Cyclohexanone, preparation

Malhotra et al. (5pyrrolidine enamine of 3-methyl-cyclohexanone, prepared under equilibrating conditions, is a 3 7 mixture of A and A isomers (67 and 68) on the basis of NMR spectral data. The preponderance of the A isomer in the mixture was attributed to strain between the equatorial methyl group and the vinylic hydrogen atom... 

The asymmetric syntheses of 2-alkylcyclohexanones can be effected by the alkylation of the anions of chiral imines of cyclohexanones, prepared from either chiral a-amino-acid esters or chiral polymer-bound amines. Similarly, anions of chiral phenylethyl aldimines are alkylated to give an asymmetric aldehyde synthesis. ... 

Adipic acid is conveiiiently prepared by the oxidation of cyc/ohexanol (or cyclohexanone) with concentrated or with 50 per cent, nitric acid ... 

An interesting application is the preparation of 1 2 3 4-tetrahydrocarb azole (VI), which is formed when phenylhydrazine is added to a boiling aolutiai of cyclohexanone in acetic acid the plienylhydrazone (V) Intermediately produced undergoes ring closure directly ... 

Diacetates of 1,4-butenediol derivatives are useful for double allylation to give cyclic compounds. l,4-Diacetoxy-2-butene (126) reacts with the cyclohexanone enamine 125 to give bicyclo[4.3.1]decenone (127) and vinylbicy-clo[3.2.1]octanone (128)[85,86]. The reaction of the 3-ketoglutarate 130 with cij-cyclopentene-3,5-diacetate (129) affords the furan derivative 131 [87]. The C- and 0-allylations of ambident lithium [(phenylsulfonyl)methylene]nitronate (132) with 129 give isoxazoline-2-oxide 133, which is converted into c -3-hydroxy-4-cyanocyclopentene (134)[S8]. Similarly, chiral m-3-amino-4-hyd-roxycyclopentene was prepared by the cyclization of yV-tosylcarbamate[89]. 

When planning the synthesis of a compound using an organometallic reagent or indeed any synthesis the best approach is to reason backward from the product This method is called retrosynthetic analysis Retro synthetic analysis of 1 methylcyclohexanol suggests it can be prepared by the reaction of methylmagnesmm bromide and cyclohexanone... 

Organic chemists often use enantiomencally homogeneous starting materials for the synthe SIS of complex molecules (see Chiral Drugs p 296) A novel preparation of the S enantiomer of compound B has been descnbed using a bacterial cyclohexanone monooxygenase enzyme system... 

Ketones are an important class of industrial chemicals that have found widespread use as solvents and chemical intermediates. Acetone (qv) is the simplest and most important ketone and finds ubiquitous use as a solvent. Higher members of the aUphatic methyl ketone series (eg, methyl ethyl ketone, methyl isobutyl ketone, and methyl amyl ketone) are also industrially significant solvents. Cyclohexanone is the most important cycHc ketone and is primarily used in the manufacture of y-caprolactam for nylon-6 (see Cyclohexanoland cyclohexanone). Other ketones find appHcation in fields as diverse as fragrance formulation and metals extraction. Although the industrially important ketones are reviewed herein, the laboratory preparation of ketones is covered elsewhere (1). 

A Methylamino)phenol. This derivative, also named 4-hydroxy-/V-methy1ani1ine (19), forms needles from benzene which are slightly soluble in ethanol andinsoluble in diethyl ether. Industrial synthesis involves decarboxylation of A/-(4-hydroxyphenyl)glycine [122-87-2] at elevated temperature in such solvents as chlorobenzene—cyclohexanone (184,185). It also can be prepared by the methylation of 4-aminophenol, or from methylamiae [74-89-5] by heating with 4-chlorophenol [106-48-9] and copper sulfate at 135°C in aqueous solution, or with hydroquinone [123-31 -9] 2l. 200—250°C in alcohoHc solution (186). 

PUtzing erReaction. Quinoline-4-carboxyhc acids are easily prepared by the condensation of isatin [91-56-5] (16) with carbonyl compounds (50). The products may be decarboxylated to the corresponding quinolines. The reaction of isatin with cycHc ketones has been reported, eg, the addition of cyclohexanone gives the tricycHc intermediate (17) [38186-54-8] which upon oxidation produces quinoline-2,3,4-tricarboxyhc acid [16880-83-4] (51). 

Cyclohexanone [108-94-17 is a colorless, mobile Hquid with an odor suggestive of peppermint and acetone. Cyclohexanone is used chiefly as a chemical iatermediate and as a solvent for resias, lacquers, dyes, and iasecticides. Cyclohexanone was first prepared by the dry distillation of calcium pimelate [19455-79-9] OOC(CH2 )5COO Ca , and later by Bouveault by the catalytic dehydrogenation of cyclohexanol. 

G-20 Dicarboxylic Acids. These acids have been prepared from cyclohexanone via conversion to cyclohexanone peroxide foUowed by decomposition by ferrous ions in the presence of butadiene (84—87). Okamura Oil Mill (Japan) produces a series of commercial acids based on a modification of this reaction. For example, Okamura s modifications of the reaction results in the foUowing composition of the reaction product C-16 (Linear) 4—9%, C-16 (branched) 2—4%, C-20 (linear) 35—52%, and C-20 (branched) 30—40%. Unsaturated methyl esters are first formed that are hydrogenated and then hydrolyzed to obtain the mixed acids. Relatively pure fractions of C-16 and C-20, both linear and branched, are obtained after... 

