Efficient and selective halogenation of allylic and benzylic alcohols under mild conditions

Article abstract of DOI:10.1007/s00706-004-0212-8

A simple, mild, and high yielding procedure for the halogenation of allylic and benzylic alcohols using a combination of SOCl₂, benzotriazole, and potassium halides in DMF is described. The effectiveness of the protocol is manifested in its selectivity towards allylic and benzylic alcohols whereas other simple alcohols such as primary, secondary, and tertiary are found to be unreactive. Springer-Verlag 2004.

Full text of DOI:10.1007/s00706-004-0212-8

Monatshefte f€ur Chemie 135, 1251–1255 (2004)
DOI 10.1007/s00706-004-0212-8
Efficient and Selective Halogenation
of Allylic and Benzylic Alcohols
under Mild Conditions
ꢀ
Babasaheb P. Bandgar and Sampada V. Bettigeri
Organic Chemistry Research Laboratory, School of Chemical Sciences,
Swami Ramanand Teerth Marathawada University, Vishnupuri,
Nanded-431606, India
Received February 12, 2004; accepted (revised) April 14, 2004
Published online August 13, 2004 # Springer-Verlag 2004
Summary. A simple, mild, and high yielding procedure for the halogenation of allylic and benzylic
alcohols using a combination of SOCl2, benzotriazole, and potassium halides in DMF is described. The
effectiveness of the protocol is manifested in its selectivity towards allylic and benzylic alcohols
whereas other simple alcohols such as primary, secondary, and tertiary are found to be unreactive.
Keywords. Alcohols; Halogenation; Organic fluorides; Bromides; Iodides.
Introduction
Organic halides are indispensable intermediates in organic synthesis and their
transformations to useful compounds are well documented [1]. Both organic bro-
mides and iodides are often used in the carbon–carbon bond formation via radical
or substitution reactions. In addition, they serve as intermediates in a wide variety
of reactions and rearrangements. Thus, the conversion of alcohols into the corre-
sponding halides is a very important transformation. The most common precursors
to alkyl halides are alcohols and therefore the conversion of alcohols into halides is
a frequently encountered transformation in organic synthesis [2]. Among organic
halides, iodides are the most reactive, bromides are the moderate reactive, chlo-
rides are less reactive, fluorides are the least reactive, and in some cases, iodides
show unique reactivity [3].
As the C–C bond-forming radical reactions of halides are important [4], we
were in need of a variety of organic halides. A number of methods for the trans-
formation of alcohols into organic iodides using a variety of reagent systems
ꢀ
Corresponding author. E-mail: bandgar_bp@yahoo.com

1252
B. P. Bandgar and S. V. Bettigeri
Scheme 1
such as BF3–Et2O=NaI [5], P4–I2 [6], Cl2SO–DMF=KI [7], MgI2 [8], HI [9],
ClSiMe3=NaI [10], gas phase reactions using KI in the presence of a phase transfer
catalysts [11], and others [12] are available. Organic bromides have been prepared
from the corresponding alcohols using various reagents such as HBr=AcOH [13],
triphenylphosphine–CBr4=pyridine [14], TPP–NBS [15], N,N-carbonyldiimidazole-
allyl bromide [16], trifluoroacetanhydride–LiBr [17], tetramethyl-D-bromo-
enamine [18], and others [11]. However, very few methods have been reported for
the direct conversion of alcohols into the corresponding organic fluorides and some
of the reagents known for this transformation are difluorotriphenylphosphorane
[19], diethylamino sulfurtrifluoride [20], tetraalkylammonium fluoride [21], and
HF=pyridine [22]. The reported procedures for the preparation of organic halides
suffer from one or the other drawbacks, such as low yields, long reaction times, use
of expensive reagents, drastic reaction conditions, and tedious work-up procedures.
We now investigated a novel halogenation method using the inexpensive, safe, and
easily available reagent SOCl2–benzotriazole [23], and KI, KBr, or KF in DMF,
which transforms allylic and benzylic alcohols into the corresponding organic
iodides, bromides, and fluorides (Scheme 1).
Results and Discussion
We first tried this reagent system on benzyl alcohol, which afforded benzyl iodide
in 97% within 10 minutes at room temperature (entry 1). This reagent system also
worked well for the preparation of benzyl bromides and fluorides (entries 2–3).
Subsequent scrutiny showed that this reagent system is suitable for a variety of
allylic and benzylic alcohols and culminated into a simple and mild procedure
for the conversion of alcohols into organic iodides, bromides, and fluorides (entries
4–24). The methodology worked well with ortho, meta, para, and multi-substituted
benzylic systems (entries 4–24) containing electron-donating or -withdrawing sub-
stituents furnishing excellent yields of products. It also worked well for allylic
alcohols (entries 25–27) giving high yields of the corresponding iodides and bro-
mides, whereas fluorides were obtained in poor yields. It was observed that the
iodination and bromination reactions were fast as compared to chlorination of
allylic and benzylic alcohols. It is important to note that though simple primary,
secondary, and tertiary alcohols remain unreacted (entries 34–45), homoallylic
secondary and tertiary alcohols (entries 28–33) underwent smooth halogenation
under these reaction conditions. Finally we tried a 20 mmol scale-up of the iodina-
tion reaction. Thus, 4-chlorobenzyl alcohol furnished the corresponding iodide in
almost quantitative yield (99%) after usual work-up.
Excellent selectivities were observed during inter- and intra-molecular com-
petition between benzylic and aliphatic alcohols. Thus, during intramolecular

