Chlorination of 3-Arylsydnones with Iodine Monochloride

Full text of DOI:10.1080/00304948.2017.1260398

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: http://www.tandfonline.com/loi/uopp20
Chlorination of 3-Arylsydnones with Iodine
Monochloride
Imad F. Nashashibi, Jonathan M. Tumey, Benjamin L. Owens & Kenneth
Turnbull
To cite this article: Imad F. Nashashibi, Jonathan M. Tumey, Benjamin L. Owens & Kenneth
Turnbull (2017) Chlorination of 3-Arylsydnones with Iodine Monochloride, Organic
Preparations and Procedures International, 49:1, 59-63, DOI: 10.1080/00304948.2017.1260398
To link to this article: http://dx.doi.org/10.1080/00304948.2017.1260398
Published online: 13 Jan 2017.
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Date: 13 January 2017, At: 14:00

Organic Preparations and Procedures International, 49:59–63, 2017
Copyright Ó Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2017.1260398
Chlorination of 3-Arylsydnones with Iodine
Monochloride
Imad F. Nashashibi, Jonathan M. Tumey, Benjamin L. Owens,
and Kenneth Turnbull
Department of Chemistry, Wright State University, Dayton, OH 45435, USA
Sydnones undergo electrophilic aromatic substitution at the 4-position1,2 and bromi-
nation has been the most studied reaction of this type. For the latter, a number of meth-
ods, including Br2 / NaHCO3,3 Br2 / Ac2O,4 NBS5,6 or KBrO3 / HBr,7 have been used
for the conversion of the parent sydnones 1 to their 4-bromo congeners 2. While meth-
ods for the chlorination of sydnones (1 ! 3) are available (inter alia Cl2,4 NCS/DMF,5
KClO3/HCl,7 electrochemical chlorination,8,9 PhICl210), most of them suffer from one
or more major drawback and, accordingly, there is room for improvement of the pro-
cess. We now report that iodine monochloride in dichloromethane converts 4-unsubsti-
tuted 3-arylsydnones (cf. 1) to the corresponding 4-chloro analogs 3 in moderate to
good yields under very mild conditions.
The present discovery stems from our need to prepare 4-iodo-3-arylsydnones 4 for sub-
sequent alkynyl coupling studies. Dumitrascu et al.11 had reported that the use of iodine
monochloride in acetic acid gave good yields of the corresponding 4-iodo sydnone 4 from
the 4-unsubstituted compound 1 and we utilized this approach for the preparation of a num-
ber of 4-iodosydnones. However, it was observed that the efficiency of the process dimin-
ished over time, undoubtedly due to breakdown of the reagent and, accordingly, instead of
the neat reactant we elected to use a solution of ICl in dichloromethane, which was avail-
able commercially. When the reaction of 3-phenylsydnone (1a) with this reagent was re-
examined using dichloromethane as solvent, we were surprised to find that a mixture of
Received June 13, 2016; in final form October 14, 2016
Address correspondence to Kenneth Turnbull, Department of Chemistry, Wright State Univer-
sity, Dayton, OH 45435. E-mail: kenneth.turnbull@wright.edu
59

60
Turnbull et al.
two products was obtained, the minor component being the expected 4-iodo species 4a. The
major product was isolated and identified as the 4-chloro congener 3a and, intrigued by this
result, we endeavored to optimize the parameters leading to its formation.
Accordingly, using 3-phenylsydnone (1a) as our model reactant we modified both the
reaction time and the number of equivalents of iodine monochloride employed in order to
optimize the conversion to the chlorosydnone 3a. Thus, reaction of 1a with one equivalent
of ICl gave a mixture of 1a, 3a and 4a, a mixture of 3a and 4a with two equivalents of ICl
and complete conversion to the 4-chloro product 3a in 72% yield with three equivalents of
ICl in under 1 hour at room temperature. The latter protocol was extended to the study of a
series of 3-arylsydnones 1b-i and, in all cases, complete reaction occurred in less than
2 hours at room temperature. The corresponding 4-chloro species 3b-i were obtained in
51–81% yields after recrystallization from absolute ethanol. No consistent pattern emerged
from the yields obtained with different aryl substituents but the reaction was successful in
the presence of alkyl, alkoxy, bromo or chloro groups and the position of the substituent
did not appear to affect the outcome of the reaction. The identities of the products were
confirmed by the presence of the sydnone C H O stretching vibration at »1750 cm¡1 and
the absence of the sydnone CÀÀH stretching vibration at »3150 cm¡1 and the expected
chemical shifts and splitting patterns in their proton and carbon NMR spectra. The most
informative observation was the absence of the signal for the hydrogen at the C-4 position
of the sydnone ring (typically ca. d 6:8), indicating substitution at that location.
Arene chlorination by ICl has been observed occasionally prior to the present work.
Thus, chloro products were obtained by reaction of ICl with phenolic species in glacial
acetic acid,12 an imidazole nucleoside,13 8,16-dimethyl[2.2]metacyclophane,14 HAT6,15
methoxybenzenes,16 and polycyclic aromatic hydrocarbons.17,18 It has been suggested
that an electron transfer pathway involving radical cation intermediates occurs and subse-
quent chlorination or iodination results from reaction of the latter with chloride ion or
iodine atom.16,18 It is unclear whether this mechanism is operative in the present case and
confirmation of this speculation will require further studies. Overall, however, a useful
process for the chlorination of sydnones has been developed.
Experimental Section
3-Phenylsydnone (1a) was synthesized from N-phenylglycine using a literature procedure. 19
The other starting sydnones, 3-(3,4-dimethylphenyl)sydnone (1b)20, 3-(2,3-dimethylphenyl)-
sydnone (1c)20, 3-(2,4-dimethylphenyl)sydnone (1d)20, 3-(3-methoxyphenyl)sydnone (1e)21,

