Organic Process Research & Development 1998, 2, 86−95
An Ecofriendly Catalytic Route for the Preparation of Perfumery Grade Methyl
Anthranilate from Anthranilic Acid and Methanol
G. D. Yadav* and M. S. Krishnan
Chemical Engineering DiVision, UniVersity Department of Chemical Technology, UniVersity of Mumbai,
Matunga, Mumbai 400 019, India
Abstract:
drinks and alcoholic beverages. The annual production of
methyl anthranilate was 186 tonnes (t)3 in 1964 and is
currently estimated to be over 1000 t. The major commercial
routes are based on esterification of anthranilic acid with
methanol or isatoic anhydride with methanol, and these
employ homogeneous acid catalysts, posing problems of
disposal.
Esterification is a very widely understood reaction espe-
cially in the pharmaceutical, perfumery, and flavour industry.
Several synthetic routes exist to make esters, but most of
them are not suitable to meet the stringent specifications
applied in the perfumery and flavour industry. Yadav and
Mehta2 have reviewed these methods, including catalysis.
The most acceptable method of making an ester is to react
the corresponding acid with an alcohol.4 The reaction is
catalysed by acids and is reversible. Several methods are
available to drive the reaction towards the favourable product.
One of them is to use an excess amount of alcohol, and the
other way is to remove the ester formed (or the coproduct
water) continuously. The general reaction is as follows:
Methyl anthranilate is a very important perfumery ester and
also a precursor to a number of Schiff bases which are used in
several fragrance formulations. The current practice is to use
homogeneous acids as catalysts in the manufacture of methyl
anthranilate either starting with isatoic anhydride and methanol
or by the esterification of anthranilic acid with methanol. These
routes pose problems of disposal of liquid acids after the
reaction, and substantial quantities of acids are required in
order that the amine group be initially blocked as an amine
hydrochloride. This paper deals with the application of
ecofriendly heterogeneous catalysts including ZSM-5; acid-
treated clays such as Filtrol-24 and K10; ion-exchange resins
such as Nafion-H, Indion-130, Amberlyst-15, Amberlyst-18,
Dowex M-32 and Bayer K-24; and dodecatungstophosphoric
acid, a heteropolyacid. Among these catalysts, Amberlyst-15
and Indion-130 resins were found to be the most effective. Other
heterogeneous catalysts such as ZSM-5, Filtrol-24, and dode-
catungstophosphoric acid were found to be totally ineffective.
A theoretical model was employed for the analysis of this solid-
catalysed slurry reaction, and effects of various parameters on
the rate of reaction were evaluated. There was no effect of
external as well as internal mass-transfer resistance on the rate
of reaction. The reaction was found to be intrinsically kineti-
cally controlled, and the kinetic parameters were established.
The product was isolated and confirmed by spectroscopic
methods. The odour value matched with that of the com-
mercially available perfumery grade sample.
NH2
NH2
COOH
COOCH3
H+
+ CH3OH
+ H2O
In the conventional industrial processes involving homo-
geneous acids, utilisation of heterogeneous acid catalysts as
the replacement is gaining importance due to their ecofriendly
nature.5-8 These catalysts are noncorrosive and easy to
separate from the reaction mixture. They can also be used
repeatedly over a prolonged period without any difficulty in
their handling and storage. Therefore the preparation of
methyl anthranilate over various solid acid catalysts was
undertaken including theoretical interpretation of collected
data and modelling. The product was isolated to determine
its perfume value. This paper reports these findings.
Introduction
Organic esters are most frequently used as perfumery and
flavour chemicals. They fall into a very wide category
ranging from aliphatic to aromatic with various substitutions
and multifunctional groups.1,2 Most esters have pleasant
odours reminiscent of floral to fruity notes. Methyl anthra-
nilate is one such interesting ester which occurs naturally in
several citrus fruits like orange and also in some flowers
like neroli and ylang ylang. It finds more applications in
flavouring than perfumery compositions because of its odour,
which resembles the musky-fruity-dry floral note imitating
concord grapes and orange blossom. It blends very well with
several flavours and finds usage in the flavouring of soft
Preparation of Methyl Anthranilate
Reactions with sterically hindered compounds have
always been a challenge regarding scale-up, selectivity, and
separation. The preparation of methyl anthranilate is one
(3) Bedoukian, P. Z. Perfumery and FlaVouring Synthesis, 3rd ed.; Allured
Publishing Corp.: Wheaton, IL, 1986.
(4) Carey, F. A. AdVanced Organic Chemistry; 3rd ed.; Plenum Press: New
York, 1990.
* Author to whom correspondence should be addressed. Fax: 91-22-4145614.
Tel: 91-22-4145616. E-mail: gdy@udct.ernet.in.
(5) Yadav, G. D.; Kirthivasan, N. J. Chem. Soc., Chem. Commun. 1995, 203-
204.
(1) Ogliaruso, M. A.; Wolfe J. F. Synthesis of Carboxylic Acids, Esters and
Their DeriVatiVes; John Wiley: New York, 1991.
(2) Yadav, G. D.; Mehta, P. Ind. Eng. Chem. Res. 1994, 33 (9), 2198-2208.
(6) Yadav, G. D.; Bokade, V. V. Appl. Catal., A 1996, 147, 299-323.
(7) Yadav, G. D.; Thorat, T. S. Ind. Eng. Chem. Res. 1996, 35, 721-732.
(8) Thorat, T. S.; Yadav, V. M.; Yadav, G. D. Appl. Catal., A 1992, 90, 73.
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Vol. 2, No. 2, 1998 / Organic Process Research & Development
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Published on Web 01/22/1998