Chemoselective Reduction of Trichloromethyl Compounds to gem-Dichloromethyl Groups Following Appel's Reaction Protocol

Article abstract of DOI:10.1021/acs.joc.6b02044

A simple and easy reduction of trichloroacetyl compounds following the modification of Appel's reaction protocol, using triphenylphosphine and methanol, afforded the corresponding dichloroacetyl compounds, with the exception of trichloroacetylmorpholine,

Full text of DOI:10.1021/acs.joc.6b02044

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Note
Chemoselective Reduction of Trichloromethyl Compounds to
gem-Dichloromethyl Groups Following Appel’s Reaction Protocol
Moises Abiram Romero-Reyes, Ivann Zaragoza-Galicia, Horacio F. Olivo, and MOISES ROMERO-ORTEGA
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02044 • Publication Date (Web): 13 Sep 2016
Downloaded from http://pubs.acs.org on September 13, 2016
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Chemoselective Reduction of Trichloromethyl Compounds to gem-
Dichloromethyl Groups Following Appel’s Reaction Protocol
a
a
b
Moises A. RomeroꢀReyes, Ivann ZaragozaꢀGalicia, Horacio F. Olivo, and Moises
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a
RomeroꢀOrtega *
a
Departamento de Quimica Organica, Facultad de Quimica, Universidad Autonoma del
Estado de Mexico, Paseo Colon/Paseo Tollocan, Toluca, Estado de Mexico, Mexico
b
Division of Medicinal and Natural Products Chemistry, The University of Iowa, Iowa City,
IA 52246
mromeroo@uaemex.mx
ABSTRACT: A simple and easy reduction of trichloroacetyl compounds following the
modification of Appel’s reaction protocol, using triphenylphosphine and methanol,
afforded the corresponding dichloroacetyl compounds, with the exception of
trichloroacetylmorpholine, in yields of 80ꢀ98% under very mild experimental conditions.
Likewise, when trichloromethyl heterocyclic compounds contain another reactive
functional group, the reaction is highly chemoselective giving the dichloromethyl
derivative.
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The gemꢀdichloromethyl group is an important structural framework present in a number of
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biologically active compounds such as antibiotics and diuretics. Additionally, some
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dichloromethyl derivatives are also found important within the agrochemical field and are
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wellꢀknown to be useful intermediates for the synthesis of heterocycles, α,βꢀunsaturated
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ketones, 1,4ꢀdiones, ynols and cyclopropanes. Likewise, they are widely used as
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synthetic precursors to afford the corresponding aldehydes under basic conditions as well
as precursors for gemꢀdiflouromethyl groups by the double nucleophilic substitution of the
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chlorides by fluoride ions.
General methods to prepare dichloromethyl compounds involve Lewis acidꢀcatalyzed
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acylation of arenes, oxyhalogenation of alkynes, and chlorination of ketones which
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implicates using different types of chlorine sources, such as sulfuryl chloride, thionyl
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chloride, Nꢀchlorosuccinimide, and 1,3ꢀdichloroꢀ5,5ꢀdimethylhydantoin (DCDMH).
However, few methods have been described to allow the formation of gemꢀdichloromethyl
compounds employing trichloromethyl derivatives as starting materials. In this context,
gemꢀdichloromethyl compounds can be directly synthesized by a monoꢀdechlorination
reaction of the corresponding trichloromethyl derivative via partial hydrogenation using a
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platinum on a carbonꢀcatalyzed system. Another attractive approach was demonstrated in
the seminal work of Hall and coꢀworkers, involves Grignard reagents as electron donors for
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2,2,2ꢀtrichloroꢀ1ꢀarylethanones
to
synthesize
substituted α,α−dichloroketones.
Unfortunately, these methods display limitations and disadvantages such as poor yields, use
of high temperatures, sideꢀproduct formation and low chemoselectivity. Therefore the
preparation of these compounds with a more efficient, simple, and general route is highly
desirable.
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In 2007, while our research group was developing the synthesis of 2ꢀsubstitutedꢀ1,3ꢀ
dithianes from trichloromethyl compounds, we observed that the reaction of
trichloroacetylpyrrole 1a with 5 equiv of 1,3ꢀpropanodithiol and 3 equiv of sodium hydride
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in dry THF at ꢀ40 ºC afforded a 71% yield of dichloroacetylpyrrole 2a. We envisioned
that this protocol could be applicable to the development of a convenient oneꢀpot procedure
for a direct conversion of trichloromethyl compounds into the dichloromethyl derivatives.
Scheme 1. Reduction of trichloroacetylpyrrole with thiophenolate.
We evaluated the reduction of trichloroacetyl compounds 1 in the presence of sulfur
nucleophiles, using the 2ꢀtrichloroacetylpyrrole 1a as a model. When 1a was reacted with
2
.0 equiv of sodium thiophenolate (generated from thiophenol and sodium hydride at room
temperature) in THF at ꢀ78 °C, after 10 min, a mixture of the dichloroacetylpyrrole 2a in
0% yield along with bis(phenylthio) compound 3a in 20% yield were obtained (Scheme
6
1). The latter compound is suggested to arise as a consequence of a substitution reaction of
dichloroacetylpyrrole 2a by the presence of the thiophenolate ion in the mixture reaction.
An improved yield of 2a (94%) was achieved employing 2.0 equiv of lithium thiophenolate
(generated from thiophenol and nꢀBuLi) at ꢀ78 °C and only traces of 3a was observed.
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However, the application of this reduction process to trichloroacetophenone 1c under the
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same conditions was less successful, affording dichloroacetophenone 2c in 40% yield
along with the respective dithioacetal 3c in 50% yield (Scheme 2). In fact, it is known that
the dechlorination activity is strongly influenced by the electronic environment of the
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substituents attached to the trichloromethyl group. Another setback of this methodology
was the poor chemoselectivity observed when trichloromethylpyrimidine 1m was treated
under similar conditions, giving the nucleophilic aromatic substitution product 4m as the
only isolable product in 86% yield which is possibly formed via a Meisenheimer
intermediate. Furthermore, the trichloroacetylmorpholine 1h did not react using the
previous reduction conditions even under long periods of time.
Scheme 2. Reduction process of trichloroacetyl compounds 1 with lithium
thiophenolate
O
O
O
PhS Li
SPh
CCl3
CHCl2
+
THF / -78 °C
SPh
3c 50%
1c
2c 40%
Ph
SPh
Ph
N
PhS Li
N
THF / -78 °C
Cl C
3
N
Cl C
3
N
Cl
1m
4m 86%
O
PhS Li
no reaction
N
CCl3
O
THF / -78 °C
1h
In view of these results, we decided to explore another alternative to carry out the
conversion of trichloromethyl compounds to gemꢀdichloromethyl derivatives. It is well
documented that the treatment of alcohols with Appel´s salt gives the corresponding halide,
2
1
usually in very good yields. The Appel´s salt can be formed by the reaction between one
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equivalent of triphenylphosphine and one equivalent of a tetrahalomethane such as CCl or
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CBr . Mechanistically, one equivalent of haloform is formed as byꢀproduct in this
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halogenation process. We reasoned that in this reaction, trichloromethyl compounds with
an electronꢀwithdrawing group 1 could be used instead of tetrahalomethanes to reduce
tricholoromethyl compounds to gemꢀdichloromethyl derivatives 2. Although, in 2011
Gilheany group reported the synthesis of pentachloroacetone in regular yield from
hexachloroacetone under Appel´s reaction conditions using 2ꢀnaphthol in toluene
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solution, to date no systematic work has been published employing substrates containing
other reactive functional group, to demonstrate chemoselective reactivity and the potential
use of this methodology to afford gemꢀdichloromethyl compounds from trichloromethyl
derivatives. To examine this alternative, we next studied the reactivity of trichloromethyl
compounds under Appel´s reaction conditions in order to see if the reduction process
occurs in these substrates. At the outset of our study, we used trichloroacetylpyrrole 1a as a
model to evaluate the reduction process in the presence of 2.0 equivalents of methanol with
different amounts of triphenylphosphine (Table 1).
