Allylic chlorination of terpenic olefins using a combination of MoCl 5 and NaOCl

Article abstract of DOI:10.1590/S0103-50532011000700010

MoCl₅ is applied as efficient agent in allylic chlorination of terpenic olefins in the presence of NaOCl as chlorine donor. Various terpenes are converted to the corresponding allylic chlorides in moderate to good yield under mild and optimized

Full text of DOI:10.1590/S0103-50532011000700010

J. Braz. Chem. Soc., Vol. 22, No. 7, 1259-1262, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
A
Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl
Brahim Boualy, Larbi El Firdoussi,* Mustapha Ait Ali and Abdellah Karim
Laboratoire de Chimie de Coordination, Département de Chimie, Faculté des Sciences Semlalia,
Université Cadi Ayyad, PB 2390, 40000 Marrakech, Morocco
MoCl5 é usado como eficiente agente na cloração alílica de olefinas terpênicas na presença
de NaOCl como doador de cloro. Vários terpenóides são convertidos aos cloretos de alila
correspondentes em moderados a bons rendimentos em condições reacionais brandas e otimizadas.
Diferentes precursores de molibdênio são estudados. Dentre eles, MoO3 fornece bom rendimento,
mas depois de um tempo de reação maior.
MoCl5 is applied as efficient agent in allylic chlorination of terpenic olefins in the presence
of NaOCl as chlorine donor. Various terpenes are converted to the corresponding allylic chlorides
in moderate to good yield under mild and optimized reaction conditions. Different molybdenum
precursors are also studied. Among them, MoO3 gives good yield, but after a longer reaction time.
Keywords: monoterpenes, allylic chlorination, molybdenum, sodium hypochlorite
Introduction
Results and Discussion
Allylic chlorinated terpenes represent a sustainable
supply of intermediates for several segments of the fine
chemical industry, e.g., the manufacture of flavors and
fragrances.1-4 Previously, we have reported that allylic
amines, alcohols, ketones and alkoxycarbonyl derivatives
can be obtained in good yields by the metal complex
catalyzed amination, oxidation and alkoxycarbonylation of
some monoterpenes.5-7 Chlorination represents a valuable
pathway to produce versatile starting materials that are
widely used in synthetic organic chemistry.8-11 Chloride
compounds can be prepared directly by bubbling molecular
chlorine, but the difficulty of handling chlorine gas limits
this procedure.12 Other authors have shown a convenient
method for this transformation using solid CO2 and calcium
hypochlorite13,14 or a combination of Vilsmeier reagent
and H2O2.15 However, this procedure is limited to non
acid-sensitive substrates.15 CeCl3 or InCl3 combined with
NaOCl have been reported as efficient systems for allylic
chlorination of terminal olefins.12-16
In order to optimize the allylic chlorination of natural
terpenes, b-pinene 1 was chosen as a model substrate
(Scheme 1). The reaction was conducted firstly using
various concentrations of MoCl5 in the presence of NaOCl
at room temperature in different reaction times (Table 1).
Cl
Cl
MoCl5/NaOCl
+
CH2Cl2/H2O
Cl
1
3
2
(β-pinene )
(dichlorinated
compound)
(perillyl chloride)
Scheme 1. Allylic chlorination of b-pinene promoted by
molybdenumchloride.
To confirm the role of molybdenum pentachloride,
a blank reaction was carried out under similar reaction
conditions with b-pinene 1 as substrate. In the presence of
NaOCl, no corresponding chlorinated product was observed
even after stirring for a long reaction time (entry 1). The
same result is observed when using MoCl5 without NaOCl
(entry 2) even at high temperature (80 °C). As has been
previously reported, chlorine is usually generated from
Inlinewithourcontinuousinterestinthefunctionalization
of natural terpenic olefins,5-7 we report here the result of our
investigation on the allylic chlorination using a combination
of sodium hypochlorite and molybdenum pentachloride.
*e-mail: elfirdoussi@ucam.ac.ma

