Efficient synthesis of tolunitriles by selective ammoxidation

Article abstract of DOI:10.1081/SCC-120017132

Tolunitriles have been efficiently synthesized by selective ammoxidation of methylbenzyl chlorides prepared with chlorination of xylenes. In comparison with ammoxidation of xylenes themselves, the reaction temperature of ammoxidation of methylbenzyl chlorides has been lowered more than 100°C and the selectivity forming mono-nitriles is almost 100%.

Full text of DOI:10.1081/SCC-120017132

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Efficient Synthesis of Tolunitriles by Selective
Ammoxidation
Guangyong Xie a , Qiong Zheng a , Chi Huang a & Yuanyin Chen a
a College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, P.R. China
Published online: 21 Aug 2006.
To cite this article: Guangyong Xie , Qiong Zheng , Chi Huang & Yuanyin Chen (2003) Efficient Synthesis of Tolunitriles by
Selective Ammoxidation, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 33:7, 1103-1107, DOI: 10.1081/SCC-120017132
To link to this article: http://dx.doi.org/10.1081/SCC-120017132
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 7, pp. 1103–1107, 2003
Efficient Synthesis of Tolunitriles by
Selective Ammoxidation
*
Guangyong Xie, Qiong Zheng, Chi Huang,
and Yuanyin Chen
College of Chemistry and Molecular Sciences,
Wuhan University, Wuhan, P.R. China
ABSTRACT
Tolunitriles have been efficiently synthesized by selective ammoxida-
tion of methylbenzyl chloridesprepared with chlorination of xylenes.
In comparison with ammoxidation of xylenes themselves, the
reaction temperature of ammoxidation of methylbenzyl chlorides
hasbeen lowered more than 100 ꢀC and the selectivity forming
mono-nitrilesisalmost 100%.
Key Words: Selective ammoxidation; Tolunitrile.
*Correspondence: Qiong Zheng, College of Pharmacy, Wuhan University,
Wuhan-430072, P.R. China; E-mail: ammoxid@whu.edu.cn.
1103
DOI: 10.1081/SCC-120017132
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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1104
Xie et al.
As important synthetic intermediates, tolunitriles can be converted
into methylbenzamides,[1,2] methylbenzoic acids,[3] cyanobenzoic acids,[4]
methylbenzylamines[5] and so on, from which many pharmaceuticals,
dyes, fluorescence whitener and other fine chemicals can be produced.[6,7]
The traditional synthesis routes of tolunitriles are: dehydration of
amide[8] or aldoxime,[9] cyanation of aryl chloride[10] or toluic acid,[11]
diazotization of methylbenzamine[12] and so on. These methods usually
need expensive starting materials or cause serious pollution. The method
prepared from ammoxidation of xylenescan overcome the shortcomings
mentioned above, but the yield and selectivity forming tolunitriles is very
low.[13] Because two methyl groups in xylenes are identical, and the
reaction temperature of ammoxidation of xylenesisuusally about
400ꢀC to activate methyl group in the ring, it isdifficult for only one
methyl to be converted to cyano group. The yieldsand eslectivity to
[13]
obtain tolunitrilesare very low. Angtsadt
invented a kind of new
catalysts for ammoxidation of p-xylene. According to hisreport, when
the temperature wasover 400 ꢀC, the selectivity forming tolunitrile
reached 63.9%, but the conversion of p-xylene wasonly 42.4% and the
portion of dinitrile in productswas30.9%. The productsare difficult to
be separated. In order to improve the yields and selectivity forming
mono-nitriles, Shik et al. attempted to prepare mono-nitrilesby liquid
phase ammoxidation of xylenes in 1980s.[14] Though Shik claimed that
the yield and selectivity of p-tolunitrile reached 73% and 78%
respectively, resent papers[6,7] reported that the result was not so good.
Recently we have found an effective method to synthesize tolunitriles
by selective ammoxidation. First xylenes are chlorinated to methylbenzyl
chloridesto make two methyl groupsdifferent, then the intermediatesare
ammoxidized to tolunitriles.
The routesof ammoxidation of xylenesand methylbenzyl chlorides
are shown as Sch. 1.
Scheme 1.