a
Table 1. Optimization of reaction conditions
entry
PPh3
1a (%) 2a (%) 4a (%)
(mmol)
1
2
3
1.2
1.0
0
traces
0
80
89
94
10
0
1.05
0
a
Reaction conditions: 1a (1.0 equiv, 1 mmol), MeOH (2.0 equiv), DCM (5.0 mL) under N2
at 0 °C.
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When 1.2 equiv of triphenylphosphine were used, dichloroacetylpyrrole 2a was obtained in
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0% yield and chloroacetylpyrrole 4a in 10% yield (Table 1, entry 1). The amount of
triphenylphosphine was decreased to 1.0 equiv in an attempt to avoid the formation of the
overꢀreduced chloroacetylpyrrole 4a, affording dichloroacetylpyrrole 2a in 89% yield and
trace amount of starting material. An appreciable change in the yield was observed when a
slight excess of triphenylphosphine (1.05 equiv) was used (entry 3) to afford 2a in 94%
yield.
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With the optimized reaction conditions in hand, this methodology for the generation of
dichloromethyl derivatives 2 was extended. We first investigated the monodechlorination
reaction of the more reactive trichloroacetyl derivatives 1b-1g affording efficiently their
corresponding gemꢀdichloroacetyl products 2b-2g in high yields under short periods of time
(Table 2). In contrast, although the trichloroacetylmorpholine 1h was transformed into the
2
3
dichloroacetylmorpholine 2h in acceptable yield (68%), the reaction period was longer
(24 h). The distinct reactivity difference in time between 1h and the trichloroacetyl
compounds 1a-1g could be a result of the corresponding electronic properties of 1h which
is slightly more electron rich than 1a-1g.
a
Table 2. Synthesis of dichloroacetyl compounds
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a
Reaction conditions: 1a (1.0 equiv, 1 mmol), MeOH (2.0 equiv), PPh (1.05 equiv), DCM
3
(
5.0 mL) under N at 0 °C.
2
Lastly, this reduction process was extrapolated to other trichloromethyl compounds
containing other reactive functional groups such as 1j-1o. Such derivatives afforded a
highly chemoselective reduction as it is illustrated in dichloromethyl compounds 2j-2o
(Table 3). In each case, the corresponding dichloromethyl compound 2 was the exclusive
product affording high yields under moderate periods of time, along with no significant
nucleophilic displacement on Cꢀ4 or Cꢀ5 of the trichloromethylpyrimidines as when
sodium/lithium thiophenolate was employed.
Table 3. Synthesis of dichloromethyl heterocyclic compounds
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DCM (5.0 mL) under N at 0 °C.
2
In summary, we have reported an efficient and simple procedure to prepare gemꢀ
dichloromethyl compounds using Appel´s reaction conditions from trichloromethyl
derivatives. This dechlorinantion reaction is found to be highly chemoselective and is
expected to be particularly useful in those instances where the trichloromethyl compounds
are the usual precursors of dichloromethyl derivatives which are not affordable in good
yields by other routes.
EXPERIMENTAL SECTION
General
All moistureꢀsensitive reactions were carried out in ovenꢀdried glassware under argon
atmosphere. Reagents were used without any further purification. Nuclear Magnetic
1
Resonance (NMR) spectra were measured at 300 MHz. HꢀNMR chemical shifts (δ) are
reported in parts per million (ppm) relative to Me Si (δ = 0.0 ppm) with coupling constants
4
(
J) reported in Hertz (Hz). Multiplicities are reported as singlet (s), doublet (d), triplet (t),
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quartet (q), multiplet (m), broad singlet (bs). CꢀNMR signals are reported using 77.0 ppm
(
CDCl ) as internal reference.
