Of cyclohexanone and morpholine

Condensation, of carbon dioxide and sodium methyl-i-acetylide, 42,97 of cyclohexanone and morpholine, 41, 65... 

The presence of 1,3-diaxial interaction between the C-2 alkyl group and the C-4 axial hydrogen atom is reflected in the rate of enamine formation of 2-substituted cyclohexanone. It has been shown by Hunig and Salzwedel (20) that even under forcing conditions, the yield of pyrrolidine and morpholine enamines of 2-methylcyclohexanone does not exceed 58%, whereas the C-2 unsubstituted ketones underwent enamine formation under rather milder conditions in better than 80 % yield. 

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 ... 

With 2-nitropropene as the acceptor, the enamine derived from cyclohexanone and morpholine at 0°C in ether gives heterocycle 4.1. If 4.1 is warmed to 25-30°C or if the reaction is carried out in acetonitrile (< 0°C) a mixture of the regioisomeric enamines 4.2 and 4.3 is formed. Addition of the same enamine to 1-nitropropene in petroleum ether at 0°C gives the product with the less substituted enamine (4.4, Eq. [2]). 

P,P] Risaliti and co-workers in 1966 reported the stereoselective additions of enamines derived from cyclohexanone and morpholine, piperidine, and pyrrolidine to / -nitrostyrene (Eq. [1], Scheme 15) (34). The less-substituted enamines of the general structure 15.1 were isolated prior to hydrolysis. The location of the double bond of 15.1 was established by H-NMR spectroscopy and by addition to diethyl azodicarboxylate. The... 

The interaction of enamines with sulphur in conjunction with carbon disulphide, isocyanates, or isothiocyanates results in the production of sulphur-containing heterocyclics. Cyanamide has now been shown to participate in this reaction. Treatment of enamines of type (24) with sulphur and cyanamide at room temperature in ethanol produces a range of 2-aminothiazoles (27) in 30—70% yield no catalyst is required. Initial formation of the thiolated intermediate (25) is probably followed by addition of cyanamide, yielding (26) elimination of amine finally produces the observed thiazoles (27). Since AW-dialkylcyanamides do not undergo this reaction, cyanamide may react as the tautomeric carbodi-imide. An actual example of the reaction employing the enamine derived from cyclohexanone and morpholine is also shown [(28) - (29)]. ... 

Chloral forms well-crystallized adducts (126) with diaziridines containing at least one NH group (B-67MI50800). Carbonyl addition products to formaldehyde or cyclohexanone were also described. Mixtures of aldehydes and ammonia react with unsubstituted diaziridines with formation of a triazolidine ring (128). Fused diaziridines like (128) are always obtained in ring synthesis of diaziridines (127) from aldehyde, ammonia and chloramine. The existence of three stereoisomers of compounds (128) was demonstrated (76JOC3221). Diaziridines form Mannich bases with morpholine and formaldehyde (64JMC626), e.g. (129). 

The reaction of morpholine enamine of cyclohexanone with 1 mole of phenyl isocyanate has been reported (30,31) to give the monoadduet (49), consisting largely of the trisubstituted isomer, and with 2 moles of phenyl isocyanate, the bis adduct (50). That the bis adduct is a dicarboxyanilide rather than a urea derivative (32) such as 51 was shown by its mild hydrolysis to the ketone (52). Reaction of the morpholine enamine of 2-methylcyclo-... 

In their original communication on the alkylation and acylation of enamines, Stork et al. (3) had reported that the pyrrolidine enamine of cyclohexanone underwent monoacylation with acid chlorides. For example, the acylation with benzoyl chloride led to monobenzoylcyclohexanone. However, Hunig and Lendle (33) found that treatment of the morpholine enamine of cyclopentanone with 2 moles of propionyl chloride followed by acid hydrolysis gave the enol ester (56), which was proposed to have arisen from the intermediate (55). 

Campbell and Jung (34) have reported that the reaction of 2 moles of o-halo-substituted benzoyl chloride with the morpholine enamine of cyclohexanone gave the corresponding 2,2-dibenzoyI derivative (57). 

