Efficient partial hydrogenation of trichloromethyl to gem-dichloromethyl groups in platinum on carbon-catalyzed system

Article abstract of DOI:10.1016/j.tet.2014.04.098

While gem-dichloromethyl groups can be directly synthesized by the mono-dechlorination of the corresponding trichloromethyl groups, the suppression control of the over-reduction to form chloromethyl or methyl functionalities is quite difficult. We have established the efficient and widely applicable mono-dechlorination method of the trichloromethyl groups to form the corresponding gem-dichloromethyl groups using platinum on carbon in dimethylacetamide as a specific solvent at 25 °C under a hydrogen atmosphere. The mono-dechlorination of the α,α,α- trichloromethylcarbonyl groups smoothly proceeded by the use of platinum on carbon as a catalyst in a highly chemoselective manner, while the efficient mono-dechlorination of the alkyl- and aryl-trichloromethyl groups required the combined use of Bu₃SnH.

Full text of DOI:10.1016/j.tet.2014.04.098

Accepted Manuscript
Efficient partial hydrogenation of trichloromethyl to geminal-dichloromethyl groups in
platinum on carbon-catalyzed system
Yoshinari Sawama, Takahiro Imanishi, Ryosuke Nakatani, Yuta Fujiwara, Yasunari
Monguchi, Hironao Sajiki
PII:
S0040-4020(14)00644-9
10.1016/j.tet.2014.04.098
TET 25548
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 March 2014
Revised Date: 30 April 2014
Accepted Date: 30 April 2014
Please cite this article as: Sawama Y, Imanishi T, Nakatani R, Fujiwara Y, Monguchi Y, Sajiki H, Efficient
partial hydrogenation of trichloromethyl to geminal-dichloromethyl groups in platinum on carbon-
catalyzed system, Tetrahedron (2014), doi: 10.1016/j.tet.2014.04.098.
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Efficient partial hydrogenation of
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Yoshinari Sawama, Takahiro Imanishi, Ryosuke Nakatani, Yuta Fujiwara Yasunari Monguchi, Hironao Sajiki
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196,
Japan

1
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Tetrahedron
journal homepage: www.elsevier.com
Efficient partial hydrogenation of trichloromethyl to geminal-dichloromethyl groups
in platinum on carbon-catalyzed system
Yoshinari Sawama, Takahiro Imanishi, Ryosuke Nakatani, Yuta Fujiwara, Yasunari Monguchi and
Hironao Sajiki
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
While geminal-dichloromethyl groups can be directly synthesized by the mono-dechlorination of
the corresponding trichloromethyl groups, the suppression control of the over-reduction to form
chloromethyl or methyl functionalities is quite difficult. We have established the efficeint and
widely applicable mono-dechlorination method of the trichloromethyl groups to form the
corresponding geminal-dichloromethyl groups using platinum on carbon in dimethylacetamide
Available online
o
as a specific solvent at 25 C under a hydrogen atmosphere. The mono-dechlorination of the
Keywords:
α,α,α-trichloromethylcarbonyl groups smoothly proceeded by the use of platinum on carbon as a
catalyst in a highly chemoselective manner, while the efficient mono-dechlorination of the alkyl-
and aryl-trichloromethyl groups required the combined use of Bu3SnH.
partial hydrogenation
germinal-dichloro group
trichloromethyl group
platinum on carbon
chemoselective
2009 Elsevier Ltd. All rights reserved
.
1. Introduction
method of the trichloromethyl group to the corresponding gem-
dichloromethyl group in dimethylacetamide (DMA) as the
solvent at 25 C. The present methodology is applicable to the
o
The gem-dichloromethyl group (-CHCl2) is an important and
attractive backbone in the pharmaceutical and agrichemical
fields,1 and also widely utilized as a useful synthetic precursor to
give the corresponding aldehyde by the hydrolysis of the
corresponding gem-dichloromethyl group under basic
mono-dechlorination of various trichloromethyl derivatives. The
α,α,α-trichloromethylcarbonyl derivatives were smoothly mono-
dechlorinated to gem-dichloromethylcarbonyls by the
independent use of Pt/C,7 while the additional Bu3SnH could
efficiently facilitate the mono-dechlorination of aryl- and alkyl-
trichloromethyl substrates (Scheme 1).
conditions,2
a gem-difluoromethyl group by the double
nucleophilic substitution of the fluoro anion,3 etc. Although the
transformation of the trichloromethyl group (-CCl3) to the gem-
dichloromethyl group by the mono-dechlorination (partial
hydrogenation) is regarded as a direct and efficient method due to
the easy preparation and the commercial availability of various
trichloromethyl substrates, the control and tuning of the catalyst
activity to prevent the generation of over-reduced products, such
as chloromethyl (-CH2Cl) or methyl (-CH3) functionalities, is
extremely difficult. Therefore, effective and widely applicable
methods have never been established, although a variety of
mono-dechlorinations of trichloromethyl derivatives have been
investigated.4,5
Scheme 1. Partial hydrogenation (mono-dechlorination) of the
trichloromethyl group to the gem-dichloromethyl group.
We have also continuously examined the development of
efficient reduction methods of the halogenated compounds using
heterogeneous platinum group metals on carbon.6 Herein, we
demonstrate the efficient Pt/C-catalyzed partial hydrogenation
———
. Tel.: +81-58-230-8109; fax: +81-58-230-8109; e-mail: sawama@gifu-pu.ac.jp (Y. Sawama); sajiki@gifu-pu.ac.jp (H. Sajiki)

2
Tetrahedron
simple filtration, washing with MeOH and H2O, then drying
ACCEPTED MANUSCRIPT
under reduced pressure.
2. Results and discussion
Table 2. Reuse of Pt/C.a
The dechlorination activity is strongly influenced by the
electronic and steric environment of the substituents connected to
the trichloromethyl group and the cleavage of the carbon-chlorine
(C-Cl) bond is known to be favored in the order carbonylmethyl
> benzylic > aromatic > aliphatic chlorides.8 Therefore, we first
investigated the mono-dechlorination of the more reactive α,α,α-
trichloromethylcarbonyls as substrates to give the corresponding
gem-dichloromethylcarbonyls, which are valuable synthetic
precursors for diacylfuranes,9a 1,4-diones,9b 1,2,3-triazols,9c α,β-
unsaturated ketones,9d chloroaziridines,9e cyclopropanes,9f etc.
Run
1st
88
2nd
87
3rd
88
4th
89
5th
89
Isolated yield of
2a (%)
a Catalyst was reused after the simple filtration, the wash with MeOH and
H2O then drying under vacuum.
During the 10% Pt/C-catalyzed reductive mono-dechlorination
of 2,2,2-trichloroacetophenone (1a), the desirable gem-
dichloromethylcarbonyl product (2a) could be easily over-
dechlorinated to the corresponding monochloromethyl product
Various α,α,α-trichloromethylcarbonyl derivatives (1) were
effectively transformed into the corresponding gem-
dichloromethylcarbonyl products (2) in a chemoselective manner
under Pt/C-catalyzed reductive dechlorination conditions in
DMA (Scheme 2). Not only the α,α,α-trichloroacetophenone
derivatives bearing both electron-donating (1b-d) and
withdrawing groups (1e and f) on the aromatic ring, but also the
aliphatic α,α,α-trichloroketone derivative (1g) were smoothly
mono-dechlorinated to the gem-dichloromethyl products (2b-g)
in good yields. Furthermore, the ester (1h and i), amide (1j and
k) and heteroaromatic derivatives (1l and m) could also undergo
the mono-dechlorination to the corresponding products (2h-m).
o
(7a) in MeOH at 25 C under a H2 atmosphere (1 atm) (Table 1,
entry 1). Therefore, we further investigated the solvent effect.
DMA and MeCN were found to be sufficient solvents to give 2a
in a highly chemoselective manner in comparison to MeOH, THF,
c-hex, DMF, AcOEt or acetone (entries 2 and 3 vs. 1 and 4-8).
The effect of the kinds of platinum metals on carbon was next
determined in DMA as the solvent. As the result, the use of Pt/C
(entry 2) and Rh/C (entry 9) produced an excellent ratio of the
desired mono-dechlorinated product (2a), while Ir/C and Pd/C
indicated strong catalyst activities to promote the over-
dechlorination, and Ru/C and Au/C were inactive catalysts
(entries 10-13). Consequently, it is obvious that the mono-
dechlorination of 1a using Pt/C in DMA was completed with the
shortest reaction time (0.7 h) to chemoselectively provide 2a in
88% isolated yield.10
Table 1. Optimization in mono-dechlorination of 2,2,2-
trichloroacetophenone (1a).
Entry Catalyst
Solvent
MeOH
DMA
MeCN
THF
Time (h)
Ratio of 1a/2a/7a/8aa
0/32/58/10
0/95(88)b/5/0
0/92/8/0
1
10% Pt/C
10% Pt/C
10% Pt/C
10% Pt/C
10% Pt/C
10% Pt/C
10% Pt/C
10% Pt/C
10% Rh/C
10% Ir/C
10% Pd/C
10% Ru/C
10% Au/C
0.5
0.7
5
2
3
4
1.25
4
0/85/9/6
5
c-hex
0/70/16/14
0/60/28/12
0/84/12/4
6
DMF
2
7
AcOEt
acetone
DMA
DMA
DMA
DMA
DMA
1.3
0.8
2
Scheme 2. Scope of various α,α,α-trichlorocarbonyl
a
b
compounds.:
10 mol% of Pt/C was used.
Yield was
8
0/82/12/6
determined by 1H NMR due to the inseparable property of 2 and
9
0/94/6/trace
0/86/13/1
over-reduced products.
10
11
12
13
3
While the α,α,α-trichloromethylcarbonyl derivatives (1) were
efficiently hydrogenated using 1 mol% of Pt/C, the increment of
Pt/C to 10 mol% or a further additive was required to allow the
mono-dechlorination of the trichloromethanes adjacent to the
alkyl substituent (Tables 3 and 4). Although the 1 mol% of Pt/C-
catalyzed mono-dechlorination of 1,1-bis(4-methoxyphenyl)-
2,2,2-trichloroethane (methoxychlor; 3a) was never completed
even after a 24-h reaction (Table 3, entry 1), 10 mol% of Pt/C
could facilitate the reduction to give the gem-dichloromethyl
product (4a) for 9 h with a good yield and chemoselectivity
(entry 2). Furthermore, the effect of the additives, which can
2
trace/72/10/18
100/0/0/0
6
6
100/0/0/0
a Ratio was determined by 1H NMR.
b Isolated yield.
DMA: dimethylacetamide.
Furthermore, the Pt/C could be reused without its loss of the
catalyst activity and chemoselectivity at least five times after