1260
Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl
J. Braz. Chem. Soc.
Table 1. Allylic chlorination of b-pinene 1 with MoCl5/NaOCl
the dichlorinated 3, whereas it remains stable when using
0.5 equiv. of MoCl5.
Isolated yield / %
Equiv. of
MoCl5
time /
min
Conversiona /
%
entry
2
0
3
0
1
2b
3
4
5
6
0
120
120
30
0
0
0.5
0.5
1.0
1.5
2.0
0
0
87
89
93
100
67
62
28
0
30
13
58
30
15
Complex mixture
Conditions: b-pinene (0.5 mmol), NaOCl (2 mmol) in 20 mL of a mixture
of CH2Cl2/H2O (1/1) at room temperature. aConversion is determined by
GC; breaction conducted without NaOCl.
Figure 1. Chlorination of b-pinene with MoCl5/NaOCl system; product
distribution vs. time determined by GC. Conditions: b-pinene (0.5 mmol),
MoCl5 (0.75 mmol), NaOCl (2 mmol) in 20 mL of a mixture of
CH2Cl2/H2O (1/1) at room temperature.
sodium hypochlorite.12-16 This investigation shows clearly
the role of MoCl5/NaOCl system in the activation and
orientation of the reaction toward the desired product.
As it can be seen in Table 1, the stoichiometry of the
reaction is also a key point. Using 0.5 equivalent of MoCl5,
perillyl chloride 2 was obtained selectively in 67% yield
after 30 min (entry 3). The replacement of MoCl5 by CeCl3
under similar reaction conditions gives the same product
in only 32% yield. When it was used more than 0.5 equiv.
of MoCl5, both mono- and dichlorinated compounds 2
and 3 were obtained with a variable ratio (entries 4 and 5).
At higher amounts of MoCl5 (2 equiv.), the selectivity
decreases considerably (entry 6).
A study of the influence of the nature of the molybdenum
precursor is reported in Table 2.Among the Mo compounds
studied, MoCl5 appears the most suitable (entry 3). MoO3
gives good yield but only after a long reaction time
(entry 7). In order to confirm the low activity of MoO3,
other terpenes were checked, such as carvone and limonene
with MoO3/NaOCl (0.5 equiv. of MoO3) under similar
conditions. The reaction took place, although in low yields
and after 24 h (30 and 19%, respectively). Other sources of
Mo present very low activity (entries 9 and 10).
It appears from these results that dichlorinated compound
3 formation is related to the use of high amount of MoCl5.
In this context, Ceschi et al.16 have already shown that the
conversion of b-pinene to the dichlorinated product was
achieved using InCl3 or CeCl3 in a longer reaction time.
Liu et al.17 has reported that both a-pinene and b-pinene led
to quantitative formation of monochlorinated compounds
in DMSO as solvent and phenyldichlorophosphate or
phosphorus oxychloride as chlorine donor. It can be noted
thattheobtainedcompounds2and3arechiralwithrespective
optical rotation [a]D20 = −68 (1.96) and [a]D20 = −62 (2.01)
in agreement with those reported in the literature.16
Table 2. Allylic chlorination of b-pinene by different sources of
molybdenum
Lewis acid
(equiv.)
time /
h
Conversiona /
%
Isolated
yield / %
entry
3
MoCl5 (0.5)
MoO3 (0.5)
0.5
4
87
100
100
21
67
83
78
14
16
0
7
8
MoO3 (1)
2.5
4
9
C10H14MoO6 (1)
Mo(acac)5 (1)
(NH4)6Mo7O24 (1)
10
11
4
19
24
0
Conditions: b-pinene (0.5 mmol), NaOCl (2 mmol) in 20 mL of a mixture of
In order to gain a better insight on this point, a kinetic
study was carried out with 1.5 equiv. of MoCl5 using GC
(gas chromatography) to determine the conversion and
product distribution (Figure 1).As depicted in Figure 1, the
evolution of perillyl chloride 2 and 3 versus time, shows
that 2 was formed immediately. This compound reached
a maximum after 20 min (62%) and then disappeared in
favour of 3 whose amount, insignificant at the early stage
of the reaction, rapidly increased after 5 min and then much
more slowly after 35 min. This observation proves that
perillyl chloride 2 behaves, in the presence of an excess
amount of MoCl5, as an intermediate that reacts to give
CH2Cl2/H2O (1/1) at room temperature. aConversion is determined by GC.
To assess the scope and limitation of this reaction,
different monoterpenes were studied (Table 3). With
MoCl5/NaOCl system under the optimized b-pinene
conditions,allthesubstratesareconvertedtothecorresponding
chlorinated products in good to excellent yields.
a-Pinene 4 gave perillyl chloride 2 selectively (entry 12).
However,bothmono-anddichlorinatedproducts 2and3were
obtainedwiththeincreasingoftheamountofMoCl5 (1equiv.)
(entry 13). Entry 14 shows good conversion of limonene 5 to

