Lithium aluminum hydride, reducing

Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon-carbon double bonds This makes possible the selective reduction of a carbonyl group m a molecule that contains both carbon-carbon and carbon-oxygen double bonds... 

In contrast to alcohols with their nch chemical reactivity ethers (compounds contain mg a C—O—C unit) undergo relatively few chemical reactions As you saw when we discussed Grignard reagents m Chapter 14 and lithium aluminum hydride reduc tions m Chapter 15 this lack of reactivity of ethers makes them valuable as solvents m a number of synthetically important transformations In the present chapter you will learn of the conditions m which an ether linkage acts as a functional group as well as the methods by which ethers are prepared... 

Reduction of amides (Section 22.9) Lithium aluminum hydride reduces the carbonyl group of an amide to a methylene group. Primary, secondary, or tertiary amines may be prepared by proper choice of the starting amide. R and R may be either alkyl or aryl. 

The reduction of the double bond of an enamine is normally carried out either by catalytic hydrogenation (MS) or by reduction with formic acid (see Section V.H) or sodium borohydride 146,147), both of which involve initial protonation to form the iminium ion followed by hydride addition. Lithium aluminum hydride reduces iminium salts (see Chapter 5), but it does not react with free enamines except when unusual enamines are involved 148). 

Lithium aluminum hydride reduces most sulfur compounds with cleavage of the C—S bond, including thiols. " Thioesters can be reduced with Ni2B (from NiBr2/... 

Lithium aluminum hydride reduced )J-azidoethylbenzene to j8-aminoethyl-benzene in 89% yield [600], The azido group was also reduced with aluminum amalgam (yields 71-86%) [149], with titanium trichloride (yields 54-83%) [601], with vanadous chloride (yields 70-95%) [217] Procedure 40, p. 215), with hydrogen sulfide (yield 90%) [247], with sodium hydrosulfite (yield 90%) [259], with hydrogen bromide in acetic acid (yields 84-97%) [232], and with 1,3-propanedithiol (yields 84-100%) [602]. Unsaturated azides were reduced to unsaturated amines with aluminum amalgam [149] and with 1,3-propane-dithiol [602]. 

Lithium aluminum hydride reduces preferentially the carbonyl function (p. 98) but alanes prepared by reactions of aluminum hydride with two equivalents of isopropyl or /er/-butyl alcohol or of diisopropylamine reduce the conjugated double bonds with high regioselectivity in quantitative yields [871] (p. 121). 

Lithium aluminum hydride reduced p-benzoquinone to hydroquinone (yield 70%) [576] and anthraquinone to anthrahydroquinone in 95% yield [576]. Tin reduced p-benzoquinone to hydroquinone in 88% yield [174] Procedure 35, p. 214). Stannous chloride converted tetrahydroxy-p-benzoquinone to hexa-hydroxybenzene in 70-77% yield [929], and 1,4-naphthoquinone to 1,4-di-hydroxynaphthalene in 96% yield [180]. Other reagents suitable for reduction of quinones are titanium trichloride [930], chromous chloride [187], hydrogen sulfide [248], sulfur dioxide [250] and others. Yields are usually good to excellent. Some of the reagents reduce the quinones selectively in the presence of other reducible functions. Thus hydrogen sulfide converted 2,7-dinitro-phenanthrene quinone to 9,10-dihydroxy-2,7-dinitrophenanthrene in 90% yield [248]. 

The reduction of free acids to alcohols became practical only after the advent of complex hydrides. Lithium aluminum hydride reduces carboxylic acids to alcohols in ether solution very rapidly in an exothermic reaction. Because of the presence of acidic hydrogen in the carboxylic acid an additional equivalent of lithium aluminum hydride is needed beyond the amount required for the reduction. The stoichiometric ratio is 4 mol of the acid to 3 mol of lithium aluminum hydride (Equation 12, p. 18). Trimethylacetic add was reduced to neopentyl alcohol in 92% yield, and stearic acid to 1-octadecanol in 91% yield. Dicarboxylic sebacic acid was reduced to 1,10-decanedioI even if less than the needed amount of lithiiun aluminum hydride was used [968]. 

Lithium aluminum hydride reduces exclusively the carboxyl group, even in an unsaturated acid with a, -conjugated double bonds. Sorbic acid afforded 92% yield of sorbic alcohol [968], and fumaric acid gave 78% yield of trans-2-butene-l,4-diol [97S]. If, however, the a, -conjugated double bond of an add is at the same time conjugated with an aromatic ring it is reduced (p. 141). 

Lithium aluminum hydride reduces acetylenic acids containing conjugated triple bonds to olefinic alcohols. Acetylenedicarboxylic acid gave, at room temperature after 16 hours, 84% yield of /ra s-2-butene-l,4-diol [975]. 

Since sodium borohydride usually does not reduce the nitrile function it may be used for selective reductions of conjugated double bonds in oc,/l-un-saturated nitriles in fair to good yields [7069,1070]. In addition some special reagents were found effective for reducing carbon-carbon double bonds preferentially copper hydride prepared from cuprous bromide and sodium bis(2-methoxyethoxy)aluminum hydride [7766], magnesium in methanol [7767], zinc and zinc chloride in ethanol or isopropyl alcohol [7765], and triethylam-monium formate in dimethyl formamide [317]. Lithium aluminum hydride reduced 1-cyanocyclohexene at —15° to cyclohexanecarboxaldehyde and under normal conditions to aminomethylcyclohexane, both in 60% yields [777]. 

Lespedamine (216) was first synthesized [78JCS(P1)1117] from 1-methoxyindole-3-carbaldehyde 217, which was itself isolated from Brassica oleracea (cauliflower) (87MI4) by treatment with nitromethane, giving the expected nitroethylene (218), lithium aluminum hydride reduc-... 

B is correct. The first equivalent of lithium aluminum hydride reduces the carboxylic acid to the primary alcohol, which is then completely reduced by the second equivalent of the hydride. The secondary alcohol does not reduce easily with lithium aluminum hydride. 

Lithium aluminum hydride reduces the carboxylic acid to the corresponding primary alcohol, compound E. Treatment of the vicinal chlorohydrin with base results in formation of an epoxide, compound F. 

Lithium aluminum hydride reduced 9-hydroxy-9-(4-methylphenyl)-telluraxanthene to 9-(4-methy lpheny l)-telluraxanthene1. 

Lithium aluminum hydride reduced telluraxanthone in diethyl ether to 9-hydroxytellura-xanthene1 2. 

Sodium borohydride and lithium aluminum hydride reduce ketones and aldehydes to alcohols. Reaction 1 Nucleophilic attack by the hydride ion forms an alkoxide ion. 

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. 

Lithium aluminum hydride reduces amides and nitriles to amines, providing some of the best synthetic routes to amines (Sections 19-19 and 19-20B). Primary amides and nitriles are reduced to primary amines. Secondary amides are reduced to secondary amines, and tertiary amides are reduced to tertiary amines. 

Reactions of Esters Esters are much more stable than acid chlorides and anhydrides. For example, most esters do not react with water under neutral conditions. They hydrolyze under acidic or basic conditions, however, and an amine can displace the alkoxyl group to form an amide. Lithium aluminum hydride reduces esters to primary alcohols, and Grignard and organolithium reagents add twice to give alcohols (after hydrolysis). 

---