One-pot, selective and mild conversion of benzylic alcohols to gem -dichlorides using chlorodiphenylphosphine and 2,3-dichloro-5,6-dicyanobenzoquinone as a new and neutral system

Article abstract of DOI:10.1080/10426507.2014.952003

A mild and one-pot conversion of benzylic alcohols to their corresponding gem-dichlorides is reported for the first time using chlorodiphenylphosphine (ClPPh₂) and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloromethane under neutral conditions and at room temperature. The present method can be efficiently used for preparation of gem-dichlorides even in the presence of some other functional groups with excellent chemoselectivity.

Full text of DOI:10.1080/10426507.2014.952003

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Phosphorus, Sulfur, and Silicon and the Related
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One-pot, Selective and Mild Conversion of
Benzylic Alcohols to gem-Dichlorides Using
Chlorodiphenylphosphine and 2,3-Dichloro-5,6-
dicyanobenzoquinone as a New and Neutral System
Ghasem Aghapoura & Samaneh Mohamadiana
a School of Chemistry, Damghan University, Damghan, 36715-364, Iran
Accepted author version posted online: 20 Aug 2014.
To cite this article: Ghasem Aghapour & Samaneh Mohamadian (2014): One-pot, Selective and Mild Conversion of Benzylic
Alcohols to gem-Dichlorides Using Chlorodiphenylphosphine and 2,3-Dichloro-5,6-dicyanobenzoquinone as a New and Neutral
System, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2014.952003
To link to this article: http://dx.doi.org/10.1080/10426507.2014.952003
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One-pot, Selective and Mild Conversion of Benzylic Alcohols to
gem-Dichlorides Using Chlorodiphenylphosphine and 2,3-Dichloro-5,6-
dicyanobenzoquinone as a New and Neutral System
Ghasem Aghapour,* Samaneh Mohamadian
*School of Chemistry, Damghan University, Damghan, 36715-364, Iran;
E-mail: Gh_Aghapour@du.ac.ir
A shortened title of the article to be used as the running head:
“Conversion of Alcohols to gem-Dichlorides”
Abstract: A mild and one-pot conversion of benzylic alcohols to their corresponding
gem-dichlorides is reported for first time using chlorodiphenylphosphine (ClPPh2) and 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloromethane under neutral conditions and at
room temperature. The present method can be efficiently used for preparation of gem-dichlorides
even in the presence of some other functional groups with excellent chemoselectivity.
ClPPh2, DDQ
CHCl2
45-95%
CH2OH
CH2Cl2, r.t.
1.75-8 h
X
X
X= NO2, F, Cl, Br, H.
Keywords:
Alcohol,
gem-dichloride,
chlorodiphenylphosphine,
2,3-dichloro-5,6-
dicyanobenzoquinone, Chemoselectivity.
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Introduction
Geminal dichlorides are very important compounds in organic synthesis1,2 due to their
ability as precursors to transition metal alkylidenes for carbonyl olefination.2 The product
dichloroarylmethanes are useful materials in pharmaceutical and agricultural industries.3 Several
methods have been reported for their synthesis from aldehydes or ketones such as the use of
BCl3,4 SOCl2/N,N-dimethylformamide (DMF),5 PPh3/CCl4,6 acid halides in the presence of acid
catalysts,7 WCl6,8,9 (PhO)3P/Cl2,10 and alkylboron chloride derivatives11 as chlorination reagents.
Also, synthesis of gem-dichlorides from the reaction of hydrazones with copper (II) chloride-
lithium tert-butoxide as an oxidizing agent, has been reported,12a and also in a minor
modification of this procedure, this transformation has been performed via treatment of
aldehyde- and ketone- derived N-tert-butyldimethylsilylhydrazones with CuCl2 and a catalytic
amount of Sc(OTf)3.12b However, these methods contain some disadvantages such as long
reaction times, low selectivity, use of toxic reagents, low yields, operation at high temperature or
in acidic conditions and formation of undesired products. Also, as far as we know there is no
report about the one-pot conversion of alcohols to gem-dichlorides in the literature.