Vol. 22, No. 7, 2011
Boualy et al.
1261
Table 3. Allylic chlorination of natural terpenes by MoCl5/NaOCl
entry
12a
Olefins
Products
[a]D20 (concentration)
Isolated yields / %
Ref.
16
Cl
−67 (1.95)
75
2
Cl
Cl
2: −67 (1.95)
3: −58 (1.73)
2: 58
3: 13
13b
16
Cl
2
3
Cl
Cl
2: −88 (2.13)
3: −83 (1.91)
2: 38
3: 21
14
15
16
Cl
2
3
O
O
−56 (2.13)
87
14, 18
Cl
6
7
16
17
−43 (2.0)
68
51
14, 18
−
16
Conditions: olefin (0.5 mmol); MoCl5 (0.25 mmol); NaOCl (2 mmol) in 20 mL of a mixture of CH2Cl2/H2O (1/1); 30 min at room temperature. aReaction
conducted at 0 °C for 6 h; bwith 0.5 mmol of MoCl5.
the same products 2 and 3 in 38 and 21% yields, respectively.
Thedifferenceoftheopticalrotationvaluesof2and3obtained
from the chlorination of pinenes and limonene is due to the
fact that the ring opening of the pinenes can result in partial
racemization. With carvone 6, limonene oxide 8 and geraniol
10, the reaction also works well to give the corresponding
monochlorinated derivatives (entries 15-17).
conditions to afford the expected products in moderate to
good yields. A rearrangement of a-pinene and b-pinene
to perillyl chloride is observed. Some other molybdenum
precursors have been checked and interesting results have
been obtained with MoO3/NaOCl and b-pinene as substrate.
These results lead us to believe that this allylic chlorination
method may represent a valuable alternative to the existing
procedures reported in the literature.
Conclusions
Experimental
In conclusion, we have described an efficient and
facile method for the transformation of naturally occurring
monoterpenes to the corresponding allylic chlorides using
an inexpensive and readily available Lewis acid (MoCl5).
The reaction processes in short reaction time, under mild
Instruments
NMR studies were performed on a Bruker Avance 300
spectrometer in CDCl3, chemical shifts are given in ppm