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Tolunitriles by Selective Ammoxidation
1105
After one methyl of the xyleneswaschlorinated, the ammoxidation of
methylbenzyl chloride could be carried out on VCrO/SiO2 catalyst,[15,16]
which exertsgood catalytic activity at relatively low temperature. In prac-
tice the reaction took place at the temperature near the boiling point of
methylbenzyl chloride (ca. 200ꢀC). The reaction temperature hasreduced
for more than 100ꢀC in comparison with the situation in the ammoxida-
tion of xylenes themselves, therefore the selectivity forming mono-nitriles
can be increased remarkably. It is well known that in the ammoxidation of
xylenesor other methylaromatics, H-extraction of methyl, forming benzyl
species, is the control step of the reaction. In the case of ammoxidation of
methylbenzyl chloride, the benzyl species needed can be formed by the
cleavage of C–Cl bond. The bond energy of C–Cl (339 kJ molÀ1) in chloro-
methyl group islessthan the bond energy of C–H (414 kJ mol À1) in methyl
group.[17] The former cleavesmore eaisly and the activation energy of
reaction would be decreased. So after one H is displaced by chlorine in
the chain methyl of xylenes, the ammoxidation reaction becomes milder.
The relatively lower temperature of reaction guaranteesthe high selectiv-
ity to obtain mononitrileswith high yield.
EXPERIMENTAL
Xylenesand reagentsfrom which catalytsswere prepared were
analytically or chemically pure. Productswere characterized by
1
1H NMR and IR spectra. The H NMR spectrum was measured on a
FX-90Q 1H NMR spectrometer with (CH3)4Si asinternal tsandard.
The IR spectrum was recorded on an AVATAR 380 infrared spectro-
photometer. The melting pointswere determined with a X6 microscopic
warming apparatus(the thermometer wasnot calibrated). The purity of
productswastested with SP-502 gaschromatograph.
CHLORINATION OF XYLENES
Two hundred millliter p-xylene wasadded in an equipment according
[18]
asthe literature.
The temperature wasraiesd to make xylene reflux
violently, then Cl2 (about 40 g hÀ1) was passed through the reaction zone
under UV light. The reaction process was monitored by GC. After 2 h,
the conversion of p-xylene reached 90.3%. The chlorination wasceased.
The product was shifted into a 500 mL flask for vacuum rectifying.
The product wascollected (100–102 ꢀC/10 mm Hg), obtaining 192.8 g
PMBC (yield 83.6% with purity 98% by GC).

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1106
Xie et al.
Table 1. The results of chlorination of xylenes and ammoxidation of
corresponding methylbenzyl chlorides.
Chlorination
Ammoxidation
Total
Conversion Yield Purity Conversion Yield Selectivity Purity yield
isomer
(%)
(%) (%)
(%)
(%)
(%)
(%)
(%)
o-
87.6
86.5
90.3
81.8 98.2
78.9 97.6
83.6 98.0
97.5
97.8
98.2
95.8
96.2
97.0
98.3
98.4
98.8
97.7 78.4
97.9 75.9
98.3 81.1
m-
p-
Similarly the o- and m-methylbenzyl chlorides were synthesized.
The conversions, yields and purity are shown as Table 1.
Preparation of Tolunitriles by Selective Ammoxidation
The experiment wascarried out in a 30 mm-inisde-diameter quartz
tube fixed-bed reactor[19] loaded 10 g 10 wt.% VCrO/SiO2 catalyst.
PMBC wasvaporized, then mixed with Air and NH . The mixed gas
3
was preheated, and then passed through the reactor. The reaction tem-
perature wascontrolled at 210 Æ 2ꢀC. PMBC wasentered 0.6 mL per
hour by a micropump. The molar ratio of air/PMBC and NH3/PMBC
were 25 and 5, respectively. After reaction, the product was cooled and
condensed in a condensing apparatus. White solid (at r.t. 5ꢀC) was
obtained after rushing, filtering and drying under vacuum. The reaction
can be carried out continuously. The condensing apparatus was altered
every 8 h. The test lasted nearly 80 h. 4.12 g p-methylbenzonitrile per 8 h
ꢀ
wasobtained, yield: 97%. M.p.: 25–27 C. The purity was98.3% by GC.
The product wasconfirmed by IR and 1H NMR compared with the
Sadtler Standard Spectra.
The o- or m-tolunitrile were prepared by ammoxidation of o- or
m-methylbenzyl chloride asthe asme method, except the productsare
liquid. The conversion of xylenes, the yields, selectivity and purity
of tolunitriles are also shown as Table 1.
REFERENCES
1. Sebti, S.; Rhihil, A.; Saber, A.; Hanafi, N. Tetrahedron Lett.
1996, 37, 6555.

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Tolunitriles by Selective Ammoxidation
1107
2. Kabalka, G.W.; Deshpande, S.M.; Wadgaonkar, P.P.; Chatla, N.
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Received in Japan February 11, 2002

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