The piperidine, pyrrolidine, and morpholine enamines of cyclohexanone substituted in the 3-position by methyl, phenyl, and l-butyl have been prepared (49). The complexity of the NMR spectra in the ethylenic hydrogen region indicated a mixture of isomeric enamines. Estimation of the per cent of each isomer by examination of the NMR spectra was not possible, nor were the isomeric enamines separable by vapor-phase chromatography. 

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

Cyanoallene, when treated with the morpholine enamine of cyclohexanone, undergoes a 1,3-cycloaddition reaction to form 72 (89). The reaction between cyanoallene and diendiamine 73a produces di-1,2-cycloaddition adduct 73 (i 9). The 4a-azonioanthracene ion (73b) readily undergoes a 1,4-cycloaddition reaction with nucleophilic dienophiles such as enamines (89a). The cycloaddition is stereoselective so that the a- and... 

The synthesis of a large number of y-pyrones and y-pyranols from enamines has been brought about through the use of a wide variety of bifunctional molecules. These molecules include phenolic aldehydes (126,127), phenolic Mannich bases (128), ketal esters (129), and diketene (120-132). All of these molecules have an electrophilic carbonyl group and a nucleophilic oxygen center in relative 1,4 positions. This is illustrated by the reaction between salicylaldehyde (101) and the morpholine enamine of cyclohexanone to give pyranol 102 in a quantitative yield (127). 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

A 250-ml round-bottom flask is charged with a mixture of cyclohexanone (14.7 g, 0.15 mole), morpholine (15.7 g, 0.18 mole), and / -toluenesulfonic acid monohydrate (0.15 g) in 50 ml of toluene. The flask is fitted with a water separator and a condenser and is brought to reflux (mantle). The separation of water begins immediately and the theoretical amount (2.7 ml) is obtained in about 1 hour. Without further treatment, the reaction mixture may then be distilled. After removal of the toluene at atmospheric pressure, the product is obtained by distillation at reduced pressure, bp II8-I207IO mm, 1.5122-1.5129, in about 75% yield. 

Treated with ZnBr2 followed by enamines, phenyl thioethers 829 derived from aryl aldehydes are converted to (l-(phenylthio)alkyl ketones or aldehydes 830 in moderate to good yields (Equation 19). Enamines used in these syntheses are (1) morpholine enamine derived from diethyl ketone, (2) diethylamine enamine of propiophenone, (3) piperidine enamine derived from isovaleraldehyde, and (4) pyrrolidine enamine of cyclohexanone <2000H(53)331>. 

To a 500 ml, three-necked, round-bottomed flask equipped with a Dean and Stark trap, condenser, and stirrer is added a mixture of 52.5 gm (0.60 mole) of morpholine, 49 gm (0.5 mole) of cyclohexanone, 100 ml of toluene, and 0.5 gm ofp-toluenesulfonic acid. The contents are refluxed for approximately 4 hr to remove the water of reaction. The product mixture is cooled and then distilled to afford 59 gm (71 %) of the enamine, b.p. 117°-120°C (10 mm), n 5 1.5122-1.5129. Yields of enamine have been reported to vary from 71 to 80%. 

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 separator 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-... 

Unsaturated nitro compound and nitriles do not usually suffer nucleophilic attack by enols or enolates and both are good at conjugate addition. The addition of the morpholine enamine 57 of cyclohexanone to 58 demonstrates that the nitro group is more effective than the ester at promoting conjugate addition.7... 

The morphbiinBc enamitie of cyi clohexanone, 1-morpholino-l-cyclohexene, is prepared by refluxing a mixture of 1.5 moles of cyclohexanone, 1.8 moles of morpholine, 1.5 g. of p-toluenesultonic acid, and 300 ml. of toluene in a flask fitted with a water separator under a ireflux conden iser.- Separation of water commences at once... 

Preparation from a mixture of cyclohexanone, morpholine, toluene, and a trace of p-toluenesulfonic acid is described on page 706. 

---