3
work as a hydrogen radical or hydride donor, was estimated in
ACCEPTED MANUSCRIPT
1
71%, 9 h
95%, 9 h
the presence of 1 mol% of Pt/C (entries 3-7). Consequently, the
addition of Bu3SnH11,12 (entries 3 and 4), well-known as a
hydrogen radical donor, effectively improved the reductive
mono-dechlorination and 4a was obtained in 88% isolated yield
after a 9-h reaction (entry 4).
(75%, 9 h) b
Table 3. The additive (hydrogen donor) effect on mono-
dechlorination of methoxychlor (3a).
2
3
66%, 9 h
98%, 0.3 h
80%, 0.5 h
(65%, 9 h)b
complex
mixture
Entry Additive
Time (h)
Yield (%)a
4a
45
71c
72c
95c
45
0
recovered 3a
4
5
6
54%, 24 h
89%, 0.3 h
90%, 0.3 h
84%, 3 h
1
none
24
9
50
0
(59%, 24 h) b
2b
none
3
Bu3SnH
Bu3SnH
THF
7
0
4d
5
9
0
56%, 24 h
53%, 12 h
24
24
24
49
100
36
6
Et3SiH
Ph3CH
7
55
a Yield was determined by 1H NMR.
b 10 mol% of Pt/C was used.
c Isolated yield.
d 2.0 equiv. of Bu3SnH was used.
7
34%, 24 h c
84%, 1 h
While 10% Pt/C was reused without any loss of catalyst
activity after the mono-dechlorination using 10 mol% of 10%
Pt/C (Table 4, entries 1, 2 and 4), the applicable substrates were
limited (Table 4, condition A). Meanwhile, the combined use of
only 1 mol% of 10% Pt/C and 2 equivalents of Bu3SnH realized
the efficient mono-dechlorination of a wide variety of alkyl
trichloromethane derivatives in a relatively short time (Table 4,
condition B). The benzyl ester (3b) and benzyl alcohol (3c)
derivatives were effectively transformed into the corresponding
gem-dichloromethyl products (4b, c) without hydrogenolysis of
benzylalcohol and benzyl ester moieties (entries 2 and 3).
Additionally, the 2,2,2-trichloroethoxylcarbonyl (Troc)-protected
amines and carboxylic acid 2,2,2-trichloroethyl esters could also
undergo the selective mono-dechlorination of the trichloromethyl
moiety (entries 4-9).13 Since the Pt/C-catalyzed hydrogenation
indicated the high catalyst activity toward the alkyl bromide, the
γ-bromo-α, α, α-trichloro substrate was transformed into the
gem-dichloro product (4j) resulted by the mono-dechlorination of
the trichloromethyl moiety associated with the hydrogenolysis of
the alkyl bromide functionality (entry 10).
8
9
51%, 6 h
88%, 2 h
91%, 2 h
complex
mixture
O
10
trace, 12 h
91%, 6 h
O
CHCl2
CCl3
4j
O
O
Br
substrate
a Isolated yields were shown in Table.
b Using recovered Pt/C.
Table 4. Scope of mono-dechlorination using various
trichloromethane substrates.a
c 1 mol% of Pt/C was used.
The Pt/C-catalyzed dechlorination of trichloromethyl benzene
(benzotrichloride; 5a) occurred with the accompanying
undesirable products such as the dimer (9a), which was probably
generated via the homo-coupling of the gem-dichloromethyl
radical. This problematic issue was also resolved by the addition
of Bu3SnH12 (Table 5). As a result of the optimization, the use of
1.2 equivalents of Bu3SnH most efficiently promoted the desired
Entry Product (4)
Condition A
Condition B

4
Tetrahedron
Pt/C-catalyzed mono-dechlorination to give 6a in a moderate
As the result of reuse test of Pt/C in the mono-dechlorination
ACCEPTED MANUSCRIPT
yield (entry 3).
of 3a using additive Bu3SnH, Pt/C could be also easily recovered
and reused at least five times without the effect of additive
Bu3SnH (Table 5).
Table 5. Pt/C-catalyzed mono-dechlorination using
benzotrichloride.
Table 7. Reuse of Pt/C in mono-dechlorination of 3a using
additive Bu3SnH a
.
Entry
X
Yield of 6a (%)a
1
2
3
4
0
0
0.5
1.2
2.0
14
53
22
Run
1st
95
2nd
95
3rd
97
4th
96
5th
96
Isolated yield of
4a (%)
a Yield was determined by GC.
a Catalyst was reused after the simple filtration, the wash with AcOEt then
drying under vacuum.
The combination of Pt/C and Bu3SnH could be applied to
various mono-dechlorinations of the trichloromethyl benzene
derivatives along without the dechlorination of the aromatic
chloride (Table 6). Although the 4-chloro or 3,4-
dichloro(trichloromethyl) benzenes (5b and c) were transformed
into the corresponding gem-dichloromethyl products, the
resulting products were isolated as aldehydes (10b, c) after the
hydrolysis under basic conditions in the presence of
dimethylamine2,14 because the undesirable coupling products
were inseparable from the gem-dichloromethyl products (entries
2 and 3). Furthermore, the pyridine derivative (5d) was also
applicable for the mono-hydrodechlorination to give 6d in 75%
yield (entry 4).
Two possible reaction mechanisms are considerable for the
Pt/C-catalyzed
mono-hydrodechlorination
of
the
trichloromethylcarbonyl substrates (1) [Scheme 3, eq. 1, routes a
and b]. A direct single electron transfer (SET) from the H2-
activated the Pt metal to the trichloro-substituted carbon
generates the dichloromethyl radical (A) in association with the
elimination of a chloride ion, which is transformed into the gem-
dichloro product (2) by the hydrogen radical donation from the
Pt-activated H2 (route a). During route a, SET from the
eliminated chloride anion to Pt cation radical might allow the
regeneration of the Pt0 species and
a chloride radical.
Alternatively, the anion radical intermediate (B) is generated via
SET from the H2-activated Pt metal to the carbonyl group of the
substrate and the following elimination of the chloride anion
afforded the enolate radical (C). In both cases, the carbonyl
functionality can stabilize the adjacent anion radical. Therefore,
the mono-decholorination of the trichloromethylcarbonyl
substrates (1) can smoothly proceed. Meanwhile, the
dichloromethyl radical (D) is comparatively unstable in the case
of the alkyl trichloromethane substrates (3 and 5), and the
additional Bu3SnH may facilitate the elimination of the chloride
radical from the substrates (eq. 2, step A).15 Since the mono-
dechlorination of the aryl trichloromethane substrate can proceed
via a reactive radical intermediate (D), the homo-coupling of D
significantly proceeds to give the byproduct (9) in the absence of
Bu3SnH. The additional Bu3SnH may play the main role as a
hydrogen radical source in Step B to give the resulting gem-
dichloromethyl products (4 and 6) and the generated stannyl
radical can again promote the dechlorination of the substrate (3
and 5) in Step A. Pt/C, H2 and Bu3SnH can play multiple roles
and synergistically work in each reaction.
Table 6. Scope of mono-dechlorination using benzotrichloride
derivatives.
Entry Substrate
1
Product
Time (h)
2
Yield (%)
53a
2
3
3
2
55b
51b
4
1
75
a Yield was determined by GC.
b Products were isolated after the hydrolysis using 40% dimethyl amine aq. to
aldehydes.