Efficient and Selective Halogenation
1253
Table 1. Halogenation of alcohols using SOCl2, benzotriazole in CH2Cl2, and KI=KBr=KF in DMF
Entry
Substrate
Product
Time
Yielda
%
min (h)
1
2
3
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Benzyl iodide
Benzyl bromide
Benzyl fluoride
10
97
99
82
30
(10)
4
5
6
4-Bromobenzyl alcohol
4-Bromobenzyl alcohol
4-Bromobenzyl alcohol
4-Bromobenzyl iodide
4-Bromobenzyl bromide
4-Bromobenzyl fluoride
6
96
90
62
13
(10.5)
7
8
9
4-Chlorobenzyl alcohol
4-Chlorobenzyl alcohol
4-Chlorobenzyl alcohol
4-Chlorobenzyl iodide
4-Chlorobenzyl bromide
4-Chlorobenzyl fluoride
5
99
99
70
16
(10)
10
11
12
2,4-Dichlorobenzyl alcohol
2,4-Dichlorobenzyl alcohol
2,4-Dichlorobenzyl alcohol
2,4-Dichlorobenzyl iodide
2,4-Dichlorobenzyl bromide
2,4-Dichlorobenzyl fluoride
8
5
98
91
71
(9)
13
14
15
4-Methoxybenzyl alcohol
4-Methoxybenzyl alcohol
4-Methoxybenzyl alcohol
4-Methoxybenzyl iodide
4-Methoxybenzyl bromide
4-Methoxybenzyl fluoride
30
85
79
78
50
(12)
16
17
18
3,4-Methylenedioxybenzyl alcohol
3,4-Methylenedioxybenzyl alcohol
3,4-Methylenedioxybenzyl alcohol
3,4-Methylenedioxybenzyl iodide
3,4-Methylenedioxybenzyl bromide
3,4-Methylenedioxybenzyl fluoride
6
96
90
70
13
(10.5)
19
20
21
6-Chloro-3,4-methylenedioxybenzyl alcohol
6-Chloro-3,4-methylenedioxybenzyl alcohol
6-Chloro-3,4-methylenedioxybenzyl alcohol
6-Chloro-3,4-methylenedioxybenzyl iodide
6-Chloro-3,4-methylenedioxybenzyl bromide
6-Chloro-3,4-methylenedioxybenzyl fluoride
6
96
90
62
13
(10.5)
22
23
24
4-Nitrobenzyl alcohol
4-Nitrobenzyl alcohol
4-Nitrobenzyl alcohol
4-Nitrobenzyl iodide
4-Nitrobenzyl bromide
4-Nitrobenzyl fluoride
45
97
91
63
50
(11)
25
26
27
Cinnamyl alcohol
Cinnamyl alcohol
Cinnamyl alcohol
Cinnamyl iodide
Cinnamyl bromide
Cinnamyl fluoride
(1)
(4)
(8)
98
92
25
28
29
30
4-(4-Chlorophenyl)-4-hydroxy-1-butene
4-(4-Chlorophenyl)-4-hydroxy-1-butene
4-(4-Chlorophenyl)-4-hydroxy-1-butene
4-(4-Chlorophenyl)-4-iodo-1-butene
4-(4-Chlorophenyl)-4-bromo-1-butene
4-(4-Chlorophenyl)-4-fluoro-1-butene
(6)
84
81
23
(8)
(18)
31
32
33
4-(4-Chlorophenyl)-4-hydroxy-1-pentene
4-(4-Chlorophenyl)-4-hydroxy-1-pentene
4-(4-Chlorophenyl)-4-hydroxy-1-pentene
4-(4-Chlorophenyl)-4-iodo-1-pentene
4-(4-Chlorophenyl)-4-bromo-1-pentene
4-(4-Chlorophenyl)-4-fluoro-1-pentene
(8)
82
80
00
(11)
(24)
34
35
36
1-Octanol
1-Octanol
1-Octanol
1-Iodo octane
(24)
(24)
(24)
00
00
00
1-Bromo octane
1-Fluoro octane
37
38
39
2-Isopropyl-5-methylcyclohexanol
2-Isopropyl-5-methylcyclohexanol
2-Isopropyl-5-methylcyclohexanol
2-Isopropyl-5-methyl iodocyclohexane
2-Isopropyl-5-methyl bromocyclohexane
2-Isopropyl-5-methyl fluorocyclohexane
(24)
(24)
(24)
00
00
00
40
41
42
Triphenylmethanol
Triphenylmethanol
Triphenylmethanol
Triphenyliodomethane
Triphenylbromomethane
Triphenylfluoromethane
(24)
(24)
(24)
00
00
00
(continued)

