Cyclohexanone compounds

A -Chloromethylamine attacks ketones in alkaline solution with formation of oxaziranes with cyclohexanone, compound 17 is produced in 50% yield. The reaction with aldehydes with zV-chloromethyl-amine yields predominantly acid amides. However, oxaziranes are also produced here as by-products. From benzaldehyde and A -chloro-methylamine, 2-raethyl-3-phenyloxazirane (15) was obtained in 10% yield. 

Cycloaddition of furans followed by a subsequent transformation is still adopted as a useful strategy to prepare fluorine-containing benzene derivatives and isoquinoline compounds <00SL550>. The cycloaddition adduct can also be converted to a trifluoromethyl substituted cyclohexanone compound via hydrogenation and hydrolysis. Examples of these transformations are illustrated below. 

A systematic study on various salts used to catalyse the well known conversion of hex-S-enose derivatives into cyclohexanone compounds has revealed palladium(II) chloride to be the best, even working without the assistance of... 

Dissolve 8 8 g. (9 0 ml.) of cyclohexanone in 50 ml. of glacial acetic acid, add 8 ml. of phenylhydrazine, and boil the solution under reflux for 5 minutes. Cool the solution, when the tetrahydrocarbazole will crystallise out. Filter at the pump, drain well, and recrystallise either from aqueous ethanol or (better) from aqueous acetic acid. The recrystallisation should be performed rapidly, for the tetrahydrocarbazole undergoes atmO" spheric oxidation in hot solutions after recrystallisation, the compound should be dried in a vacuum desiccator and not in an oven. Repeated recrystallisation should be avoided. The tetrahydrocarbazole, after thorough drying, is obtained as colourless crystals, m.p. 118° yield of recrystallised material, 11 g. 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

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... 

Thermal decomposition of hydroxyalkyl hydroperoxyalkyl peroxides produces mixtures of starting carbonyl compounds, mono- and dicarboxyHc acids, cycHc diperoxides, carbon dioxide, and water. One specific hydroxyalkyl hydroperoxyalkyl peroxide from cyclohexanone (2, X = OH, Y = OOH) is a soHd that is produced commercially as a free-radical initiator and bleaching agent (see Table 5). On controlled decomposition, it forms 1,12-dodecanedioic acid (150). 

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). 

Hydrocarbon Oxidation. The oxidation of hydrocarbons (qv) and hydrocarbon derivatives can be significantly altered by boron compounds. Several large-scale commercial processes, such as the oxidation of cyclohexane to a cyclohexanol—cyclohexanone mixture in nylon manufacture, are based on boron compounds (see Cylcohexanoland cyclohexanone Eibers, polyamide). A number of patents have been issued on the use of borate esters and boroxines in hydrocarbon oxidation reactions, but commercial processes apparently use boric acid as the preferred boron source. The Hterature in this field has been covered through 1967 (47). Since that time the Hterature consists of foreign patents, but no significant appHcations have been reported for borate esters. 

Cyclohexanone purity is most readily deteanined by gas-Hquid chromatography over DC-710 or carbowax 20M-on-chromosorb. Impurities such as cyclohexane, ben2ene, cyclohexanol, and phenol do not interfere. In the absence of other carbonyl compounds cyclohexanone may be deterrnined by treatment with hydroxylamine hydrochloride, which forms the oxime, as follows ... 

Formation of a 1,2-disubstituted hydrazine by acid hydrolysis of an appropriately substituted pyrazolidine has been noted (67HC(22)l), but the most interesting ring fission of pyrazolidines involves the N(l)—N(2) bond of 1-phenylpyrazolidines (421). If, instead of phenylhydrazone, compound (421) is used in the Fischer indole synthesis, N- aminopropylin-doles are formed (73T4045). Scheme 39 shows the reaction with cyclohexanone. 

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). 

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 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. 

More frequently either methyl ethyl ketone peroxide or cyclohexanone peroxide is used for room temperature curing in conjunction with a cobalt compound such as a naphthenate, octoate or other organic solvent-soluble soap. The peroxides (strictly speaking polymerisation initiators) are referred to as catalysts and the cobalt compound as an accelerator . Other curing systems have been devised but are seldom used. 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

Common reagents such as lithium diisopropylamide (LDA see Chapter 11, Problem 5) react with carbonyl compounds to yield lithium enolate salts and diisopropylamine, e.g., for reaction with cyclohexanone. 

A variety of l,2,3,4-tetrahydro-j8-carbolines have been prepared from 3-piperidone phenylhydrazone derivatives. Used initially to obtain pentacyclic derivatives (35) related to the yohimbe alkaloids, this route was later extended to the synthesis of tetracyclic compounds (36). l-Methyl-5,6,7,8-tetrahydro-j8-carboline (37) was prepared in low yield by heating cyclohexanone 2-methyl-3-pyridylhydrazone with zinc chloride, a synthesis probably based on the similar preparation of the tetracyclic compound 38 starting from the corresponding quinolylhydrazine. Abramovitch and Adams extended this approach to the cyclization of cyclohexanone 3-pyri-dylhydrazone (39) itself. The main product was 6,7,8,9-tetrahydro-8-carboline (40), a smaller amount of the j8-isomer (41) also being obtained. This provides a convenient and readily reproducible route to the otherwise difficultly accessible 8-carboline ring system. The favored attack at carbon-2 over carbon-4 of the pyridine nucleus... 

Several improved methods for the preparation of known unsaturated azlactones as well as some interesting new compounds of this type have been reported. Crawford and Little observed that the direct use of 2-phenyl-5-oxazolone (1) in the Erlenmeyer reaction gave much improved yields (35-74%) of unsaturated azlactones with aliphatic aldehydes and with ketones such as acetone and cyclohexanone [Eq, (1)], The usual procedure of mixing a carbonyl compound, hippuric acid, acetic anhydride, and sodium (or lead) acetate affords poor yields in the aliphatic series. 

A synthesis of an indolo[3,2-fl]carbazole (2) was reported in 1951—the first preparation of a compound belonging to this class (Scheme 13). This was accomplished commencing with cyclohexanone, via conversion to the bishydrazone 108, which underwent Fischer indolization in glacial acetic acid to furnish the octahy-dro derivative 109. After a final dehydrogenation step, the desired product 2 was obtained (51JCS809). 

Compounds which contain two oxazirane rings are obtainable from Schiff s bases of glyoxal or terephthalic dialdehyde, e.g. (6). A bifunctional oxazirane is also obtained from ethylene diamine and cyclohexanone (7)d ... 

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