Rings Ring Ketones

Five-ring ketones corresponding open-chain ketones 1750-1740 a,/3 Unsaturation, a,/3,a, /3 unsaturation, etc.. 

Four-ring ketones ca 1780 have a similar effect on these values as on those of open-chain ketones. 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

Moreover, fermentation of various a-substituted cycloalkanone enol esters results in optically active six-, eight-, ten-, and twelve-membered ring ketones with 70—96% ee (84). Isolated enzymes catalyze similar transformations, bacillus coagulans and Candida glindracea]i 2Lse OF (Meito Sangyo) hydrolyze a number of cycHc and acycHc enol esters, giving ketones in 40—80% yield and 14—85% ee (85,86). 

Synthesis of large ring alkanes and lactones from smaHer ring ketones via peroxides... 

The carbonyl group of the 17/ -acetyl side chain is generally less reactive than nonhindered 6-membered ring ketones and more reactive than the pentacychc 17-ketone. Changes in the environment of the carbonyl group may however alter the reactivity relationships. Thus substitutions at C-17 and C-21 strongly reduce the reactivity of the 20-ketone. 

A-ring conjugated ketones do not normally interfere with the epoxidation reaction, but hydride reduction will reduce any ketone groups to alcohols. These can be reoxidized by conventional means. 

A-ring unsaturated ketones and the sensitive 11 j5-hydroxyl group will survive conditions of the Mattox rearrangement. 

Treatment of 5a-cholestanone (lb) in this way gives a mixture from which 7-and 8-membered ring ketones can be isolated. The yields of crude ketones are A-homo-4-one (3b), 40-50% A-homo-3-one (5b), 10% and a A-bis-homo ketone 5 %. The structure of the bis-homocholestanone has not been rigorously established. 

Johnson s procedure can be used to prepare A-homo-4a-ene-3-keto steroids or, more generally, any 7-membered ketone having an olefinic linkage. For simple saturated 6-ring ketones, Parham s procedure offers an alternate approach to the preparation of cycloheptenones. 

Reaction of the morpholine or piperidine enamine of cyclopentanone, however, gives an unstable adduct which rearranges under the reaction conditions and an aqueous work-up to give the ring expanded ketone 2-chloro-2-cyclohexen-l-one (203) (138,139). 

Enamines formed in this way may be distilled or used in situ. The ease of formation of the enamine depends on the structure of the secondary amine as well as the structure of the ketone. Thus pyrrolidine reacts faster than morpholine or piperidine, as expected from a rate-controlling transition state with imonium character. Six-membered ring ketones without a substituents form pyrrolidine enamines even at room temperature in methanol (20), and morpholine enamines are generated in cold acetic acid (21), but a-alkylcyclohexanones, cycloheptanone, and linear ketones react less readily. In such examples acid catalysis with p-toluenesulfonic acid or... 

Similarly, the method has been applied to the synthesis of five- (244) and seven- (245,246) membered-ring ketone analogs of (0-tetralone. 

The formation of a-acetoxyketones by oxidation of enamines with thallic acetate has been studied in detail (27) and found to be of preparative value (80 % yields) particularly in five- and six-membered-ring ketone derivatives. Enamines of linear or seven-membered-ring ketones were oxidized also, but at very much slower rates. Enamines of aldehydes with a-hydrogen substituents underwent self-eondensations during the oxidation reactions. Lead tetraacetate was less satisfactory as an oxidizing agent. 

The chemical reduction of enamines by hydride again depends upon the prior generation of an imonium salt (111,225). Thus an equivalent of acid, such as perchloric acid, must be added to the enamine in reductions with lithium aluminum hydride. Studies of the steric course (537) of lithium aluminum hydride reductions of imonium salts indicate less stereoselectivity in comparison with the analogous carbonyl compounds, where an equatorial alcohol usually predominates in the reduction products of six-membered ring ketones. 

An enamine provides synthon (21) and the cleavage of (20) to (17) occurs in aqueous base. Attack on the slightly strained five-ring ketone isfaster than on the exocyclic ketone. 

In general, it is better to make such compounds by hydroxylation of the alkene, There is no problem with the alkene rearrangement here, the ring expanded ketone (20) being formed in good yield. This product can also be made by another rearrangement route (see p 120). Synthesis... 

The reaction of ketones with diazomethane sometimes leads to a ring-expanded ketone in synthetically useful yields.79 The reaction occurs by addition of the diazomethane, followed by elimination of nitrogen and migration. 

Some five- and six-membered ring ketones undergo efficient decarbonyla-tion upon photolysis ... 

Big ring ketones (cf. the acyloin condensation, p.218) may be obtained also by working at high dilution, i.e. the carbanion carbon atom then has a greater chance of reacting with the ester carbonyl carbon atom at the other end of its own chain than with one that is attached to a different molecule (intermolecular reaction). 

Das sonderbare Verhalten elektronen-angeregter 4-Ring-Ketone. 

The Peculiar Behavior of Electronically Excited 4-Membered Ring Ketones... 

---