1254
B. P. Bandgar and S. V. Bettigeri
Table 1 (continued)
Entry
Substrate
Product
Time
Yielda
%
min (h)
43
44
45
1,10-Didecanol
1,10-Didecanol
1,10-Didecanol
1,10-Diiododecane
1,10-Dibromodecane
1,10-Difluorodecane
(24)
(24)
(24)
00
00
00
46
25
90
47
48
4-Chlorobenzyl alcohol þ 1-Hexanol
Cinnamyl alcohol þ Cyclohexanol
4-Chlorobenzyl iodide þ 1-Hexanol
Cinnamyl iodide þ Cyclohexanol
5
85 þ 97
93 þ 98
(1)
a
Yields of pure isolated products
competition (entry 46) benzylic alcohol selectively underwent iodination in the
presence of aliphatic primary alcohol. Similarly, when a equimolecular mixture
of 4-chlorobenzyl alcohol and l-hexanol (entry 47) is subjected to iodination,
selectively 4-chlorobenzyl alcohol underwent iodination in excellent yield whereas
1-hexanol remained unreacted. Selective iodination of cinnamyl alcohol in the
presence of cyclohexanol (entry 48) was also observed under these reaction con-
ditions. Recently, SOCl2–benzotriazole has been reported [23] as highly efficient
reagent for rapid conversion of alcohols into the corresponding chlorides. There-
fore, this procedure has been applied for the preparation of bromides, iodides, and
fluorides. The alcohols might be first converted into the corresponding chlorides,
which further underwent smooth bromination, iodination and flourination with
KBr, KI and KF involving SN2 mechanism.
In conclusion, the present method shows unique selectivity and constitutes a
useful alternative to commonly accepted halogenation procedures of alcohols.
Moreover, the superiority and flexibility of the protocol lies in its ease of operation
and simplicity in work-up. Efficient, and high yielding procedure applicable to
allylic, benzylic, and homoallylic alcohols under mild conditions using the inex-
pensive and easily available reagent system make this simple protocol economi-
cally attractive. In addition, this method is amenable to scale-up.
Experimental
IR spectra were recorded on Bomem MB-104 FTIR spectrometer, whereas 1H NMR were scanned on a
AC-300F NMR (300 MHz) instrument using CDCl3 as solvent and TMS as internal standard.
Typical Procedure
A mixture of 5 mmol of benzyl alcohol, 5.5 mmol of thionyl chloride, and 5 mmol of benzotriazole in
10cm3 of CH2Cl2 was stirred for 5 min. Then to this mixture 5 mmol of KI in 10 cm3 of DMF were
added and stirring was continued until the reaction was complete (TLC, 10min). The product was
extracted with 3 ꢁ 10 cm3 of ether, washed with 3 ꢁ 5 cm3 of aq. sodium thiosulfate (5%), and
3 ꢁ 10cm3 of H2O. The organic layer was dried with Na2SO4 and the solvent removed under reduced

Efficient and Selective Halogenation
1255
pressure to furnish the crude product, which was purified by column chromatography (pet. ether). The
products were characterized by IR, NMR, elemental analysis, and comparison with authentic samples.
References
[1] a) Chambers RD, James SR (1979) In: Barton DHR, Ollis WD (eds) Comprehensive Organic
Chemistry. Pergamon Press: Oxford 1: 493; b) Bohlmann R (1991) In: Trust BM, Fleming I (eds)
Comprehensive Organic Synthesis. Pergamon Press: Oxford 6: 203 (c) Hudlicky T (1983) In:
Patai S, Rapport Z (eds) Chemistry of Functional Groups, Supplement D. Wiley, New York, 1021
[2] Marsden SP (1996) Contemp Org Synth 4: 118
[3] Villieras J, Bacquet C, Nonnat JF (1975) Bull Chem Soc Fr 1997
[4] a) Kita Y, Gotanda K, Sano A, Oka M, Murata K, Suemura M, Matsugi M (1997) Tetrahedron
Lett 48: 8345; b) Kita Y, Gotanda K, Sano A, Yamaguchi T, Oka M, Gotanda K, Matsugi M
(1997) Tetrahedron 38: 3549; c) Kita Y, Sano A, Yamaguchi T, Oka M, Gotanda K, Matsugi M
(1999) J Org Chem 64: 675; d) Kita Y, Nambu H, Ramesh NG, Anilkumar G, Matsugi M (2001)
Org Lett 3: 1157; e) Kita Y, Matsugi M (2001) In: Renaud P, Sibi MP (eds) Radicals in Organic
Synthesis. Wiley-VCH, Weinheim, p 1
[5] a) Mandal AK, Mahajan SW (1985) Tetrahedron Lett 26: 3863; b) Vankar YD, Rao CT (1985)
Tetrahedron Lett 26: 2717
[6] Jung ME, Omstein PL (1977) Tetrahedron Lett 31: 2659
[7] Fendez I, Garcia B, Munoz S, Pedro JR, Salud R (1993) Synlett 489
[8] Martinez AG, Alvarez RM, Vilar ET, Fraile AG, Bamica JO, Hanack M, Subramanian LR (1987)
Tetrahedron Lett 28: 6441
[9] Stone H, Shechter H (1963) Org Synth 4: 323
[10] Olah GA, Nargang SC, Gupta BGB, Malhotra R (1979) J Org Chem 44: 1247
[11] Tundo P, Venturello P (1979) Synthesis 952
[12] Larock RC (1999) In: Comprehensive Organic Transformation 2nd ed. Wiley VCH, New York,
695 and references cited therein
[13] Anri AE, Benazza M, Gilles Demailly CF (1993) Tetrahedron Lett 34: 3741
[14] Belkhouya N, Frechou C, Benazza M, Beaupere D, Gilles Demailly RU (1991) Tetrahedron Lett
32: 3977
[15] a) Bose AK, Lal B (1973) Tetrahedron Lett 3937; b) Hanessian S, Ponpipom MM, Lavallee P
(1972) Carbohydrate Res 24: 45
[16] Kamijo T, Harada H, Iizuka K (1983) Chem Pharm Bull 31: 4189
[17] Camps F, Gasol V, Guerrero A (1987) Synthesis 511
[18] Munyemana F, Frisque-Hesbain AM, Devos A, Ghosez L (1989) Tetrahedron Lett 30: 3077
[19] Kobayashi Y, Akashi C (1968) Chem Pharma Bull 16: 1009
[20] Roth G, Marshall D, Chen SH (1995) Tetrahedron Lett 36: 1609; b) Ballereau S, Guedat P, Spiess
B, Rehnberg N, Schlewer G (1995) Tetrahedron Lett 36: 7449
[21] Shimizu M, Nakahara Y, Yoshioka H (1985) Tetrahedron Lett 26: 4207
[22] Hirschmann RF, Miller R, Wood J, Jones RE (1956) J Am Chem Soc 78: 4956
[23] Choudhari SS, Akamanchi KG (1999) Synlett 11: 1763