Synthesis of Novel 3-Aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines

Article abstract of DOI:10.1002/jhet.3558

The first synthetic approach to hitherto unknown 3-aryl-5-dichloromethyl-Δ²-1,2,4-oxadiazolines, of synthetic and biological interest, has been developed involving high-yield reactions between N-(2,2-dichlorovinyl)benzimidoyl chlorides and hydr

Full text of DOI:10.1002/jhet.3558

Month 2019
Antonio Guirado,
Synthesis of Novel 3-Aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines
a
José A. Sandoval,a Enrique Alarcón,a María Vera,a Delia Bautista,a and Jesús Gálvezb
*
aDepartamento de Química Orgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo, 3100 Murcia,
Spain
bDepartamento de Química Física, Facultad de Química, Universidad de Murcia, Campus de Espinardo, 3100 Murcia,
Spain
*E-mail: anguir@um.es
Received October 9, 2018
DOI 10.1002/jhet.3558
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
The first synthetic approach to hitherto unknown 3-aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines, of syn-
thetic and biological interest, has been developed involving high-yield reactions between N-(2,2-
dichlorovinyl)benzimidoyl chlorides and hydroxylamine. The molecular structure of one member of this
new family of compounds—5-dichloromethyl-3-(4-fluorophenyl)-1,2,4-oxadiazoline—has been determined
by X-ray crystallography. Density functional theory calculations supporting the proposed reaction pathway
for the formation of these products have been carried out.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
types of bioactive compounds such as cytochrome P-450
inhibitors [36], antibiotics [37], diuretics [38], analgesics
[39], anticancer [40] agents, and herbicidal [41] agents.
Therefore, the research of effective methods to
incorporate dichloromethyl groups into organic molecules
is a subject that has attracted attention and is still
receiving successful effort [39,42–44].
Given the high interest in expanding the range of
oxadiazolines available, and to complete a main issue of
our research project on the synthesis of heterocyclic
compounds through chloral derivatives, we report here
the first synthesis of 3-aryl-5-dichloromethyl-Δ2-1,2,4-
oxadiazolines 6 (Scheme 4). The preparation of these
hitherto unknown compounds is in itself highly
significant in order to encourage the development of
future plausible biological studies, but so too is the
presence in these products of a dichloromethyl functional
group. It should be noted that it shows a versatile
reactivity [45,46], which is able to undergo a variety of
transformations via nucleophilic attack [47], as well as
elimination [48], coupling [49], and exchange [50]
The chemistry, properties, and applications of
heterocyclic compounds comprising a 1,2,4-oxadiazole
ring have been thoroughly reviewed [1–15], showing that
this nucleus confers a wide variety of biological and
pharmacological activities. Regarding oxadiazolines, 4,5-
dihydro-1,2,4-oxadiazoles (Δ2-1,2,4-oxadiazolines) are
distinguished as substances of significant synthetic [5,16–
19] and biological [20–26] interest. For example, they
have been reported to possess antifungal [20,22,23,25],
antitumor [24], anti-HIV [26], antidiabetic [21], and anti-
inflammatory [27] properties. Therefore, the synthesis of
these substances has received considerable attention. The
oldest preparative method is by Tiemann [28], who
discovered that aldehydes react with amidoximes to give
Δ2-1,2,4-oxadiazolines (Scheme 1a). Over the years, the
earlier preparative method and some procedures
developed from it have been exploited to prepare many
of these compounds [5,16,21,27,29–32]. 1,3-Dipolar
cycloadditions between nitrile oxides and imines
[16,17,19,21,33,34] (Scheme 1b) have proved to be
highly useful. Conversions of 1,2,4-oxadiazoles to Δ2-
1,2,4-oxadiazolines have also been reported (Scheme 1c
[31]; Scheme 1d [35]).
processes. Therefore, compounds
6 could have a
significant synthetic impact, making access to a variety of
oxadiazoline and oxadiazole derivatives feasible.
