Alcohols chloride reductions

The only industrially important processes for the manufacturing of synthetic benzaldehyde involve the hydrolysis of benzal chloride [98-87-3] and the air oxidation of toluene. The hydrolysis of benzal chloride, which is produced by the side-chain chlorination of toluene, is the older of the two processes. It is no longer utilized ia the United States. Other processes, including the oxidation of benzyl alcohol, the reduction of benzoyl chloride, and the reaction of carbon monoxide and benzene, have been utilized ia the past, but they no longer have any iadustrial appHcation. 

The mechanism of ester (and lactone) reduction is similar to that of acid chloride reduction in that a hydride ion first adds to the carbonyl group, followed by elimination of alkoxide ion to yield an aldehyde. Further reduction of the aldehyde gives the primary alcohol. 

This procedure illustrates a general method for the stereoselective synthesis of ( P)-disubstitnted alkenyl alcohols. The reductive elimination of cyclic /3-halo-ethers with metals was first introduced by Paul3 and one example, the conversion of tetrahydrofurfuryl chloride [2-(chloromethyl)tetrahydrofuran] to 4-penten-l-ol, is described in an earlier volume of this series.4 In 1947 Paul and Riobe5 prepared 4-nonen-l-ol by this method, and the general method has subsequently been applied to obtain alkenyl alcohols with other substitution patterns.2,6-8 (I )-4-Hexen-l-ol has been prepared by this method9 and in lower yield by an analogous reaction with 3-bromo-2-methyltetra-hydropyran.10... 

Halocarbons, ketone-alcohol reduction, 84 Halogenation, 4-methylbenzyl chloride [reductive halogenation of aldehyde to benzyl chloride], 124 Hemiacetals, reduction of, 97-99 Hemiaminals, reduction of, 99-100 Hemiketals, reduction of, 97-99 Heptene derivatives, alkene to alkane reductions, disubstituted alkenes, 36-38... 

Lithium aluminum hydride reduces acids, acid chlorides, anhydrides, and esters to primary alcohols. (The reduction of acids was covered in Section 20-13.) Acid chlorides are more reactive than the other acid derivatives. Either lithium aluminum hydride or sodium borohydride converts acid chlorides to primary alcohols. 

In the absence of alcohol the reduction may be halted at the dihydro stage, but with difficulty. Stoichiometric control (3 equiv. of metal) gives reasonable results, but it seems to be most effective to use 5 equiv. of lithium with added iron(III) chloride. Thus, from the reduction of (112), quenching with ammonium chloride gives either the 1,2- or 1,4-dihydro products (114) and (115), respectively, while reaction with methyl iodide affords excellent yields of the 2-methyl-1,2-dihydro derivatives (113 Scheme 20). 

Dimethylaniline has been prepared by reduction of the corresponding nitro compound, either chemically or catalyti-cally. It has been prepared from 3,4-dimethylphenol by heating with ammonia, ammonium bromide, and zinc bromide from w-toluidine hydrochloride by alkylation with methanol at high temperatures from anhydro-4-amino-2-methylbenzyl alcohol by dry distillation from calcium hydroxide from 2-methyl-S-aminobenzyl alcohol by reduction with sodium from 2-methyl-5-nitrobenzyl chloride and 2-methyl-S-nitrobenzyl acetate by catalytic reduction from o-xylene by direct amination with hy-droxylamine hydrochloride in the presence of aluminum chloride and from 3,4-dimethylacetophenone by the Beckmann rearrangement of the oxime.i" The present method has been published. ... 

Newer methods of chemical analysis led to the isolation of the major alkaloids from crude drug preparations. By 1833, aconitine, atropine, codeine, hyoscyamine, morphine, nicotine, and strychnine had been isolated from plants. Color tests for alkaloids were developed between 1861 and 1882 by 1890 quantitative analysis methods became available. Physiological tests for alkaloids, particularly strychnine, first used in 1856, were employed well into the twentieth century. Tests for alcohol, devised by Lieben (iodoform crystal test, 1870) and others, were later perfected for the quantitative analysis of alcohol in body fluids and tissues. Qualitative tests for carbon monoxide in the blood were developed about this time and in 1880, Fodor developed a palladium chloride reduction method to quantitate carbon monoxide in blood. 

Access to the aldehyde function has always been very important in organic chemistry. The two main transformations to introduce this function are oxidation of a primary alcohol to the aldehyde or reduction of an acid derivatives to the aldehyde. This second reaction has not found any general simple solution. If some progress has been made, the main methods used today are either the Rosenmund10 reaction on the acid chloride, reduction of the ester using a sophisticated hydride, or reduction of the ester to the alcohol followed by reoxidation of the alcohol function to the aldehyde. 

A newly discovered alkaloid, cherylline, has been shown to have a novel structure (5) derived from 4-phenylisoquinoline. It has been synthesised from the appropriate benzophenone by way of the alcohol, chloride, nitrile, and primary amine, followed by formylation, isoquinoline ring closure, reduction, and methylation. ... 

Michael addition of methyl vinyl ketone to 24, followed by base-catalyzed cyclization, afforded the j8-diketone 25. Reaction of 25 with phosphorus oxychloride in dimethylformamide gave the vinylogous acid chloride 26 which afforded the corresponding chloro alcohol on reduction with lithium aluminum tri-f-butoxyhydride. Hydrolysis and concomitant dehydration of this chloro alcohol then gave the desired unsaturated ketone (23). 

The most convenient method for preparing 2,1 -benzisoxazolin-3-ones is by zinc-ammonium acetate (or chloride) reduction of o-nitrobenzoates.248,249 The resulting o-hydroxyaminoesters undergo rapid acid- or base-catalyzed intramolecular displacement of alcohol with concomitant formation of the benzisoxazolin-3 -one. 

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