1262
Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl
J. Braz. Chem. Soc.
relative to external TMS (tetramethylsilane) and coupling
constant (J) in Hz. Mass spectra were recorded on AMD
402 spectrometer (70 eV, EI). All the spectroscopic data
of the known products were compared with those reported
in the literature. The reaction mixtures were analyzed on
a Trace GC Thermo Finnigan chromatograph equipped
with an FID detector (flame ionization detector). GC
parameters for capillary columns BP (25 m × 0.25 mm,
SGE): injector 250 °C; detector 250 °C; oven 70 °C for
5 min then 3 °C min-1 until 250 °C for 30 min; column
pressure 20 kPa, column flow 6.3 mL min-1; linear velocity
53.1 cm s-1; total flow 138 mL min-1. Optical rotations were
measured in anATAGO polax-D polarimeter with a 0.1 dm
cell at a temperature of 20 °C. Liquid chromatography was
performed on silica gel (Merk 60, 220-440 mesh; eluent:
hexane).Analytical thin-layer chromatography (TLC) was
conducted on Merck aluminium plates with 0.2 mm of
silica gel 60F-254. All the reagents and solvents used in
the experiments were purchased from commercial sources
and used as received without further purification (Aldrich,
Acros).
References
1. Erman,W. E.; Chemistry of the Monoterpenes:An Encyclopedic
Handbook, Marcel Dekker: New York, 1985; vol. 1, p. 832.
2. Botteghi, C.; Marchetti, M.; Paganelli, S. In Transition Metals
for Organic Synthesis; Beller, M.; Bolm, C., eds.; Wiley-VCH:
Weinheim, 1998, vol. 1, p. 25.
3. Gusevskaya, E.V.; Quim. Nova 2003, 26, 242.
4. Chalk, A. J. In Catalysis of Organic Reactions; Rylander, P.N.;
Greenfield, H.;Augustine R.L., eds.; Marcel Dekker: NewYork,
1988, vol. 22, p. 43.
5. El Houssame, S.; Anane, H.; El Firdoussi, L.; Karim, A.; Cent.
Eur. J. Chem. 2008, 6, 470.
6. AitAllal, B.;ElFirdoussi, L.;Allaoud, S.;Karim,A.;Castanet,Y.;
Mortreux, A.; J. Mol. Catal. A: Chem. 2003, 200, 177.
7. El Houssame, S.; El Firdoussi, L.; Allaoud, S.; Karim, A.;
Castanet,Y.; Mortreux, A.; J. Mol. Catal. A: Chem. 2001, 168,
15.
8. Groesbeek, M.; Smith, S. O.; J. Org. Chem. 1997, 62, 3638.
9. Brocksom, T. J.; Zanotto, P.R.; Brocksom, U.; Tetrahedron Lett.
2005, 46, 2397; Brocksom, T. J.; Santos, R. B.;Varanda, N. A.;
Brocksom, U.; Synth. Commun. 1988, 18, 1403.
10. Pisoni, D. S.; Silva, D. B.; Schenato, R. A.; Ceschi, M. A.;
J. Braz. Chem. Soc. 2004, 15, 652.
General procedure
In a typical experiment, olefin (0.5 mmol) in 10 mL
of CH2Cl2 was added to a vigorously stirred solution
of MoCl5 (0.25 mmol) in 10 mL of water. It was added
2 mmol (0.95 mL) of NaOCl (13% m/m) To the resulting
mixture and the reaction mixture was stirred for 30 min
at room temperature. The reaction was quenched by the
slow addition of saturated aqueous Na2SO3. The layers
were separated and the aqueous layer was extracted with
CH2Cl2 (2 × 10 mL). The combined organic layer was dried
over anhydrous Na2SO4. The solvent was removed under
reduced pressure. Pure chlorinated products were obtained
by column chromatography over silica gel (weight ratio
of silica gel to compound mixture: 220/1) using hexane as
eluent. All isolated pure products were fully characterized
by 1H and 13C NMR and MS, and then compared with the
known compounds.
11. Easton, C. J.; Edwards, A. J.; McNabb, S. B.; Merrett, M. C.;
O’Connell, J. L.; Simpson, G. W.; Simpson, J. S.; Willis, A. C.;
Org. Biomol. Chem. 2003, 1, 2492.
12. Moreno-Dorado,F.J.;Guerra,F.M.;Manzano,F.L.;Aladro,F.J.;
Jorge, Z. D.; Massanet, G. M.; Tetrahedron Lett. 2003, 44, 6691.
13. Hegde, S. G.;Vogel, M. K.; Saddler, J.; Hrinyo, T.; Rockwell, N.;
Haynes, R.; Olever, M.; Wolinsky, J.; Tetrahedron Lett. 1980,
21, 441.
14. Hegde, S. G.; Wolinsky, J.; J. Org. Chem. 1982, 47, 3148.
15. Xiong, Z. M.;Yang, J.; Li,Y. L.; Tetrahedron: Asymmetry 1996,
9, 2607.
16. Pisoni, D. S.;Gamba, D.;Fonseca, C.V.;daCosta, J. S.;Petzhold,
C. L.; de Oliveira, E. R.; Ceschi, M. A.; J. Braz. Chem. Soc.
2006, 17, 321.
17. Liu, H. J.; Nyangulu, J. M.; Tetrahedron Lett. 1989, 30, 5097.
18. Matsuda, F.; Kito, M.; Sakai, T.; Okada, N.; Miyashita, M.;
Shirahama, H.; Tetrahedron 1999, 55, 14369.
Supplementary Information
Submitted: October 10, 2010
Supplementary information (1H and 13C NMR and MS
data for compounds 2, 3, 7, 9 and 11) is available free of
charge at http://jbcs.org.br as a PDF file.
Published online: March 1, 2011