In a recent work, we significantly improved the
It should also be pointed out that a dichloromethyl group
is an important structural framework present in different
synthesis
of
N-(1,2,2,2-tetrachloroethyl)benzimidoyl
chlorides 3 by treatment of chloralamides 2 with a
© 2019 Wiley Periodicals, Inc.

A. Guirado, J. A. Sandoval, E. Alarcón, M. Vera, D. Bautista, and J. Gálvez
Vol 000
Scheme 1. Preparative methods of Δ2-1,2,4-oxadiazolines.
Scheme 3. Reaction of N-(1,2,2,2-tetrachloroethyl)benzimidoyl chlorides
3 with hydroxylamine.
Scheme 4. Synthesis of 3-Aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines
6.
phosphorus pentachloride/phosphorus oxychloride mixture
(Scheme 2). Compounds 3 were then successfully used as
dielectrophilic agents to react with hydrazine, resulting in
a highly convenient new approach to 3-aryl-1,2,4-
triazoles [51]. These results suggested a straightforward
preparation of the still unavailable products 6 through
compounds 3 to react with hydroxylamine, but this
strategy was unsuccessful. Fortunately, an alternative
route involving N-(2,2-dichlorovinyl)benzamides 9 gave
satisfactory results (Scheme 4).
In order to check this strategy, N-(1,2,2,2-
tetrachloroethyl)-4-chlorobenzimidoyl
chloride
3d
RESULTS AND DISCUSSION
(Ar = 4-Cl-C6H4) was taken as a model compound.
However, when it was subjected to hydroxylamine
treatment, and formation of the expected products, 4d
In the search for an effective synthetic method of
compounds 6, we first attempted an approach involving
intermediates 3. On this basis, and taking into
consideration that an imidoyl halide function is capable
of reacting with hydroxylamine, providing hydroxamic
acid derivatives [52], one might reasonably expect that
reactions of compounds 3 with hydroxylamine could lead
to N0-hydroxy-N-(1,2,2,2-tetrachloroethyl)benzamidines
4, whose two active centers of opposite polarity could
internally react to give 5-trichloromethyl-1,2,4-
oxadiazolines 5 (Scheme 3). Finally, electroreduction of
products 5 in the presence of a proton donor [53] would
provide the targeted oxadiazolines 6.
or 5d, did not take place. Instead,
undescribed
a previously
substance—4-chloro-N0-hydroxy-N-(2,2,2-
trichloro-1-(hydroxyamino)ethyl)benzamidine 7d—was
obtained, whose formation clearly corresponds to a
indiscriminate double attack on the part of hydroxylamine
at both electrophilic sites of 3d. When an experiment
between equimolar amounts of reactants, but with the
slow addition of a solution of hydroxylamine to a
solution of 3d, was carried out, the exclusive formation
of 7d (accompanied by unaltered 3d) instead product 4d
or 5d was observed, even though the reaction occurred at
a high concentration of 3d versus hydroxylamine. This
result clearly showed that preparation of the targeted
products 6 was unfeasible.
Scheme 2. Synthesis of N-(1,2,2,2-tetrachloroethyl)benzimidoyl
chlorides 3 through chloralamides 2.
Though unfavorable, the aforementioned results were
helpful in overcoming the synthetic adversity found.
Hence, we considered that N-(2,2-dichlorovinyl)
benzimidoyl chlorides 10 exhibit only one potentially
active electrophilic center able to react directly with
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthetic approach to 3-aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines by a se-
quence of chemical and electrochemical reactions
Figure 1. X-ray crystal structure of compound 6c (thermal ellipsoids drawn at the 50% probability level). [Color figure can be viewed at
wileyonlinelibrary.com]
hydroxylamine. However, they also contain another
masked electrophilic function, which could be liberated
after the total consumption of hydroxylamine during the
generation of the corresponding intermediates 11.
Therefore, we focused our attention on exploiting the
reaction sequence displayed in Scheme 4. This synthetic
approach involves effective conversions of chloralamides
2 to N-(1,2,2,2-tetrachloroethyl)benzamides 8 followed by
electrochemical reduction to give N-(2,2-dichlorovinyl)
benzamides 9 [54]. Efficient and easy chlorination of
compounds 9 would provide intermediates 10.