Consequently, there is a need for the development of convenient methods for the conversion of
alcohols to these important compounds.
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Results and Discussion
Herein, in continuation of our works on the new applications of trivalent phosphorus13, 14
and also 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)14, 15 in organic synthesis including the
conversion of aldehydes and ketones to gem-dichlorides,16 we now report for first time a mild
and one-pot conversion of benzylic alcohols to their corresponding gem-dichlorides using
chlorodiphenylphosphine (ClPPh2) and DDQ in dichloromethane as solvent at room temperature
(Scheme 1).
Scheme 1
First, we selected 4-chlorobenzyl alcohol as a model and optimized the reaction
conditions for its conversion to 1-chloro-4-dichloromethylbenzene using ClPPh2 and DDQ. In
these reactions, in order to avoid the formation of 4-chlorobenzyl chloride, firstly the alcohol was
treated with DDQ producing the related aldehyde and then ClPPh2 was added to the reaction
mixture. The results of this study are shown in Table 1.
Table 1
We tried to perform this conversion with two equiv. amount of ClPPh2 and DDQ in
CH2Cl2 at room temperature. In this case, the corresponding gem-dichloride was produced in
70% yield after 2 h (Table 1, entry 1). Increasing of the molar ratio of the reagents to 2.5:2.5
caused an increase in both the yield and the rate of this transformation (Table 1, entry 2). On the
other hand, decreasing of the amount of DDQ caused a decrease in the rate and/ or the yield of
this reaction (Table 1, entries 2-5). The result of this reaction was not satisfactory under reflux or
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solvent-free conditions nor in CCl4 or CH3CN as the solvent instead of CH2Cl2 (Table 1, entries
6-9). Also, no product formation was observed using N-chlorosuccinimide (NCS) instead of
DDQ. In this case, the alcohol was completely remained intact after 4 h (Table 1, entry 10). This
result obviously shows the more efficiency of DDQ compared to NCS for performing of this
important one-pot reaction.
Finally, with respect to the results from Table 1, the conditions mentioned in entry 3 of
this Table (Alcohol:ClPPh2:DDQ (1:2.5:2); CH2Cl2, r.t.) affording the desired gem-dichloride in
85% yield after 1.75 h, was selected as the optimized conditions for performing this valuable
synthetic transformation and then applied for the one-pot conversion of other benzylic alcohols
to their corresponding gem-dichlorides. The results are shown in Table 2.
Table 2
As shown in this table, primary benzylic alcohols, as well as Cinamyl alcohol, are
conveniently converted to their corresponding gem-dichlorides using ClPPh2 and DDQ in CH2Cl2
at room temperature in moderate to excellent yields. However, the application of the present
method on the conversion of 4-methoxybenzyl alcohol gave 1-dichloromethyl-4-
methoxybenzene in only 20% yield after 1 h. This unsatisfactory yield is probably related to the
methoxy group in the para position, which decreases the stability of this product toward
hydrolysis as described in the literature.16, 17 Also, the application of the present method to the
conversion of secondary benzylic alcohols such as benzhydrol and 1-phenyl ethanol was
unsuccessful. In these cases, only the related ketones were produced immediately and no gem-
dichloride formation was observed. On the basis of this result, we decided to study of the
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possibility of the conversion of primary benzylic alcohols to their corresponding gem-dichlorides
in the presence of ketones and also some other compounds containing a specific functional group
in binary mixtures. For this purpose, a mixture of 4-chlorobenzyl alcohol and another compound
(1:1) was treated with DDQ (2 equiv.) in CH2Cl2 at room temperature producing 4-
chlorobenzaldehyde followed by the addition of ClPPh2 (2.5 equiv.) to the reaction mixture. The
conversion yields of these selective reactions are shown in Scheme 2.
Scheme 2
As shown in this scheme, primary benzylic alcohols can be converted to their
corresponding gem-dichlorides in the presence of epoxides, carboxylic esters and amides,
ketones and phenols with excellent chemoselectivity via the present method.
Although the exact mechanism of this reaction is not clear, on the basis of the reports on
the reaction of trivalent phosphorus with DDQ14, 18 or N-chlorosuccinimide (NCS)16 it is assumed
19
that the produced aldehyde from the oxidation of primary benzylic alcohol with DDQ
is
treated with the complex A resulted from the reaction of ClPPh2 with remained DDQ producing
B (Scheme 3). Then, this intermediate reacts with the released chloride anion affording the
intermediate C. Finally, the desired gem-dichloride is formed via attacking of the second
chloride anion to this intermediate. The aromatization of DDQ ring and the double bond
formation between oxygen and oxophilic phosphorus are assumed as the major driving forces of
this transformation.
Scheme 3
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Experimental
Solvents, reagents and chemicals were obtained from Merck (Germany) and Fluka
(Switzerland) chemical companies. Products are known compounds4,5,16,20 and were
1
characterized by comparison of their physical data, IR, H and 13C NMR spectra with those
prepared according to literature procedures. Fourier transform infrared (FT-IR) spectra were
recorded on a Perkin Elmer RXI spectrophotometer. NMR spectra were recorded on a Brucker
Avance DRX-500 spectrometer. Thin layer chromatography (TLC) was carried out on silica-gel
254 analytical sheets obtained from Fluka. Characterization of an example product is presented
in the Supplemental Materials (Figures S 1 and S 2)
Typical procedure for the one-pot conversion of 4-nitrobenzyl alcohol to 1-
dichloromethyl-4-nitrobenzene using ClPPh2 and DDQ:
4-Nitrobenzyl alcohol (0.153 g, 1 mmol) was added to a flask containing DDQ (0.54 g, 2
mmol) in CH2Cl2 (5 mL) at room temperature. ClPPh2 (0.45 mL, 2.5 mmol) was added to the
reaction mixture after TLC showed the complete conversion of this alcohol to its corresponding
aldehyde and stirring was continued for 8 h. The solvent was evaporated. 1-Dichloromethyl-4-
nitrobenzene was obtained after short column chromatography of the crude mixture on silica gel
60 (0.063-0.200 mm) using petroleum ether-ethyl acetate (40:1) as eluent in 90% yield, 0.186 g;
1
mp 45-46oC (lit.20b 46oC); H-NMR (CDCl3, 500 MHz): δ 6.77(s, 1H), 7.75-7.78(m, 2H), 8.25-
8.27(m, 2H) ppm; 13C-NMR (CDCl3, 125.77 MHz): δ 70.2, 124.5, 127.8, 146.6, 148.9 ppm.
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Conclusions
In conclusion, the present investigation has demonstrated that the use of DDQ and
ClPPh2 offers a simple, novel, convenient and one-pot method, avoiding the use of molecular
halogen with its harsh handling for the conversion of primary benzylic alcohols to their
corresponding gem-dichlorides. As far as we know the present method is the first method
converting alcohols to gem-dichlorides in a direct and one-pot manner. Availability and ease of
handling of the reagent; excellent selectivity; avoidance the isolation of the aldehyde, easy
workup; and operation at room temperature in neutral media can be considered as other
advantages of this new method.
FUNDING
We gratefully acknowledge the support of this work by Damghan University Research
Council.
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ClPPh2, DDQ
CH2Cl2, r.t.
CHCl2
CH2OH
X
X
X= NO2, F, Cl, Br, H.
