Sodium in liquid ammonia, reduction

In the first sodium in liquid ammonia reduction of an aporphine, bulbocapnine (LXIV) was converted into 2,11-dihydroxy-lO-methoxy-aporphine (LXV) (54). Since that time several other reductions of aporphines have been carried they are outlined below. The aporphines that have been reduced with sodium in liquid ammonia include bulbocapnine (LXIV), nantenine (LXVI), domesticine (LXVII), 0,0-dimethylcorytuberine (LVIII), glaucine (XXXII), nuciferine (LXVIII), 1-methoxy-2-hydro.xyaporphine (LXIX), and A -aeetylnornuciferine (LXX). 

The structures of all alkaloids from Menispermum dauricum were elucidated by the usual two key reactions, sodium in liquid ammonia reduction and Hofmann degradation.1030 264 The alkaloids isolated from Thalictrum foetidum... 

Tetraphenylcyclobutadieneiron tricarbonyl (XIII) on reduction with lithium aluminum hydride gave 1,2,3,4-tetraphenylbutadiene (52) [formerly thought to be the trans,trans isomer but now established as the cis,cis (LXI) (43)], while a sodium in liquid ammonia reduction gave 1,2,3,4-tetraphenyl-butane (52). 

Amines.— The deuteriated ammonium iodide (341) is converted into its ylide irreversibly by n-butyl-lithium in pentane, but reversibly by potassium amide in liquid ammonia. Hence cis- and truns-cyclo-octene were obtained in a ratio of 70 30, respectively, together with labelled iViV-dimethylbutylamine when (341) was treated with n-butyl-lithium in pentane, and in a ratio of 32 68, respectively, together with unlabelled NN-dimethylbutylamine when (341) was treated with potassium amide in liquid ammonia. Sodium in liquid ammonia reduction of the oxime of 3,4-benzocyclohept-3-enone gives 4-amino-1,2-benzocycloheptene, which has interesting pharmacological properties. 

Sodium in liquid ammonia reduction of norbornadiene at — 33 °C in THF, with Bu OH present as a proton source, afforded nortricyclene and norbornene in 1 19 ratio in the absence of Bu OH a 1 200 ratio was obtained for the much slower reaction.According to the commonly accepted mechanisms of metal-ammonia reductions, the anionic species XH is the penultimate intermediate irrespective of whether the mechanism involves the preliminary formation of the dianion X (in the absence of a proton source) or of the radical HX- (presence of a proton source). The single carbanion species thus requires that the product ratio be independent of the presence or absence of a proton source more powerful than ammonia, contrary to the experimental observations. Hence, the existence of a least two discrete car-banions, namely (439) (440), is suggested. Consistent with this proposal are the results obtained for the Na-NDj reduction (CD3OD as proton source) of norbornadiene, and of the Na-NHg reduction of benzonorbornadiene. 

The sodium reduction has been extended to esters. Thus, methyl 2-ethylmercapto-5-ethyIthiophen-3-carboxylate (128) yielded the amide (129) as the main product upon treatment with four equivalents of sodium in liquid ammonia. Reduction of aldimines such as (118) with LiAlH4 gives thenylamines such as (130) in high yield, which can be condensed... 

It is well established that sodium in liquid ammonia reduction of tetrahydrobenzyl-isoquinoline methiodides leads to cleavage of the C-1 to N-2 bond see K. W. Bentley and A. W. Murray, J. Chem. Soc., 2501 (1963). 

Terminal acetylenes are often used as precursors to the E- and Z-olefins. A typical synthesis is that reported by Schwarz and Waters (187) (Scheme 80). The alkali metal salt of the acetylene is coupled with an appropriate alkyl halide to give the acetylenic tetrahydropyranyl ether (444). Sodium in liquid ammonia reduction of the ether stereo-specifically affords.pure -olefins, which can be hydrolyzed to an alcohol and then acetylated. For Z-isomers, the protecting group must first be removed and the alcohol acetylated. Reduction over quinoline-poisoned... 

Methylthio- and 2-ethylthio-4-methylthiazoles undergo reductive ring opening when treated by sodium in liquid ammonia (204). The first step of this reaction consists of the formation of the A-4-thiazoline anion (80). The next steps are analogous to those given for 80a to 83. 

Cyclic enamines can also be obtained by the reduction of pyridine and isoquinoline with lithium aluminum hydride (163-165), and the latter reduction has also been accomplished with sodium in liquid ammonia (166). 

