Homogeneous system for the synthesis of benzyl salicylate

Article abstract of DOI:10.1021/op010058d

Synthesis of benzyl salicylate from sodium salicylate and benzyl chloride in the absence of a PTC and with dimethyl formamide as a solvent has been reported. Almost complete conversion of benzyl chloride can be achieved in 1.5 h at 110°C. The batch time and the reaction temperature are considerably less than that for the commercial process using a PTC. Kinetics of the reaction have been investigated.

Full text of DOI:10.1021/op010058d

Organic Process Research & Development 2002, 6, 149−151
Homogeneous System for the Synthesis of Benzyl Salicylate
Sri Sivakumar, Vishwas G. Pangarkar, and Sudhir B. Sawant*
Institute of Chemical Technology, UniVersity of Mumbai, Matunga, Mumbai - 400 019, India
Abstract:
Synthesis of benzyl salicylate from sodium salicylate and benzyl
chloride in the absence of a PTC and with dimethyl formamide
as a solvent has been reported. Almost complete conversion of
benzyl chloride can be achieved in 1.5 h at 110 °C. The batch
time and the reaction temperature are considerably less than
that for the commercial process using a PTC. Kinetics of the
reaction have been investigated.
1. Introduction
Most of the perfumery and flavour compounds are
oxygenated compounds that is, esters, aldehydes, ketones,
alcohols, and so forth. Esters of the aromatic carboxylic acids
such as benzoic acids, salicylic acid and cinnamic acid have
more value in the perfumery and flavour industries. Benzyl
salicylate is one such ester. Naturally occuring benzyl
salicylate is isolated from an essential oil, for example . that
from Dianthus caryophyllus.1 Benzyl salicylate is used as a
fixative in perfumes and also in sunscreen preparations. It
is frequently used in flavour compositions as well. There
are four different routes for the synthesis of benzyl salicy-
late: (1) By the reaction of benzyl alcohol and salicylic
acid,2-4 (2) by the reaction of benzyl chloride (BnCl) and
sodium salicylate using a phase transfer catalyst,5-8 (3) by
the trans-esterification of benzyl alcohol with methyl sali-
cylate using sodium methyl salicylate as catalyst,9 and (4)
by the reaction of benzyl chloride and salicylic acid using a
phase-transfer catalyst.10,11
Figure 1. Effect of temperature on the conversion of benzyl
chloride. Moles of benzyl chloride ) 0.2. Moles of sodium
salicylate ) 0.3. Speed of agitation ) 2000.
ester preparation would be even more commercially attrac-
tive because benzyl chloride gives a less expensive benzyl
group than does benzyl alcohol. It may be noted that benzyl
salicylate is prepared from sodium salicylate and benzyl
chloride using phase-transfer catalysts (PTC). When an
aqueous solution of sodium salicylate is used, a number of
by-products (benzyl alcohol, benzyl benzoate, salicylic acid,
dibenzyl ether, and some high-boiling compounds) are
formed. With dry sodium salicylate powder, it takes 8-12
h to get near-complete conversion of benzyl chloride
using a PTC. The heterogeneous reaction system neces-
sitates the use of a PTC to enhance the rate of the reaction.
In addition a solvent is necessary to provide an easily stir-
rable reaction mixture. Often the solvent used is benzyl
salicylate itself. To avoid the use of a PTC, it was desirable
to carry out the reaction in an homogeneous system.
Accordingly, a number of solvents were tried. Dimethyl
formamide was finally selected because sodium salicylate
and benzyl chloride are highly soluble in it. Thus, the
reactants are available in an homogeneous liquid phase. The
product sodium chloride precipitates as the reaction proceeds
due to its poor solubility in dimethyl formamide. The reaction
takes place in an homogeneous liquid phase.
The sodium salt of salicylic acid is inexpensive and readily
available by Kolbe synthesis. Furthermore, this method of
* To whom correspondence may be addressed. Fax: +91-22-4145614.
E-mail: sbs@udct.ernet.in.
(1) Arctander, S. Perfumer and FlaVour Chemicals; Arctander S.: Montclair,
NJ, 1969; Vol. 1.
(2) Ueno, R.; Tsuchiya, H.; Itoh, S.; Yamamoto, I., Eur. Pat. Appl. EP 117,-
502, 1984; Chem. Abstr. 1985, 102, 45629c.
(3) Yamazaki, K.; Yoneyama, T.; Vchama, N.; Matsuoka, T.; Mishima, A.;
Nyugaku, H. Jpn. Kokai Tokkyo Koho JP 01,186,846, 1989; Chem. Abstr.
1990, 112, 20787w.
(4) Yamada, M.; Takahashi, K. Jpn. Kokai Tokkyo Koho JP 02,04,735, 1990;
Chem. Abstr. 1990, 113, 23387x.
(5) Normant, H.; Laurenco, C. C. R. Hebd. Seances Acad. Sci. Ser. C. 1976,
283(11), 4836; Chem. Abstr. 1977, 86, 106129q.
(6) Henry, E. H.; James, P. E., Jr.; Collins L. R.; Leonard R. T. Ind. Eng.
Chem. Prod. Res. DeV. 1967, 6(3), 193-195.
(7) Barry, J.; Bram, G.; Decodts, G.; Loupy, A.; Orange, C.; Petit, A.; Sansoulet,
J. Synthesis 1985, 1, 40-45.
(8) Crohemore, M. Eur. Pat. Appl. EP 534,817, 1993: Chem. Abstr. 1993,
118, 254409a.
(9) Ger. Offen DE 3,404,310, 1985; Chem. Abstr. 1985, 103, 183394u.
(10) Doehler, P.; Reichelt, P. Ger. (East) 91,052, 1972; Chem. Abstr. 1973, 78,
19464a.
(11) Desmurs, J. R.; Ratton S. Eur. Pat. Appl. EP 467,727, 1992; Chem. Abstr.
1992, 116, 193922x.
10.1021/op010058d CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/14/2002
Vol. 6, No. 2, 2002 / Organic Process Research & Development
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149