CONCLUSIONS
Novel 3-aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines
of biological and preparative interest have been
synthesized using a proficient and general new method
involving N-(2,2-dichlorovinyl)benzimidoyl chlorides to
react with hydroxylamine. Versatility, good yields, easy
availability of starting materials, mildness, and a simple
experimental procedure are noteworthy advantages of this
approach, which allows a privileged access to previously
unattainable products. A plausible reaction pathway has
been proposed, supported by density functional theory
computational calculations. The development of
syntheses for some other classes of heterocycles by
applying a similar strategy also appears feasible.
As expected, compounds 10 were found to be crucial
to circumvent the double nucleophilic attack on the
part of hydroxylamine, given that these reactions
directly led to the compounds 6 being sought out. The
formation of these products can be explained by a first
reaction with hydroxylamine to produce N-(2,2-
dichlorovinyl)-N0-hydroxybenzamidines
11,
whose
EXPERIMENTAL
isomerization could provide N-(2,2-dichloroethylidene)-
N0-hydroxybenzamidine intermediates 12 able to undergo
intramolecular additions to give the final products 6.
Complementary support for this plausible reaction
pathway was obtained with computational theoretical
calculations [55] of the relative stabilities of isomers 11a,
12a, and 6a (as regards compound 12a), which were
determined at the B3LYP/6-316(d) level of theory, with
the result that 11a and 12a are very close in energy
(ΔE = +1.4 kcal molꢀ1), whereas 6a is considerably more
stable than 12a (ΔE = ꢀ14.4 kcal molꢀ1).
General. NMR spectra were determined at 25°C on
Bruker AV-200, Bruker AV-300, or Bruker AV-400
(Bruker Corp., Billerica, MA) with tetramethylsilane as
internal reference. High-resolution mass spectra (HRMS)
were obtained using an Agilent TOF 6220 time-of-flight
instrument (Agilent Technologies, Santa Clara, CA)
equipped
with
electrospray
ionization
(ESI).
Microanalyses were performed on a Carlo Erba (Milan,
Italy) EA 1108 analyzer. IR spectra were recorded on a
Nicolet Impact 400 Spectrometer (Thermo Fisher,
Madison, MI). Melting points were determined on a
Büchi (Essen, Germany) Melting point B-540 and are
uncorrected. Compounds 2, 8, and 9 were prepared in
high yields as previously reported in detail [54]. Chloral
hydrate, benzamides, and hydroxylamine were purchased
from Sigma-Aldrich Corp. (St. Louis, MO) and were
used directly without purification.
General procedure for the synthesis of compounds 6. To
hydroxylamine hydrochloride (0.09 mol) in triethylamine
(15 mL), a solution of the corresponding N-(2,2-
dichlorovinyl)benzimidoyl chloride 10 (0.015 mol) in dry
tetrahydrofuran (30 mL) was added dropwise. The
reaction mixture was stirred at r.t. under nitrogen
Key intermediates in this new synthetic approach are
N-(2,2-dichlorovinyl)benzamides 9, which were easily
available in near quantitative yields through our improved
preparative method involving the electrochemical
reduction [54] of N-(1,2,2,2-tetrachloroethyl)benzamides
8. Intermediates 9 were efficiently converted to N-(2,2-
dichlorovinyl)benzimidoyl chlorides [56,57] 10 (91–
95%), which reacted with hydroxylamine directly to
provide 3-aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines 6
in good to high yields of 75% to 85%.
Structural features of this class of compounds were
obtained by single-crystal X-ray diffraction analysis of 6c.
