Ketones conversion into acetals

In the case of the reaction of aldehyde with ethanol, the per cent conversion into acetal in a mixture of five moles of alcohol with one mole of aldehyde is, for acetaldehyde, 78 per cent for dimethyl-acetaldehyde, 71 per cent and for trimethylacetaldchyde 56 per cent. Similarly, when the ketone is allowed to react with ethyl orthoformate to form the ketal, the order of decreasing amount of ketal formed is dimethyl ketone, methylethyl ketone, diisopropyl ketone, methyl butyl ketone, ethyl leri-butyl ketone, butyl isopropyl ketone and di-butyl ketone. Thus one is led to expect that the... 

The largest offtake of acetone is its conversion into solvents, used mainly in lacquers and other synthetic resin applications. These solvents include diacetone alcohol, methyl isobutyl ketone, methyl isobutyl carbinol (methyl amyl alcohol), and methyl amyl acetate. The following equations (22), in each of which the raw material is the product of the previous reaction, show a possible procedure by which these solvents may be made ... 

Pyrrole- and indole-carboxylic acid chlorides react with dialkyl- and diaryl-cadmium to yield the ketones and it is noteworthy that the reaction of the anhydride of indole-2,3-dicarboxylic acid with diphenylcadmium produces 3-benzoylindole-2-carboxylic acid and not its isomer (53JCS1889). The ability of l-methylindole-2-carboxylic acid to react with nucleophiles is enhanced by conversion into the mixed anhydride with methanesulfonic acid. The mixed anhydride reacts with carbanions derived from diethyl malonate and from methyl acetate to yield the indolyl (3- keto esters (80TL1957). 

An alternative stereospecific synthesis of emetine has been accomplished from ethyl trans-5-ethyl-2-oxopiperidine-4-acetate by conversion into the lactim ether (107), which was allowed to react with 3,4-dimethoxyphenacyl bromide to give the ketone (108 R R2 = O). Reduction of this with sodium borohydride, followed by hydrogenolysis of the resulting alcohol, gave (108 R1 = R2 = H), which has previously been converted into emetine.135 The reaction of (107) with 3-benzyloxy-4-methoxyphenacyl bromide and with 4-benzyloxy-3-methoxyphenacyl bromide afforded analogues of (108 RJR2 = O), which were converted into 9-O-desmethylpsychotrine (109 R1 = H, R2 = Me) and 10-0-desmethylpsychotrine (109 R1=Me, R2 = H) respectively.136,137... 

Thioacetals. Aldehydes, ketones, or acetals, both cyclic and acyclic, can be converted into thioacetals by reaction with a thiol or dithiol and MgBr2 (2.1 equiv.) in ether at 25°. The difference in reactivity between acetals and ketones permits selective conversion of acetals into thioacetals without acetalization of a ketone. 

The absolute configuration and enantiomeric excess of amino ketones 20 were evaluated by gas chromatography (GC) and, 3C NMR studies after conversion into the diastereomeric acetals 21. The reaction proceeds via addition of the nitrene 18 to the double-bond of 19. The yield and diastereoselectivity of this reaction were significantly enhanced when using chiral enol ethers 23, generated from C2 symmetric 22. The best result (36 % yield and 50 % ee) was obtained using a fivefold excess of reagent 6e and equimolar amount of triethylamine [12d] (Scheme 9). 

An alternative to the direct a-deprotonation of a ketone is the conversion of its enol ether (in particular, TMS enol ethers) or ester (in particular, acetates) into the corresponding lithium enolate. The advantage of this detour is that the enol ethers and esters can either be prepared as a single isomer or the mixture of isomers can be separated by distillation or chromatography108, while their conversion into enolates takes place in a regio-and stereospecific manner. 

Enol acetylation. An a-halo-a-arylacetophenone such as (1) cannot be converted into the enol acetate by reaction with isopropenyl acetate, and conversion into the sodium enolate by sodium methoxide followed by treatment with acetyl chloride gives low yields. However, Cooper and Owen28 found that, if the ketone is treated with dry methanol and sodium hydride and the mixture let stand until evolution of hydrogen has ceased and then treated with acetyl chloride, the enol acetate is obtained in yield of50-70%. 

The synthesis of oxazole A-oxidcs from a-hydroxyimino ketones and aldehydes, and their reductive conversion into oxazoles has already been described (Section II, K). Attempted A-oxidation of 2,5-diphenyloxazole with hydrogen peroxide in acetic acid failed it led to ring-opening.418 Oxazole A-oxides show a strong absorption band around 1240 cm-1 in their infrared spectra, indicative of an aromatic A-oxide group.419 Recently, NMR data for several oxazole A-oxides have been reported.148... 

These are potential sources of malondialdehyde. Similar unsaturated aldehydes are obtained also from acetals and are useful for conversion into other products. Formylation of ketones has found wider application in synthesis because the / -chloro-a>unsaturated aldehydes produced are interesting starting materials for further elaboration 850... 

The synthesis of 3-benzoyl-A-homo-3-aza-5) -androstan-16-one (37), an analogue of the alkaloid samanine (36) from Salamandra maculosa, has been reported. Sodium borohydride reduction of the known compound (38) followed by tosylation alTorded the tosylate (39) the nitrile group was reduced by diborane and cyclized by benzoic anhydride-pyridine to the derivative (40a) similar cyclization with acetic anhydride-pyridine yielded the related acetamide (40b). This cyclization requires one equivalent of anhydride and the uncyclized amide is not an intermediate in the reaction. Jones oxidation of (40a) was followed by conversion into a benzylidene ketone derivative (41) with benzaldehyde-KOH in methanol. Reduction of (41) with sodium borohydride and acetylation furnished (42). Treatment of compound (42) with ozone followed by mild zinc reduction produced an acetoxy-ketone, which was further reduced by Zn-HBr-CH2Cl2 to the ketone (37). 

An ingenious synthesis of steroidal annulenes has appeared. The close relationship of annulenes to the classical aromatic substance naphthalene stimulated the synthesis of l,6-methano-[10]annuleno-steroids, which are analogues of equilenin (97). The y,5-cyclopropyl-a -unsaturated ketone (98) was the initial target. Treatment of the cyclopropyl ketone (98) with acetic anhydride and methyl orthoformate in the presence of an acid catalyst then gave (99). Conversion of the cycloheptatriene (99) into the requisite 10 c-electron system (100) was then accomplished by dehydrogenation. ... 

Acetone (CH 3 CO.CH 3 ), or dimethyl ketone, is formed when iso-propyl alcohol is oxidised with potassium bichromate and sulphuric. It is also produced in eonsiderable quantities during the dry distillation of wood, and many other organie compounds. Cmde wood spirit, which has been freed from acetic acid, consists in the main of a mixture of acetone and methyl- alcohol. The two substances may be roughly separated by the addition of ealeium chloride, whieh eombines with the methyl-alcohol. On subsequent distillation crude aeetone passes over, and may be purified by conversion into the bisulphite compound. 

Certain functionalised esters combine the virtues of acyl protection (ease of introduction, electronic deactivation, lability to base) with the ability to be deprotected under specialised conditions that leave other esters unaffected. Of these, the only example that has seen reasonably widespread application is the levulinate (Lev) derivative which, in chemistry that parallels the cleavage of ClAc derivatives with soft nucleophiles, are cleavable by conversion of the comparitively reactive ketone functionality into a nucleophilic entity that can cyclise onto the ester carbonyl releasing the protected hydroxyl. The example in Figure 2.45 shows that the acetates survive unscathed in Lev deprotection with hydrazine so that only the 2-OH is released [63]. 

Ri =s R2 = Ph). 4-Aryl-l,2-dithiolium salts of type (36 R = Me or Ph, R = H) yield 1,2-dithiolylidene ketones (37) when heated in ethanol, but this reaction fails when the dithiolium salt has a 5-amino-substituent (36 R = NRa). The 5-amino-compounds have been found to give 1,3-dithiole derivatives on treatment with phosphorus pentasulphide in pyridine. The structure of one of the products (38) was established by conversion into the 6a-thiathiophthen (39), which was also prepared by sulphurization of the dithiolylidene ketone (37 R = Ar = Ph, R = MeaN) obtained by the triethylamine-acetic acid route. 

Also, the conversion of 1,5-cyclooctadiene to cyclooct-4-en-l-one and acetic anhydride " is best explained by a 1, 2-addition process, which is followed by a second addition, reductive elimination, and conversion of the 1,1-diacetoxy group into acetic anhydride and ketone (Scheme 15). 

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