Surface-mediated hydrohalogenation of isoprene: A facile preparation of prenyl halides

Article abstract of DOI:10.1081/SCC-120021495

The reaction of isoprene with SOCl₂ (0.5 mol equiv.) or PBr₃ (0.4 mol equiv.) or PI₃ (0.4 mol equiv.) in the presence of SiO₂ at -10°C produced prenyl chloride (82%), or bromide (70%) or iodide (65%), respectively, in less than 30 min reaction time.

Full text of DOI:10.1081/SCC-120021495

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Surface-Mediated Hydrohalogenation of Isoprene: A
Facile Preparation of Prenyl Halides
a
b
Marcio C. S. de Mattos & Antonio Manzolillo Sanseverino
a
Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio de
Janeiro, Rio de Janeiro, Brazil
b
Escola de Ciências Biológicas, Departamentos de Ciências Naturais, Universidade Federal
do Rio de Janeiro, Rio de Janeiro, Brazil
Version of record first published: 17 Aug 2006.
To cite this article: Marcio C. S. de Mattos & Antonio Manzolillo Sanseverino (2003): Surface-Mediated Hydrohalogenation
of Isoprene: A Facile Preparation of Prenyl Halides, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:13, 2181-2186
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 13, pp. 2181–2186, 2003
Surface-Mediated Hydrohalogenation of
Isoprene: A Facile Preparation of Prenyl Halides
1
,
Marcio C. S. de Mattos * and
Antonio Manzolillo Sanseverino
2
1
Instituto de Quı
´
mica, Departamento de Quı
´
mica
gicas,
ncias Naturais, Universidade
2
Orgaˆ nica, and Escola de Cieˆ ncias Biolo
´
Departamentos de Cie
ˆ
Federal do Rio de Janeiro,
Rio de Janeiro, Brazil
ABSTRACT
The reaction of isoprene with SOCl
(
2
(0.5 mol equiv.) or PBr
3
0.4 mol equiv.) or PI
ꢁ
3
(0.4 mol equiv.) in the presence of SiO
10 C produced prenyl chloride (82%), or bromide (70%) or
2
at
ꢀ
iodide (65%), respectively, in less than 30 min reaction time.
*
´
Correspondence: Marcio C. S. de Mattos, Instituto de Quımica, Departamento
de Quımica Organica, Universidade Federal do Rio de Janeiro, Caixa
´
ˆ
Postal 68545 21945-970, Rio de Janeiro, Brazil; Fax: þ55-21-25627133;
E-mail: mmattos@iq.ufrj.br.
2
181
DOI: 10.1081/SCC-120021495
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2
182
de Mattos and Sanseverino
Key Words: Silica gel; Prenyl; Hydrohalogenation.
INTRODUCTION
Prenyl halides (1-halo-3-methyl-2-butenes) are important sources of
1–3]
[
prenyl groups in synthetic organic chemistry.
preparedfrom the reaction of the correspon di ng allylic alcohol or the
They are frequently
[
4–7]
isomeric 2-methyl-3-buten-2-ol with different halogenating reagents,
[
but rarely from hydrohalogenation of isoprene. Although prenyl chlo-
ride and bromide are commercially available, they are a rather expensive
andonly soldin small quantities. Furthermore, to the best of our
knowledge, the prenyl iodide is not commercially avaiable.
8]
[
9]
Surface-mediated reactions are of great utility in organic synthesis,
and in many cases the products are obtained in better yields than in a
[
10]
homogeneous media in solution. During the last decade, Kropp et al.
showed that several sources of halides undergo hydrolysis on the surface
of silica gel to generate HX in situ which adds to carbon–carbon multiple
[11]
bonds in high yields. Recently, we publishedthe hydrohalogenation of
[
12]
[13]
limonene with SOCl /SiO
2
andPBr /SiO
3
to produce the corre-
sponding a-terpinyl halides as well as the silica-mediated hydrobromina-
2
2
[14]
tion of diverse alkenes.
,4-addition to afford prenyl bromide.
Herein we communicate our further results on the silica-mediated
In this study, isoprene underwent exclusively
[
14]
1
hydrohalogenation of isoprene to produce the expensive prenyl halides.
RESULTS
The reaction of isoprene (10 mmol) with SOCl (5 mmol) or PBr
2
3
(
4 mmol) or PI (4 mmol) in the presence of SiO (5 g) in CH Cl was
2
3
2
2
ꢁ
performedat ꢀ10 C in an open flask andledto 65–82% yieldof prenyl
halides with purity greater than 99% by high-resolution gas chromatog-
andspectral
[
15,16]
[17]
raphy in less than 30 min reation time. The physical
data of the products are in accordance with literature values (Table 1
summarizes the results).
Furthermore, the safety andeconomics of the present metho do logy
are far superior to generating toxic andcorrosive anhy dr ous hy dr ogen
halides. For example, a well established preparation of prenyl bromide
takes no less than 6 h andrequires the generation andmanipulation of
dry HBr at a substantial cost from diverse reagents and drying agents
[
19]
(
HBr is generatedfrom bromine andtetralin) in a very laborious work.

