Org. Synth. 1971, 51, 96
DOI: 10.15227/orgsyn.051.0096
ESTERIFICATION OF HINDERED ALCOHOLS: tert-BUTYL p-TOLUATE
[Benzoic acid, 4-methyl-, 1,1-dimethylethyl ester]
Submitted by G. P. Crowther
1, E. M. Kaiser
2, R. A. Woodruff
2, and C. R. Hauser
13.
Checked by A. Brossi, R. A. LeMahieu, and P. LaSalle.
1. Procedure
A 200-ml., one-necked, round-bottomed flask equipped with a Claisen adapter, a condenser, an addition funnel, and a magnetic stirring bar is charged with 50 ml. of tert-butyl alcohol (Note 1). Under nitrogen, 22.6 ml. of a 1.55 M solution (0.0350 mole) of n-butyllithium in hexane (Note 2) is added slowly from a syringe (Note 3), giving a turbid reaction mixture. A water bath is used to keep the mixture near room temperature. After stirring for 15 minutes, a solution of 5.42 g. (0.0351 mole) of p-toluoyl chloride (Note 4) in 25 ml. of anhydrous diethyl ether (Note 5) is added dropwise to the stirred mixture. The resulting yellow slurry is stirred at room temperature for 15 hours (Note 6). The yellow suspension (Note 7) is transferred with 100 ml. of ether to a separatory funnel and washed with three 25-ml. portions of saturated sodium chloride, and dried over magnesium sulfate. The ether is removed by distillation, and the residual oil distilled under reduced pressure, yielding a small forerun (0.10 g.) and 5.31–5.51 g. (79–82%) of tert-butyl p-toluate, b.p. 98–101° (4.2 mm.) (Note 8).
2. Notes
1.
tert-Butyl alcohol (Eastman Organic Chemicals white label) was dried by distillation from
calcium hydride.
2.
The solution of
1.55 M n-butyllithium in hexane was obtained from Foote Mineral Company.
3.
Formation of the
lithium tert-butoxide in this manner is very exothermic and causes the
hexane to boil during addition.
4.
p-Toluoyl chloride was prepared by treating
p-toluic acid (Eastman Organic Chemicals white label) with
thionyl chloride (Eastman Organic Chemicals white label). The
p-toluoyl chloride used was distilled, b.p.
48–49° (0.1 mm.).
5.
Anhydrous
ether was distilled from
lithium aluminum hydride and stored over
sodium ribbon prior to use.
6.
In one instance an additional
75 ml. of anhydrous ether was added to make the slurry less viscous. The ester was obtained in the same yield in another run after stirring only 30 minutes.
7.
Alternatively, the reaction mixture may be concentrated with a
rotary evaporator, removing excess
tert-butyl alcohol.
Ether and water are added, and the mixture transferred to the separatory funnel; the yield of ester is unchanged.
8.
With the same procedure
tert-butyl phenylacetate has been prepared in
47% yield.
4 When esters of less common alcohols were prepared, anhydrous
ether was used as a solvent instead of excess alcohol, with equivalent amounts of alcohol,
n-butyllithium, and acid chloride employed. Thus, the
triethylcarbinol ester of p-toluic acid and the
2,2-diphenylethanol ester of benzoic acid have been prepared in
72 and
70% yields, respectively.
3. Discussion
The present procedure
4 is an especially effective method for the synthesis of esters of aromatic acids and hindered tertiary alcohols or of acid-labile alcohols such as
2,2-diphenylethanol. The yields are excellent, and the reaction procedure is simple. The method is illustrated by the preparation of
tert-butyl p-toluate, a compound that could not be prepared by a conventional method
5 of esterification involving the acid chloride and
tert-butyl alcohol in the presence of
N,N-dimethylaniline. Examples of esters prepared by this method are illustrated in Table I.
TABLE I
ESTERS PREPARED BY ALKOXIDE METHODS
|
|
Ester
|
Yield,%
|
Ester
|
Yield,%
|
|
|
C6H5CH2CO2C(CH3)3
|
47a
|
C6H5CO2CH2CH(C6H5)2
|
70b
|
|
|
|
C6H5CO2C(CH3)3
|
89c
|
|
|
|
C6H5CO2CCH3(C2H5)2
|
87c
|
|
|
|
C6H5CO2C(C2H5)3
|
94c
|
|
|
|
|
76c
|
|
|
|
C6H5CO2CH2(t-C4H9)
|
78c
|
|
|
72b
|
|
70c
|
|
|
|
|
69c
|
|
|
91c
|
|
|
|
|
94c
|
|
85d
|
|
(CH3)3CCO2C(CH3)3
|
64c
|
|
|
|
(CH3)3CCO2C(C2H5)3
|
75c
|
(i-C3H7)2CHCO2C(C2H5)3
|
88e
|
|
C6H5CH=CHCO2C(CH3)3
|
88c
|
(tC4H9)CH2CO2C(C2H5)3
|
86e
|
|
C6H5CH2CH2CO2C(CH3)3
|
72c
|
(tC4H9)2CHCO2C(C2H5)3
|
30e
|
|
a As described in the accompanying procedure.
|
b As described in the accompanying procedure except ether used as solvent (see (Note 8)).
|
c Prepared in refluxing tetrahydrofuran with 1.0 equivalent of appropriate alcohol, 1.1 equivalents of n-butyllithium, and 1.1 equivalents of acid chloride.4
|
d Prepared by adding an equivalent amount of p-toluenesulfonyl chloride to a suspension 2,2-diphenylethoxide in ether.6
|
e Prepared by adding 0.50 equivalent of acid chloride to an ether suspension of sodium triethylmethoxide, which was obtained from 0.52 equivalent of sodium amide and 0.55 equivalent of triethylcarbinol.7
|
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
2,2-diphenylethoxide
ether,
diethyl ether (60-29-7)
thionyl chloride (7719-09-7)
sodium chloride (7647-14-5)
nitrogen (7727-37-9)
sodium (13966-32-0)
N,N-dimethylaniline (121-69-7)
magnesium sulfate (7487-88-9)
sodium amide (7782-92-5)
butyllithium,
n-butyllithium (109-72-8)
Tetrahydrofuran (109-99-9)
Triethylcarbinol (597-49-9)
lithium aluminum hydride (16853-85-3)
hexane (110-54-3)
p-Toluic acid (99-94-5)
tert-butyl alcohol (75-65-0)
calcium hydride (7789-78-8)
2,2-diphenylethanol (1883-32-5)
p-Toluenesulfonyl chloride (98-59-9)
Benzoic acid, 4-methyl-, 1,1-dimethylethyl ester,
tert-Butyl p-toluate (13756-42-8)
sodium triethylmethoxide
tert-butyl phenylacetate
lithium tert-butoxide (1907-33-1)
p-toluoyl chloride (874-60-2)
triethylcarbinol ester of p-toluic acid
2,2-diphenylethanol ester of benzoic acid
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