Weygand/Hilgetag Preparative Organic Chemistry

960 Formation of new carbon-carbon bonds
solution has become grey again. For additional details about apparatus see the description
of the preparation of cyclohexylphenylacetonitrile on page 917.
Sodamide prepared in this way should not be stored as a solid (obtainable by evaporation
of the ammonia) as it can form explosive compounds.
Hauser and Walker record the use of (diethylamino)magnesium bromide as
condensing agent. 731
The presence of alcohol, even if only in traces, is essential if ester condensations
are to proceed normally, so a little dry alcohol is specially added when
necessary.
In ester condensations it is sometimes necessary to warm the mixture gently
to overcome an induction period, but cooling is often required as the
reaction proceeds, otherwise side reactions may occur, e.g., Bouveault-Blanc
reduction (see page 76). It is not always easy or possible to determine the
end of the reaction from the appearance of precipitated solids, because the
sodium may become coated mechanically and withdrawn from the reaction.
Care is thus needed during working up, which usually begins with acidification
of the reaction mixture; when possible, the acetic acid used for acidification
should not be added to the reaction flask, but the reaction mixture should
be poured into a wide, open porcelain dish and the larger pieces of sodium
should be then removed by hand.
The ethyl acetate often used for ester condensations should be purified as follows: If it
gives an acid reaction, it should be washed with sodium carbonate solution, followed by
water until the alkaline reaction disappears; in other cases two washings with water suffice.
It is then dried provisionally with a little calcium chloride; after that, it should be set aside
over a large amount of calcium chloride for 24 h, though losses due to formation of an
addition compound are unavoidable. Inglis and Roberts 732 washed the ethyl acetate only
with water and dried it over solid potassium hydroxide. The ester thus obtained still contains
alcohol and boils over a range of 2-3°. The dry ethyl acetate need not be distilled. Since it
is very hygroscopic it should be poured carefully away from the drying agent and not filtered.
Scheibler 733 has described a laboratory method of preparing acetoacetic
ester that is convenient and gives very good yields. In industry it is obtained
by use of sodium dust in autoclaves, quantitative yields being claimed 734
for this process. Occasionally acetoacetic ester is prepared by condensation
of ethyl acetate and used, without isolation, for further reactions, whereby
excellent yields of the final products are obtained. 735 Ethyl benzoate and
acetophenone give dibenzoylmethane in about 70% yield. 736 0-Hydroxyacetophenone,
condensed with ethyl propionate and sodium in ether, afford
l-(0-hydroxyphenyl)-l,3-pentanedione which is cyclized to 2-ethylchromone
in 70-75% yield by hydrochloric and acetic acid. 737
OH ^^r OH COC2H5
+ C2HSOOCC2HS > f £ J,,
5 O
731 C. R. Hauser and H. G. Walker, Jr., /. Amer. Chem. Soc, 69, 295 (1947).
732 J. K. H. Inglis and K. C. Roberts, Org. Syn., 6, 36 (1926).
733 H. Scheibler, Ann. Chem., 565, 176 (1949).
734 O. D. Frampton and J. F. Nobis, Ind. Eng. Chem., 45, 404 (1953).
735 F. Kuiban, S. Chilyanu, and F. Shcherbesku, Med. Prom. S.S.S.R. 12, No. 10, 36
(1958); Chem. Abstr., 53, 16139 (1959).
736 A. Magnani and S. M. McElvain, Org. Syn., 20, 32 (1940).
737 R. Mozingo, Org. Syn., 21, 42 (1941).