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Prenyl Halides
Table 1. Results of ‘‘hydrohalogenation’’ of isoprene.
2183
ꢁ ꢁ
t (min) Yield(%) B.p. ( C) B.p. lit.( C)
X
i
[
[
15]
15]
Cl SOCl
Br PBr
2
20
25
25
82
70
65
110
131
109
131
3
a
I
PI
3
—
40–55/
[
0 Torr
16]
1
a
[18]
Decomposes during determination of b.p.
In an attempt to test the scale up of the methodology for producing
prenyl chloride on a multigram-scale, the reaction was performed with
ꢁ
5
0 mmol of isoprene and10 g of SiO andafter 45 min at ꢀ10 C the prod-
2
uct was obtainedin 76% isolatedyield. Once more, no significant amount
of other products was detected by the analytical techniques employed.
In summary, we have developed a very attractive, cheap, and scaled
up procedure for the preparation of the valuable prenyl halides by SiO2-
mediated ‘‘hydrohalogenation’’ of isoprene.
EXPERIMENTAL
General
Isoprene, SOCl , andPBr were freshly distilled. PI was synthesized
2
3
3
[
as described in the Lit. SiO (Aldrich, 270-70 MESH, 60 A) was used
20]
˚
2
as received[the water content, ca. 15%, was de terminedby heating in a
[
domestic microwave oven until constant weight ]. H NMR and
13]
1
1
3
C NMR were acquiredon a Bruker AC-200 (200 MHz and50 MHz,
respectively) spectrometer in CDCl3 solutions with TMS as internal
standard. IR spectra were recorded on a Perkin–Elmer 1600 FT-IR
spectrometer (KBr film). MS were obtainedon a Hewlett-Packard
HP5896-A HRGC-MS using electron impact (70 eV). In our hands, prenyl
chloride and bromide are stable. On the other hand, prenyl iodide
[
21]
decomposes slowly at room temperature.