3
The 2ꢀtrichloroacetylpyrrole 1a is commercially available, whereas the trichloromethyl
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compounds 1b-g, 1i-j and 1p-q were easily synthesized in good yields by literature
methods. The trichloroacetylmorpholine 1h was prepared from trichloroacetyl chloride and
morpholine.
General procedure for synthesis of gem-dichloromethyl compounds (2).
Under nitrogen atmosphere, to a solution of the respective trichloromethyl compound 1 (1.0
mmol, 1.0 equiv) and methanol (80.0 ꢀL, 2.0 mmol, 2.0 equiv) in anhydrous
dichloromethane (3.0 mL) at 0 °C, a solution of triphenylphosphine (275 mg, 1.05 mmol,
1.05 equiv) in anhydrous dichloromethane (1.5 mL) was added dropwise at 0 °C . The
reaction mixture was stirred for the time indicated in Tables 2 and 3. In the reactions that
were more than 10 min, the temperature was allowed to rise to room temperature. After
completion, the reaction was concentrated under vacuum. The desired dichloromethyl
product 2 was purified through flash column chromatography on silica gel and eluted with
hexaneꢀEtOAc mixtures.
1
7a
2-(Dichloroacetyl)pyrrol (2a).
This compound was purified by flash column
chromatography using hexanesꢀEtOAc (9:1) and obtained as a white solid (167 mg, 94%
1
yield); crystallization (hexanesꢀCH Cl ); mp 90ꢀ91 °C. H NMR (300 MHz, CDCl ): δ
2
2
3
1
0.05 (brs, 1H), 7.24ꢀ7.22 (m, 1H), 7.20ꢀ7.17 (m, 1H), 6.52 (s, 1H), 6.38 (td, J = 4.2, 2.5
13
Hz, 1H). C {1H} NMR (75 MHz, CDCl ): δ 177.0, 128.2, 126.0, 119.3, 111.8, 67.2.
3
+
HRMS (ESI+): calcd for C H Cl NO [M + H] 177.9826, found 177.9823.
6
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2
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17b
2
-(Dichloroacetyl)thiopene (2b).
This compound was purified by flash column
chromatography using hexanesꢀEtOAc (98:2) and obtained as pale yellow oil (177 mg,
1
91% yield). H NMR (300 MHz, CDCl ): δ 8.01 (dd, 1H, J = 3.9, 1.2 Hz), 7.81 (dd, 1H, J =
3
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.9, 1.2 Hz), 7.21 (dd, 1H, J = 4.9, 3.9 Hz), 6.51 (s, 1H). C {1H} NMR (75 MHz, CDCl ):
3
+
δ 179.7, 137.0, 136.4, 134.8, 128.6, 67.9. HRMS (ESI+): calcd for C H Cl OS [M + H]
6
5
2
1
94.9438, found 194.9435.
17a
Dichloroacetophenone (2c).
This compound was purified by flash column
chromatography using hexanesꢀEtOAc (98:2) and obtained as colorless oil (183 mg, 97%
1
yield). H NMR (300 MHz, CDCl ): δ 8.08 (d, 2H, J = 7.2 Hz), 7.65 (t, 1H, J = 7.5 Hz,),
3
1
3
7
.52 (t, 2H, J = 8.1 Hz), 6.70 (s, 1H). C {1H} NMR (75 MHz, CDCl ): δ 185.9, 134.5,
3
+
131.3, 129.7, 128.9, 67.7. HRMS (ESI+): calcd for C H Cl O [M + H] 188.9874, found
8
7
2
1
88.9874.