The type of synthesis in which the two-atom fragment supplies C-5 + C-6 is uncommon but useful in preparing pyrimidine- and 5,6,7,8-tetrahydroquinazoline-2,4-diamines. Thus, dicyandiamide (S78) with benzyl methyl ketone (S77) yields 6-methyl-5-phenylpyrimidine-2,4-diamine (S79), or with acetophenone it yields 6-phenylpyrimidine-2,4-diamine (62JOC2708). Likewise, with cyclohexanone it yields the tetrahydroquinazolinediamine (SSO) and by using N- substituted dicyandiamides, 2- and/or 4-alkylamino groups may be introduced (65JOC1837). 

The reaction of vinylogous amides, or ketoaldehydes, with hydroxylamine produced 4,5,6,7-tetrahydro-l,2-benzisoxazole. A side product is the 2,1-benzisoxazole (Scheme 173) (67AHC(8)277). The ring system can also be prepared by the reaction of cyclohexanone enamines with nitrile oxides (Scheme 173) (78S43, 74KGS901). Base treatment produced ring fission products and photolysis resulted in isomerization to benzoxazoles (76JOC13). 

Also due to the high barrier of inversion, optically active oxaziridines are stable and were prepared repeatedly. To avoid additional centres of asymmetry in the molecule, symmetrical ketones were used as starting materials and converted to oxaziridines by optically active peroxyacids via their ketimines (69CC1086, 69JCS(C)2648). In optically active oxaziridines, made from benzophenone, cyclohexanone and adamantanone, the order of magnitude of the inversion barriers was determined by racemization experiments and was found to be identical with former results of NMR study. Inversion barriers of 128-132 kJ moF were found in the A-isopropyl compounds of the ketones mentioned inversion barriers of the A-t-butyl compounds lie markedly lower (104-110 kJ moF ). Thus, the A-t-butyloxaziridine derived from adamantanone loses half of its chirality within 2.3 days at 20 C (73JCS(P2)1575). 

To prepare alkylhydrazlnes, cyclohexanone is treated with a primary amine and hydroxyl-amine-O-sulfonic acid in a one-pot procedure hydrolysis to the alkylhydrazine is carried out without isolation of the diaziridine (68JPR(37)257). Yields are between 60 and 70%. 

The cyclohexylidene ketal, prepared from a catechol and cyclohexanone (AI2O3/ TsOH, CH2CI2, reflux, 36 h), is stable to metalation conditions (RX/BuLi) that cleave aiyl methyl ethers. The ketal is cleaved by acidic hydrolysis (coned. HCl/ EtOH, reflux, 1.5 h, 20°, 12 h) it is stable to milder acidic hydrolysis that cleaves tetrahydropyranyl ethers (1 AHCl/EtOH, reflux, 5 h, 91% yield). ... 

We present here examples of this condensation with an aromatic aldehyde and a cyclic ketone. Both of these examples are useful because, although other methods are available for their preparation, problems often attend these syntheses. In the synthesis of cyclohexy11deneaceton1tr11e, for example, the standard method results exclusively In the g.y-lsomer and none of the a,g-Isomer. In Part A of this procedure, cyclohexanone Is condensed with acetonitrile to give predominantly the conjugated Isomer (80-83%) whicfi is then separated from the nonconjugated isomer by selective bromination. 

Other methods for the preparation of cyclohexanecarboxaldehyde include the catalytic hydrogenation of 3-cyclohexene-1-carboxaldehyde, available from the Diels-Alder reaction of butadiene and acrolein, the reduction of cyclohexanecarbonyl chloride by lithium tri-tcrt-butoxy-aluminum hydride,the reduction of iV,A -dimethylcyclohexane-carboxamide with lithium diethoxyaluminum hydride, and the oxidation of the methane-sulfonate of cyclohexylmethanol with dimethyl sulfoxide. The hydrolysis, with simultaneous decarboxylation and rearrangement, of glycidic esters derived from cyclohexanone gives cyclohexanecarboxaldehyde. 

The unsaturated tetraoxaquaterene (accompanied by linear condensation products) was first synthesized in 18.5% yield by the acid-catalyzed condensation of furan with acetone in the absence of added lithium salts. Other ketones also condensed with furan to give analogous products in 6-12% yield.A corresponding macrocycle was also prepared in 9% yield from pyrrole and cyclohexanone. The macrocyclic ether products have also been obtained by condensation of short linear condensation products having 2, 3, or 4 furan rings with a carbonyl compound. ... 

It is interesting to note that these crystalline materials do not dissolve in tetrahydrofuran or cyclohexanone at room temperature, indicating that PVC is too weak a proton donor to overcome extensive crystallisation. Crystalline PVC has a greater tensile strength and creep resistance than conventional polymer. It is, however, brittle, and whilst most conventional impact modifiers appear ineffective, EVA polymers are said to be quite useful. Plasticised compounds may also be prepared although mixing temperatures of up to 190°C are necessary. 

Typically, the reaetion would be carried out at 140°C in white spirit with potassium carbazole as a catalyst. Davidge ° has reported problems in polymerisation of V-vinyl carbazole prepared from carbazole obtained from coal tar, attributing this to the presence of sulphur. To overcome these problems carbazole has been prepared synthetically by reactions of cyclohexanone with... 

Triphenylene has been prepared by self-condensation of cyclohexanone using sulfuric acid or polyphosphoric acid followed by dehydrogenation of the product, palladium-charcoal, or selenium by electrolytic oxidation of cycloliexanone from chlorobenzene and sodium or phenyllilhium from 2-cyclolu xyl-l-phenylcyelohexanol or... 

The spiro peroxide A, which is readily prepared from cyclohexanone and hydrogen peroxide, decomposes thermally to give substantial amounts of cyclodecane (B) and... 

---