Scheme 1: The mild and one-pot conversion of benzylic alcohols to gem-dichlorides using
ClPPh2 and DDQ at room temperature. <TI>Comp- make red text in scheme black and add AQ
asking author if it is okay to have changed it to black</TI>
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Cl
CH2OH
O
Cl
CHCl2
O
80%
2.5 h
1)
100%
O
O
Cl
CH2OH
Cl
CHCl2
70%
4 h
2)
100%
CO2CH2CH3
CO2CH2CH3
Cl
CH2OH
Cl
CHCl2
80%
1.75 h
3)
O
O
CH2CNH2
100%
CH2CNH2
Cl
CH2OH
COCH3
Cl
CHCl2
70%
1.75 h
4)
100%
COCH3
O2N
O2N
Cl
CH2OH
Cl
CHCl2
OH
75%
1.25 h
5)
100%
OH
Scheme 2: Various chemoselectivities in the one-pot conversion of 4-chlorobenzyl alcohol to 1-
chloro-4-dichloromethylbenzene using ClPPh2 (2.5 equiv.) and DDQ (2 equiv.) in CH2Cl2 at
room temperature.
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O
DDQ
RCH2OH
RCH
R= aryl
+
Ph2P Cl
..
ClPPh2
O
O
Cl
Cl
CN
CN
Cl
Cl
CN
RCHO
-
-Cl
CN
..
O
O
Ph2P
..
PPh2
(A)
Cl
Ph
Ph
+
P
+
PPh2
RHC
O
Cl
RHClC
-
O
O
O
Cl
Cl
Cl
Cl
CN
CN
-
CN
Cl
Cl
CN
..
..
O
O
Ph2P
Ph2P
(C)
(B)
O
PPh2
O
Cl
CN
CN
+
RCHCl2
Cl
..
O
Ph2P
(D)
Scheme 3: The suggested mechanism of the one-pot conversion of benzylic alcohols to gem-
dichlorides using ClPPh2 and DDQ.14,16,18
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Table 1: Conversion of 4-chlorobenzyl alcohol to 1-chloro-4-dichloromethylbenzene using
ClPPh2 and DDQ at room temperature in various conditions.a
Entry
Solvent
Molar ratio
(Alcohol:ClPPh2:DDQ)
1:2:2
Time
(h)
2
Yield
(%)
70
1
2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
-
1:2.5:2.5
1:2.5:2
1.25
1.75
2.5
1
85
3
85
4
1:2.5:1.5
1:2.5:1
50
5
15
6
1:2.5:2
2
40b
0c
7
1:2.5:2
2.25
2
8
CCl4
1:2.5:2
20
9
CH3CN
CH2Cl2
1:2.5:2
1.5
4
60
10
1:2.5:2
0d
a
In these reactions, first alcohol was treated with DDQ producing the
related aldehyde and then ClPPh2 was added to the reaction mixture. b In this
c
case, the reaction was carried out under reflux condition. In this case, the
reaction was performed via grinding of the reactants in a glass test tube. d In
this case, N-chlorosuccinimid (NCS, 2 eq.) was used instead of DDQ.
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Table 2: One-pot conversion of benzylic alcohols to gem-dichlorides using ClPPh2 (2.5 eq.) and
DDQ (2 eq.) in CH2Cl2 at room temperature.a
Entry
Alcohol
gem-Dichloride
Time
(h)
Yield
(%)b
1
2
1.75
6
80
Cl
CH2OH
Cl
CHCl2
61c
CHCl2
CH2OH
CH2OH
Cl
Cl
Cl
Cl
3
7
48c
CHCl2
4
5
8
4
90
O2N
CHCl2
O2N
CH2OH
88c
CHCl2
CH2OH
O2N
Br
O2N
Br
6
7
2.25
3.5
95
92
CHCl2
CH2OH
CH2OH
CHCl2
Br
F
Br
F
8
4
85
CHCl2
CH2OH
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9
4
70
CH2OH
CHCl2
F
F
Table 2: continued
10
1.25
8
62
45
CH=CHCHCl2
CHCl2
CH=CHCH2OH
11
CH2OH
a In all of these reactions, first alcohol was treated with DDQ producing the related aldehyde and
then ClPPh2 was added to the reaction mixture. b Isolated yields. c In this case, ClPPh2 and DDQ
were used in 2.5:2.5 molar ratio.
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