Figure 1 shows a view of the structure determined.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Guirado, J. A. Sandoval, E. Alarcón, M. Vera, D. Bautista, and J. Gálvez
Vol 000
atmosphere for 5 h. The solvent was then removed under
reduced pressure, leaving a residue, which was washed
with water (50 mL). The solid precipitate was collected by
filtration, dried, and crystallized from petroleum ether or
hexane.
refined anisotropically against F2 (program SHELXTL)
[58]. The hydrogen atoms were refined using a riding
model and the NH as free. The final wR2 value was
0.0940 for all reflections and 140 parameters, with R1
0.0344 for reflections with I > 2 s(I); max. Dr
0.815 e Åꢀ3, S 1.055. Complete crystallographic data
(excluding structure factors) have been deposited at the
Cambridge Crystallographic Data Centre under the
number CCDC 1573712. Copies of the data can be
obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44
(0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
5-Dichloromethyl-3-phenyl-1,2,4-oxadiazoline (6a).
Pale
yellow powder (pet ether), yield 82%, mp 102–105°C; ir
(potassium bromide): 3151, 1604, 1510, 1468, 1400,
1339, 1303, 1205, 1126, 1093, 846, 777, 766, 692 cmꢀ1
;
1H NMR δ (CDCl3, 200 MHz): 5.63 (d, 1H, J = 4.2 Hz),
5.66 (br s, 1H), 5.92 (t, 1H, J = 3.2 Hz), 7.41–7.49 (m,
3H), 7.70 (d, 2H, J = 7.0 Hz); 13C NMR δ (CDCl3,
50.4 MHz): 72.11, 93.94, 123.95, 126.67, 128.82,
131.42, 155.30; HRMS (ESI) m/z: (M + H)+: calcd for
C9H9Cl2N2O 231.0086, found 231.0093. Anal. Calcd for
C9H8Cl2N2O: C, 46.78; H, 3.49; N, 12.12. Found: C,
5-Dichloromethyl-3-(4-chlorophenyl)-1,2,4-oxadiazoline
(6d). Brown powder (pet ether), yield 75%, mp 117–
120°C; ir (potassium bromide): 3138, 1597, 1440, 1400,
1354, 1283, 1208, 1109, 1091, 1015, 920, 846, 828, 786,
762, 716, 470 cmꢀ1 1H NMR δ (CDCl3, 400 MHz):
;
46.84; H, 3.53; N, 12.17.
5-Dichloromethyl-3-(4-methylphenyl)-1,2,4-oxadiazoline
(6b). Beige powder (hexane), yield 80%, mp 115–118°C;
5.59 (br s, 1H), 5.66 (d, 1H, J = 4.4 Hz), 5.93 (t, 1H,
J = 4.0 Hz), 7.26 (d, 2H, J = 8.0 Hz), 7.62 (d, 2H,
J = 8.0 Hz); 13C NMR δ (CDCl3, 100.8 MHz): 72.09,
94.14, 122.49, 128.01, 129.16, 137.52, 154.61; HRMS
(ESI) m/z: (M + H)+: calcd for C9H8Cl3N2O 264.9697,
found 264.9689. Anal. Calcd for C9H7Cl3N2O: C, 40.71;
H, 2.66; N, 10.55. Found: C, 40.57; H, 2.68; N, 10.63.
5-Dichloromethyl-3-(2-methylphenyl)-1,2,4-oxadiazoline
(6e). Brown powder (pet ether), yield 80%, mp 89–91°C;
ir (potassium bromide): 3151, 1663, 1607, 1592, 1502,
ir (potassium bromide): 3363, 1644, 1609, 1524, 1456,
1368, 1298, 1105, 848, 823, 759, 714, 697, 657 cmꢀ1; 1H
NMR δ (CDCl3, 400 MHz): 2.39 (s, 3H), 5.55 (br s, 1H),
5.62 (d, 1H, J = 4.8 Hz), 5.89 (t, 1H, J = 4.0 Hz), 7.23 (d,
2H, J = 8.0 Hz), 7.58 (d, 2H, J = 8.0 Hz); 13C NMR δ
(CDCl3, 100.8 MHz): 21.48, 72.16, 93.87, 121.09,
126.60, 129.52, 141.89, 155.24; HRMS (ESI) m/z:
(M + H)+: calcd for C10H11Cl2N2O 245.0243, found
245.0245. Anal. Calcd for C10H10Cl2N2O: C, 49.00; H,
4.11; N, 11.43. Found: C, 49.18; H, 4.06; N, 11.49.