Figure 2. Kinetics plot, first-order dependence. Moles of benzyl
chloride ) 0.2. Moles of sodium salicylate ) 0.3. Speed of
agitation ) 2000 rpm.
Figure 4. Flow sheet.
the samples were analysed by gas chromatography to
determine the conversion of benzyl chloride and the yield
of benzyl salicylate.
Analysis. To the known quantity (1 mL) of the reaction
mixture sample, 20%w/w solution (2 mL) of NaCl was
added. The mixture was then extracted with two volumes of
ethylene dichloride. The ethylene dichloride layer was
analysed by gas chromatography using a 2 m 10% OV-17
column. This method of sample preparation for analysis was
first developed and standardized using identical synthetic
samples containing known quantities of benzyl salicylate and
benzyl chloride. Nitrogen was the carrier, and the detector
was FID. Other parameters are given below.
injection temperature
detector temperature
nitrogen flow rate
300 °C
325 °C
30 mL/min
Figure 3. Arrhenius plot. Moles of benzyl chloride ) 0.2. Moles
of sodium salicylate ) 0.3. Speed of agitation ) 2000 rpm.
temperature programming
135 °C for 2 min
135-290 °C at 25 °C/min
290 °C maintained for 5 min
2. Experimental Section
2.1. Method. All the experiments were carried out in a
batch manner. A 500-mL borosilicate glass reactor with a
stirrer and four baffles was used. A constant-temperature oil
bath was used for maintaining the desired reaction temper-
ature.
3. Results and Discussion
The terms conversion and yield have been defined as
follows:
Predetermined quantities of dimethyl formamide and
sodium salicylate were added into the reactor. The temper-
ature of the oil bath was raised to the predetermined value
and maintained there. The measured quantity of benzyl
chloride preheated to the desired temperature was then added,
and the experiment was started. Small (1 mL) samples of
reaction mixtures were withdrawn at regular intervals, and
% conversion of benzyl chloride )
mol of benzyl chloride consumed
× 100
× 100
mol of benzyl chloride charged
% yield of benzyl salicylate )
mol of benzyl salicylate formed
mol of benzyl chloride consumed
150
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Figure 1 shows the effect of reaction temperature. The
experiments are carried out using 120 mL of dimethyl
formamide, 0.3 mol of sodium salicylate and 0.2 mol of
benzyl chloride. It can also be seen from Figure 1 that the
rate of reaction is increased appreciably when the temperature
changes from 90 to 110 °C. The yield of benzyl salicylate
is almost 100% in all the experiments.
3.1. Kinetics. For the present reaction, assuming first-
order with respect to each reactant, benzyl chloride and
sodium salicylate, the rate expression can be written as:
temperature. Figure 3 shows the Arrhenius plot for these k
values. The activation energy is found to 23.4 kcal/mol.
3.2. Material balance. A reaction was performed to
establish the material balance. The reaction was carried out
by using 0.5 mol of benzyl chloride, 0.55 mol of sodium
salicylate, and 220 mL of dimethyl formamide at temperature
110 °C at 2000 rpm. The reaction was carried out for 1.5 h.
GC analysis showed 100% conversion of benzyl chloride.
The flow sheet shows the material balance (Figure 4).
4. Conclusions
Benzyl salicylate can be prepared in an homogeneous
system with dimethyl formamide as a solvent. This process
does not need a PTC. The reaction temperature (∼100 °C)
is considerably lower than that for the conventional process
(∼150 °C). Further complete conversion of benzyl chloride
can be achieved in a shorter batch time of about 1.5 h.
-rA ) k(CACB)
(1)
In the integrated form eq 1 can be written as
(M - XA)
-ln
) kCA0(M - 1)t
(2)
[
]
M(1 - XA)
NOMENCLATURE
CA ) concentration of benzyl chloride, mol/L
CB ) concentration of sodium salicylate, mol/L
XA ) fractional conversion of benzyl chloride
Thus, validity of the first-order dependence can be
checked by plotting -ln[(M - XA)/M × (1 - XA)] versus
time, t. A straight line passing through the origin will confirm
the first-order with respect to each reactant and can be used
to evaluate the second-order rate constant.
M
) mole ratio of sodium salicylate: benzyl chloride
0
CA ) initial concentration of benzyl chloride, mol/L
) rate constant, L/min‚mol
Figure 2 shows that straight-line plots are obtained using
the data from Figure 1. This confirms first-order dependence
on the concentration of each reactant. From the slopes of
these straight-line values of k are calculated for each reaction
k
Received for review July 23, 2001.
OP010058D
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