Reduction of the enamine system of an aminostilbene by sodium in liquid ammonia 189) and of a 17-enaminosteroid by aluminum and mercuric chloride in alcohol 560) have also been reported. 

Thiophenethiols are prepared by reduction of the sulfonyl chlorides or, more conveniently, by the reaction of Grignard rea-gents or thienyllithium compounds with sulfur. They have also been obtained by cleavage or thienyl alkyl sulfides with sodium in liquid ammonia. 3-Thiophenethiol is a by-product in the commercial thiophene synthesis. Thiophenethiols have recently also been prepared by a synthesis involving Friedel-Crafts reaction of 2,4-dinitrobenzenesulfenyl chloride with thiophenes, followed by basic cleavage of the resulting sulfide. ... 

Truce also examined a few examples of the cleavage of sulphones with sodium in liquid ammonia97 and found essentially similar results except that diaryl sulphones were reduced to sulphinate salts instead of to arylthiolates as with the lithium reductions. Dialkyl sulphones were unreactive towards sodium in liquid ammonia. 

The inertness of ordinary double bonds toward metallie hydrides is quite useful, since it permits reduction of, say, a carbonyl or nitro group, without disturbing a double bond in the same molecule (see Chapter 19 for a discussion of selectivity in reduction reactions). Sodium in liquid ammonia also does not reduce ordinary double bonds, although it does reduce alkynes, allenes, conjugated dienes, and aromatic rings (15-14). 

Reduction of (24) by Lindlaar hydrogenation gives a cis double bond and sodium in liquid ammonia gives the trans double bond,... 

The benzyl group can serve as a hydroxy-protecting group if acidic conditions for ether cleavage cannot be tolerated. The benzyl C—O bond is cleaved by catalytic hydrogenolysis,176 or by electron-transfer reduction using sodium in liquid ammonia or... 

Dissolving-Metal Reduction of Aromatic Compounds and Alkynes. Dissolving-metal systems constitute the most general method for partial reduction of aromatic rings. The reaction is called the Birch reduction,214 and the usual reducing medium is lithium or sodium in liquid ammonia. An alcohol is usually added to serve as a proton source. The reaction occurs by two successive electron transfer/proto-nation steps. 

Detailed discussion of these findings will be presented elsewhere. Here we only wish to point out that responses to a hydrogen donor tend to be critically affected by minor structural differences between the compounds. Thus, while diphenyl ether remains substantially unaffected by the donor, its hydroxy-derivatives (phenoxy phenols) often display fairly high reactivity. Taken in conjunction with the failure of low-rank coals (7) and phenoxy phenols (10) to suffer reductive cleavage when treated with sodium in liquid ammonia, this lends some support for the existence of phenoxy phenol entities in low rank coals. 

The pyrroloquinolizine 456 has been prepared by the treatment of amide 455 with POCl3 followed by NaBH4. Quaternization of the quinolizine nitrogen with methyl iodide followed by reduction with sodium in liquid ammonia gives the pyrroloazecine 457 (Scheme 101) <2001AP241>. 

The bimolecular reduction of ketones to pinacols by magnesium may involve ketyls as intermediates, the bivalence of magnesium favoring the bimolecular reduction product. Ketyl formation with sodium in liquid ammonia eventually leads to the reduction of the ketone to the alcohol. The corresponding pinacol is also cleaved to the alcohol under the same conditions.128... 

Simple synthesis of ( )-17-epiyohimbol (73) has been reported by Mori et al. (214). yV-Benzyloctahydroindolo[2,3-a]quinolizinone (126), prepared according to the procedure of Novdk and Szdntay (97) was coverted to the corresponding pyrrolidine enamine, which was treated with methyl vinyl ketone to give N-benzylyohimbenone (379). Reduction of 379 with sodium in liquid ammonia... 

FIGURE 3.4 Deprotection of functional groups by reduction with sodium in liquid ammonia [du Vigneaud et al., 1930]. As in Figure 3.3, except reduction is effected by solvated electrons and protons are provided by water at the end of the reaction. Excess sodium is destroyed by NH4C1. This is a simplified presentation of the reaction. AH benzyl-based protectors as well as -Arg(N02)-, -Arg(Tos)-, and -His(Tos)- are sensitive to sodium in liquid ammonia. 

---