1445, 1400, 1345, 1302, 1230, 1199, 1141, 1113, 965,
874, 864, 843, 764, 604, 569, 545, 508, 479, 446 cmꢀ1
;
5-Dichloromethyl-3-(4-fluorophenyl)-1,2,4-oxadiazoline
(6c). Orange powder (pet ether), yield 84%, mp 82–85°C;
1H NMR δ (CDCl3, 300 MHz): 2.49 (s, 3H), 5.40 (br s,
1H), 5.62 (br s, 1H), 5.87 (br s, 1H), 7.22–7.49 (m, 4H);
13C NMR δ (CDCl3, 75.4 MHz): 21.22, 72.21, 93.18,
123.35, 125.97, 128.64, 130.80, 131.37, 138.11, 155.32;
HRMS (ESI) m/z: (M + H)+: calcd for C10H11Cl2N2O
245.0243, found 245.0248. Anal. Calcd for
C10H10Cl2N2O: C, 49.00; H, 4.11; N, 11.43. Found: C,
ir (potassium bromide): 3139, 1654, 1608, 1573, 1523,
1461, 1400, 1242, 1162, 1117, 926, 848, 790, 608,
1
518 cmꢀ1; H NMR δ (CDCl3, 300 MHz); 5.63 (d, 1H,
J = 4.5 Hz), 5.76 (br s, 1H), 5.92 (t, 1H, J = 3.6 Hz), 7.10
(t, 2H, J = 8.4 Hz), 7.69 (dd, 2H, J = 5.1 Hz, J = 3.3 Hz);
13C NMR δ (CDCl3, 75.4 MHz): 72.09, 94.03, 116.07 (d,
J = 22.16 Hz), 120.23 (d, J = 3.24 Hz), 128.90 (d,
J = 8.75 Hz), 154.61, 162.78 HRMS (ESI) m/z:
(M + H)+: calcd for C9H8Cl2FN2O 248.9992, found
248.9989. Anal. Calcd for C9H7Cl2FN2O: C, 43.40; H,
2.83; N, 11.25. Found: C, 43.56; H, 2.78; N, 11.33.
48.88; H, 4.16; N, 11.38.
5-Dichloromethyl-3-(4-methoxyphenyl)-1,2,4-oxadiazoline
(6f). Pale orange powder (hexane), yield 85%; mp 108–
111°C; ir (potassium bromide): 3357, 3137, 1609, 1524,
1461, 1440, 1400, 1296, 1259, 1182,1027, 837, 762,
1
696, 656, 618, 592, 520, 463 cmꢀ1; H NMR δ (CDCl3,
400 MHz): 3.82 (s, 3H), 5.60 (d, 1H, J = 4 Hz), 5.61 (br
s, 1H), 5.86 (d, 1H, J = 3.6 Hz), 6.89 (d, 1H,
J = 8.4 Hz), 7.61 (d, 2H, J = 8.4 Hz); 13C NMR δ
(CDCl3, 100.8 MHz): 55.38, 72.22, 93.81, 114.25,
116.18, 128.37, 155.06, 162.02; HRMS (ESI) m/z:
(M + H)+: calcd for C10H11Cl2N2O2 261.0192, found
261.0199. Anal. Calcd for C10H10Cl2N2O2: C, 46.00; H,
3.86; N, 10.73. Found: C, 46.22; H, 3.91; N, 10.75.
General procedure for the synthesis of compounds 10.
To a suspension of N-(2,2-dichlorovinyl)benzamide 9
(0.05 mol) in dry toluene (55 mL), phosphorus
pentachloride (0.053 mol) was added in small portions.
