Sodium hydroxide hydride reductions

An aiyl methane- or toluenesulfonate ester is stable to reduction with lithium aluminum hydride, to the acidic conditions used for nitration of an aromatic ring (HNO3/HOAC), and to the high temperatures (200-250°) of an Ullman reaction. Aiyl sulfonate esters, formed by reaction of a phenol with a sulfonyl chloride in pyridine or aqueous sodium hydroxide, are cleaved by warming in aqueous sodium hydroxide. ... 

It is intriguing to note that this reaction scheme for the reduction of a sulphone to a sulphide leads to the same reaction stoichiometry as proposed originally by Bordwell in 1951. Which of the three reaction pathways predominates will depend on the relative activation barriers for each process in any given molecule. All are known. Process (1) is preferred in somewhat strained cyclic sulphones (equations 22 and 24), process (2) occurs in the strained naphtho[l, 8-hc]thiete 1,1-dioxide, 2, cleavage of which leads to a reasonably stabilized aryl carbanion (equation 29) and process (3) occurs in unstrained sulphones, as outlined in equations (26) to (28). Examples of other nucleophiles attacking strained sulphones are in fact known. For instance, the very strained sulphone, 2, is cleaved by hydride from LAH, by methyllithium in ether at 20°, by sodium hydroxide in refluxing aqueous dioxane, and by lithium anilide in ether/THF at room temperature. In each case, the product resulted from a nucleophilic attack at the sulphonyl sulphur atom. Other examples of this process include the attack of hydroxide ion on highly strained thiirene S, S-dioxides , and an attack on norbornadienyl sulphone by methyllithium in ice-cold THF . ... 

Oxidative conversion of palmatine, berberine, and coptisine to polycarpine, polyberbine, and its analog was described in Section II,B. These products were further transformed to aporphine alkaloids having a phenolic hydroxyl group at C-2 in the bottom ring (55). Hydrolysis with concomitant air oxidation of polyberbine (66) furnished 3,4-dihydrorugosinone, which was further air-oxidized in ethanolic sodium hydroxide to give rise to rugosinone (501) (Scheme 105). Successive reduction of the enamide 68 with lithium aluminum hydride and sodium borohydride afforded a mixture of ( )-norledecorine and (+ )-ledecorine (502). N-Methylation of the former with formaldehyde and sodium borohydride led to the latter. 

All four dissolution procedures studied were found to be suitable for arsenic determinations in biological marine samples, but only one (potassium hydroxide fusion) yielded accurate results for antimony in marine sediments and only two (sodium hydroxide fusion or a nitricperchloric-hydrofluoric acid digestion in sealed Teflon vessels) were appropriate for determination of selenium in marine sediments. Thus, the development of a single procedure for the simultaneous determination of arsenic, antimony and selenium (and perhaps other hydride-forming elements) in marine materials by hydride generation inductively coupled plasma atomic emission spectrometry requires careful consideration not only of the oxidation-reduction chemistry of these elements and its influence on the hydride generation process but also of the chemistry of dissolution of these elements. 

If the reduction has been carried out in ether, the ether layer is separated after the acidification with dilute hydrochloric or sulfuric acid. Sometimes, especially when not very pure lithium aluminum hydride has been used, a gray voluminous emulsion is formed between the organic and aqueous layers. Suction filtration of this emulsion over a fairly large Buchner funnel is often helpful. In other instances, especially in the reductions of amides and nitriles when amines are the products, decomposition with alkalis is in order. With certain amounts of sodium hydroxide of proper concentration a granular by-product - sodium aluminate - may be separated without problems [121],... 

Reduction of unsaturated ketones to saturated alcohols is achieved by catalytic hydrogenation using a nickel catalyst [49], a copper chromite catalyst [50, 887] or by treatment with a nickel-aluminum alloy in sodium hydroxide [555]. If the double bond is conjugated, complete reduction can also be obtained with some hydrides. 2-Cyclopentenone was reduced to cyclopentanol in 83.5% yield with lithium aluminum hydride in tetrahydrofuran [764], with lithium tris tert-butoxy)aluminium hydride (88.8% yield) [764], and with sodium borohydride in ethanol at 78° (yield 100%) [764], Most frequently, however, only the carbonyl is reduced, especially with application of the inverse technique (p. 21). 

The reduction of a dinitro ketone to an azo ketone is best achieved with glucose. 2,2 -Dinitrobenzophenone treated with glucose in methanolic sodium hydroxide at 60° afforded 82% of dibenzo[c,f [i 2]diazepin-l 1-one whereas lithium aluminum hydride yielded 24% of bis(o-nitrophenyl)methanol [575], Conversion of aromatic nitro ketones with a nitro group in the ring into amino ketones has been achieved by means of stannous chloride, which reduced 4-chloro-3-nitroacetophenone to 3-amino-4-chloroacetophenone in 91% yield [178]. A more dependable reagent for this purpose proved to be iron which, in acidic medium, reduced m-nitroacetophenone to m-aminoacetophenone in 80% yield and o-nitrobenzophenone to o-aminobenzophenone in 89% yield (stannous chloride was unsuccessful in the latter case) [903]. Iron has also been used for the reduction of o-nitrochalcone, 3-(o-nitrophenyl)-l-phenyl-2-propen-l-one, to 3-(o-aminophenyl)-l-phenyl-2-propen-l-one in 80% yield [555]. 

Results of reductions of cyclic anhydrides to lactones with sodium amalgam or with zinc are inferior to those achieved by complex hydrides [1020]. However, 95.6% yield of phthalide was obtained by reduction of phthalimide with zinc in sodium hydroxide [1021]. 