5
4.2.2. Typical Procedure B (Table 4, condition B;
Table 6, entries 1 and 4)
ACCEPTED MANUSCRIPT
A mixture of the substrate (0.5 mmol), 10% Pt/C (9.8 mg, 1
mol% of substrate) and Bu3SnH (262.2 ꢀL, 1.0 mmol) in DMA
(1 mL) in a test tube was stirred using a personal organic
synthesizer (1500 rpm, Chemistation, EYELA, Tokyo) under
ordinary (balloon) hydrogen pressure at 25 °C for the appropriate
time. After the trichloromethyl substrate was perfectly consumed,
the mixture was passed through a Celite pad to remove the Pt/C.
The filtrate was extracted with EtOAc (10 mL) and H2O (10 mL),
then the aqueous layer was further extracted with EtOAc (10 mL
×2). The combined organic layers were dried over Na2SO4 and
concentrated in vacuo. The residue was purified by flash column
chromatography on 10w/w% K2CO3-containg silicagel.12 (n-
hexane/EtOAc after n-hexane (100mL)) to give the
corresponding dichloromethyl product.
4.2.3. Typical Procedure C (Table 6, entries 2 and
3)
A mixture of substrate (0.5 mmol), 10% Pt/C (9.8 mg, 1 mol%
of substrate) and Bu3SnH (157.3 ꢀL, 0.6 mmol) in DMA (1 mL)
in a test tube was stirred using a personal organic synthesizer
(1500 rpm, Chemistation, EYELA, Tokyo) under ordinary
(balloon) hydrogen pressure at 25 °C for the appropriate time.
After the trichloromethyl substrate was perfectly consumed, the
mixture was quenched with sat. KF aq. and stirred for 24 h. The
reaction mixture was passed through a celite pad to remove the
Pt/C and stannyl salt. The filtrate was extracted with ether (10
mL) and H2O (10 mL), then the aqueous layer was further
extracted with ether (10 mL×2). The combined organic layers
were dried over Na2SO4 and concentrated in vacuo. To the
residue in a test tube, 50% dimethyl amine aq. (4 mL) and H2O (1
mL) were added. The reaction mixture was refluxed under
ordinary (balloon) argon pressure for 3 h. The residue was
extracted with ether (10 mL), 1 N HCl aq. (50 mL), then brine
(10 mL), and the aqueous layer was further extracted with ether
(10 mL × 2). The combined organic layers were dried over
Na2SO4 and concentrated in vacuo. The residue was purified by
flash column chromatography on 10w/w% K2CO3-containg
silicagel12 (n-hexane and n-hexane/ether) to give the
corresponding aldehyde.
Scheme 3. Proposed reaction mechanism.
3. Conclusion
We established the efficient mono-hydrodechlorination
(partial hydrogenation) of the trichloromethyl group to the
corresponding gem-dichloromethyl functionality in the presence
of Pt/C under a H2 atmosphere. The trichloromethylcarbonyl
substrates (1) can be easily transformed into the corresponding
gem-dichloromethylcarbonyl products (2) using only Pt/C
without an additive. On the other hand, the mono-dechlorination
of alkyl- and aryl-trichloromethanes (3 and 5) could efficiently
proceed under the Pt/C-H2-Bu3SnH12 combined conditions. The
generated gem-dichloromethyl products (2, 4 and 6) possess
useful substructures for use in pharmaceuticals and
agrichemicals, and are valuable synthetic precursors to be
transformed into aldehydes and gem-difluoromethyl compounds.
4. Experimental Section
4.3. Spectral data of products
4.1. General
4.3.1. 2,2-Dichloroacetophenone (2a)
10% Pt/C, Rh/C, Ir/C, Pd/C, Ru/C and Au/C were supplied by
the N. E. Chemcat Corporation (Tokyo, Japan). 1i, 1l-m, 3a-c
and 5a-d were purchased from commercial sources and used
without further purification. 1a-h, 1j-k, 3d, 3f and 3g were
prepared as depicted in the literature 7. 3j was prepared in
accordance to the reference 16
1
Colorless oil; IR (ATR, cm-1): 2971, 1711, 1602; H NMR
(400MHz; CDCl3): δ 8.09 (d, 2H, J = 7.7 Hz), 7.66 (t, 1H, J = 7.7
Hz), 7.52 (t, 2H, J = 7.7 Hz), 6.69 (s, 1H). 13C NMR (100 MHz;
CDCl3): δ 186.0, 134.7, 131.4, 129.9, 129.1, 67.9; HRMS (FABꢀ
): calcd for C8H5OCl2 [Mꢀ]: 186.9718; found: 186.9722.
4.3.2. 2,2-Dichloro-4’-methoxyacetophenone (2b)
4.2. Typical procedure
Pale yellow oil; IR (ATR, cm-1): 3011, 2938, 2842, 1691,
1596, 1572, 1511; 1H NMR (400 MHz; CDCl3): δ 8.06 (d, 2H, J
= 9.0 Hz), 6.97 (d, 2H, J = 9.0 Hz), 6.65 (s, 1H), 3.89 (s, 3H). 13C
NMR (100 MHz; CDCl3): δ 184.7, 164.7, 132.3, 124.0, 114.3,
68.0, 55.8; HRMS (EI): calcd for C9H8O2Cl2 [M+]: 217.9901;
found: 217.9911.
4.2.1. Typical Procedure A (Table 1 and Scheme 2)
A mixture of the substrate (0.5 mmol) and 10% Pt/C (9.8 mg,
1 mol% of substrate) in DMA (1 mL) in a test tube was stirred
using a personal organic synthesizer (1500 rpm, Chemistation,
EYELA, Tokyo) under ordinary (balloon) hydrogen pressure at
25 °C for the appropriate time. After the trichloromethyl
substrate was perfectly consumed, the mixture was passed
through a celite pad to remove the Pt/C. The filtrate was
extracted with EtOAc (10 mL) and H2O (10 mL), then the
aqueous layer was further extracted with EtOAc (10 mL×2).
The combined organic layers were dried over Na2SO4 and
concentrated in vacuo. The residue was purified by flash silicagel
column chromatography (n-hexane/EtOAc) to give the
corresponding dichloromethyl product.
4.3.3. 2,2-Dichloro-3’-methoxyacetophenone (2c)
Pale yellow oil; IR (ATR, cm-1): 3008, 2941, 2838, 1702,
1
1597, 1581; H NMR (400 MHz; CDCl3): δ 7.65 (d, 1H, J = 8.1
Hz), 7.58 (d, 1H, J = 2.0 Hz), 7.42 (t, 1H, J = 8.1 Hz), 7.19 (dd,
1H, J = 8.1, 2.0 Hz), 6.89 (s, 1H), 3.88 (s, 3 H); 13C NMR (100
MHz; CDCl3): δ 185.9, 160.1, 132.7, 130.0, 122.1, 121.2, 114.1,
67.8, 55.7; HRMS (EI): calcd for C9H8O2Cl2 [M+]: 217.9901;
found: 217.9893.

6
Tetrahedron
4.3.4. 2,2-Dichloro-2’-methoxyacetophenone (2d)
Obtained as mixture of 2m and byproducts. Main spectra of 2k
ACCEPTED MANUSCRIPT
1
1
Pale brown oil; IR (ATR, cm-1): 2945, 2840, 1739, 1598; H
were depicted. H NMR (500 MHz; DMSO): δ 12.4 (brs, 1H),
8.61 (d, 1H, J = 3.0 Hz), 8.17 (d, 1H, J = 7.0 Hz), 7.61 (s, 1H),
7.54 (d, 1H, J = 7.0 Hz), 7.31ꢁ7.26 (m, 2H); 13C NMR (125
MHz; DMSO): δ 180.8, 136.9, 135.9, 125.7, 123.8, 122.8, 121.2,
112.7, 110.5, 68.7; HRMS (EI): calcd for C10H7NOCl2 [M+]:
226.9905; found: 226.9913.
NMR (400 MHz; CDCl3): 7.83 (d, 1H, J = 8.0 Hz), 7.58ꢁ7.54
(m, 1H), 7.09 (s, 1H), 7.09ꢁ7.05 (m, 1H), 7.00 (d, 1H, J = 8.0
Hz), 3.96 (s, 3H); 13C NMR (100 MHz; CDCl3): δ 188.0, 158.5,
135.5, 132.5, 123.1, 121.6, 111.9, 71.0, 56.1; HRMS (EI): calcd
for C9H8O2Cl2 [M+]: 217.9901; found: 217.9897.
4.3.14. 1,1-Bis(p-methoxyphenyl)-2,2-
4.3.5. 2,2-Dichloro-4’-chloroacetophenone (2e)
Colorless solid; M.p. 60ꢁ62 oC; IR (ATR, cm-1): 2928, 1709,
dichloroethane (4a)
o
Colorless solid; M.p. 116ꢁ118 C; IR (ATR, cm-1): 2943,
1
1689, 1588; H NMR (400 MHz; CDCl3): δ 8.05 (d, 2H, J = 8.8
1
Hz), 7.50 (d, 2H, J = 8.8 Hz), 6.59 (s, 1H). 13C NMR (100 MHz;
CDCl3): δ 185.0, 141.3, 131.3, 129.6, 129.4, 67.9; HRMS (EI):
calcd for C8H5OCl3 [M+]: 221.9407; found: 221.9413.
2831; H NMR (500 MHz; CDCl3): δ 7.25 (d, 4H, J = 8.8 Hz),
6.86 (d, 4H, J = 8.8 Hz), 6.30 (d, 1H, J = 8.0 Hz), 4.49 (d, 1H, J
= 8.0 Hz), 3.78 (s, 6H). 13C NMR (100 MHz; CDCl3): δ 158.9,
132.3, 129.6, 114.1, 75.4, 61.1, 55.4; HRMS (EI): calcd for
C16H16O2Cl2 [M+]: 310.0527; found: 310.0534.
4.3.6. 2,2-Dichloro-4’-trifluoromethylacetophenone
(2f)
1
Colorless oil; IR (ATR, cm-1): 2970, 1719, 1581, 1511; H
4.3.15. α-(Dichloromethyl)-benzylacetate (4b)
Colorless oil; IR (ATR, cm-1): 2924, 2852, 1747; H NMR
1
NMR (500 MHz; CDCl3): δ 8.23 (d, 2H, J = 8.0 Hz), 7.79 (d, 2H,
J = 8.0 Hz), 6.62 (s, 1H); 13C NMR (125 MHz; CDCl3): δ185.2,
135.7 (q, J = 32.1 Hz), 134.1, 130.4, 126.0 (q, J = 3.5 Hz), 123.3
(q, J = 271.8 Hz), 67.9.; HRMS (ESI): calcd for C9H3OF3Cl2 [M-
H-]:254.9597; found: 254.9598.
(500 MHz; CDCl3): δ 7.44ꢁ7.43 (m, 2 H), 7.40ꢁ7.39 (m, 3H),
6.10 (d, 1H, J = 5.5 Hz), 5.90 (d, 1H, J = 5.5 Hz), 2.18 (s, 3H);
13C NMR (125 MHz; CDCl3): δ 169.5, 134.7, 129.5, 128.6,
128.0, 78.1, 72.7, 21.0; HRMS (EI): calcd for C10H10O2Cl2 [M+]:
232.0054; found: 232.0058.
4.3.7. 2,2-Dichloromethyl-n-nonylketone (2g)
1
Colorless oil; IR (ATR, cm-1): 2955, 2924, 2854, 1734; H
4.3.16. 2,2-Dichloro-1-phenylethanol (4c)
Colorless oil; IR (ATR, cm-1): 2924, 2852, 1747; 1H NMR
(500 MHz; CDCl3): 7.43ꢁ7.39 (m, 5H), 5.83 (d, 1H, J = 5.5
Hz), 4.99ꢁ4.98 (m, 1H), 2.95 (br, 1H); 13C NMR (125 MHz;
CDCl3): δ 137.4, 129.2, 128.6, 127.2, 78.9, 76.5; HRMS (EI):
calcd for C8H8OCl2 [M+]: 189.9952; found: 189.9941.
NMR (400 MHz; CDCl3): δ 5.80 (s, 1H), 2.80 (t, 2H, J = 7.4 Hz),
1.69ꢁ1.62 (m, 2H), 1.30ꢁ1.27 (m, 12H), 0.88 (t, 3H, J = 6.8
Hz); 13C NMR (100 MHz; CDCl3): δ 197.5, 70.1, 35.1, 32.0,
29.5, 29.4, 29.4, 29.1, 23.9, 22.8, 14.2; HRMS (EI): calcd for
C11H20OCl2 [M+]: 238.0891; found: 238.0885.
4.3.17. 2,2-Dichloroethyl-N-phenyl carbamate (4d)
4.3.8. Phenyldichloroacetate (2h)
Colorless solid; M.p. 70ꢁ72 oC; IR (ATR, cm-1): 3330, 3061,
2957, 2854, 1711, 1600, 1532; 1H NMR (500 MHz; CDCl3): δ
7.39 (m, 2H), 7.33 (d, 2H, J = 7.6 Hz), 7.11 (t, 1H, J = 7.6 Hz),
6.76 (brs, 1H), 5.90 (t, 1H, J = 6.2 Hz), 4.52 (d, 2H, J = 6.2 Hz);
13C NMR (125 MHz; CDCl3): δ 152.2, 137.2, 129.3, 124.2,
118.9, 69.0, 68.8; HRMS (EI): calcd for C9H9NO2Cl2 [M+]:
233.0010; found: 233.0020.
1
Colorless oil; IR (ATR, cm-1): 2986, 1711, 1596, 1500; H
NMR (400 MHz; CDCl3): δ 7.44 (t, 2H, J = 8.4 Hz), 7.31 (t, 1H,
J = 8.4 Hz), 7.19 (d, 2H, J = 8.4 Hz), 6.17 (s, 1H); 13C NMR (100
MHz; CDCl3): δ 163.1, 150.3, 129.8, 127.0, 120.9, 64.3; HRMS
(EI): calcd for C8H6O2Cl2 [M+]: 203.9745; found: 203.9749.
4.3.9. Ethyldichloroacetate (2i)
1H NMR (400 MHz; CDCl3): δ 5.93 (s, 1H), 4.33 (q, 2H, J =
1
4.3.18. 2,2-Dichloroethyl-N-toluyl carbamate (4e)
7.4 Hz), 1.36 (t, 3H, J = 7.4 Hz). H NMR spectrum of the
Colorless solid; M.p. 76ꢁ78 oC; IR (ATR, cm-1): 3331, 3042,
2946, 2921, 1706, 1597, 1534; 1H NMR (500 MHz; CDCl3): δ
7.27 (d, 2H, J = 8.0 Hz), 7.13 (d, 2H, J = 8.0 Hz), 6.68 (brs, 1H),
5.90 (t, 1H, J = 5.8 Hz), 4.51 (d, 2H, J = 5.8 Hz), 2.32 (s, 3H);
13C NMR (125 MHz; CDCl3): δ 152.4, 134.6, 133.8, 129.8,
119.0, 68.9, 68.8, 20.9; HRMS (EI): calcd for C10H11NO2Cl2
[M+]: 247.0167; found: 247.0170.
product was identical to that of the reference 17.
4.3.10. 2,2-Dichloroacetoanilide (2j)
Yellow solid; M.p. 120ꢁ122 oC; IR (ATR, cm-1): 3324, 2984,
1737, 1604, 1551; 1H NMR (400 MHz; CDCl3): δ 8.14 (brs, 1H),
7.56 (d, 2H, J = 7.8 Hz), 7.38 (t, 2H, J = 7.8 Hz), 7.21 (t, 1H, J =
7.8 Hz), 6.05 (s, 1H). 13C NMR (125 MHz; CDCl3): δ 161.9,
136.3, 129.4, 125.8, 120.3, 67.0; HRMS (EI): calcd for
C8H7NOCl2 [M+]: 202.9905; found: 202.9909.
4.3.19. 2,2-Dichloroethyl-N-n-octanyl carbamate
(4f)
Colorless oil; IR (ATR, cm-1): 3335, 2925, 2855, 1705,
1527;1H NMR (500 MHz; CDCl3): δ 5.83 (t, 1H, J = 5.5 Hz),
4.93 (s, 1H), 4.39 (d, 2H, J = 5.5 Hz), 3.19ꢁ3.15 (m, 2H), 1.50
ꢁ1.48 (m, 2H), 1.28ꢁ1.26 (m, 10H), 0.86 (t, 3H, J = 7.0 Hz).
13C NMR (125 MHz; CDCl3): δ 155.1, 69.1, 68.6, 41.2, 31.7,
29.7, 29.1, 29.1, 26.6, 22.6, 14.0; HRMS (EI): calcd for
C11H21NO2Cl2 [M+]: 269.0949; found: 269.0953.
4.3.11. 2,2-Dichloro-N-octylacetoamide (2k)
Obtained as mixture of 2k and byproducts. Main spectra of 2k
1
were depicted. H NMR (500 MHz; CDCl3): δ 6.57 (brs, 1H),
5.92 (s, 1H), 3.31 (m, 2H), 1.56 (m, 2H), 1.30ꢁ1.26 (m, 10H),
0.87 (m, 3H); 13C NMR (125 MHz; CDCl3): δ 164.2, 66.7, 40.5,
31.9, 29.3, 29.2, 27.0, 26.8, 22.7, 14.2; HRMS (EI): calcd for
C10H19NOCl2 [M+]: 239.0844; found: 239.0834.
4.3.12. 2-(Dichloroacetyl)pyrrole (2l)
4.3.20. Benzoic acid 2,2-dichloroethyl ester (4g)
o
Red-brown solid; M.p. 90ꢁ92 C; IR (ATR, cm-1): 3294,
1
Colorless oil; IR (ATR, cm-1): 2955, 1725, 1602, 1584; H
1
3138, 3019, 2924, 1655, 1542; H NMR (500 MHz; CDCl3): δ
NMR (500 MHz; CDCl3): δ8.08 (d, 2H, J = 8.0 Hz), 7.61 (t, 1H,
J = 7.0 Hz), 7.49ꢁ7.46 (m, 2H), 5.98 (t, 1H, J = 6.0 Hz), 4.69 (d,
2H, J = 6.0 Hz); 13C NMR (125 MHz; CDCl3): δ 165.7, 133.8,
130.0, 129.1, 128.7, 68.8, 68.6; HRMS (EI): calcd for C9H8O2Cl2
[M+]: 217.9901; found: 217.9899.
9.46 (brs, 1 H), 7.19ꢁ7.18 (m, 2H), 6.48 (s, H), 6.39 (d, 1H, J =
4.0 Hz); 13C NMR (100 MHz; CDCl3): δ 177.1, 127.6, 126.2,
119.1, 112.0, 67.4; HRMS (EI): calcd for C6H5NOCl2 [M+]:
176.9748; found: 176.9753.
4.3.13. 3-(Dichloroacetyl)indole (2m)

