With LAH

The least troublesome routes to 3,4-dihydro- and 1,2,3,4-tetrahydro-quinazoline are probably the reduction of quinazoline by sodium borohydride, in water for the former or in methanol for the latter. Both must be isolated as salts. The dihydroquinazoline may be formed also by reduction with LAH in ether (65JHC157). In contrast, 5,6,7,8-tetrahy-droquinazoline is best made by primary synthesis from 2-formylcyclohexanone and for-mamide (57CB942) or from cyclohexanone and trisformamidomethane (60CB1402). 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxylic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyl-5-methylisoxazole (215) (7308(53)70). 

Oxidation and reduction can initiate changes leading to heterocycle-heterocycle conversions. The reaction of tetraphenylfuran with singlet oxygen (Scheme 34) (B-73MI50303) and that of isoxazoles with LAH (Scheme 35) are examples. 

Enantiopure (7 )-3-alkylpiperidines (38, R = Me, Et) were obtained when perhydropyrido[2,l-Z)][l,3]benzoxazin-9-ones (37, R = H, Me) were treated first with an excess of AIH3, then with PCC, followed by a 2.5 N solution of KOH (99TL2421). Treatment of optically active perhydropyr-ido[2,l-Z)][l,3]benzoxazines 39 and 40 with LAH in the presence of AICI3 and DIBALH (if R = COOEt) yielded 3-substituted piperidines 41 (00TA2809). 

Racemic or optically active perhydropyrido[l,2-a]pyrazines were obtained by reduction of 9a5-perhydropyrido[l,2-u]pyrazin-4-one with LAH in Et20 at room temperature (99H(51)2065) and by reduction of perhydropyr-ido[l,2-u]pyrazine-l,4-diones with LAH in boiling THF (97USP5703072, 00JAP(K)00/86659). Treatment of (9uS)-2-(fcrf-butoxycarbonyl)perhydro-pyrido[l,2-u]pyrazin-4-one with LAH in Lt20 afforded (9uS)-2-fcrf-butox-ycarbonyl-l,6,7,8,9,9a-hexahydro-2//-pyrido[l,2-a]pyrazine (99H(51)2065). 

Reduction of ethyl 3-[(2-fcrf-butoxycarbonylperhydropyrido[l,2-a]pyra-zin-7-yl)methoxy]benzoate with LAH in THF at room temperature yielded... 

When N-sulfinylaziridine-2-carboxylate 242 (Scheme 3.89) was treated with LAH, followed by N-acetylation and sulfide oxidation, (+)-thiamphenicol (243) was isolated in 72 % yield [63], Thiamphenicol is a broad-spectrum synthetic antibacter-... 

Si-H containing functional initiators have been obtained by reduction with LAH of the corresponding Si-Cl containing compounds. Conditions have been developed under which the benzylic chloride remains unchanged while the Si-Cl bond is converted to Si-H (for experimental details see Sect. H.C.). The initiators obtained are shown in Table 1. 

Meinwald and coworkers71 studied the chemistry of naphtho[l, 8-bc]thiete and its S-oxides. The reaction of the sulphone 2 with LAH (equation 29) is of particular and direct relevance to this section since it is different from the reductions that have been discussed thus far, because the major reaction pathway is now cleavage of an S—C bond, rather than a deoxygenation of the sulphur atom. The major product (equation 29) was isolated in 65% yield two minor products accounted for a further 15% yield. One of the minor products is 1-methylthionaphthalene and this was most probably produced by an initial reduction of the strained 1,8-naphthosulphone, 2, to the thiete, which was then cleaved to the thiol and subsequently methylated. Meinwald also showed71 that the thiete was subject to cleavage by LAH as well as that both molecules were susceptible to attack and cleavage by other nucleophiles, notably methyllithium. These reactions are in fact very useful in attempts to assess a probable mechanism for the reduction of sulphones by LAH and this will be discussed at the end of this section. 

Notice that with LAH, two separate steps are required. 

ANSWER This is a secondary alcohol. We have seen many ways to make secondary alcohols. We can start with a ketone, and reduce with LAH or NaBH4 ... 

Alkylation of l-(2-pyrimidyl)piperazine (129) with 3-chloro-l-cyanopropane gives nitrile 130, which is reduced with LAH and then acylated with spiro-glutaric anhydride 131 to synthesize the tranquilizer buspirone (132).40... 

Treatment of l,3,4,6,7,llb-hexahydro[l,3]oxazino[3,4- ]quinazolin-l-one with LAH in boiling THF gave 2-(2-hydroxyethyl)-l-methylquinoline <2003T6785>. Pyrimidinone 107 was obtained from trequinsin 106 on the action of NaH, followed by the treatment with Mel (Equation 17) <1997IJB349>. The reaction of7-(benzotriazol-l-yl)-6,7-dihydro-l//,3/7,5//-pyrido[3,2,l-zy][3,l ]bcnzoxazine with PhMgBr led to ring-opened l-benzyl-4-(benzotriazol-l-yl)-8-hydroxymethyl-l, 2,3,4-tetrahydroquinoline < 1995JOC3993>. 

Treatment of 3-phenylperhydropyrido[ 1,2-/ 1,3 oxazin-l -one with LAH gave a 1 9.5 mixture of 3-phenylphenylper-hydropyrido[l,2-c][l,3]oxazine and l-methyl-2-(2-phenyl-2-hydroxyethyl)piperidine <20050BC520>. Reduction of ds- >,4a- I-/ra .v-8-H-3-incthyl-8-pentyIperhydropyrido[ 1 1,3 oxazin-6-onc with NaBH4 at room temperature... 

Reaction of 266a with suitable methyl alkyl amines having an asymmetric center at the neighboring carbon atom provided optically active amides 302, which after reduction with LAH gave optically active py razolylmethy-lamines 303 (92CB701). 

Table III. Products of the reduction of CpgFegCCO) with LAH in the presence of 3C0.

Reaction of Cp2Fe2(C0K with NaBHt, led to similar reduction products though the yield was less than 5% of that seen with LAH. Reaction of LiBEt3H effected reduction in less than 0.3% of that observed with LAH. 

The differences in products (both gaseous and in solution) between the reduction of the acetyl complex, CH3C(0)FeCp(C0)2, and the methyl and ethyl complexes suggest that different intermediates are involved. The rapidity of the reduction of the acetyl complex to hydrocarbons rules out the ethyl complex as an intermediate in the reduction of CH3C(0)FeCp(C0)2 with LAH. Reduction of the acetyl to the ethyl complex has been observed.1—... 

For the reductions of the methyl and ethyl complexes with LAH the Cn+] alkane was the major product with the Cn product present to a significant extent. These two products could arise by the following sequence. 

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