Crystal data: C9H7Cl2FN2O, Mr = 249.07, triclinic,
space group P21/n, a = 12.6252(7), b = 4.9144(3),
c = 16.3239(9) Å, b = 94.334(2), V = 1009.92(10) Å3 at
100(2) K; Z = 4, Dx = 1.638 g cmꢀ3, F(000) = 504,
m = 0.629 mmꢀ1. Data collection: A colorless lath
measuring 0.03 × 0.12 × 0.35 mm was mounted in inert
oil on a glass fiber and transferred to the cold gas stream
of the diffractometer (Bruker D8 QUEST). Measurements
were performed to 2qmax 61.22° with monochromated
Mo-Kα radiation. Of 33,059 measured reflections, 3114
were unique (Rint = 0.0434) and were used for all
calculations. Structure refinement: The structures were
Journal of Heterocyclic Chemistry
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Month 2019
Synthetic approach to 3-aryl-5-dichloromethyl-Δ2-1,2,4-oxadiazolines by a se-
quence of chemical and electrochemical reactions
The mixture was stirred at 45°C for 2 h. The suspension
turned to total dissolution while gaseous hydrogen
chloride was expelled. The solvent was then removed
under reduced pressure, leaving a solid residue (oil for
10c), which was crystallized from petroleum ether.
N-(2,2-Dichlorovinyl)-2-methylbenzimidoyl chloride (10e).
Pale yellow oil, yield 95%; ir (neat): 1626, 1456, 1282,
1228, 1128, 1113, 943, 890, 780, 762, 716, 657, 620,
1
582 cmꢀ1; H NMR δ (CDCl3, 300 MHz): 2.59 (s, 3H),
7.24–7.35 (m, 3H), 7.52 (s, 1H), 7.83 (d, 1H,
J = 8.0 Hz); 13C NMR δ (CDCl3, 75.4 MHz): 22.25,
125.88, 126.74, 130.81, 130.93, 131.57, 132.64, 135.16,
138.52, 144.06; MS (EI) m/z (%): 247 (M+, 17), 249
(M++2, 17), 212 (M+-Cl, 100), 214 (71), 177 (21), 116
(24), 89 (16). Anal. Calcd for C10H8Cl3N: C, 48.33; H,
3.24; N, 5.64. Found: C, 48.01; H, 3.18; N, 5.64.
N-(2,2-Dichlorovinyl)benzimidoyl chloride (10a).
White
needless (peth ether), yield 92%, mp 42–43°C (lit. [56],
mp 41–43°C); ir (potassium bromide): 1620, 1446, 1288,
1233, 1127, 943, 890, 852, 763, 682, 665, 610,
1
559 cmꢀ1; H NMR δ (CDCl3, 300 MHz): 7.41–7.53 (m,
4H), 8.13 (d, 2H, J = 7.2 Hz); 13C NMR δ (CDCl3,
75.4 MHz): 126.60, 128.53, 129.47, 132.37, 132.58,
135.01, 144.74; MS (EI) m/z (%): 233 (M+, 24), 235
(M++2, 24), 198 (M+-Cl, 100), 200 (71), 104 (33), 77
(14). Anal. Calcd for C9H6Cl3N: C, 46.09; H, 2.58; N,
5.97. Found: C, 45.98; H, 2.60; N, 6.01.
N-(2,2-Dichlorovinyl)-4-methoxylbenzimidoyl
chloride
(10f). Pale yellow needless (peth ether), yield 94%, mp
71–72°C; ir (potassium bromide): 1624, 1603, 1569,
1502, 1419, 1325, 1307, 1291, 1258, 1244, 1176, 1131,
1108, 1028, 941, 893, 853, 832, 647, 612, 606, 541,
1
466 cmꢀ1; H NMR δ (CDCl3, 300 MHz): 3.86 (s, 3H),
N-(2,2-Dichlorovinyl)-4-methylbenzimidoyl
chloride
6.92 (d, 2H, J = 8.9 Hz), 7.49 (s, 1H), 8.09 (d, 2H,
J = 8.9 Hz); 13C NMR δ (CDCl3, 75.4 MHz): 55.49,
113.87, 125.07, 127.52, 131.43, 132.68, 144.30, 163.11;
MS (EI) m/z (%): 263 (M+, 16), 265 (M++2, 16), 228
(M+-Cl, 100), 230 (69), 134 (10). Anal. Calcd for
C10H8Cl3NO: C, 45.40; H, 3.05; N, 5.29. Found: C,
45.31; H, 3.01; N, 5.41.
