1-Morpholino-l -

A mixture of 100 g (0.6 mole) of 1-morpholino-l-cyclohexene, 28.8 g (0,4 mole) of /3-propiolactone, and 100 ml of chlorobenzene is placed in a 500-ml round-bottom flask fitted with a condenser (drying tube). The mixture is refluxed for 4 hours. The solvent and excess enamine are removed by distillation at aspirator pressure. (The residue may be distilled to afford the pure morpholide, bp 187-18871 rnm, 1.5090.) Basic hydrolysis may be carried out on the undistilled morpholide. To the crude amide is added 400 ml of 10% sodium hydroxide solution. The mixture is cautiously brought to reflux, and refluxing is continued for 2 hours. The cooled reaction mixture is made acidic (pH 4) and is extracted three times with ether. The combined ether extracts are washed twice with 5 % hydrochloric acid solution and twice with water. The ethereal solution is dried (sodium sulfate), then filtered, and the solvent is removed (rotary evaporator). The residue may be recrystallized from petroleum ether-benzene, mp 64°. 

Morpholino-l-cyclohexene (Chapter 9, Section I) A Methyl vinyl ketone MCB, A... 

A. 2,2 Sebacoyldicyclokexanone. A solution of 167 g. (1.00 mole) of 1-morpholino-l-cyclohexene 2 and 101 g. (139 ml., 1.00 mole) of anhydrous triethylamine in 500 ml. of dry chloroform (Note 1) is put in a 5-1., three-necked, round-bottomed flask equipped with a mechanical stirrer, a dropping funnel, and a reflux condenser. Tubes of calcium chloride are inserted in the open ends of the dropping funnel and reflux condenser. The reaction flask is immersed in a water bath at 35°, and a solution of 120 g. (0.50 mole) of sebacoyl chloride (Note 2) in 200 ml. of dry chloroform is added to the well-stirred reaction mixture over a period of about 1.5 hours. The reaction mixture gradually as-... 

Molecular orbital theory, 329 m-Mononitroazoxybenzene, 365 1-Morpholino-l-cyclohexene, 92 trans-1 -(4-Morpholino)-l, 2-diphenylethy-trans-1 -(4-Morpholino)-1,2-diphenylethy-lene, 106... 

Morpholino-l-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. 

Enamines contain electron-rich double bonds and thus react readily with azides (in many cases at room temperature). Only one addition product is formed, namely a 5-amino-A2-triazoline, a result of electronic control.22 -223 Thus l-(p-nitrophenyl)-4-ethyl-5-morpholino-A2-triazoline (44) arises from the addition of p-nitrophenyl azide to 1-morpholino-l-butene (43). The addition products rearrange by heating into amidines (45).224... 

Simpler alkenylmorpholines, such as 4-vinylmorpholine (148), would seem to be interesting heterocyclic monomers. While monomer (148) is unstable, substituted enamines such as 1-morpholino-l-butene (149) have been incorporated into copolymers with acrylonitrile. Copolymers containing up to 30% of units derived from monomer (148), however, may be prepared according to Scheme 45 (70MI11102). 

Several groups have described syntheses of chromones which involve the use of enamines. Reaction of salicylaldehyde with 1-morpholinocyclohexene gives the chromanol which is readily oxidized to the chromone (66JOC1232). Other examples include the use of 1-morpholino-l-phenylethylene which gives flavene, whilst N-styrylmorpholine yields isoflavone. The enamine reaction is considered to proceed in the normal manner with subsequent cyclization involving the neighbouring phenolic group (Scheme 163). 

Perfluoro-2-methyl-2-penten-3-yl isothiocyanate, which was prepared from perfluoro-2-methyl-2-pentene and KSCN in benzonitrile in high yield by direct substitution of fluorine, is a stable and versatile educt for heterocyclic synthesis. This a,p-unsaturated isothiocyanate reacted with enamines, such as 1-methylindole and 2-methyl-1-morpholino-l-propene, to yield 2-(l-methylindol-3-yl)-perfluro-4,5-dihydro-5,5-dimethyl-4-ethylidene-l,3-thiazole and its analogue in fair yield. [95H1015]... 

From a preparative point of view, the acylation of ketones via enamines is of particular interest. In comparison with pyrrolidine and piperidine enamines, the less reactive morpholine enamines give better yields, as found by Hiinig et al.2iZ j8-Diketones are the products of acylation with an acyl halide followed by acid hydrolysis, whereas with ethyl chloroformate, /J-ketoesters are obtained.212 Hiinig and his collaborators242-247 have used the acylation of 1-morpholino-l-cyclopentene and 1-morpholino-l-cyclohexene to lengthen the chains of acids by five and six carbon atoms, respectively. The reaction may... 

Treatment of 1-morpholino-l-cyclohexene with ketene gives l-morpholino-2-acetyl-l-cyclohexene251 as the main product, whereas enamines prepared from aliphatic aldehydes yield cyclo-butanones.252,253 Ketene may be generated directly in the reaction medium from acid chlorides and triethylamine. 

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