A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1961, 41, 65
DOI: 10.15227/orgsyn.041.0065
[Morpholine, 4-(1-cyclohexenyl)-]
Submitted by S. Hünig, E. Lücke, and W. Brenninger1.
Checked by B. C. McKusick and F. E. Mumford.
1. Procedure
A solution of 147 g. (1.50 moles) of cyclohexanone, 157 g. (1.80 moles) of morpholine (Note 1), and 1.5 g. of p-toluenesulfonic acid in 300 ml. of toluene is heated to boiling in a 1-l. round-bottomed flask to which is attached a water separator2 under a reflux condenser. The separation of water begins at once and ceases after 4 or 5 hours. An indented Claisen stillhead is attached to the flask, and the reaction mixture is distilled. Most of the toluene is removed at atmospheric pressure. 1-Morpholino-1-cyclohexene is collected as a colorless liquid at 118–120°/10 mm.; nD25 1.5122–1.5129 (Note 2). It weighs 180–200 g. (72–80%).
2. Notes
1. An excess of morpholine is required because the water that separates during the reaction always contains a considerable amount of it in solution.
2. 1-Morpholino-1-cyclohexene is very easily hydrolyzed. Accordingly one must be careful to keep moisture out. On long standing in a refrigerator, the compound generally becomes somewhat yellowish, but this does not affect its usefulness in subsequent reactions.
3. Discussion
The procedure is that of Hünig, Benzing and Lücke.3 It is based on earlier work on the preparation of enamines.4,5
4. Merits of Preparation
This is a general method of preparing enamines from a secondary aliphatic amine and cyclohexanone or cyclopentanone. Acylation of such enamines is the first step in a general procedure for increasing the chain length of a carboxylic acid by 5 or 6 carbon atoms and of a dicarboxylic acid by 10 or 12 carbon atoms.6 Alkylation of enamines of cyclohexanones by alkyl halides5,7 or electrophilic olefins,8 followed by hydrolysis, is a good route to α-monoalkylcyclohexanones. The chemistry of enamines has been reviewed.9
This preparation is referenced from:

References and Notes
  1. University of Marburg, Marburg, Germany.
  2. S. Natelson and S. Gottfried, Org. Syntheses, Coll. Vol. 3, 381 (1955).
  3. S. Hünig, E. Benzing, and E. Lücke, Ber., 90, 2833 (1957).
  4. M. E. Herr and F. W. Heyl, J. Am. Chem. Soc., 74, 3627 (1952); 75, 1918 (1953).
  5. G. Stork, R. Terrell, and J. Szmuszkovicz, J. Am. Chem. Soc., 76, 2029 (1954).
  6. S. Hünig, E. Lücke, and E. Benzing, this volume, p. 533; Ber., 91, 129 (1958); S. Hünig and E. Lücke, Ber., 92, 652 (1959); S. Hünig and W. Lendle, Ber., 93, 909, 913 (1960).
  7. D. M. Locke and S. W. Pelletier, J. Am. Chem. Soc., 80, 2588 (1958).
  8. G. Stork and H. K. Landesman, J. Am. Chem. Soc., 78, 5128 (1956).
  9. J. Szmuszkovicz., Advan. Org. Chem., 4, 1 (1963).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

Cyclohexanone (108-94-1)

carbon (7782-42-5)

toluene (108-88-3)

Cyclopentanone (120-92-3)

morpholine (110-91-8)

Morpholine, 4-(1-cyclohexenyl)- (670-80-4)

p-toluenesulfonic acid (104-15-4)