J. Braz. Chem. Soc., Vol. 22, No. 7, S1-S5, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Supplementary Information
SI
Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl
Brahim Boualy, Larbi El Firdoussi,* Mustapha Ait Ali and Abdellah Karim
Laboratoire de Chimie de Coordination, Département de Chimie, Faculté des Sciences Semlalia,
Université Cadi Ayyad, PB 2390, 40000 Marrakech, Morocco
The monoterpene substrates, commercially available,
were used in the experiments as received without further
purification : S-(−)-limonene, 96%, [α]D20 −94 (Aldrich);
(−)-limonene oxide, mixture of cis and trans, 97%;
[α]D20 −69 (Aldrich); R-(−)-larvone, 98%, [α]D20 −61
(Aldrich); (−)-β-pinene, 98%, [α]D20 −20 (Acros);
(−)-α-pinene, 97%, [α]D20 −42 (Fluka).
(5R)-5-(1-Chloromethylvinyl)-2-methylcyclohex-2-
enone, (7)
[α]D20 −56 (2.13, CHCl3); Ref. 16: [α]D20 −54 (1.84,
CHCl3); 1H NMR (300 MHz) d 6.7 (m, 1H, =CH), 5.15 (s,
1H, =CH2), 4.9 (s, 1H, =CH2), 3.9 (s, 2H, Cl–CH2–), 2.85
(m, 1H, CH), 2.5 (m, 2H, CH2), 2.3 (m, 2H, CH2), 1.65
(s, 3H, –CH3). 13C NMR (75 MHz) d 197.8 (C=O), 146.8
(=C–), 143.4 (=C–), 135.7 (=CH–), 115.0 (=CH2), 46.8
(CH2Cl), 43.0 (CH2), 38.0 (CH), 31.5 (CH2), 15.8 (CH3).
(4S)-1-Chloromethyl-4-isopropenylcyclohexene, (2)
[α]D20 −68 (1.96, CHCl3); Ref. 16: [α]D20 −72 (1.78,
CHCl3) from β-pinene; −67 (1.95, CHCl3) from α-pinene;
−88 (2.13, CHCl3) from limonene; 1H NMR (300 MHz)
d 5.75 (m, 1H, =CH), 4.80 (s, 2H, CH2–Cl), 3.85 (s, 2H,
=CH2), 1.0-2.30 (m, 7H), 0.8 (s, 3H, –CH3).13C NMR (75
MHz) d 148.9 (=C–), 134.2 (=C–), 126.5 (=CH–), 113.6
(=CH2), 50.2 (CH2Cl), 39.7 (CH), 30.1 (CH2), 27.4 (CH2),
+
+
m/z: 186 (4%, M+2⌉ ), 184 (13%, M⌉ ).
(4S)-4-[1-(chloromethyl)vinyl]-1-methyl-7-oxabicyclo[4.1.0]
heptanes, (9)
[α]D20 −43 (2.0, CHCl3); Ref.16 [α]D20 −47 (1.64, CHCl3);
1HNMR(300MHz)d4.71(s, 1H, =CH2), 4.64(s, 1H, =CH2),
3.80 (s, 2H, Cl–CH2–), 2.90 (m, 1H, –O–CH–), 2.3 (m, 1H,
CH), 1.60-1.85 (m, 6H), 1.20 (s, 3H, –CH3). 13C NMR (75
MHz) d 149.10 (=C–), 110.20 (=CH2), 59.23 (O–C), 57.40