7
Antunes, E. M.; Afolayan, A. F.; Chiwakata, M. T.; Fakee, J.; Knott,
4.3.21. n-Heptanoic acid 2,2-dichloroethyl ester
(4h)
ACCEPTED MANUSCRIPT
M. G.; Whibley, C. E.; Hendricks, D. T.; Bolton, J. J.; Beukes, D. R.
Phytochemistry 2011, 72, 769-772.
2. (a) Clark, A. J.; Battle, G. M.; Bridge, A. Tetrahedron Lett. 2001, 42,
1999-2001; (b) Bankston, D. Synthesis 2004, 283-289; (c) Li, W.; Li, J.;
DeVincentis, D.; Mansour, T. S. Tetrahedron Lett. 2004, 45, 1071-
1074.
3. Recent selected papers: (a) Yang, H.; Quan, H.; Tamura, M.; Sekiya, A.
J. Mol. Catal. A: Chem. 2005, 233, 99-104; (b) Belter, R. K.; Sweval,
M. S.; Iikubo, Y. J. Fluorine Chem. 2006, 127, 816-820; (c) Dolbier Jr.,
W. R.; Duan, J.-X.; Rong, X. X. J. Fluorine Chem. 2007, 128, 1091-
1093; (d) Zeghida, W.; Debray, J.; Chierici, S.; Dumy, P.; Demeunynck,
M. J. Org. Chem. 2008, 73, 2473-2475; (e) Kremsner, J. M.; Rack, M.;
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Piou, A.; Celerier, S.; Brunet, S. J. Fluorine Chem. 2012, 134, 103-106.
4. For review: Chukovskaya, E. C.; Freidlina, R. K.; Kuzmina, N. A.
Synthesis 1983, 773-784.
Colorless oil; IR (ATR, cm-1): 2956, 2927, 2857, 1744; H
NMR (500 MHz; CDCl3): δ 5.83 (t, 1H, J = 6.5 Hz), 4.43 (d, 2H,
J = 6.5 Hz), 2.37 (t, 2H, J = 7.5 Hz), 1.67ꢁ1.61 (m, 2H), 1.31ꢁ
1.27 (m, 8H), 0.87 (t, 3H, J = 6.8 Hz); 13C NMR (125 MHz;
CDCl3): δ 173.0, 68.6, 68.2, 34.0, 31.8, 29.1, 29.0, 24.9, 22.7,
14.2; HRMS (EI): calcd for C10H18O2Cl2 [M+]: 240.0684; found:
240.0685.
1
4.3.22. 4-n-Butylbenzoic acid 2,2-dichloroethyl
ester (4i)
Colorless oil; IR (ATR, cm-1): 2957, 2931, 2860, 1723, 1610;
1H NMR (500 MHz; CDCl3): δ 7.98 (d, 2H, J = 8.5 Hz), 7.27 (d,
2H, J = 8.5 Hz), 5.97 (t, 1H, J = 6.0 Hz), 4.67 (d, 2H, J = 6.0
Hz), 2.67 (t, 2H, J = 7.8 Hz), 1.63ꢁ1.58 (m, 2H), 1.38ꢁ1.33
(m, 2H), 0.93 (t, 3H, J = 7.5 Hz); 13C NMR (125 MHz; CDCl3) :
δ 165.8, 149.5, 130.1, 128.8, 126.5, 68.7, 68.7, 35.9, 33.4, 22.4,
14.0; HRMS (EI): calcd for C13H16O2Cl2 [M+]: 274.0527; found:
274.0520.
5. The related reports before 1982, see reference 4.: (a) Blum, J.; Shtelzer,
S.; Albin, P. J. Mol. Catal. 1982, 16, 167-174; (b) Takamatsu, M;
Terao, Y.; Sekiya, M. Chem. Pharm. Bull. 1982, 30, 2682-2687; (c)
Nome, F.; Rezende, M. C.; Sérgio de Souza, N. J. Org. Chem. 1983, 48,
5357-5359; (d) Hirao, T.; Kohno, S.; Ohshiro, Y.; Agawa, T. Bull.
Chem. Soc. Jpn. 1983, 56, 1881-1882; (e) Castro, C. E.; Wade, R. S. J.
Org. Chem. 1985, 50, 5342-5351; (f) Casadei, M. A.; Moracci, F. M.;
Occhialini, D.; Inesi, A. J. Chem. Soc., Perkin Trans. 2 1987, 1887-
1892; (g) Baasner, B.; Klauke, E. J. Fluorine Chem. 1988, 40, 359-364;
(h) Tanaka, H.; Yamashita, S.; Yamanoue, M.; Torii, S. J. Org. Chem.
1989, 54, 444-450; (i) Folli, U.; Goldoni, F.; Iarossi, D.; Sbardellati, S.;
Taddei, F. J. Chem. Soc., Perkin Trans. 2 1995, 1017-1020; (j) Bryans,
J. S.; Large, J. M.; Parsons, A. F. J. Chem. Soc., Perkin Trans. 1 1999,
2897-2904. (k) Ellis, D. A.; Hart, D. J.; Zhao, L. Tetrahedron Lett.
2000, 41, 9357-9360; (l) Ranu, B. C.; Samanta, S.; Das, A. Tetrahedron
Lett. 2002, 43, 5993-5995; (m) Mori, T.; Kubo, J.; Morikawa, Y. Appl.
Catal. A 2004, 271, 69-76; (n) Seigal, B. A.; Fajardo, C.; Snapper, M. L.
J. Am. Chem. Soc. 2005, 127, 16329-16332; (o) Shimakoshi, H.; Kudo,
S.; Hisaeda, Y. Chem. Lett. 2005, 1096-1097; (p) Naito, T.; Saito, A.;
Ueda, M.; Miyata, O. Heterocycles 2005, 65, 1857-1869; (q) Koch, F.
M.; Peters, R. Angew. Chem. Int. Ed. 2007, 46, 2685-2689; (r) Rivera,
N. G.; Becerril, D. C.; Guadarrama-Pérez, C.; Covarrubias-Zuñiga, A.;
Avila-Zárraga, J. G.; Romero-Ortega, M. Tetrahedron Lett. 2007, 48,
1201-1204; (s) Tiseni, P. S.; Peters, R. Angew. Chem. Int. Ed. 2007, 46,
5325-5328; (t) Mineno, T.; Kansui, H.; Kunieda, T.; Tetrahedron Lett.
2007, 48, 5027-5030; (u) Zajac, M.; Peters, R. Chem. Eur. J. 2009, 15,
8204-8222; (v) Essa, A. H.; Lerrick, R. I.; Tuna, F.; Harrington, R. W.;
Clegg, W.; Hall, M. J. Chem. Commun. 2013, 2756-2758.
6. (a) Sajiki, H.; Kume, A.; Hattori, K.; Hirota, K. Tetrahedron Lett. 2002,
43, 7247-7250; (b) Sajiki, H.; Kume, A.; Hattori, K.; Nagase, H.;
Hirota, K. Tetrahedron Lett. 2002, 43, 7251-7254; (c) Monguchi, Y.;
Kume, A.; Hattori, K.; Maegawa, T.; Sajiki, H. Tetrahedron 2006, 62,
7926-7933; (d) Monguchi, Y.; Kume, A.; Sajiki, H. Tetrahedron 2006,
62, 8384-8392; (e) Kume, A.; Monguchi, Y.; Hattori, K.; Nagase, H.;
Sajiki, H. Appl. Catal. B: Environ. 2008, 81, 274-282; (f) Monguchi, Y.;
Ishihara, S.; Ido, A.; Niikawa, M.; Kamiya, K.; Sawama, Y.; Nagase,
H.; Sajiki, H. Org. Process. Res. Dev. 2010, 14, 1140-1146; (g)
Sawama, Y.; Yabe, Y.; Shigetsura, M.; Yamada, T.; Nagata, S.;
Fujiwara, Y.; Maegawa, T.; Monguchi, Y.; Sajiki, H. Adv. Synth. Catal.
2012, 354, 777-782.
4.3.23. 6-Acetoxy-1,1-dichlorohexane (4j)
1
Colorless oil; IR (ATR, cm-1): 2949, 2864, 1734; H NMR
(500 MHz; CDCl3): δ 5.75 (t, 1H, J = 5.5 Hz), 4.07 (t, 2H, J = 6.5
Hz), 2.23-2.18 (m, 2H), 2.05 (s, 3H), 1.68ꢁ1.59 (m, 4H), 1.45-
1.38 (m, 2H); 13C NMR (125 MHz; CDCl3) : δ 171.3, 73.5, 64.3,
43.5, 28.5, 25.7, 25.2, 21.2; HRMS (EI): calcd for C8H14O2Cl2Na
[M+Na]+: 235.0263; found: 235.0297.
4.3.24. Benzyl dichloride (6a)
1H NMR (500 MHz; CDCl3): δ 7.56 (d, 2H, J = 6.5 Hz), 7.41
ꢁ7.37 (m, 3H), 6.70 (s, 1H) .1H NMR spectrum of the product
was identical to that of the reference 18.
4.3.25. 4-Chlorobenzaldehyde (10b)
1H NMR (500 MHz; CDCl3): δ 9.99 (s, 1H), 7.83 (d, 2H, J =
1
8.0 Hz), 7.53 (d, 2H, J = 8.0 Hz). H NMR spectrum of the
product was identical to that of the reference 19.
4.3.26. 3,4-Dichlorobenzaldehyde (10c)
1H NMR (500 MHz; CDCl3): δ 9.95 (s, 1H), 7.97 (s, 1H), 7.73
(d, 1H, J = 8.0 Hz), 7.64 (d, 1H, J = 8.0 Hz). 1H NMR spectrum
of the product was identical to that of the reference 20.
4.3.27. 2,6-Dichloro-4-dichloromethyl pyridine (6d)
Colorless oil; IR (ATR, cm-1): 3082, 2957, 1582, 1547; H
1
NMR (400 MHz; CDCl3): δ 7.46 (s, 2H), 6.57 (s, 1H); 13C NMR
(100 MHz; CDCl3): δ 153.1, 151.5, 120.4, 67.7; HRMS (EI):
calcd for C6H2NCl4 [M-H]-: 227.8947; found: 227.8957.
7. The mono-dechlorination of α,α,α-trichloromethylcarbonyl derivatives
etc. by the independent use of Pt/C has been reported by us as a
communication. See, Imanishi, T.; Fujiwara, Y.; Sawama, Y.;
Monguchi, Y.; Sajiki, H. Adv. Synth. Catal. 2012, 354, 771-776.
8. Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2002, 102, 4009-
4092.
9. (a) Kraus, G. A.; Wan, Z. Synlett 1997, 1259-1260; (b) Peppe, C.; das
Chagas, R. P. Synlett 2004, 1187-1190; (c) Raghavendra, M. S.; Lam,
Y. Tetrahedron Lett. 2004, 45, 6129-6132; (d) Concellón, J. M.;
Rodríguez-Solla, H.; Concellón, C.; Díaz, P. Synlett 2006, 837-840; (e)
Giubellina, N.; Mangelinckx, S.; Törnroos, K. W.; Kimpe, N. D. J. Org.
Chem. 2006, 71, 5881-5887; (f) Peppe, C.; das Chagas, R. P.; Burrow,
R. A. J. Organomet. Chem. 2008, 693, 3441-3445.
Acknowledgments
We thank N.E. Chemcat Corporation for the kind gift of the
catalysts and Ihara Nikkei Chemical Industry Co. Ltd. for the gift
of 5b. We would also like to appreciate Sugiyama Drugs Co.,
Ltd. to open the door for the continuation of T.I.’s research at
Gifu Pharmaceutical University.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at.
10. In general, mono-chloromethyl and methyl products have similar polar
characteristics and could not be separated by the silicagel column
chromatography. On the other hand, the trichloromethyl, gem-
dichloromethyl and mono-chloromethyl compounds were easily
separated.
References and notes
11. Bu3SnH has been utilized in the dechlorination of benzotrichloride, etc.
However, the reactivity using only Bu3SnH was too low and the
substrates were limited. See Kuivila, H. G.; Menapace, L. W. J. Org.
Chem. 1963, 28, 2165-2167.
1. Selected references: (a) Miller, N. E.; Halpert, J. Mol. Pharmacol. 1986,
29, 391-398; (b) Teraoka, R.; Matsushima, Y.; Sugimoto, I.; Inoue, K.;
Morita, S.; Kitagawa, S. Chem. Pharm. Bull. 2009, 57, 1343-1347; (c)