-Methoxy(dichloro)acetophenone (2d). This compound was purified by flash column
1
7a
3
chromatography using hexanesꢀEtOAc (9:1) and obtained as a yellow solid (195 mg, 89%
1
yield); crystallization (hexanesꢀCH Cl ); mp 37ꢀ39 °C. H NMR (300 MHz, CDCl ): δ 7.65
2
2
3
(
d, J = 7.8 Hz, 1H), 7.60 – 7.57 (m, 1H), 7.42 (t, 1H, J = 8.1Hz), 7.19 (dd, 1H, J = 8.1, 2.1
1
3
Hz), 6.69 (s, 1H), 3.87 (s, 3H). C {1H} NMR (75 MHz, CDCl ): δ 185.7, 159.9, 132.6,
3
+
1
29.8, 122.0, 121.1, 114.0, 67.7, 55.5. HRMS (ESI+): calcd for C H Cl O [M + H]
9 9 2 2
218.9979, found 218.9984.
1
7a
4
-Methoxy(dichloro)acetophenone (2e). This compound was purified by flash column
chromatography using hexanesꢀEtOAc (9:1) and obtained as pale yellow oil (191 mg, 87%
1
yield). H NMR (300 MHz, CDCl ): δ 8.08 (d, 2H, J = 9Hz), 6.98 (d, 2H, J = 9Hz), 6.65 (s,
3
13
1
6
H), 3.90 (s, 3H). C {1H} NMR (75 MHz, CDCl ): δ 184.6, 164.6, 132.2, 123.9, 114.2,
3
+
7.8, 55.6. HRMS (ESI+): calcd for C H Cl O [M + H] 218.9979, found 218.9974.
9
9
2
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-Bromo-2-methoxy(dichloro)acetophenone (2f) This compound was purified by flash
column chromatography using hexanesꢀEtOAc (9:1) and obtained as a white solid (250 mg,
1
84% yield); crystallization (hexanesꢀCH Cl ); mp 86ꢀ87 °C. H NMR (500 MHz, CDCl ):
2
2
3
10
11
12
13
14
15
16
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δ 7.90 (d, 1H, J = 2.5 Hz), 7.61 (dd, 1H, J = 8.9, 2.5 Hz), 7.01 (s, 1H), 6.88 (d, 1H, J = 8.9
1
3
Hz), 3.94 (s, 3H). C {1H} NMR (125 MHz, CDCl ): δ 186.5, 157.3, 137.7, 134.6, 124.4,
3
+
1
13.8, 113.7, 70.6, 56.3. HRMS (ESI+): calcd for C H BrCl O [M + H] 298.9064, found
9
8
2
2
2
98.9072.
2-Nitro(dichloro)acetophenone (2g). This compound was purified by flash column
chromatography using hexanesꢀEtOAc (9:1) and obtained as an pale yellow solid (197 mg,
1
8
4% yield); crystallization (hexanesꢀCH Cl ); mp 83ꢀ84 °C. H NMR (300 MHz, CDCl ): δ
2
2
3
8.28 (dd, 1H, J = 8.4, 1.2 Hz), 7.85 (dt, 1H, J = 7.5, 1.2 Hz), 7.75 (td, 1H, J = 8.4, 1.5 Hz),
13
7
1
.62 (dd, 1H, J = 7.5, 1.5 Hz), 6.38 (s, 1H). C {1H} NMR (75 MHz, CDCl ): δ 189.5,
3
45.3, 135.0, 132.6, 131.7, 123.0, 124.4, 69.6. HRMS (ESI+): calcd for C H Cl NO [M +
8
6
2
3
+
H] 233.9724, found 233.9723.
23
Dichloroacetylmorpholine (2h).
This compound was purified by flash column
chromatography using hexanesꢀEtOAc (95:5) and obtained as a white solid (135 mg, 68%
1
yield); crystallization (hexanesꢀCH Cl ); mp 64ꢀ65 °C. H NMR (300 MHz, CDCl ): δ 6.21
2
2
3
13
(
s, 1H), 3.76 – 3.72 (m, 6H), 3.67 – 3.64 (m, 2H). C {1H} NMR (75 MHz, CDCl ): δ
3
+
162.1, 66.5, 66.1, 65.4, 46.9, 43.3. HRMS (ESI+): calcd for C H Cl NO [M + H]
6
10
2
2
1
98.0088, found 198.0087.