(O–CH), 51.20 (CH2Cl), 40.60 (CH), 30.40 (CH2), 28.0
+
26.5 (CH2), 21.0 (CH3). m/z: 172 (4%, M+2⌉ ), 170 (10%,
+
M⌉ ).
+
(4S)-1-Chloromethyl-4-(1-chloromethylvinyl)
cyclohexene, (3)
(CH2), 25.20 (CH2), 23.7 (CH3). m/z: 188 (3%, M+2⌉ ), 186
+
(10%, M⌉ ).
[α]D20 −62 (2.01, CHCl3); Ref. 16: [α]D20 −66 (1.82,
CHCl3) from β-pinene; −58 (1.73, CHCl3) from α-pinene;
−83 (1.91, CHCl3) from limonene; 1H NMR (300 MHz)
d 5.83 (m, 1H, =CH), 5.2 (s, 1H, =CH2), 5.0 (s, 1H, =CH2),
4.11 (s, 2H, CH2-Cl), 4.01 (s, 2H, CH2–Cl), 0.8-2.4 (m, 7H).
13C NMR (75 MHz) d 149.5 (=C–), 134.4 (=C–), 127.3
(=CH–), 109.1 (=CH2), 50.5 (CH2Cl), 47.5 (CH2Cl), 38.0
(CH), 27.5 (CH2), 27.6 (CH2), 26.5 (CH2). m/z: 208 (2%,
6-Chloro-3,7-dimethylocta-2,7-dien-1-ol, (11)
1H NMR (300 MHz) d 5.42 (t, J 6.8, 1H, =CH–), 5.01
(s, 1H, CH2), 4.90 (s, 1H, CH2), 4.35 (t, J 6.5, 1H, CH),
4.16 (d, J 6.8, 2H, CH2–O–), 1.80-2.24 (m, 4H), 1.81 (s,
3H, –CH3), 1.68 (s, 3H, -CH3). 13C NMR (75 MHz) d
144.2 (=C–), 138.0 (=C–), 124.3 (=CH–), 114.3 (=CH2),
59.3 (CH2OH), 66.2 (CHCl), 34.5 (CH2), 29.7 (CH2), 17.0
+
+
+
+
+
M+4⌉ ), 206 (13%, M+2⌉ ), 204 (21%, M⌉ ).
(CH3), 16.3 (CH3). m/z: 190 (4%, M+2⌉ ), 188 (13%, M⌉ ).
*e-mail: elfirdoussi@ucam.ac.ma

2
Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl
J. Braz. Chem. Soc.
Figure S1. 1H NMR spectrum of 2.
Figure S2. 13C{1H} spectrum of 2.
Figure S3. Dept 135 NMR spectrum of 2.
Figure S4. 1H NMR spectrum of 3.

Vol. 22, No. 7, 2011
Boualy et al.
3
Figure S5. 13C{1H} spectrum of 3.
Figure S6. Dept 135 NMR spectrum of 3.
Figure S7. 1H NMR spectrum of 7.
Figure S8. 13C{1H} spectrum of 7.

4
Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl
J. Braz. Chem. Soc.
Figure S9. Dept 135 NMR spectrum of 7.
Figure S10. 1H NMR spectrum of 9.
Figure S11. 13C{1H} NMR spectrum of 9.
Figure S12. Dept 135 NMR spectrum of 9.

Vol. 22, No. 7, 2011
Boualy et al.
5
Figure S13. 1H NMR NMR spectrum of 11.
Figure S14. 13C{1H} NMR spectrum of 11.
Figure S15. Dept 135 NMR spectrum of 11.