Reduction etherate

Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with EtySiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269... 

The reductive ether formation from keto epoxides is an acid-catalyzed process (Eqs. 234407 and 235408). 

An orf/io-directed lithiation allows the conversion of 25 to aryl iodide 40. Reductive ether formation of aldehyde 40 with crotyl alcohol yields compound 41. Intramolecular Heck reaction of 41 affords a mixture of the olefins 42 and 43. The undesired alkene 42 can be isomer-ized quantitatively to the desired enol ether 43 with Wilkinson s catalyst. Sharpless dihydroxylation ee 94 %) of the enol ether 43 provides lactol 44, which is oxidized directly to lactone 45. Finally, the pyridone-O-methyl ester is cleaved under acid conditions (45 — 7). 

Reduction. Ethereal solutions of zinc borohydride are almost neutral thus it is useful for reduction of substances that are sensitive in alkali. Thus Gensler et al. wanted to reduce podophyllotoxone (1) to podophyllotoxin (2). Lithium... 

Mild and highly selective reductive ether splitting could develop into a very general and highly attractive alternative to Lewis acid catalysis therefore, we present two perfectly directed examples from this field. 

Reduction - Ether soluble AlH may be made by treatment of LIAIH with... 

Reductive Ethereal Ring Opening of 7-Oxabicyclo[2.2.1]heptanones. 172... 

Three more general techniques have greatly improved the earlier yields. Discussion of the solid-phase adsorption method is included in more recent reviews. It probably remains the method of choice in selected cases and sometimes has results different from those of other methods. For example, the predominant reduction to cyclopentanone in the intramolecular reaction of iV-acetyl-iV-allylpropargylamine (eq 58) and the reductive ether cleavage when related ethers react on alumina (eq 59), is avoided on silica, in the presence of oxygen, with formation of the expected bicyclic products. 

Boron forms a whole series of hydrides. The simplest of these is diborane, BjH. It may be prepared by the reduction of boron trichloride in ether by lithium aluminium hydride. This is a general method for the preparation of non-metallic hydrides. 

Pure phosphine can be prepared by the reduction of a solution of phosphorus trichloride in dry ether with lithium aluminium hydride ... 

Used particularly for ethers. Cannot be used for any compound affected by alkalis, or easily subject to reduction (owing to the hydrogen evolved during dehydration). 

In an experiment, a slight excess of the hydride is employed to ensure the complete reduction the unused hydride must then be destroyed. This can be done by the cautious addition of (rt) water, or (6) ordinary undried ether, which will ensure that the supply of water is both small and gradual, or (c) an ester such as ethyl acetate, which will be reduced to ethanol. The first of these methods, namely the addition of water, is hazardous and should be avoided. 

Now cool the mixture thoroughly in ice-water, and run in over a period of 45 minutes a solution of 6 o g. of dry salicylic acid in 75 ml. of dry ether. When the addition of the acid to the stirred solution is complete, heat the mixture under reflux on the water-bath for 15 minutes to ensure completion of the reduction. Then thoroughly chill the mixture in ice-water, and hydrolyse any unused hydride by the slow addition of 50 ml. of ordinary undried ether, followed similarly by 75 ml. of dilute sulphuric acid. 

In absolute ethanol solution, the ethyl ether and the corresponding hydrocarbon are formed, the latter by reduction of the diazonium compound by the ethanol, which is itself oxidised to acetaldehyde ... 

With higher alcohols, the formation of the ether becomes negligible, the reaction being limited almost entirely to reduction to the hydrocarbon. 

Metallic sodium. This metal is employed for the drying of ethers and of saturated and aromatic hydrocarbons. The bulk of the water should first be removed from the liquid or solution by a preliminary drying with anhydrous calcium chloride or magnesium sulphate. Sodium is most effective in the form of fine wire, which is forced directly into the liquid by means of a sodium press (see under Ether, Section II,47,i) a large surface is thus presented to the liquid. It cannot be used for any compound with which it reacts or which is affected by alkalis or is easily subject to reduction (due to the hydrogen evolved during the dehydration), viz., alcohols, acids, esters, organic halides, ketones, aldehydes, and some amines. 

The reduction takes place at a comparatively low temperature and is fairiy rapid for acetophenone. With higher ketones, the upper layer of the initial distillate should be returned to the contents of the flask and the refluxing continued for 3-6 hours. The reaction mixture and aqueous distillate are then combined, extracted with ether, etc. 

Reduction of A-nitrosomethylaniline. Into a 1 litre round-bottomed flask, fitted with a reflux condenser, place 39 g. of A-nitroso-methylaniline and 75 g. of granulated tin. Add 150 ml. of concentrated hydrochloric acid in portions of 25 ml. (compare Section IV.34) do not add the second portion until the vigorous action produced by the previous portion has subsided, etc. Heat the reaction mixture on a water bath for 45 minutes, and allow to cool. Add cautiously a solution of 135 g. of sodium hydroxide in 175 ml. of water, and steam distil (see Fig. II, 40, 1) collect about 500 ml. of distillate. Saturate the solution with salt, separate the organic layer, extract the aqueous layer with 50 ml. of ether and combine the extract with the organic layer. Dry with anhydrous potassium carbonate, remove the ether on a water bath (compare Fig. II, 13, 4), and distil the residual liquid using an air bath (Fig. II, 5, 3). Collect the pure methylaniline at 193-194° as a colourless liquid. The yield is 23 g. 

Reduction of methyl orange to />-aminodimethylaniline. Method 1. Dissolve 2 0 g. of methyl orange in the minimum volume of hot water and to the hot solution add a solution of 8 g. of stannous chloride in 20 ml. of concentrated hydrochloric acid until decolourisation takes place gentle boiling may be necessary. Cool the resulting solution in ice a crystalline precipitate consisting of sulphanilic acid and some p-aminodimethylaniline hydrochloride separates out. In order to separate the free base, add 10 per cent, sodium hydroxide solution until the precipitate of tin hydroxide redisaolves. Extract the cold solution with three or four 20 ml. portions of ether, dry the extract... 

Reduction to hydroquinone. Dissolve, or suspend, 0-5 g. of the quinone in 5 ml. of ether or benzene and shake vigorously with a solution of 1 0 g. of sodium hydrosulphite (Na2S204) in 10 ml. of N sodium hydroxide until the colour of the quinone has disappeared. Separate the alkaline solution of the hydroquinone, cool it in ice, and acidify with concentrated hydrochloric acid. Collect the product (extract with ether, if necessary) and recrystalhse it from alcohol or water. 

Lithium aluminium hydride LiAlH is a useful and conveuient reagent for the selective reduction of the carbonyl group and of various other polar functional groups. It is obtained by treatment of finely powdered lithium hydride with an ethereal solution of anhydrous aluminium chloride ... 

The compound is generally employed in solution in dry ether this solution is conducting and the reduction may be due to the transfer of a hydride ion ... 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

Reduction of a nitrosamine to a secondary amine. Proceed as for a nitro compound. Determine the solubility of the residue after evaporation of the ether and also its behaviour towards benzenesulphonyl (or p-toluenesulphonyl) chloride. 

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