-N,N-Dimethylamino-4-(dichloromethyl)-1,3,5-triazine (2i). This compound was purified
2
by flash column chromatography using hexanesꢀEtOAc (95:5) and obtained as pale yellow
1
oil (195 mg, 94% yield). H NMR (300 MHz, CDCl ): δ 8.63 (s, 1H), 6.37 (s, 1H), 3.24 (d,
3
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J = 1.5 Hz, 6H). C {1H} NMR (75 MHz, CDCl ): δ 172.0, 166.6, 164.3, 70.3, 36.5, 36.3.
3
+
HRMS (ESI+): calcd for C H Cl N [M + H] 207.0204, found 207.0203.
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9
2
4
2
6
Dimethyl 2-(dichloromethyl)pyrimidine-4,5-dicarboxylate (2j). This compound was
0
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purified by flash column chromatography using hexanesꢀEtOAc (95:5) and obtained as a
1
colorless oil (274 mg, 98% yield). H NMR (300 MHz, CDCl ): δ 9.37 (s, 1H), 6.81 (s,
3
1
3
1
H), 4.05 (s, 3H), 4.00 (s, 3H). C {1H} NMR (75 MHz, CDCl ): δ 167.4, 164.3, 162.6,
3
+
1
60.3, 159.4, 121.4, 69.6, 53.6, 53.4. HRMS (ESI+): calcd for C H Cl N O [M + H]
9
9
2
2
4
278.9939, found 278.9945.
4
-Chloro-2-(dichloromethyl)pyrimidine (2k). This compound was purified by flash
column chromatography with hexanesꢀEtOAc (95:5) and obtained as a white solid (174 mg,
1
88% yield); crystallization (hexanesꢀCH Cl ); mp 66ꢀ68°C. H NMR (300 MHz, CDCl ): δ
2
2
3
13
8
.74 (d, 1H, J = 5.4 Hz), 7.40 (d, 1H, J = 5.4 Hz), 6.72 (s, 1H). C {1H} NMR (75 MHz,
+
CDCl ): δ 165.9, 162.1, 159.0, 121.8, 69.8. HRMS (ESI+): calcd for C H Cl N [M + H]
3
5
4
3
2
196.9440, found 196.9437.
4
-Chloro-2-(dichloromethyl)-5-methylpyrimidine (2l). This compound was purified by
flash column chromatography using hexanesꢀEtOAc (98:2) and obtained as a colorless oil
1
(
148 mg, 70% yield). H NMR (500 MHz, CDCl ): δ 8.61 (d, J = 0.5 Hz, 1H), 6.71 (s,
3
13
1
H), 2.42 (d, J = 0.5 Hz, 3H). C {1H} NMR (75 MHz, CDCl ): δ 163.5, 161.7, 158.8,
3
+
130.7, 69.8, 16.3. HRMS (ESI+): calcd for C H Cl N [M + H] 210.9596, found 210.9596.
6
6
3
2
4
-Chloro-2-(dichloromethyl)-5-phenylpyrimidine (2m) This compound was purified by
flash column chromatography using hexanesꢀEtOAc (98:2) and obtained as a white solid
1
(225 mg, 82% yield); crystallization (hexanesꢀCH Cl ); mp 82ꢀ84 °C. H NMR (500 MHz,
2
2
13
CDCl ) δ 8.73 (s, 1H), 7.53 – 7.51 (m, 3H), 7.50 – 7.47 (m, 2H), 6.77 (s, 1H). C {1H}
3
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NMR (75 MHz, CDCl ): δ 164.1, 159.9, 159.0, 134.6, 132.7, 129.5, 129.2, 128.8, 69.7.
3
+
HRMS (ESI+): calcd for C H Cl N [M + H] 272.9753, found 272.9764.