(10b). Pale yellow needless (peth ether), yield 92%, mp
72–73°C; ir (potassium bromide): 1618, 1568, 1287,
1247, 1232, 1182, 1133, 1120, 945, 902, 855, 820, 786,
617, 609, 457 cmꢀ1 1H NMR δ (CDCl3, 300 MHz):
;
2.40 (s, 3H), 7.22 (d, 2H, J = 8.0 Hz), 7.51 (s, 1H), 8.01
(d, 2H, J = 8.3 Hz); 13C NMR δ (CDCl3, 75.4 MHz):
21.55, 125.88, 129.27, 129.49, 132.36, 132.65, 143.22,
144.83; MS (EI) m/z (%): 247 (M+, 22), 249 (M++2, 22),
212 (M+-Cl, 100), 214 (69), 118 (21), 91 (11). Anal.
Calcd for C10H8Cl3N: C, 48.33; H, 3.24; N, 5.64. Found:
C, 48.24; H, 3.06; N, 5.77.
N-(2,2-Dichlorovinyl)-4-fluorobenzimidoyl chloride (10c).
Acknowledgment. We gratefully acknowledge the financial
support of the Fundación Séneca of the Comunidad Autónoma
de la Región de Murcia (project 19249/PI/14).
White needless (peth ether), yield 95%, mp 40–42°C; ir
(potassium bromide): 1621, 1598, 1570, 1503, 1401,
1294, 1237, 1158, 1132, 1098, 945, 905, 853, 836, 615,
REFERENCES AND NOTES
604, 539, 466 cmꢀ1
;
1H NMR δ (CDCl3, 400 MHz):
[1] Clapp, L. B. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R.; Rees, C. W. Eds.; Pergamon Press: Oxford, 1984; Vol
6 Chap 4.21.
[2] Grimmett, M. R.; Iddon, B. Heterocycles 1995, 41, 1525.
[3] Jochims, J. C. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A.; Rees, C.; Scriven, E. Eds.; Pergamon Press: Oxford,
1996; Vol 4 Chap 4.04.
7.12 (t, 2H, J = 8.6 Hz), 7.50 (s, 1H), 8.14 (dd, 2H,
J = 9.0 Hz, J = 5.3 Hz); 13C NMR δ (CDCl3,
100.8 MHz): 115.72 (d, J = 22.1 Hz), 126.71, 131.23 (d,
J = 3.2 Hz), 131.74 (d, J = 9.1 Hz), 132.45, 143.36,
165.45 (d, J = 254.7); MS (EI) m/z (%): 251 (M+, 17),
253 (M++2, 17), 216 (M+-Cl, 100), 218 (66), 122 (63),
95 (37). Anal. Calcd for C9H5Cl3FN: C, 42.81; H, 2.00;
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N, 5.55. Found: C, 42.98; H, 2.03; N, 5.68.
N-(2,2-Dichlorovinyl)-4-chlorobenzimidoyl chloride (10d).
Pale yellow needless (peth ether), yield 91%, mp 91–
93°C; ir (potassium bromide): 1687, 1614, 1592, 1561,
1484, 1458, 1400, 1297, 1236, 1131, 1089, 1013, 938,
899, 854, 833, 724, 604, 584, 461, 442 cmꢀ1 1H
;
NMR δ (CDCl3, 300 MHz): 7.41 (d, 2H, J = 8.8 Hz),
7.50 (s, 1H), 8.06 (d, 2H, J = 8.8 Hz); 13C NMR δ
(CDCl3, 75.4 MHz): 127.19, 128.82, 130.61, 132.43,
133.44, 138.82, 143.40; MS (EI) m/z (%): 267 (M+,
24), 269 (M++2, 31), 271 (M++4, 14), 232 (M+-Cl,
98), 234 (100), 236 (38), 138 (33). Anal. Calcd for
C9H5Cl4N: C, 40.19; H, 1.87; N, 5.21. Found: C,
40.28; H, 1.81; N, 5.32.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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SUPPORTING INFORMATION
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Additional supporting information may be found online in
the Supporting Information section at the end of the article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet