Cyanuric chloride-mediated synthesis of allylic chloride - Ipso- versus tele-substitution

Article abstract of DOI:10.1080/00397910701578206

Synthesis of unsymmetrical allylic chlorides has been accomplished using cyanuric chloride in combination with DMF through ipso-substitution and tele-substitution by judicious choice of the substituents at appropriate positions of unsymmetrical allyl alcohols, taking care of their electronic and steric properties. Copyright Taylor & Francis Group, LLC.

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Cyanuric Chloride–Mediated Synthesis of
Allylic Chloride—ipso‐ versus tele‐Substitution
Sanchita Roy a , Tarak Das a , Manabendra Saha a , Subrata Kumar Chaudhuri
a & Sanjay Bhar a
a Department of Chemistry, Organic Chemistry Section, Jadavpur University,
Kolkata, India
Version of record first published: 14 Dec 2007.
To cite this article: Sanchita Roy, Tarak Das, Manabendra Saha, Subrata Kumar Chaudhuri & Sanjay Bhar
(2007): Cyanuric Chloride–Mediated Synthesis of Allylic Chloride—ipso‐ versus tele‐Substitution, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:24,
4367-4370
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Synthetic Communicationsw, 37: 4367–4370, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701578206
Cyanuric Chloride–Mediated Synthesis
of Allylic Chloride—ipso- versus
tele-Substitution
Sanchita Roy, Tarak Das, Manabendra Saha,
Subrata Kumar Chaudhuri, and Sanjay Bhar
Department of Chemistry, Organic Chemistry Section,
Jadavpur University, Kolkata, India
Abstract: Synthesis of unsymmetrical allylic chlorides has been accomplished
using cyanuric chloride in combination with DMF through ipso-substitution and
tele-substitution by judicious choice of the substituents at appropriate positions of
unsymmetrical allyl alcohols, taking care of their electronic and steric properties.
Keywords: allylic chloride, electrophilic halogenating agent, regioselectivity,
substitution
INTRODUCTION
Conversion of allylic alcohols to the corresponding chlorides is an important
organic transformation[1] that often brings about allylic rearrangement along
with normal substitution. Numerous reagents[1–3] have been developed for
this purpose where the product spread often depends upon the nature of the sub-
strates as well as the reagents. There are also few reports of allylic chlorination[4]
of simple olefins, but the products are complicated because of simultaneous side
reactions such as vinylic chlorination, addition of chlorine across the double
bond and regioisomeric allylic halogenation. We report herein a mild, cost-
effective, and operationally simple protocol using cyanuric chloride[5] (TCT)
in combination with DMF for the conversion of unsymmetrically substituted
Received in India May 21, 2007
Address correspondence to Sanjay Bhar, Department of Chemistry, Organic
Chemistry Section, Jadavpur University, Kolkata 700 032, India. E-mail:
sanjaybharin@yahoo.com or sssbhar@lycos.com or sbhar@chemistry.jdvu.ac.in
4367

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S. Roy et al.
Scheme 1.
allylic alcohols to chlorides (Scheme 1) where the product spread depends on
the electronic and steric nature of the substitutens (Table 1).
It appears (entries 1, 2, 4, and 5 in Table 1) that the addition of chlorine
occurs in such a way that it experiences less steric hindrance. Accordingly,
ipso- (entries 1 and 2 in Table 1) and tele-substitution (entries 4 and 5 in
Table 1) took place. Another driving force for this differential behavior is the
newly formed double bond with extended conjugation with the aromatic ring,
rendering extra stabilization. This is supported from the fact that 38-allylic
alcohol underwent in situ elimination to yield the conjugated diene in good
yield (entry 3 in Table 1). Steric factor seems to play an important role as
reflected in complete tele-substitution (entry 6 in Table 1) where attainment
of extended conjugation is not possible. Competitive steric interactions
between the alkyl substituents have been reflected in the product spread
(entries 7 and 8 in Table 1). It is interesting to note that the presence of an
electron-withdrawing group (e.g., COOMe) at the allylic position with respect
to the OH group has a strong influence on the outcome of the reaction;
ipso-substitution occurs preferentially over the tele-substitution (entry 9 in
Table 1) despite the possibility of gaining extra stabilization of the product
due to extended conjugation. This may be due to the destabilizing role of the
COOMe group to accommodate the incipient electron-deficient center at the
carbon to which it is attached where the incoming nucleophile would attack,
leading to tele-substitution. Aryl homoallylic alcohol underwent predominant
ipso-substitution as expected (entry 10 in Table 1) because there is no
question of attainment of extended conjugation. Aryl-substituted-1,3-diene
was obtained as the minor product in this case through elimination (entry 10
in Table 1). Therefore, a novel method has been developed for the regioselective
synthesis of unsymmetrical allyl chlorides from easily accessible precursors
using readily available reagents under mild reaction conditions.
EXPERIMENTAL
General Procedure for the Reaction of Allylic Alcohols
with TCT/DMF
2,4,6-Trichloro-1,3,5-triazine (274 mg, 1.5 mmol) was added with vigorous
stirring to anhydrous DMF (0.4 mL) at 0–58C. Stirring was continued for

Table 1. Reaction of Cyanuric Chloride with unsymmetrical allylic alcohols
Entry
Substrate
Product
Time (min)
Yield (%)a
1
2
60
60
80
75
3
60
70
4
5
50
79
73
120
6
7
50
60
71
74 (30:70)b
8
60
72 (67:33)b
9
50
50
81 (83:17)b
84 (86:14)b
10
aYields refer to those of isolated products, characterized spectroscopically.
1
bRatio of products determined by H NMR.

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S. Roy et al.
30 min at room temperature while a white precipitate was obtained. A solution
of the substrate allylic alcohol (1 mmol) in anhydrous dichloromethane
(2.0 mL) was added dropwise to it. The reaction mixture was stirred at room
temperature for 2 h until completion of the reaction (monitored with thin-
layer chromatography on silica gel). Then diethyl ether (6 mL) was added to
the reaction mixture, which was stirred for 10 min, filtered, and the solid
residue was repeatedly washed with ether (3 Â 10 mL). The combined
organic extract was washed with saturated aqueous sodium carbonate
solution (2 Â 10 mL) and brine (1 Â 10 mL) and dried over anhydrous
sodium sulfate. The solvent was evaporated to furnish the crude product. The
products, if needed, were further purified by filtration chromatography on a
short column of silica gel using hexane as eluent.
ACKNOWLEDGMENTS
Financial support from the Council of Scientific and Industrial Research, New
Delhi, Government of India [Grant No. 01(1673)/00/EMR-II dated 07-12-
2000], is gratefully acknowledged. S. R. thanks the University Grants Com-
mission, New Delhi, Government of India, for a senior research fellowship,
and M. S. thanks the Council of Scientific and Industrial Research, New
Delhi, Government of India, for a senior research fellowship. The authors
express profound thanks to N. Dutta of Indian Association for the Cultivation
of Science, Kolkata, and professor S. R. Raychaudhuri of Jadavpur University,
Kolkata for necessary assistance.
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