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184
de Mattos and Sanseverino
General Procedure for the Preparation of Prenyl Halides
To a stirredsuspension of isoprene (0.68 g, 10 mmol) andSiO (5 g)
2
ꢁ
in CH Cl (25 mL) at ꢀ10 C in an open flask, a solution of the
2
2
appropriate halogen donor in CH Cl (25 mL) was added during
2
2
1
5 min. After completing addition, the suspension was stirred for several
ꢁ
minutes at ꢀ10 C, allowedto warm to RT andthen filtere d. The SiO
2
was washedwith CH Cl (20 mL), the combinedliquids was washedwith
2
2
10% NaHCO , water, andthe extract was dr ied(Na SO ). The solvent
3 2 4
was distilled off to give prenyl chloride and bromide pure (we noted that
the yields were somewhat reduced if the solvent was evaporated in a
rotatory evaporator at reduced pressure). On the other hand, in the
case of prenyl iodide the solvent must be evaporated in a rotatory
[
18]
evaporator at reduced pressure to avoid its decomposition.
Prenyl chloride. From 0.60 g (5 mmol) of SOCl were obtained0.85 g
2
ꢁ ꢁ
82%). B.p.: 110 C [Lit. 109 C]. ꢀ (CDCl ): 1.66 (s, 3H), 1.70 (s, 3H),
H 3
[15]
(
4
.02 (d, J 8.01 Hz, 2H, CH Cl), 5.39 (t, J 8.00 Hz, 1H, ¼CH-CH Cl)
2
2
ppm. ꢀ (CDCl ): ꢀ 17.8 (CH ), 25.8 (CH ), 41.4 (CH Cl), 120.7 (CH),
2
C
3
3
3
139.5 (C) ppm.
Prenyl bromide. From 1.08 g (4 mmol) of PBr were obtained1.04 g
3
ꢁ ꢁ
70%). B.p.: 131 C [Lit. 131 C]. ꢀ (CDCl ): 1.71 (s, 3H), 1.76 (s, 3H),
H 3
[15]
(
3
.99 (d, J 8.42 Hz, 2H, CH Br), 5.49 (t, J 8.42 Hz, 1H, ¼CH-CH Br)
2
2
ppm. ꢀ (CDCl ): ꢀ 18.1 (CH ), 25.9 (CH ), 29.9 (CH Br), 120.9 (CH),
C 3 3 3 2
1
8
40.3 (C) ppm. ꢁ: 3031, 2975, 2933, 2916, 2857, 1644, 1378, 1202,
40 cm
ꢀ1
.
Prenyl iodide. From 1.64 g (4 mmol) of PI were obtained1.27 g
3
(
65%). ꢀH (CDCl ): 1.72 (s, 3H), 1.76 (s, 3H), 3.80 (d, J 8.40 Hz, 2H,
3
CH I), 5.53 (t, J 8.40 Hz, 1H, ¼CH-CH I) ppm. ꢀ (CDCl ): ꢀ 3.8 (CH I),
2
2
C
3
2
17.5 (CH ), 25.0 (CH ), 122.0 (CH), 138.3 (C) ppm.
3 3
ACKNOWLEDGMENTS
AMS thanks CNPq for a fellowship. We thank Gabriela F. Mendonc
Francesco Spano, andMilton R. Salles for preparation of PI . We also
¸
a,
3
thank W. Bruce Kover andJoel Jones Jr. for helpful di scussions.
REFERENCES
1. Simas, A.B.C.; da Silva, A.J.M.; Coelho, A.L.; Costa P.R.R.
Regioselective lithiation of a pterocarpan skeleton: the first synthesis

