Org. Synth. 1964, 44, 56
DOI: 10.15227/orgsyn.044.0056
ETHYL β-HYDROXY-β,β-DIPHENYLPROPIONATE
[Hydracrylic acid, 3,3-diphenyl, ethyl ester]
Submitted by W. R. Dunnavant and Charles R. Hauser
1.
Checked by William E. Parham and J. E. Burcsu.
1. Procedure
Caution! This preparation should be carried out in a hood to avoid exposure to ammonia.
A Suspension of lithium amide (0.25 mole) (Note 1) in liquid ammonia is prepared in a 1-l. three-necked flask equipped with a condenser, a ball-sealed mechanical stirrer, and a dropping funnel. In the preparation of this reagent commercial anhydrous liquid ammonia (500 ml.) is introduced from a cylinder through an inlet tube. To the stirred ammonia is added a small piece of clean lithium metal. After the appearance of a blue color a few crystals of ferric nitrate hydrate (about 0.25 g.) are added, followed by small pieces of freshly cut lithium metal (Note 2) until 1.73 g. has been added. After all the lithium has been converted to the amide (Note 3), 17.6 g. (0.2 mole) of ethyl acetate (Note 4) is added, and the gray suspension is stirred for about 30 seconds. To the gray suspension is added 36.4 g. (0.2 mole) of benzophenone (Note 4) dissolved in 100 ml. of anhydrous ether. The mixture is stirred for 30 minutes and is then neutralized by the addition of 13.4 g. (0.25 mole) of ammonium chloride. The liquid ammonia is then removed by use of a steam bath while 200–300 ml. of ether is being added (Note 5). When the ammonia has been removed, 200 ml. of cold water is added. The ether layer is separated, and the aqueous layer is further extracted with two 100-ml. portions of ether. The combined ether extract is dried over magnesium sulfate and filtered, and the solvent is evaporated. The residue is dissolved in 50 ml. of hot 95% ethanol, treated with Norit®, filtered, and allowed to cool. The yield of ethyl β-hydroxy-β,β-diphenylpropionate, obtained as colorless, needle-like crystals melting at 85–86°, is 40.5–45.5 g. (75–84%). The filtrate, on reduction in volume and cooling, yields small amounts of benzophenone, m.p. 46–47°.
2. Notes
1.
This preparation may be accomplished by using one molecular equivalent of
lithium amide; special reaction procedures must be employed, however, and the yields are not reproducible.
2 The preparation may also be accomplished (with reduced yield) by using
sodium amide, but only under special reaction conditions.
3
2.
The
lithium wire or ribbon is cut in about 0.25-g. pieces, stored under kerosene, and blotted with filter paper before addition.
3.
Conversion is indicated by the discharge of the blue color.
4.
Ethyl acetate and benzophenone as supplied by the Eastman Kodak Company were used without further purification.
5.
The checkers added
ether and permitted the
ammonia to evaporate overnight. If a
steam bath is employed, care must be exercised to prevent charring of the product.
3. Discussion
This procedure is an adaptation of ones described by Dunnavant and Hauser.
2,4 Ethyl β-hydroxy-β,β-diphenylpropionate has been prepared previously using the Reformatsky reaction by condensing
ethyl α-bromoacetate with
benzophenone by means of
zinc metal.
5
4. Merits of the Preparation
This procedure illustrates the use of lithio esters for the preparation of β-hydroxy esters.
Isopropyl and t-butyl β-hydroxy-β,β-diphenylpropionate may be prepared in approximately
80% yields by using
isopropyl or t-butyl acetates in place of
ethyl acetate.
2 This procedure is generally more convenient than the Reformatsky reaction for the preparation of such esters. Under similar conditions
ethyl acetate may conveniently be condensed with various aldehydes or ketones to give the corresponding β-hydroxy esters.
4
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Isopropyl and t-butyl β-hydroxy-β,β-diphenylpropionate
isopropyl or t-butyl acetates
ethanol (64-17-5)
ammonia (7664-41-7)
ethyl acetate (141-78-6)
ether (60-29-7)
ammonium chloride (12125-02-9)
Norit (7782-42-5)
Benzophenone (119-61-9)
zinc (7440-66-6)
lithium (7439-93-2)
magnesium sulfate (7487-88-9)
ethyl α-bromoacetate (105-36-2)
sodium amide (7782-92-5)
lithium amide (7782-89-0)
ferric nitrate hydrate
Ethyl β-hydroxy-β,β-diphenylpropionate,
Hydracrylic acid, 3,3-diphenyl, ethyl ester (894-18-8)
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved