C-C linkage by replacement of OR by carbon 959If a compound containing an acidic CH group is treated with formaldehyde
and sodium benzenesulfinate the derived (phenylsulfonyl)methyl derivative
is formed; e.g., indole gives a 93% yield in the following reaction:
727CH 2 SO 2 C 6 H 5+ CH 2 O + C 6 H 5 SO 2 Na —^ » " ^IV. C-C linkage by replacement of OR by carbon- Ester condensation^10601 '^728
The designation "ester condensations" includes all reactions of carboxylic
or carbonic esters with compounds that contain an activated methylene or
methine group. These reactions occur in an alkaline medium, with loss of an
alcohol and formation of a new carbon-carbon bond, and can be formulated
generally as:
NaOR'
RCOOR' + CH 2 R"R"' > RCOCHR"R'" + R'OHA few of the many possible condensations are: that of two molecules of an
ester to give a /?-oxo ester, of an ester with a ketone to give a 1,3-diketone,
of a formic ester with a ketone to give a 3-oxo aldehyde, of an oxalic ester
with a ketone to give a dioxo ester, and of an alkyl carbonate with a nitrile
to give an #-cyano carboxylic ester.
The condensing agent may be an alkali metal (usually sodium), sodamide, a
sodium alkoxide, or sodium hydride.
729Sodium metal is used in the form of
wire or slices. If a group in one of the reactants is liable to alteration by "nas-
cent" hydrogen the use of a sodium alkoxide is indicated.
For some unknown reason, large batches often give better yields in ester
condensations than do small batches.
Care is essential when working with sodamide because it may detonate
violently for no visible reason; old samples, not entirely free from suspicion,
must without qualification be rejected. The following is a convenient and safe
method for preparation of sodamide:
730Powdered iron(m) nitrate hexahydrate is added to liquid ammonia (500 ml, placed in a
2-1 flask). The mixture is stirred and sodium (about 1 g) is added. Stirring is continued until
the blue color changes to grey, then further small pieces of sodium are introduced seriatim
as the color changes each time to grey, until all the sodium (26 g, 1.13 moles) has been added.
The mixture is finally stirred for a further 15 min after all the sodium has been added and the
(^727) H. Hellmann and K. Muller, Chem. Ber.
728 9 98, 638 (1965).
C. R. Hauser and B.E.Hudson, Jr., Org. Reactions, 1, 266 (1942); C. R. Hauser,
F. W. Swamer, and J. T. Adams, Org. Reactions, 8, 59 (1954).
(^729) F. B. La Forge and S. B. Soloway, /. Amer. Chem. Soc, 69, 2932, 2677 (1947); N.
Green and F. B. La Forge, /. Amer. Soc, 70, 2287 (1948).
(^730) T. H. Vaughn, R. R. Vogt, and J. A. Nieuwland, /. Amer. Chem. Soc, 56, 2120
(1934); A. C. Cope and E. M. Hancock, /. Amer. Chem. Soc, 60, 2644 (1938); D. A. Shirley,
"Preparation of Organic Intermediates," John Wiley and Sons, Inc., New York, 1951, p. 267;
E. M. Hancock and A. C. Cope, Org. Syn., IS, 25 (1945); K. N. Campbell and B. C. Camp-
bell, Org. Syn., 30, 72 (1950).