8
Tetrahedron
12. The mono-dechlorination of alkyl- and aryl-trichloromethyl
ACCEPTED MANUSCRIPT
compounds required the addition of toxic BuSn3H and the stannyl
sludge residue in the products was a concern. This problem was easily
alleviated by purification using K2CO3-containing silicagel column
chromatography. See Harrowven, D. C.; Curran, D. P.; Kostiuk, S. L.;
Wallis-Guy, I. L.; Whiting, S.; Stenning, K. J.; Tang, B.; Packard, E.;
Nanson, L. Chem. Commun. 2010, 46, 6335-6337.
13. Deprotection of the 2,2,2-trichloroethoxylcarbonyl-protected amines
and carboxylic acid 2,2,2-trichloroethyl esters via the dichloromethyl
radical intermediates was considered as depicted below. A related
deprotection method of the 2,2,2-trichloroethyl ester was reported in
reference [5t].
14. See the detail in experimental section.
15. Although Bu3SnH itself can play the role as a radical initiator, the
efficiency is not so high (see reference 11). Therefore, the present
reaction can be mainly activated by the chloride radical generated by the
SET cycle between the Pt and substrate as depicted in Scheme 3, eq.1.
16. Sawama, Y.; Nakatani, R.; Imanishi, T.; Fujiwara, Y.; Monguchi, Y.;
Sajiki, H. RSC Adv. 2014, 4, 8657-8660.
17. Gupta, S. K. J. Org. Chem. 1973, 38, 4081-4082.
18. Aghapour, G.; Afzali, A. Synth. Commun. 2008, 38, 4023-4035.
19. Karimi, B.; Farhangi, E. Chem. Eur. J. 2011, 17, 6056-6060.
20. Figiel, P. J.; Leskelä, M.; Repo, T. Adv. Synth. Catal. 2007, 349, 1173-
1179.

ACCEPTED MANUSCRIPT
Supporting Information
Efficient Partial Hydrogenation of Trichloromethyl to Geminal-Dichloromethyl
Groups in Platinum on Carbon-Catalyzed System
Yoshinari Sawama,* Takahiro Imanishi, Ryosuke Nakatani, Yuta Fujiwara,
Yasunari Monguchi and Hironao Sajiki*
Laboratory of Organic Chemistry, Department of Organic and Medicinal Chemistry, School of Pharmaceutical
Sciences, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
Contents
1. General.
2. Preparation of substrate.
3. General procedure
4. Spectroscopic data of products
5. References.
6. Spectra of newly synthesized compounds.
1. General.
10% Pt/C, Rh/C, Ir/C, Pd/C, Ru/C and Au/C were supplied by the N. E. Chemcat Corporation
(Tokyo, Japan). 5b was supplied by the Ihara Nikkei Chemical Industry Co., Ltd. (Shizuoka, Japan).
1i, 1l, 1m, 3a, 3b, 3c, 5a, 5c and 5d were purchased from commercial sources and used without
further purification. 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1j, 1k, 3d, 3f and 3g were depicted in the
literature 1. 3j was prepared in accordance to the literature 1. All other substrates were prepared
according to the procedure shown in section 2. Flash column chromatography was performed with
Silica Gel 60 N (Kanto Chemical Co., Inc., 63–210 μm spherical, neutral). 1H and 13C NMR spectra
were recorded on a JEOL EX 400, AL 400 or ECA 500 spectrometer (1H NMR; 400 MHz for 2a,
2b, 2c, 2d, 2e, 2g, 2h, 2i, 2j, 3e and 6d, or 500 MHz for 2f, 2k, 2l, 2m, 3h, 3i, 4a, 4b, 4c, 4d, 4e, 4f,
4g, 4h, 4i, 4j, 6a, 10b and 10c, and 13C NMR; 100 MHz for 2a, 2b, 2e, 3e, 4a and 6d, or 125 MHz
for 2j, 3h, 3i, 4c, 4e, 4h, 4i and 4j). Chemical shifts (δ) are expressed in ppm and are internally
referenced (7.26 ppm for CDCl3 for 1H NMR and 77.16 ppm for CDCl3, for 13C NMR). EI and FAB
mass spectra was taken on a JEOL JMS-SX102A instrument. GC/MS was taken on a JEOL JMS-Q
1000GC MK2 instrument. LC/MS was taken on a Shimazu LCMS-IT-TOF instrument.
2. Preparation of substrates (3e, 3h, 3i, 3j, 3k, 3l, 1i, 1j, 1o, 1p and 1q).
2,2,2-Trichloroethyl-N-tolyl carbamate (3e):
S1