Chlorination of 3-Arylsydnones
61
3-(4-methoxyphenyl)sydnone (1f)22, 3-(4-tolyl)sydnone (1g)23, 3-(4-bromophenyl)sydnone
(1h)24 and 3-(4-chlorophenyl)sydnone (1i)23 were prepared according to the reported proce-
dure. 20 All other starting materials and reagents were purchased commercially and used with-
out purification unless otherwise noted. Melting points were determined on a Mel-Temp
melting point device and are uncorrected. The infrared spectra were taken as KBr pellets on a
Nicolet 6700 FTIR. NMR spectra were obtained on a Bruker Avance 300 MHz NMR and
are reported relative to tetramethylsilane (TMS) as an internal standard. Elemental analyses
were carried out by Midwest Microlab LLC, Indianapolis, IN 46250.
Preparation of 4-Chloro-3-arylsydnones 3a-i from Reaction of 3-Arylsydnones 1a-i
with ICl: General Procedure
Iodine monochloride (1M in dry dichloromethane, 3 equiv.) was added dropwise at room tem-
perature to a stirred solution of the 3-arylsydnone (1 equiv.) and anhydrous sodium acetate (3
equiv.) in dry dichloromethane (4 mL / 0.1 g) under an atmosphere of nitrogen gas. After the
reaction was complete (usually 0.5 h to 1 h, monitored by TLC on silica gel, dichloromethane:
ethyl acetate (25:1 v.v) as eluant), the reaction mixture was poured into aqueous sodium sulfite
(2%, 30 mL / 0.1 g), extracted 3 times with dichloromethane and the combined extracts were
washed with saturated aqueous sodium bicarbonate (25 mL / 0.1 g), dried with magnesium sul-
fate, filtered and evaporated in vacuo. The resultant solid was recrystallized from hot ethanol.
4-Chloro-3-phenylsydnone (3a)
3-Phenylsydnone (1a) [0.204 g, 1.258 mmol] for 1 h by the general procedure gave 3a as
colorless crystals (0.182 g, 0.926 mmol, 72%), mp. 116.5–117 ꢀC, identical to an authen-
tic sample.10
4-Chloro-3-(3,4-dimethylphenyl)sydnone (3b)
3-(3,4-Dimethylphenyl)sydnone (1b) [0.100 g, 0.524 mmol] for 1 h by the general proce-
dure gave 3b as colorless crystals (0.074 g, 0.323 mmol, 62%), mp. 130–2 ꢀC. IR: 3055,
1761 (sydnone C D O), 1500, 1461 cm¡1. 1H-NMR (CDCl3): d 7.39 (d, 1 H), 7.38 (d, 1
H), 7.11 (s, 1 H), 2.40 (s, 3 H), 2.24 (s, 3 H). 13C-NMR (CDCl3): d 164.1 (sydnone C D
O), 142.3, 139.3, 139.2, 131.1, 130.8, 126.1, 98.3 (sydnone C-4), 20.2, 20.0.
Anal. Calcd for C10H9ClN2O2 ꢁ 0.5 H2O: C, 51.41; H, 4.31; N, 11.99. Found: C,
51.65; H, 3.98; N, 11.73.
4-Chloro-3-(2,3-dimethylphenyl)sydnone (3c)
3-(2,3-Dimethylphenyl)sydnone (1c) [0.100 g, 0.524 mmol] for 2 h by the general proce-
dure gave 3c as colorless crystals (0.082 g, 0.365 mmol, 70%), mp. 120–122 ꢀC, identical
to an authentic sample.25
4-Chloro-3-(2,4-dimethylphenyl)sydnone (3d)
3-(2,4-Dimethylphenyl)sydnone (1d) [0.100 g, 0.524 mmol] for 2 h by the general proce-
ꢀ
dure gave 3d as colorless crystals (0.072 g, 0.319 mmol, 61%), mp. 120–122 C, identi-
cal to an authentic sample.26
4-Chloro-3-(3-methoxyphenyl)sydnone (3e)
3-(3-Methoxyphenyl)sydnone (1e) [0.201 g, 1.046 mmol] for 0.5 h by the general proce-
dure gave 3e as colorless crystals (0.174 g, 0.77 mmol, 74%), mp. 93–94 ꢀC, identical to
an authentic sample.10

62
Turnbull et al.
4-Chloro-3-(4-methoxyphenyl)sydnone (3f)
3-(4-Methoxyphenyl)sydnone (1f) [0.202 g, 1.05 mmol] for 0.5 h by the general proce-
dure gave 3f as colorless crystals (0.161 g, 0.710 mmol, 68%), mp. 101–102 ꢀC, identical
to an authentic sample.6
4-Chloro-3-(4-tolyl)sydnone (3g)
3-(4-Tolyl)sydnone (1g) [0.202 g, 1.144 mmol] for 0.5 h by the general procedure gave
ꢀ
3g as colorless crystals (0.194 g, 0.923 mmol, 81%), mp. 138.5–139 C, identical to an
authentic sample.10
4-Chloro-3-(4-bromophenyl)sydnone (3h)
3-(4-Bromophenyl)sydnone (1h) [0.202 g, 0.839 mmol] for 0.75 h by the general proce-
ꢀ
dure gave 3h as colorless crystals (0.164 g, 0.596 mmol, 71%), mp. 111–112 C, identi-
cal to an authentic sample.6
4-Chloro-3-(4-chlorophenyl)sydnone (3i)
3-(4-Chlorophenyl)sydnone (1i) [0.201 g, 1.02 mmol] for 0.5 h by the general procedure
ꢀ
gave 3i as colorless crystals (0.167 g, 0.723 mmol, 71%), mp. 108–109 C, identical to
an authentic sample.10
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