Reduction, aromatic carbonyl groups

The methods which are available for the protection of the aromatic carbonyl group are similar to those for the aliphatic and alicyclic analogues (Section 5.8.8, p. 623). It should be noted however, that when a cyclic acetal is used as the protecting group, a Birch reduction (Section 7.5) on the protected compound usually results in hydrogenolysis of the protecting acetal. 

Figure 1. The combination of NaBH4 reduction of aromatic carbonyl groups and methylation of phenolic hydroxyl groups delays light-induced yellowing for 1.5 hours (data obtained from reference 13).

Since aliphatic aldehydes and ketones are not hydrogenated over palladium, this reaction provides a means of selectively removing an aromatic carbonyl group in the presence of an aliphatic aldehyde or ketone (Eqn. 18.10).32 The palladium catalyzed hydrogenolysis of aryl aldehydes and ketones is preferable to any of the chemical reduction procedures such as the Wolff-Kishner or Clemmenson reactions for the removal of an aryl carbonyl group. 

Effect of Aromatic Carbonyl Croups The action spectra of Forsskahl and Tylli show that light of 320-330 nm induces yellowing most efficiently, consistent with the hypothesis that aromatic carbonyl groups are the most important sensitizers of the reactions. However, several authors [124,125] have noted that thorough borohydride reduction of mechanical pulps reduces light-induced yellowing only marginally. 

One of the most common uses of [ C]acetyl chloride is its Lewis acid- (AICI3, SnCLi) catalyzed Friedel-Crafts reaction with aromatic or heteroaromatic substrates to produce labeled aryl/heteroaryl methyl ketones. As these intermediates are subject to several types of transformations, they have been used as key intermediates for the synthesis of a wide variety of a,)8-functionalized aryl/heteroaryl alkyl target compounds. For example, aryl/ heteroaryl methyl ketones can be (a) halogenated in the methyl group to provide substrates for reaction with carbon or nitrogen nucleophiles, (b) deprotonated so as to react with appropriate electrophilic partners, (c) subjected to stereoselective carbonyl group reduction to alcohols, or (d) reduced to aryl/heteroaryl alkyls. Such transformations can be conducted sequentially in many combinations. 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

The styrene double bond in 9(ll)-dehydroestradiol 3-methyI ether (1) or its 8-dehydro counterpart is reduced by potassium or lithium in ammonia without affecting the aromatic ring estradiol 3-methyl ether (2) is formed from both compounds. Reduction of the corresponding 17-ketones occurs with partial or complete reduction of the carbonyl group. Lithium... 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

An isoindol1 none moiety forms part of the aromatic moiety of yet another antiinflammatory propionic acid derivative. Carboxylation of the anion from -nitro-ethylbenzene (45) leads directly to the propionic acid (46). Reduction of the nitro group followed by condensation of the resulting aniline (47) with phthalic anhydride affords the corresponding phthalimide (48). Treatment of that intermediate with zinc in acetic acid interestingly results in reduction of only one of the carbonyl groups to afford the isoindolone. There is thus obtained indoprofen (49). ... 

Condensation of adipic acid derivative 17 with phenylethylamine in the presence of carbo-nyldiimidazole affords the bis-adipic acid amide 18. The synthesis is completed by reduction of the carbonyl groups with diborane followed by demethylation of the aromatic methoxy groups with hydrogen bromide the afford dopexamine (19) [3]. 

Aldehydes and ketones are similar in their response to hydrogenation catalysis, and an ordering of catalyst activities usually applies to both functions. But the difference between aliphatic and aromatic carbonyls is marked, and preferred catalysts differ. In hydrogenation of aliphatic carbonyls, hydrogenolysis seldom occurs, unless special structural features are present, but with aryl carbonyls either reduction to the alcohol or loss of the hydroxy group can be achieved at will. 

A variety of catalysts including copper, nickel, cobalt, and the platinum metals group have been used successfully in carbonyl reduction. Palladium, an excellent catalyst for hydrogenation of aromatic carbonyls is relatively ineffective for aliphatic carbonyls this latter group has a low strength of adsorption on palladium relative to other metals (72,91). Nonetheless, palladium can be used very well with aliphatic carbonyls with sufficient patience, as illustrated by the difficult-to-reduce vinylogous amide I to 2 (9). 

Platinum, especially as platinum oxide, has been used by many investigators. If this catalyst contains residual alkali, it is apt to be ineffective for aromatic ring reduction unless an acidic solvent is used (1,3,19) or unless the compound also contains a carbonyl group, as in acetophenone, where 1,4-and 1,6-addition are possible (46). Nickel, unless especially active, requires vigorous conditions—conditions that may promote side reactions. 

Reduction of carbonyl groups Terpene and aromatic aldehydes (lOOppm) were reduced by microalgae. In a series of chlorinated benzaldehyde, m - or p-chlorobenzaldehyde reacted faster than the o-derivative. Due to toxicity, the substrate concentrations are difficult to increase. Asymmetric reductions of ketones by microalgae were reported. Thus, aliphatic " and aromatic " ketones were reduced. 

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