11
7
3
2
4,5-Dichloro-6-methyl-2-(dichloromethyl)pyrimidine (2n). This compound was purified
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by flash column chromatography using hexanesꢀEtOAc (99:1) and obtained as a white solid
1
(
172 mg, 70% yield); crystallization (hexanesꢀCH Cl ); mp 52ꢀ53 °C. H NMR (300 MHz,
2
2
1
3
CDCl ): δ 6.65 (s, 1H), 2.72 (s, 3H). C {1H} NMR (125 MHz, CDCl ): δ 168.0, 161.8,
3
3
+
1
59.2, 129.2, 69.4, 23.3. HRMS (ESI+): calcd for C H Cl N [M + H] 244.9206, found
6
5
4
2
244.9212.
5
-Bromo-4-chloro-2-(dichloromethyl)pyrimidine (2o). This compound was purified by
flash column chromatography using hexanesꢀEtOAc (96:4) and obtained as colorless oil
1
13
(224 mg, 81% yield). H NMR (300 MHz, CDCl ): δ 8.89 (s, 1H), 6.69 (s, 1H). C {1H}
3
NMR (75 MHz, CDCl ): δ 163.9, 161.1, 160.6, 120.5, 69.2. HRMS (ESI+): calcd for
3
+
C H BrCl N [M + H] 276.8524, found 276.8524.
5
3
3
2
2-(Dichloromethyl)quinazoline (2p). This compound was purified by flash column
chromatography with hexanesꢀEtOAc (95:5) and obtained as a white solid (181 mg, 85%
1
yield); crystallization (hexanesꢀCH Cl ); mp 124ꢀ125°C. H NMR (300 MHz, CDCl ): δ
2
2
3
1
3
9
.53 (s, 1H), 8.10 – 7.99 (m, 3H), 7.77ꢀ 7.75 (m, 1H), 6.95 (s, 1H). C {1H} NMR (125
MHz, CDCl ): δ 162.0, 161.3, 149.6, 135.0, 129.1, 128.7, 127.2, 124.1, 71.4. HRMS
3
+
(ESI+): calcd for C H Cl N [M + H] 212.9986, found 212.9983.
9
7
2
2
2
-(Dichloromethyl)-4-methylquinazoline (2q). This compound was purified by flash
column chromatography with hexanesꢀEtOAc (95:5) and obtained as a white solid (182 mg,
1
80% yield); crystallization (hexanesꢀCH Cl ); mp 138ꢀ141°C. H NMR (300 MHz, CDCl ):
2
2
3
δ 8.14 (d, 1H, J = 8.1 Hz), 8.07 (d, 1H, J = 8.4 Hz), 7.97 – 7.90 (m, 1H), 7.73 – 7.68 (m,
1
3
1
H), 6.89 (s, 1H), 3.03 (s, 3H). C {1H} NMR (125 MHz, CDCl ): δ 170.5, 160.5, 149.2,
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34.3, 129.3, 128.6, 125.1, 123.6, 71.7, 21.9. HRMS (ESI+): calcd for C H Cl N [M +
10
9
2
2
+
H] 227.0142, found 227.0142.
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AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: mromeroo@uaemex.mx
Notes
The authors declare no competing financial interest.
Acknowledgments
The Consejo Nacional de Ciencia y Tecnologia is gratefully acknowledged for a
postdoctoral fellowship to Ivann Zaragoza (CONACyTꢀ231282). The authors wish to
thank M. Sc. Maria de las Nieves Zavala Segovia (CCIQS UNAMꢀUAEM) for obtaining
NMR spectra and to Prof. Joseph M. Muchowski (UNAM) for helpful discussions and
interests in our work.
Supporting Information
The Supporting Information is available free of charge on the ACS Publications
website at DOI:
1
13
Copies of H NMR and C NMR spectra for all products (PDF).
REFERENCES
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) a) Dolbier,W. R., Jr.; Duan, J.ꢀX.; Rong, X. X. J. Fluorine Chem. 2007, 128, 1091ꢀ
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