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Prenyl Halides
2185
0
of (þ/À)-4 -dehydroxycabenegrin A-I. Tetrahedron Lett. 2001, 42
25), 4111–4113.
. Morales-Rios, M.S.; Sua
(
2
´
rez-Castillo, O.R.; Trujillo-Serrato, J.J.;
Joseph-Nathan, P. Total synthesis of five indole alkaloids from
marine bryozoan Flustra foliacea. J. Org. Chem. 2001, 66 (4),
1186–1192.
3
4
5
. Crimmins, M.T.; Emmitte, K.A.; Katz, J.D. Diastereoselective
alkylations of oxazolidinone glycolates: a useful extension of the
evans asymmetric alkylation. Org. Lett. 2000, 2 (14), 2165–2167.
. Kanai, T.; Irifune, S.; Ishii, Y.; Ogawa, M. One-pot synthesis of
homoallylic alcohols via a facile conversion of allylic alcohols,
into allylic iodides. Synthesis 1989, (4), 283–286.
. Magid, R.M.; Fruchey, O.S.; Johnson, W.L.; Allen, T.G.
Hexachloroacetone-triphenylphosphine-mildreagent for the
regioselective and stereospecific production of allylic chlorides
from the alcohols. J. Org. Chem. 1979, 44 (3), 359–363.
6
. Barbot, F.; Miginiac, P. Action of Me C¼CHCH M (M¼MgX,
2
2
ZnBr, Li) prenylic type organometal derivatives with diisopropyl-
ketone—reversibility of reaction. Bull. Soc. Chim. Fr. 1977, (1,2),
113–116.
7
. Crombie, L.; Harper, S.H.; Sleep, K.C. Experiments on the
synthesis of the pyrethrins. Part XIII. Total synthesis of (þ/À)-cis-
and- trans-chrysanthemumdicarboxylic acid, (þ/À)-cis- and -trans-
pyrethric acid, and rethrins II. J. Chem. Soc. 1957, (6), 2743–2754.
¨
8. Staudinger, H.; Kreis, W.; Schilt, W. Uber die addition von
halogenwasserstoff an isopren. Hel. Chim. Acta 1922, 5 (2), 743–756.
. Prenyl chloride: US$ 23.70/5 g or US$ 80.40/25 g; prenyl bromide:
US$ 12.00/1 g or US$ 25.20/10 g (Aldrich Handbook of Fine
Chemicals, 2000–2001).
9
1
1
0. Clark, J.H.; Macquarrie, D.J. Environmentally friendly catalytic
methods. Chem. Soc. Rev. 1996, 25 (5), 303–310.
1. Kropp, P.J.; Daus, K.A.; Tubergen, M.W.; Kepler, K.D.;
Wilson, V.P.; Craig, S.L.; Baillargeon, M.M.; Breton, G.W.
Surface-mediated reactions. 3. Hydrohalogenation of alkenes. J.
Am. Chem. Soc. 1993, 115 (8), 3071–3079.
1
2. de Mattos, M.C.S.; Sanseverino, A.M. A convenient and simplified
preparation of both enantiomers of a-terpinyl chloride. Synth.
Commun. 2000, 30 (11), 1975–1983.
1
3. Sanseverino, A.M.; de Mattos, M.C.S.; Kover, W.B. Surface-
mediated chemospecific hydrobromination of limonene: stereoselec-
tive transformation of the enantiomers of limonene into a-terpinyl
bromide. J. Chem. Res. 2000, (7), 346–347.

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2
186
de Mattos and Sanseverino
1
4. Sanseverino, A.M.; de Mattos, M.C.S. Hydrobromination
of alkenes with PBr /SiO : a simple andefficient regiospecific
3
2
preparation of alkyl bromides. J. Braz. Chem. Soc. 2001, 12 (5),
85–687.
5. Lide, D.R., Ed. Handbook of Chemistry and Physics, 78th Ed.; CRC
6
1
1
1
Press: Boca Raton, 1997–1998.
6. Spa
273–2279.
7. Prenyl chloride: Ref. Prenyl bromide: Pouchert, C.P.; Behnke, J.
¨
th, E.; Spitzy, W. Synthesis of galegine. Chem. Ber. 1925, 58B,
2
[5]
1
3
1
The Aldrich Library of C and H FT NMR Spectra; Aldrich
[
Chemical Co, 1993; Vol. 1, 139. Prenyl Iodide: Ref.
4]
1
8. Miller, J.A.; Scrimgeour, C.M.; Black, R.; Larkin, J.; Nonhebel,
D.C.; Wood, H.C.S. Formation of 1,1-dimethylallyl derivatives by
reaction of 3,3-dimethylallyl halides with copper(II) chelates of
acetylacetone andmethyl acetoacetate. J. Chem. Soc. Perkin
Trans. 1 1973, (6), 603–606.
1
2
2
9. Furniss, B.S.; Hannaford, A.J.; Smith, P.W.G.; Tatchell, A.R.
Vogel’s Textbook of Practical Organic Chemistry, 5th Ed.;
Longman: Singapore, 1996; 437–438, 576–578.
0. Germann, F.E.E.; Traxler, R.N. Preparation andmelting points
of pure di- and tri-iodide of phosphorus. J. Am. Chem. Soc. 1927,
49 (2), 307–312.
1. Lasne, M.-C.; Cairon, P.; Villemin, D. Rapidsynthesis of a,b unsat-
urated iodides: iodination under vacuum with solid diphosphorous
tetraiodide. Synth. Commun. 1990, 20 (1), 41–44.
Receivedin the USA October 28, 2002