To a solution of 4-methylaniline (2.1 g, 20.0 mmol) in anhydrous pyridine (1.7 mL, 21.0 mmol) and
ACCEPTED MANUSCRIPT
anhydrous CH2Cl2 (100 mL), 2,2,2-trichloroethyl chloroformate (2.6 mL, 21.0 mmol) was added
dropwise. After stirring for 2 h, the mixture was diluted with CH2Cl2 (60 mL), and extracted with
H2O (50 mL), 5% aqueous HCl (100 mL) then 5% aqueous NaOH (100 mL) in turn. The organic
phase was dried over Na2SO4, and concentrated in vacuo. The residue was purified by
recrystallization (hexane/EtOAc=1/1) in 30% yield (1.67 g) as a colorless solid (melting point 82－
84 oC); IR (ATR, cm-1) : 3322, 2952, 1716, 1599, 1523; 1H NMR (400 MHz; CDCl3): δ 7.30 (d, 2H,
J = 8.0 Hz), 7.14 (d, 2H, J = 8.0 Hz), 6.85 (brs, 1H), 4.82 (s, 2H), 2.32 (s, 3H); 13C NMR (100
MHz; CDCl3): δ 151.7, 134.6, 134.0, 129.8, 119.2, 95.5, 74.6, 20.9; MS (FAB) m/z (%) [M－], 280
(6) 219 (12) 150 (9) 127 (44) 117 (7) 106 (10) 77 (17) 43 (45). HRMS (FAB): calcd for
C10H9NO2Cl3 [M+]: 279.9699; found: 279.9703.
n-Heptanoic acid 2,2,2-trichloroethylester (3h):
To a solution of a dicyclohexyl carbodiimide (3.26 g, 15.8 mmol), n-octanoic acid (2.09 mL, 13.2
mmol) and 4-dimethylaminopyrridine (806.3 mg, 6.6 mmol) in anhydrous CH2Cl2 (100 mL),
2,2,2-trichloroethanol (1.5 mL, 15.8 mmol) was added dropwise at 0 oC. The mixture was stirred at
room temperature for 21 h. The reaction mixture was filtrated through funnel padded with cotton.
The mixture was extracted with CH2Cl2 (30 mL), 1 mol/L HCl (25 mL×2), then aqueous NaHCO3
solution (50 mL×2), dried over Na2SO4, and concentrated in vacuo. The residue was purified by
flash silicagel columun chromatography (n-hexane/EtOAc=50/1) to give 3h as a colorless oil (423.0
mg, 11%); IR (ATR, cm-1) : 2955, 2927, 2857, 1755; 1H NMR (500 MHz; CDCl3): δ 4.73 (s, 2H),
13
2.48 (t, 2H, J = 9.5 Hz), 1.72―1.64 (m, 2H), 1.36―1.23 (m, 8H), 0.87 (t, 3H, J = 8.5 Hz); C
NMR (125 MHz; CDCl3): δ 172.3, 95.2, 74.0, 34.1, 31.8, 29.1, 29.0, 24.9, 22.7, 14.2; MS (EI) m/z
(%) [M+], 274 (5) 239 (14) 203 (20) 190 (68) 167 (6) 127 (99) 115 (5) 98 (16) 84 (16) 60 (56) 41
(37). HRMS (EI): calcd for C10H17O2Cl3 [M+]: 274.0295; found: 274.0287.
4-n-Butylbenzoic acid 2,2,2-trichloroethylester (3i):
To a solution of a dicyclohexyl carbodiimide (3.26 g, 15.8 mmol), 4-n-butylbenzoic acid (2.35 g,
13.2 mmol) and 4-dimethylaminopyrridine (806.3 mg, 6.6 mmol) in anhydrous CH2Cl2 (100 mL),
2,2,2-trichloroethanol (1.5 mL, 15.8 mmol) was added dropwise at 0 oC. The mixture was stirred at
room temperature for 21 h. The reaction mixture was filtrated through funnel padded with cotton.
The mixture was extracted with CH2Cl2 (30 mL), 1 mol/L HCl (25 mL×2), then aqueous NaHCO3
solution (50 mL×2), dried over Na2SO4, and concentrated in vacuo. The residue was purified by
flash silicagel columun chromatography (n-hexane/EtOAc=20/1) to give 3i as a colorless oil (3.39 g,
82%); IR (ATR, cm-1) : 2956, 2931, 2860, 1731, 1610, 1576, 1509; 1H NMR (500 MHz; CDCl3): δ
8.04 (d, 2H, J = 8.0 Hz), 7.29 (d, 2H, J = 8.0 Hz), 4.96 (s, 2H), 2.69 (t, 2H, J = 7.8 Hz), 1.65―1.59
(m, 2H), 1.38―1.34 (m, 2H), 0.93 (t, 3H, J = 7.5 Hz); 13C NMR (125 MHz; CDCl3): δ 165.1, 149.8,
130.3, 128.8, 126.2, 95.3, 74.5, 35.9, 33.4, 22.4, 14.0; MS (EI) m/z (%). [M+], 308 (17) 273 (9) 267
(19) 230 (5) 161 (99) 135 (14) 125 (15) 118 (30) 103 (18) 95 (6) 91 (72) 77 (19) 65 (10) 51 (6) 41
(21). HRMS (EI): calcd for C13H15O2Cl3 [M+]: 308.0138; found: 308.0140.
S2

ACCEPTED MANUSCRIPT
3. General procedure.
General procedure A: A mixture of substrate (0.5 mmol), 10% Pt/C (9.8 mg, 1 mol% of substrate)
in DMA (1 mL) in a test tube was stirred using a personal organic synthesizer (1500 rpm,
Chemistation, EYELA, Tokyo) under ordinary (balloon) hydrogen pressure at 25 °C for the
appropriate time. After the trichloromethyl substrate was perfectly consumed, the mixture was
passed through a Celite pad to remove Pt/C. The filtrate was extracted with EtOAc (10 mL) and
H2O (10 mL), and then the aqueous layer was further extracted with EtOAc (10 mL×2). The
combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was
purified by flash silicagel column chromatography (n-hexane/EtOAc) to give the corresponding
dichloromethyl product.
General procedure B: A mixture of substrate (0.5 mmol), 10% Pt/C (9.8 mg, 1 mol% of substrate)
and Bu3SnH (262.2 μL, 1.0 mmol) in DMA (1 mL) in a test tube was stirred using a personal
organic synthesizer (1500 rpm, Chemistation, EYELA, Tokyo) under ordinary (balloon) hydrogen
pressure at 25 °C for the appropriate time. After the trichloromethyl substrate was perfectly
consumed, the mixture was passed through a Celite pad to remove Pt/C. The filtrate was extracted
with EtOAc (10 mL) and H2O (10 mL), and then the aqueous layer was further extracted with
EtOAc (10 mL×2). The combined organic layers were dried over Na2SO4 and concentrated in
vacuo. The residue was purified by flash column chromatography on 10w/w% K2CO3-containg
silicagel2 (n-hexane/EtOAc after n-hexane (100mL)) to give the corresponding dichloromethyl
product.
General procedure C: A mixture of substrate (0.5 mmol), 10% Pt/C (9.8 mg, 1 mol% of substrate)
and Bu3SnH (157.3 μL, 0.6 mmol) in DMA (1 mL) in a test tube was stirred using a personal
organic synthesizer (1500 rpm, Chemistation, EYELA, Tokyo) under ordinary (balloon) hydrogen
pressure at 25 °C for the appropriate time. After the trichloromethyl substrate was perfectly
consumed, the mixture was quenched with sat. KF aq. and stirred for 24 h. The reaction mixture
was passed through a Celite pad to remove Pt/C and stannyl salt. The filtrate was extracted with
ether (10 mL) and H2O (10 mL), and then the aqueous layer was further extracted with ether (10
mL×2). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. To the
residue in a test tube, 50% dimethyl amine aq. (4 mL) and H2O (1 mL) were added. The reaction
mixture was refluxed under ordinary (balloon) argon pressure for 3 h. The residue was extracted
with ether (10 mL), 1 N HCl aq. (50 mL), then brine (10 mL), and the aqueous layer was further
extracted with ether (10 mL×2). The combined organic layers were dried over Na2SO4 and
concentrated in vacuo. The residue was purified by flash column chromatography on 10w/w%
K2CO3-containg silicagel (n-hexane and n-hexane/ether) to give the corresponding aldehyde.
4. Spectroscopic data of products
S3