Countless reductions of esters to alcohols have been accomplished using lithium aluminum hydride. One half of a mol of this hydride is needed for reduction of 1 mol of the ester. Ester or its solution in ether is added to a solution of lithium aluminum hydride in ether. The heat of reaction brings the mixture to boiling. The reaction mixture is decomposed by ice-water and acidified with mineral acid to dissolve lithium and aluminum salts. Less frequently sodium hydroxide is used for this purpose. Yields of alcohols are frequently quantitative [83,1059]. Lactones afford glycols (diols) [575]. 

Complex hydrides were used for reductions of organometallic compounds with good results. Trimethyllead chloride was reduced with lithium aluminum hydride in dimethyl ether at —78° to trimethylplumbane in 95% yield [1174, and 2-methoxycyclohexylmercury chloride with sodium borohydride in 0.5 n sodium hydroxide to methyl cyclohexyl ether in 86% yield [1175]. 

Diclofenac Diclofenac, 2-[(2,6-dichlorophenyl)-amino]-phenylacetic acid (3.2.42), is synthesized from 2-chIorobenzoic acid and 2,6-dichloroaniline. The reaction of these in the presence of sodium hydroxide and copper gives iV-(2,6-dichlorophenyl)anthranyIic acid (3.2.38), the carboxylic group of which undergoes reduction by lithium aluminum hydride. The resulting 2-[(2,6-dicholorphenyl)-amino]-benzyl alcohol (3.2.39) undergoes further chlorination by thionyl chloride into 2-[(2,6-dichlorophenyl)-amino]-ben-zylchloride (3.2.40) and further, upon reaction with sodium cyanide converts into... 

IV-acetylhyellazole, which on deacetylation with sodium hydroxide under phase transfer conditions afforded hyellazole (245) (538,539). Removal of the acetyl group from N-acetylcarazostatin (691b), by reduction with lithium aluminum hydride, provided carazostatin (247) (595) (Scheme 5.60). 

Reductant A solution of 1% w/v sodium borohydride (NaBHJ should be freshly prepared in 0.1 M sodium hydroxide (NaOH), and placed in the reductant reagent compartment of the PS Analytical continuous flow hydride generator. 

Numerous methods for the synthesis of salicyl alcohol exist. These involve the reduction of salicylaldehyde or of salicylic acid and its derivatives. The alcohol can be prepared in almost theoretical yield by the reduction of salicylaldehyde with sodium amalgam, sodium borohydride, or lithium aluminum hydride by catalytic hydrogenation over platinum black or Raney nickel or by hydrogenation over platinum and ferrous chloride in alcohol. The electrolytic reduction of salicylaldehyde in sodium bicarbonate solution at a mercury cathode with carbon dioxide passed into the mixture also yields saligenin. It is formed by the electrolytic reduction at lead electrodes of salicylic acids in aqueous alcoholic solution or sodium salicylate in the presence of boric acid and sodium sulfate. Salicylamide in aqueous alcohol solution acidified with acetic acid is reduced to salicyl alcohol by sodium amalgam in 63% yield. Salicyl alcohol forms along with -hydroxybenzyl alcohol by the action of formaldehyde on phenol in the presence of sodium hydroxide or calcium oxide. High yields of salicyl alcohol from phenol and formaldehyde in the presence of a molar equivalent of ether additives have been reported (60). Phenyl metaborate prepared from phenol and boric acid yields salicyl alcohol after treatment with formaldehyde and hydrolysis (61). 

Precursor y-halogeno alcohols are frequently prepared by the classic sequence of addition of hydrogen halide to a,/3-unsaturated aldehydes, ketones, acids or esters, followed by Grignard reaction or hydride reduction. Recently a novel and general synthesis of 3-methoxyoxetanes from 3-phenylseleno-2-propenal was reported. This method comprises a sequence of Grignard addition to the aldehyde function, treatment with two equivalents of MCPBA, and then reaction with methanolic sodium hydroxide (equation 78) (80JOC4063). 

A large variety of reducing agents have been proposed for this reduction. However, zinc and sodium hydroxide offer the most common system, and lithium aluminum hydride merits consideration. The reduction of azoxy compounds with lithium aluminum hydride has value mainly in structural determinations. Its importance as a preparative procedure is limited normally such a reaction sequence would be a matter of putting the cart before the horse. The reduction of azines has potential value because of the accessibility of azines unfortunately, only under specialized circumstances has it been possible simply to add the required gram-molecule of hydrogen to the structure. Usua-ally, chlorine is added to an azine structure to produce dichloro azo compounds. An extension of the reaction permits the preparation of a,a -diacyl-oxyazoalkanes from azines. 

From the standpoint of laboratory-scale preparations, probably the most commonly used method is the reduction with zinc in a sodium hydroxide medium. The use of lithium aluminum hydride also merits consideration. 

Reduction of 83 (R = H, R = CH2Ph, R" = C6H4S03H) with Raney nickel alloy and sodium hydroxide gave 1-benzyldioxindole and with lithium aluminum hydride gave 1-benzylindoline.216... 

The last of the butyl isomers, the tert-butyl compound, was made from a much more obvious starting material. This is the commercially available tert-butyl hydroquinone. It was methylated in sodium hydroxide with methyl iodide, and then carried through the above sequence (benzaldehyde. mp 124 °C from cyclohexane, nitrostyrene, yellow crystals from methanol, mp 95-96.5 °C, and lithium aluminum hydride reduction) to give 2,5-dimethoxy-4-(l,l-dimethylethyl)amphetamine hydrochloride (DOTB, mp 168 °C). Rats trained in a process called the Sidman Avoidance Schedule gave behavior that suggested that DOTB had no activity at all, and in human trials, doses of up to 25 milligrams were totally without effect. 

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