOAC :
hexane, 3 : 1). During the reaction period the carbon tetrachloride layer
changed to dark brown colour. The mixture was extracted by Et O
2
(
2 Â 20 ml) and the combined extracts were dried (MgSO ) and evaporated
4
to give a brown solid. Recrystalization from n-hexane furnished 2,3,4,4,5,6-
hexachlorocyclohexa-2,5-dienone (4) (0.22 g, 0.74 mmol) in 83% yield, m.p.
1
also confirmed by spectroscopic analysis (IR, C NMR and mass).
ꢀ ꢀ
17
05–106 C (m.p. 107.8–108.2 C). The structure of this known dienone was
1
3
General Procedure for the Chlorination by
N-Chloro-2,3,4,4,5,6-hexachloro-2,5-dienylideneamine (3)
To a magnetically stirred solution of the phenols (phenol, o-cresol)
0.74 mmol) in the appropriate solvent (5 ml), N-chloro-2,3,4,4,5,6-hexa-
(
chlorocyclohexa-2,5-dienylideneamine (0.74 mmol) was added at the desired
temperature (Tables 1–3). The progress of the reaction was monitored by
TLC (EtOAc : n-hexane, 3 : 1). After completion of the reaction, the solvent
was evaporated in vacuo and the residue was extracted by HCl 5%
(
(
2 Â 15 ml) and washed with water (2 Â 20 ml). The organic phase dried
MgSO ) and evaporated in vacuo to produce the chlorinated products.
4

ORDER
REPRINTS
7
40
MAMAGHANI, ZOLFIGOL, AND SHOJAEI
The ratio of chloro-phenols (ortho/para) was determined by GC (SE 30 and
OV225) using standard authentic samples.
The combined aqueous solution was made alkaline (NaOH 5%) and
extracted by ether (2 Â20 ml). The ethereal solution was dried (MgSO ) and
4
evaporated in vacuo to provide pentachloroaniline in ca. 70% yield.
ACKNOWLEDGMENT
We are thankful to Dr. M. A. Zanjanchi and the Research Council of
Guilan University.
REFERENCES
1. Ashton, Floyd M.; Monaco, Thomas J. Weed Science, Principles and
Practice, 3rd Ed.; John Wiley & Sons Inc., 1991.
2. Watson, W.D. Tetrahedron Lett. 1976, 2591; J. Org. Chem. 1985, 50,
2145.
3. Zanka, A.; Kubota, A. Synlett 1999, 12, 1984–1986.
4. Muathen, H.A. Monatsh. Chem. 1999, 130(12), 493–498.
5. Olah, G.A.; Ohannesian, L.; Arvanaghi, M. Synthesis 1986, 868.
6. Butters, M.; Nay, B.; Smith, K. B. P. Appl. GB 2165244A/1986.
7. Smith, K.; Butters, M.; Nay, B. Synthesis 1986, 1158.
8. Laszio, P.; Delaude, L. J. Org. Chem. 1990, 55, 5260.
9. Hausladen, M.C. App. Catal. 2000, A190(1–2), 269–281.
1
1
0. Guy, A.; Lemaire, M.; Guette, J.P. Tetrahedron 1982, 38, 2339.
1. Lindsay Smith, John R.; Mckeer, Linda C.; Taylor, Jonathan M.
J. Chem. Soc. Perkin Trans. II 1987, 1533.
12. Lindsay Smith, John R.; Mckeer, Linda C.; Taylor, Jonathan M.
J. Chem. Soc. Perkin Trans. II 1988, 385.
13. Lindsay Smith, John R.; Mckeer, Linda C.; Taylor, Jonathan M.
J. Chem. Soc. Perkin Trans. II 1989, 1537.
1
1
1
1
4. Sheldon, R.A.; Gnaim, J.M. Tetrahedron Lett. 1995, 36, 3893.
5. Mamaghani, M.; Banks, R.E. Unpublished results.
6. Goldschmidt, S.; Strohmenger, L. Ber. 1922, 55, 2450.
7. Svec, P.; Zbirovsky, M. V Praze Organicka Chemie a Technologie
1
974, 21, 23.
8. (a) Mallakpour, S.E.; Zolfigol, M.A. Indian J. Chem. 1995, 34B, 302;
b) Mallakpour, M.A. Indian J. Chem. 1999, 38B, 777.
1
(
Received in the UK January 7, 2001

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC120002512