2,2-Dichloroacetophenone (2a):
ACCEPTED MANUSCRIPT
Synthesized accoriding to the general precedure A.
A colorless oil; IR (ATR, cm-1) : 2971, 1711, 1602; 1H NMR (400MHz; CDCl3): δ 8.09 (d, 2H, J =
7.7 Hz), 7.66 (t, 1H, J = 7.7 Hz), 7.52 (t, 2H, J = 7.7 Hz), 6.69 (s, 1H); 13C NMR (100 MHz;
CDCl3): δ 186.0, 134.7, 131.4, 129.9, 129.1, 67.9; MS HRMS (FAB－): calcd for C8H5OCl2 [M－]:
186.9718; found: 186.9722.
2,2-Dichloro-4’-methoxyacetophenone (2b):
Synthesized accoriding to the general precedure A.
A pale yellow oil; IR (ATR, cm-1) : 3011, 2938, 2842, 1691, 1596, 1572, 1511; H NMR (400
1
13
MHz; CDCl3): δ 8.06 (d, 2H, J = 9.0 Hz), 6.97 (d, 2H, J = 9.0 Hz), 6.65 (s, 1H), 3.89 (s, 3H); C
NMR (100 MHz; CDCl3): δ 184.7, 164.7, 132.3, 124.0, 114.3, 68.0, 55.8; MS HRMS (EI): calcd
for C9H8O2Cl2 [M+]: 217.9901; found: 217.9911.
2,2-Dichloro-3’-methoxyacetophenone (2c):
Synthesized accoriding to the general precedure A.
A pale yellow oil; IR (ATR, cm-1) : 3008, 2941, 2838, 1702, 1597, 1581; H NMR (400 MHz;
1
CDCl3): δ 7.65 (d, 1H, J = 8.1 Hz), 7.58 (d, 1H, J = 2.0 Hz), 7.42 (t, 1H, J = 8.1 Hz), 7.19 (dd, 1H,
13
J = 8.1, 2.0 Hz), 6.69 (s, 1H), 3.88 (s, 3 H); C NMR (100 MHz; CDCl3): δ 185.9, 160.1, 132.7,
130.0, 122.1, 121.2, 114.1, 67.8, 55.7; MS HRMS (EI): calcd for C9H8O2Cl2 [M+]: 217.9901;
found: 217.9893.
2,2-Dichloro-2’-methoxyacetophenone (2d):
Synthesized accoriding to the general precedure A.
A pale brown oil; IR (ATR, cm-1) : 2945, 2840, 1739, 1598; 1H NMR (400 MHz; CDCl3): δ7.83 (d,
1H, J = 8.0 Hz), 7.58―7.54 (m, 1H), 7.09 (s, 1H), 7.09―7.05 (m, 1H), 7.00 (d, 1H, J = 8.0 Hz),
3.96 (s, 3H); 13C NMR (100 MHz; CDCl3): δ 188.0, 158.5, 135.5, 132.5, 123.1, 121.6, 111.9, 71.0,
56.1; HRMS (EI): calcd for C9H8O2Cl2 [M+]: 217.9901; found: 217.9897.
2,2-Dichloro-4’-chloroacetophenone (2e):
Synthesized accoriding to the general precedure A.
Colorless solid; M.p. 60―62 C; IR (ATR, cm-1): 2928, 1709, 1689, 1588; H NMR (400 MHz;
o
1
13
CDCl3): δ 8.05 (d, 2H, J = 8.8 Hz), 7.50 (d, 2H, J = 8.8 Hz), 6.59 (s, 1H); C NMR (100 MHz;
CDCl3): δ 185.0, 141.3, 131.3, 129.6, 129.4, 67.9; MS HRMS (EI): calcd for C8H5OCl3 [M+]:
221.9407; found: 221.9413.
2,2-Dichloro-4’-trifluoromethylacetophenone (2f):
Synthesized accoriding to the general precedure A.
A colorless oil; IR (ATR, cm-1) : 2970, 1719, 1581, 1511; H NMR (500 MHz; CDCl3): δ 8.23 (d,
1
2H, J = 8.0 Hz), 7.79 (d, 2H, J = 8.0 Hz), 6.62 (s, 1H); 13C NMR (125 MHz; CDCl3): δ185.2, 135.7
S4

(q, J = 32.1 Hz), 134.1, 130.4, 126.0 (q, J = 3.5 Hz), 123.3 (q, J = 271.8 Hz), 67.9.; HRMS (ESI):
ACCEPTED MANUSCRIPT
calcd for C9H3OF3Cl2 [M-H-]:254.9597; found: 254.9598.
2,2-Dichloromethyl-n-nonylketone (2g):
Synthesized accoriding to the general precedure A.
A colorless oil; IR (ATR, cm-1) : 2955, 2924, 2854, 1734; H NMR (400 MHz; CDCl3): δ 5.80 (s,
1
1H), 2.80 (t, 2H, J = 7.4 Hz), 1.69―1.62 (m, 2H), 1.30―1.27 (m, 12H), 0.88 (t, 3H, J = 6.8 Hz);
13C NMR (100 MHz; CDCl3): δ 197.5, 70.1, 35.1, 32.0, 29.5, 29.4, 29.4, 29.1, 23.9, 22.8, 14.2;
HRMS (EI): calcd for C11H20OCl2 [M+]: 238.0891; found: 238.0885.
Phenyldichloroacetate (2h):
Synthesized accoriding to the general precedure A.
A colorless oil; IR (ATR, cm-1) : 2986, 1711, 1596, 1500; H NMR (400 MHz; CDCl3): δ 7.44 (t,
1
13
2H, J = 8.4 Hz), 7.31 (t, 1H, J = 8.4 Hz), 7.19 (d, 2H, J = 8.4 Hz), 6.17 (s, 1H); C NMR (100
MHz; CDCl3): δ 163.1, 150.3, 129.8, 127.0, 120.9, 64.3; HRMS (EI): calcd for C8H6O2Cl2 [M+]:
203.9745; found: 203.9749.
Ethyldichloroacetate (2i):
Synthesized accoriding to the general precedure A.
1H NMR (400 MHz; CDCl3): δ 5.93 (s, 1H), 4.33 (q, 2H, J = 7.4 Hz), 1.36 (t, 3H, J = 7.4 Hz);
1H NMR spectrum of the product was identical to that of the reference 3.
2,2-Dichloroacetoanilide (2j):
Synthesized accoriding to the general precedure A.
A yellow solid; M.p. 120―122 oC; IR (ATR, cm-1) : 3324, 2984, 1737, 1604, 1551; 1H NMR (400
MHz; CDCl3): δ 8.14 (brs, 1H), 7.56 (d, 2H, J = 7.8 Hz), 7.38 (t, 2H, J = 7.8 Hz), 7.21 (t, 1H, J =
7.8 Hz), 6.05 (s, 1H); 13C NMR (125 MHz; CDCl3): δ 161.9, 136.3, 129.4, 125.8, 120.3, 67.0;
HRMS (EI): calcd for C8H7NOCl2 [M+]: 202.9905; found: 202.9909.
2,2-Dichloro-N-octylacetoamide (2k):
Synthesized accoriding to the general precedure A.
obtained as mixture of 2k and byproducts. Main spectra of 2k were depicted. 1H NMR (500 MHz;
CDCl3): δ 6.57 (brs, 1H), 5.92 (s, 1H), 3.31 (m, 2H), 1.56 (m, 2H), 1.30―1.26 (m, 10H), 0.87 (m,
3H); 13C NMR (125 MHz; CDCl3): δ 164.2, 66.7, 40.5, 31.9, 29.3, 29.2, 27.0, 26.8, 22.7, 14.2;
HRMS (EI): calcd for C10H19NOCl2 [M+]: 239.0844; found: 239.0834.
2-(Dichloroacetyl)pyrrole (2l):
Synthesized accoriding to the general precedure A.
A red-brown solid; M.p. 90―92oC; IR (ATR, cm-1) : 3294, 3138, 3019, 2924, 1655, 1542; 1H NMR
(500 MHz; CDCl3): δ 9.46 (brs, 1 H), 7.19―7.18 (m, 2H), 6.48 (s, H), 6.39 (d, 1H, J = 4.0 Hz);
S5

13C NMR (100 MHz; CDCl3): δ 177.1, 127.6, 126.2, 119.1, 112.0, 67.4; HRMS (EI): calcd for
ACCEPTED MANUSCRIPT
C6H5NOCl2 [M+]: 176.9748; found: 176.9753.
3-(Dichloroacetyl)indole (2m):
Synthesized accoriding to the general precedure A.
obtained as mixture of 2m and byproducts. Main spectra of 2k were depicted. 1H NMR (500 MHz;
DMSO): δ 12.4 (brs, 1H), 8.61 (d, 1H, J = 3.0 Hz), 8.17 (d, 1H, J = 7.0 Hz), 7.61 (s, 1H), 7.54 (d,
13
1H, J = 7.0 Hz), 7.31―7.26 (m, 2H); C NMR (125 MHz; DMSO): δ 180.8, 136.9, 135.9, 125.7,
123.8, 122.8, 121.2, 112.7, 110.5, 68.7; HRMS (EI): calcd for C10H7NOCl2 [M+]: 226.9905; found:
226.9913.
1,1-Bis(p-methoxyphenyl)-2,2-dichloroethane (4a):
Synthesized accoriding to the general precedure B.
Colorless solid; M.p. 116―118 C; IR (ATR, cm-1): 2943, 2831; H NMR (500 MHz; CDCl3): δ
o
1
7.25 (d, 4H, J = 8.8 Hz), 6.86 (d, 4H, J = 8.8 Hz), 6.30 (d, 1H, J = 8.0 Hz), 4.49 (d, 1H, J = 8.0 Hz),
13
3.78 (s, 6H); C NMR (100 MHz; CDCl3): δ 158.9, 132.3, 129.6, 114.1, 75.4, 61.1, 55.4; HRMS
(EI): calcd for C16H16O2Cl2 [M+]: 310.0527; found: 310.0534.
α-(Dichloromethyl)-benzylacetate (4b):
Synthesized accoriding to the general precedure B.
A colorless oil; IR (ATR, cm-1) : 2924, 2852, 1747; 1H NMR (500 MHz; CDCl3): δ 7.44―7.43 (m,
2 H), 7.40―7.39 (m, 3H), 6.10 (d, 1H, J = 5.5 Hz), 5.90 (d, 1H, J = 5.5 Hz), 2.18 (s, 3H); 13C NMR
(125 MHz; CDCl3): δ 169.5, 134.7, 129.5, 128.6, 128.0, 78.1, 72.7, 21.0; HRMS (EI): calcd for
C10H10O2Cl2 [M+]: 232.0054; found: 232.0058.
2,2-Dichloro-1-phenylethanol (4c):
Synthesized accoriding to the general precedure B.
A colorless oil; IR (ATR, cm-1) : 3378, 3034, 2927, 2854, 1710, 1609; 1H NMR (500 MHz; CDCl3):
13
δ7.43―7.39 (m, 5H), 5.83 (d, 1H, J = 5.5 Hz), 4.99―4.98 (m, 1H), 2.95 (br, 1H); C NMR (125
MHz; CDCl3): δ 137.4, 129.2, 128.6, 127.2, 78.9, 76.5; HRMS (EI): calcd for C8H8OCl2 [M+]:
189.9952; found: 189.9941.
2,2-Dichloroethyl-N-phenyl carbamate (4d):
Synthesized accoriding to the general precedure B.
o
Colorless solid (M.p. 70―72 C); IR (ATR, cm-1) : 3330, 3061, 2957, 2854, 1711, 1600, 1532; 1H
NMR (500 MHz; CDCl3): δ 7.39 (m, 2H), 7.33 (d, 2H, J = 7.6 Hz), 7.11 (t, 1H, J = 7.6 Hz), 6.76
(brs, 1H), 5.90 (t, 1H, J = 6.2 Hz), 4.52 (d, 2H, J = 6.2 Hz); 13C NMR (125 MHz; CDCl3): δ 152.2,
137.2, 129.3, 124.2, 118.9, 69.0, 68.8; HRMS (EI): calcd for C9H9NO2Cl2 [M+]: 233.0010; found:
233.0020.
S6

