Nitrosation, of ketones

The Knorr synthesis also proceeds via y0-enaminone intermediates 16 [40]. Frequently, the a-amino ketones are not employed as such but generated in situ by reduction of a-oximino ketones. The latter are obtained by nitrosation of ketones with alkyl nitrites in the presence of sodium methoxide ... 

Examples of such compounds are products of nitrosation of ketones arising from autoxidation of hpids. Their oximes and... 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

The above procedure2 is modeled after that described for the nitrosation of arylethyl ketones.4-5 w-Chloroisonitroso-acetophenone has been prepared by the chlorination of isonitro-... 

The ready accessibility of 1,2-dioximes (glyoximes) and the ease with which they are dehydrated has ensured that this is the most common route to furazans. The starting materials are usually prepared by oximation of the appropriately substituted 1,2-diketone or, more often, by a-nitrosation of an alkyl ketone followed by oximation of the resulting 1,2-dione monooxime (Scheme 16). 1,2-Dioximes can also be prepared by reduction of furoxans (Section 4.05.5.2.4) and, in cases where the furoxan is more readily available than the furazan, for example, by nitrile oxide dimerization, this furoxan-> glyoxime-> furazan sequence represents a viable synthetic strategy for symmetrically substituted derivatives. 

In the nitrosation of ethyl isopropyl ketone (Preparation 2-4), acetyl chloride is used as a catalyst. While aqueous hydrochloric acid has also been used to catalyze this reaction, anhydrous hydrogen chloride or acetyl chloride evidently is more effective as far as the yield is concerned. To be noted here is that the greater yield is that of the true nitroso compound. However, the secondary carbon atom of the ethyl group is converted into an oxime on nitrosation. 

Treatment of aliphatic active methylene compounds with such reagents normally leads to oxime formation. An exception is the nitrosation of compounds with active tertiary carbon atoms such as ethyl isopropyl ketone which are convertible into C-nitroso compounds. 

After development has taken place in a layer containing silver halide, two images are present a negative one in metallic silver and a positive one in silver halide. The silver halide can be converted to a silver salt of a thiobarbituric acid, which is less soluble than the silver halide. Nitrosation of this insoluble silver salt produces an a-oximino ketone, which when treated with iron(II) ion yields a positive image in blue-green iron chelate.136... 

The three preparative methods which are illustrated in this section are (a) the oxidation, or (b) the nitrosation, of the a-methylene group in a symmetrical ketone or an aryl alkyl ketone (Expts 5.99 and 5.100), and (c) the oxidation of alkynes under PTC conditions (Expt 5.101). 

The 2-hydroxy-2-methoxyoxime 272, prepared by a-nitrosation of the ketone 271 using nitrosyl chloride in dry methanol solution, upon treatment with KOH gives rise to 3-hydroxyimidazole 1-oxide 267 (1977JOC2748). Only one example is reported but the sequence could have a broader preparative potential (Scheme 79). 

We used this strategy in chapter 6 under two-group C-X disconnections where bromination of ketones was the usual functionalisation. More relevant here are conversions of carbonyl compounds into 1,2-dicarbonyl compounds by reaction with selenium dioxide SeC>2 or by nitrosation. So acetophenone 57 gives the ketoaldehyde10 58 with SeC>2. These 1,2-dicarbonyl compounds are unstable but the crystalline hydrate 59 is stable and 58 can be reformed on heating. Since aromatic ketones such as 57 would certainly be made by a Friedel-Crafts reaction the disconnection 58a is not between the two carbonyl groups and offers an alternative strategy. 

Ketone 3.45 itself is readily prepared by nitrosation of ethyl acetoacetate followed by O-methylation. 

The most frequently used method for the synthesis of monocyclic furazans involves the dehydration of the appropriately substituted a-dioxime. Its utility stems from the ready availability of the precursor. Reduction of furoxans, which may themselves be formed from a variety of sources (Scheme 17) including glyoximes (see Section 4.22.4.2.1), oximation of 1,2-diones, and a -nitrosation-oximation of ketones are among the most favored approaches. 

Nitrolic acids, which can be isolated from sources such as nitroalkanes and aldoximes, are also probable intermediates in a wide variety of furoxan preparations involving nitric and nitrous acid, and nitrogen oxides. Diacylfuroxans have been synthesized via nitrosation of methyl ketones for example acetone reacts with anhydrous dinitrogen tetroxide or nitric acid/sodium nitrite to give diacetylfuroxan. 

Ketone semicarbazones undergo acid catalyzed reversible cyclization to 3,3-disubstituted 1,2,4-triazolidinones (76JHC1257). The only example available in the literature where a fused triazoline was obtained involves the nitrosation of ethyl 2-isopropylidenehydrazonothiazole-4-acetate, resulting in the formation of a 3,3-dimethyl-2H-s-triazolo[3,4-f ]thiazole (Scheme 14) (78JHC40l).The reaction may be classified as a 1,5-electrocydization. 

The compound to be cyclised having been obtained by nitrosation of a ketone... 

Nitrous acid has been used to effect yet another fission of the enamine double bond of neostrychnine (LXVII) to give an iVa-formyl-21 -oxim ino compound (see reaction sequence, Section I) (32) this reaction is related to the oxidative nitrosating ring fission of ketones, a well-known example of which is the conversion of CXCIV into CXCV (157). 

Methyl selenien-2-yl glyoxal,118 the simplest a-diketone of the selenophene series, has been obtained in two ways by oxidation of 2-propionylselenophene by selenium dioxide and by hydrolysis of the product resulting from nitrosation of that ketone. Its UV spectrum has three characteristic maxima (Amax 277, 283, and 310 mp). When... 

N-Nitrosation of oximes by nitrosyl halides or nitrite esters often results in the formation of N-nitrimines, R R C=NN02, these compounds being formed by rearrangement of the initial adducts. N-Amination of oximes by chloramine or by hydroxylamine-O-sulfonic acid can result in the formation of diazo compounds (Scheme 28). The reaction, known as the Forster reaction, has been used for the preparation of aryldiazoalkanes, although better methods are usually available. Diazo ketones of the general formula (49) have also been prepared by this method from the oximes. "... 

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