Morpholino-1-cyclohexene

A solution of 147 g. (1.50 moles) of cyclohexanone, 157 g. (1.80 moles) of morpholine (Note 1), and 1.5 g. of / -toluenesulfonic add in 300 ml. of toluene is heated to boiling in a 1-1. 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. D 1.5122-1.5129 (Note2). It weighs 180-200 g. (72-80%). 

An excess of morpholine is required because the water that separates during the reaction always contains a considerable amount of it in solution. 

1-Morpholino-l-cydohexene 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. 

The procedure is that of Hiinig, Benzing and Liicke. It is based on earlier work on the preparation of enamines.4 6 

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Methyl phenyl sulfide, see Thioanisole Methyl phenyl sulfoxide, 46, 78 from methylsulfinyl chloride and benzene with anhydrous alumi num chloride, 46, 80 Methyl vinyl ketone, reaction with 1-morpholino 1 cyclohexene, 45,... 

Thus, freshly prepared 1-morpholino-1-cyclohexene was mixed thoroughly with 16-DPA and basic alumina and this was irradiated in a dedicated... 

This triethanolamine procedure was used also in a synthesis of docosanedioiC acid starting with the condensation of cyclohexanone with morpholine to form 1 morpholino-1-cyclohexene (1), and acylation of this enamine with sebacoyl chlorid ... 

A conjugated nitrone, a-styryl /V-phenylnitrone (10m), also reacts with olefins to give the normal cycloadducts e.g., with styrene and allyl chloride, isoxazolidines of type I are formed.84 A reaction with 1-morpholino-1 -cyclohexene is described.85... 

Schaefer and Weinberg have reported (126) that the deuterolysis of 4-t-butyl-1-morpholino cyclohexene (477) produced specifically 2-8-deuterio-4-1 -butyl-cyclohexanone (478). Malhotra and Johnson (148) have shown that the enamine of 2-methylcyclohexanone gives on hydrolysis the oU-deuteromethylcyclohexanone 481. This enamine is known to exist in conformation 479 with the methyl group axial. Consequently, axial protonation must have taken place on 479 to give first the imini urn ion 480 which was then hydrolyzed to 481. 

A [2+4] cycloadduct is also obtained from N-(3-oxo-l-cyclohexenyl)-N -phenylcarbo-diimide and l-(l -morpholino)cyclohexene. ... 

M ethyl-1 -morpholino-cyclohexene (81) l-Dimethylamino-6-methylcydohexene (278) l-Diethylamino-6-methyl-cyclohexene (279) 6-Methyl-1 -( -methyl-JV-phenylamino)cyclo-hexene (280)... 

The reaction of ketene with the enamine (113) is reported (88) to give l-morpholino-2-acetyl-l-cyclohexene i.e., the enamino ketone expected from acylation of (113). The pyrrolidine enamine (28), however, has been shown to react (73) with excess ketene to give the a-pyrone (124). On the... 

Acryloyl chloride can be used to cause ring enlargement with the production of a bicyclodiketone when it is treated with a cyclohexanone enamine. This is shown by the reaction of acryloyl chloride (25) with 1-N-morpholino-1-cyclohexene (26), affording diketone 27 upon hydrolysis (32,33). 

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-... 

Dibenzofuranols are available by Michael addition of l-morpholino-1-cyclohexenes (198) to 1,4-benzoquinones (197, Scheme 50). Treatment of the intermediate adducts 199 with acid affords 6,7,8,9-tetrahydro-2-dibenzofuranols (200), which on dehydrogenation with sulfur or palladized charcoal afford the dibenzofuranols 201 in good yield. 

Analog erhalt man mit 1-Nitro-cyclohexen 9-Hydroxy-9-methyl-8-morpholino-l-nitro-bi-cyclo[4.3.0]non-7-en (Schmp. 180— 182°)1 ... 

Azadienes of this sort were studied simultaneously by Mariano et al., who reacted mixtures of (1 ,3 ) and (1E, 3Z)-l-phenyl-2-aza-l,3-pentadiene 275 with several electron-rich alkenes, e.g., enamines and enol ethers (85JOC5678) (Scheme 61). They found the (l ,3 )-stereoisomer to be reactive in this process affording stereoselectively endo 276 or exo 277 piperidine cycloadducts in 5-39% yield, after reductive work-up with sodium borohydride. The stereochemistry of the resulting adducts is in agreement with an endo transition state in the case of dienophiles lacking a cis alkyl substituent at the /8-carbon (n-butyl vinyl ether, benzyl vinyl ether, and 1-morpholino cyclopentene), whereas an exo transition state was involved when dihydropyrane or c/s-propenyl benzyl ether were used. Finally, the authors reported that cyclohexene and dimethyl acetylenedi-carboxylate failed to react with these unactivated 2-azadienes. 

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... 

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