2,2-Dichloroethyl-N-toluyl carbamate (4e):
ACCEPTED MANUSCRIPT
Synthesized accoriding to the general precedure B.
o
Colorless solid (M.p. 76－78 C); IR (ATR, cm-1) : 3331, 3042, 2946, 2921, 1706, 1597, 1534; 1H
NMR (500 MHz; CDCl3): δ 7.27 (d, 2H, J = 8.0 Hz), 7.13 (d, 2H, J = 8.0 Hz), 6.68 (brs, 1H), 5.90
13
(t, 1H, J = 5.8 Hz), 4.51 (d, 2H, J = 5.8 Hz), 2.32 (s, 3H); C NMR (125 MHz; CDCl3): δ 152.4,
134.6, 133.8, 129.8, 119.0, 68.9, 68.9, 20.9; MS (EI) m/z (%) [M+] 247 (40) 151 (20) 133 (32) 106
(100) 77 (33) 61 (16) 51 (7). HRMS (EI): calcd for C10H11NO2Cl2 [M+]: 247.0167; found:
247.0170.
2,2-Dichloroethyl-N-n-octanyl carbamate (4f):
Synthesized accoriding to the general precedure B.
A colorless oil; IR (ATR, cm-1) : 3335, 2925, 2855, 1705, 1527; H NMR (500 MHz; CDCl3): δ
1
5.83 (t, 1H, J = 5.5 Hz), 4.93 (s, 1H), 4.39 (d, 2H, J = 5.5 Hz), 3.19―3.15 (m, 2H), 1.50―1.48 (m,
2H), 1.28―1.26 (m, 10H), 0.86 (t, 3H, J = 7.0 Hz). 13C NMR (125 MHz; CDCl3): δ 155.1, 69.1,
68.6, 41.2, 31.7, 29.7, 29.1, 29.1, 26.6, 22.6, 14.0; HRMS (EI): calcd for C11H21NO2Cl2 [M+]:
269.0949; found: 269.0953.
Benzoic acid 2,2-dichloroethyl ester (4g):
Synthesized accoriding to the general precedure B.
A colorless oil; IR (ATR, cm-1) : 2955, 1725, 1602, 1584; H NMR (500 MHz; CDCl3): δ8.08 (d,
1
2H, J = 8.0 Hz), 7.61 (t, 1H, J = 7.0 Hz), 7.49―7.46 (m, 2H), 5.98 (t, 1H, J = 6.0 Hz), 4.69 (d, 2H,
J = 6.0 Hz). 13C NMR (125 MHz; CDCl3): δ 165.7, 133.8, 130.0, 129.1, 128.7, 68.8, 68.6; HRMS
(EI): calcd for C9H8O2Cl2 [M+]: 217.9901; found: 217.9899.
n-Heptanoic acid 2,2-dichloroethyl ester (4h):
Synthesized accoriding to the general precedure B.
Colorless oil; IR (ATR, cm-1) : 2956, 2927, 2857, 1744; 1H NMR (500 MHz; CDCl3): δ 5.83 (t, 1H,
J = 6.5 Hz), 4.43 (d, 2H, J = 6.5 Hz), 2.37 (t, 2H, J = 7.5 Hz), 1.67―1.61 (m, 2H), 1.31―1.27 (m,
13
8H), 0.87 (t, 3H, J = 6.8 Hz); C NMR (125 MHz; CDCl3): δ 173.0, 68.6, 68.2, 34.0, 31.8, 29.1,
29.0, 24.9, 22.7, 14.2; MS (EI) m/z (%) [M+], 240 (12) 211 (5) 197 (10) 169 (25) 156 (40) 127 (99)
105 (14) 96 (35) 73 (18) 60 (22). HRMS (EI): calcd for C10H18O2Cl2 [M+]: 240.0684; found:
240.0685.
4-n-Butylbenzoic acid 2,2-dichloroethyl ester (4i):
Synthesized accoriding to the general precedure B.
Colorless oil; IR (ATR, cm-1) : 2957, 2931, 2860, 1723, 1610; 1H NMR (500 MHz; CDCl3): δ 7.98
(d, 2H, J = 8.5 Hz), 7.27 (d, 2H, J = 8.5 Hz), 5.97 (t, 1H, J = 6.0 Hz), 4.67 (d, 2H, J = 6.0 Hz), 2.67
13
(t, 2H, J = 7.8 Hz), 1.63―1.58 (m, 2H), 1.38―1.33 (m, 2H), 0.93 (t, 3H, J = 7.5 Hz); C NMR
(125 MHz; CDCl3) : δ 165.8, 149.5, 130.1, 128.8, 126.5, 68.7, 68.7, 35.9, 33.4, 22.4, 14.0; MS (EI)
S7

m/z (%) [M+], 274 (15) 231 (23) 178 (29) 161 (99) 136 (33) 125 (6) 118 (12) 107 (9) 103 (6) 91
ACCEPTED MANUSCRIPT
(50) 77 (6). HRMS (EI): calcd for C13H16O2Cl2 [M+]: 274.0527; found: 274.0520.
6-Acetoxy-1,1-dichlorohexane (4j):
Synthesized accoriding to the general precedure B.
Colorless oil; IR (ATR, cm-1) : 2949, 2864, 1734; 1H NMR (500 MHz; CDCl3): δ 5.75 (t, 1H, J =
5.5 Hz), 4.07 (t, 2H, J = 6.5 Hz), 2.23-2.18 (m, 2H), 2.05 (s, 3H), 1.68―1.59 (m, 4H), 1.45-1.38 (m,
13
2H); C NMR (125 MHz; CDCl3) : δ 171.3, 73.5, 64.3, 43.5, 28.5, 25.7, 25.2, 21.2; HRMS (EI):
calcd for C8H14O2Cl2Na [M+Na]+: 235.0263; found: 235.0297.
Benzal chloride (6a):
Synthesized accoriding to the general precedure B.
1H NMR (500 MHz; CDCl3): δ 7.56 (d, 2H, J = 6.5 Hz), 7.41―7.37 (m, 3H), 6.70 (s, 1H)
1H NMR spectrum of the product was identical to that of the reference 4.
4-Chlorobenzaldehyde (10b):
Synthesized accoriding to the general precedure C.
1H NMR (500 MHz; CDCl3): δ 9.99 (s, 1H), 7.83 (d, 2H, J = 8.0 Hz), 7.53 (d, 2H, J = 8.0 Hz). 1H
NMR spectrum of the product was identical to that of the reference 5.
3,4-Dichlorobenzaldehyde (10c):
Synthesized accoriding to the general precedure C.
1H NMR (500 MHz; CDCl3): δ 9.95 (s, 1H), 7.97 (s, 1H), 7.73 (d, 1H, J = 8.0 Hz), 7.64 (d, 1H, J =
8.0 Hz). 1H NMR spectrum of the product was identical to that of the reference 6.
2,6-dichloro-4-dichloromethyl pyridine (6d):
Synthesized accoriding to the general precedure B.
Colorless oil; IR (ATR, cm-1) : 3082, 2957, 1582, 1547; 1H NMR (400 MHz; CDCl3): δ 7.46 (s, 2H),
6.57 (s, 1H); 13C NMR (100 MHz; CDCl3) : δ 153.1, 151.5, 120.4, 67.7; HRMS (EI): calcd for
C6H2NCl4 [M-H]-: 227.8947; found: 227.8957.
5. References.
[1] Y. Sawama, R. Nakatani, T. Imanishi, Y. Fujiwara, Y. Monguchi, H. Sajiki, RSC Adv. 2014, 4,
8657-8660.
[2] D. C. Harrowven, D. P. Curran, S. L. Kostiuk, I. L. Wallis-Guy, S. Whiting, K. J. Stenning, B.
Tang, E. Packarda and L. Nansona, Chem. Commun. 2010, 46, 6335–6337.
[3] S. K. Gupta, J. Org. Chem. 1973, 38, 4081-4082.
[4] G. Aghapour, A. Afzali, Synth. Commun. 2008, 38, 4023-4035.
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[5] B. Karimi, E. Farhangi, Chem. Eur. J. 2011, 17, 6056-6060.
ACCEPTED MANUSCRIPT
[6] P. J. Figiel, M. Leskelä, T. Repo, Adv. Synth. Catal. 2007, 349, 1173-1179.
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6. Spectra of newly synthesized compounds.
ACCEPTED MANUSCRIPT
O
CHCl2
2a
PPM
0
9
8
7
6
5
4
3
2
1
O
CHCl2
2a
PPM
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
S10

ACCEPTED MANUSCRIPT
O
CHCl2
MeO
2b
PPM
0.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
O
CHCl2
MeO
2b
PPM
200.0
190.0
180.0
170.0
160.0
150.0
140.0
130.0
120.0
110.0
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
S11

ACCEPTED MANUSCRIPT
O
CHCl2
OMe
2c
PPM
0
9
8
7
6
5
4
3
2
1
O
CHCl2
OMe
2c
PPM
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
S12

T.I- 4- 62Fr. 2H/ CDCl 3/ 400 MHz
ACCEPTED MANUSCRIPT
O
CHCl2
OMe
2d
PPM
0
9
8
7
6
5
4
3
2
1
O
CHCl2
OMe
2d
PPM
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
S13

ACCEPTED MANUSCRIPT
O
CHCl2
Cl
2e
PPM
0.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
O
CHCl2
Cl
2e
PPM
200.0
190.0
180.0
170.0
160.0
150.0
140.0
130.0
120.0
110.0
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
S14

ACCEPTED MANUSCRIPT
O
CHCl2
F3C
2f
PPM
0.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
O
CHCl2
F3C
2f
PPM
200.0
190.0
180.0
170.0
160.0
150.0
140.0
130.0
120.0
110.0
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
S15

ACCEPTED MANUSCRIPT
O
C8H17
CHCl2
2g
PPM
0
8
7
6
5
4
3
2
1
O
C8H17
CHCl2
2g
PPM
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
S16

ACCEPTED MANUSCRIPT
O
O
CHCl2
2h
PPM
0.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
O
O
CHCl2
2h
PPM
200.0
190.0
180.0
170.0
160.0
150.0
140.0
130.0
120.0
110.0
100.0
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
S17

ACCEPTED MANUSCRIPT
O
EtO
CHCl2
2i
PPM
0
9
8
7
6
5
4
3
2
1
O
N
CHCl2
H
2j
PPM
0
S18

ACCEPTED MANUSCRIPT
O
N
H
CHCl2
2j
PPM
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
O
C7H15
N
H
CHCl2
2k
PPM
0
9
8
7
6
5
4
3
2
1
S19

ACCEPTED MANUSCRIPT
O
C7H15
N
H
CHCl2
2k
PPM
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
O
N
H
CHCl2
2l
PPM
0
10
9
8
7
6
5
4
3
2
1
S20