Reduction reactions Sodium-Alcohol

SchifT s bases A -Arylimides, Ar-N = CR2, prepared by reaction of aromatic amines with aliphatic or aromatic aldehydes and ketones. They are crystalline, weakly basic compounds which give hydrochlorides in non-aqueous solvents. With dilute aqueous acids the parent amine and carbonyl compounds are regenerated. Reduction with sodium and alcohol gives... 

Most commercial liquid ammonia contains up to several ppm of colloidal iron compounds, possibly the iron oxide catalyst commonly used in manufacturing ammonia. Reduction converts these compounds to colloidal iron which strongly catalyzes the reaction between alcohols and sodium and potassium. The reaction of lithium with alcohols is also catalyzed by iron but to a markedly lesser degree. The data in Table 1-4 illustrate the magnitude of these catalytic effects. The data of Table 1-5 emphasize how less than 1 ppm... 

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

Toluene from Toluidine.—It is often desirable to obtain tbe hydiocarbon from the base. The process of diazotisntion offers the only convenient method. The diazonium salt may be reduced by alcohol (Reaction 1, p. 162) or, as in the piesent instance, by sodium stannite. Less direct methods are the con-veision of the diazonium compound into (i) the hydrazine (see p. 174), (2) the acid and distillation with lime (p. 200), (3) the halogen derivative and reduction with sodium amalgam, 01, finally (4) the phenol and distillation with zinc dust. 

Sodium cyanoborohydride. reductive ami nation with, 931 Sodium cyclamate, LP50 of, 26 Sodium hydride, reaction with alcohols, 605... 

The rigidity of the hexacyclic cage structure of koumine (18) renders some of its chemical behavior quite unusual, for instance, the resistance to Hofmann degradation shown by /Va-acetyldihydrokoumine methyl hydroxide (27). However, owing to the presence of a /J-aromatic imino system in 18, reductive cleavage by sodium-alcohol to yield dihydrokouminol (39) proceeds smoothly. This reaction has been considered to occur through a radical-anion mechanism as indicated in Scheme 12 (27). 

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

The carbanions take up 02 and these take up protons to give hydroperoxides in good yields. But because they are explosive in nature, they are not usually isolated and on reduction with sodium sulphite on trialkyl phosphite give alcohols. Alcohols can also be prepared via hydroperoxy molybdenum complexes and alkyl boranes. These reactions are summarized as follows ... 

The facile homogeneous catalysed reduction of acid chlorides to alcohols has many advantages over reduction with sodium borohydride in hydroxylic solvents where rapid reaction of the acid chloride with the solvent can occur [10]. The procedure has been incorporated into a simple one-pot conversion of aroyl chlorides into the corresponding benzyl chlorides (Scheme 11.1) under liquidrliquid or solid-liquid two-phase conditions [11], The reduction of a limited number of aryl compounds was reported with ca. 70% overall yields, although poorer yields result from the reduction of 4-nitro-, 2-cyano- and 2,4-dichlorobenzoyl chlorides, and the reduction failed completely with terphthaloyl chloride and with its 2,3,5,6-tetrafluoro derivative [11]. 

Isolation of products from the reductions with sodium borohydride is in the majority of cases much simpler. Since the reaction is carried out in aqueous or aqueous-alcoholic solution, extraction with ether is usually sufficient. Acidification of the reaction mixture with dilute mineral acids may precede the extraction. 

The CD fragment 1s synthesized starting with resolved bicyclic acid 129. Sequential catalytic hydrogenation and reduction with sodium borohydride leads to the reduced hydroxy acid 1. The carboxylic acid function is then converted to the methyl ketone by treatment with methyl-lithium and the alcohol is converted to the mesylate. Elimination of the latter group with base leads to the conjugated olefin 133. Catalytic reduction followed by equilibration of the ketone in base leads to the saturated methyl ketone 134. Treatment of that intermediate with peracid leads to scission of the ketone by Bayer Villiger reaction to afford acetate 135. The t-butyl protecting... 

In a similar manner, coccinelline (99) and precoccinelline (100) have been synthesized from 2,6-lutidine (351) (336,450). Thus, treatment of the monolithium derivative (153) of 351 with P-bromopropionaldehyde dimethylacetal gave an acetal, which was converted to the keto acetal (412) by treatment with phenyllithium and acetonitrile. Reaction of 412 with ethylene glycol and p-toluenesulfonic acid followed by reduction with sodium-isoamyl alcohol gave the cw-piperidine (413). Hydrolysis of 413 with 5% HCl gave the tricyclic acetal (414) which was transformed to a separable 1 1 mixture of the ketones (415 and 416) by treatment with pyrrolidine-acetic acid. Reaction of ketone 416 with methyllithium followed by dehydration with thionyl chloride afforded the rather unstable olefin (417) which on catalytic hydrogenation over platinum oxide in methanol gave precoccinelline (100). Oxidation of 100 with m-chloroperbenzoic acid yielded coccinelline (99) (Scheme 52) (336,450). 

Schkeryantz and Pearson (59) reported a total synthesis of ( )-crinane (298) using an intramolecular azide-alkene cycloaddition (Scheme 9.59). The allylic acetate 294 was first subjected to an Ireland-Claisen rearrangement followed by reduction to give alcohol 295, which was then converted into the azide 296 using Mitsunobu conditions. Intramolecular cycloaddition of the azide 296 in refluxing toluene followed by extrusion of nitrogen gave the imine 297 in quantitative yield. On reduction with sodium cyanoborohydride and subsequent reaction with... 

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

Several glycidin estershave been foand1"8-181 to give alcohols on reduction with sodium in pentanol or eth nol (Eqs. 324 and 325). Intermediate stages in the reduction proeeas can be isolated in certain instances, but these provide little insight into the detailed course of reaction. 

Polystyrene-bound carboxylic esters have been reduced with diisobutylaluminum hydride or lithium aluminum hydride. Use of the latter reagent can, however, lead to the formation of insoluble precipitates, which could readily cause problems if reactions are performed in fritted reactors. An alternative procedure for reducing carboxylic esters to alcohols involves saponification, followed by activation (e.g. as the mixed anhydride) and reduction with sodium borohydride (Entries 10 and 11, Table... 

Dichloro-2,2-difluoroethylene, 105 (Diethylamino)sulfur trifluoride, 110 Reduction reactions (see also Deoxygenation, Reductive. . . ) of acetals and ketals Dibromoalane, 237 Diisobutylaluminum hydride, 237 Triethylsilane-Tin(IV) chloride, 237 of acetates and other esters to alkanes Nickel boride, 197 Triphenylsilane, 334 of acyl halides to alcohols Sodium cyanoborohydride-Tin(II) chloride, 280... 

Reaction LXV. (a) Reduction of Phenolic Acids to the corresponding Aldehydes by the action of Sodium Amalgam and Boric Acid in the presence of a Primary Aromatic Amine. (B., 41, 4147.)—This is one of the few methods of reducing an acid to the corresponding aldehyde in satisfactory yield. The presence of the primary aromatic base is essential to protect the aldehyde it condenses with it as formed, and inhibits further reduction to the alcohol. A weak acid such as boric acid is used partly because salt formation by the base would hinder condensation and partly to avoid hydrolysis of the condensation product. 

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