Ketones diazomethane

Before giving up oti the samarium-mediated fragmentation approach, we decided to investigate one additional substrate that would not be able to form a cyclobutane because one of the 1,4-dicarbonyl partners was an ester (186, Scheme 35). The requisite substrate was readily accessed by converting aldehyde 186 to carboxylate 187 using a Pinnick oxidation followed by treatment with TMS diazomethane. Ketone 186 reacted with samarium diiodide but no fragmentation took place, only reduction of the ketone to a mixture of secondary alcohol products, one of which further reacted to form lactone 189. 

The oxidation of hydrazones has provided two new methods for the preparation of substituted diazomethanes. Ketone hydrazones, upon treatment with sodium in ether and subsequent aerial oxidation, gave diazomethanes (52) in excellent yields (Scheme 50). Similarly, hydrazonoethylidene derivatives yield diazoethylidenes (53) upon oxidation with Mn02 (Scheme 51). ... 

Reaction of the acid chloride with a cold solution of excess of diazomethane to yield a diazo ketone ... 

Reaction of cyclic ketones with diazoraethane leads to ring enlargement. Thus cyctohexanone (I) (1 mol) and diazomethane (1 mol) give /oheptanone (II) in about 60 per cent, yield together with a little epoxide (III) as by product and some cj/cioootanone (IV) resulting from further reaction of cyctoheptanone with diazomethane. ... 

Thiazole acid chlorides react with diazomethane to give the diazoketone. The later reacts with alcoholic hydrogen chloride to give chloroacetylthiazole (Scheme 16). However, the Wolff rearrangement of the diazoketone is not consistently satisfactory (82). Heated with alcohol in the presence of copper oxide the 5-diazomethylketone (24) gives ethyl 5-thiazoleacetate (25) instead of the expected ethoxymethyl 5-thiazolyl ketone (Scheme 17) (83). 

Carbon—nitrogen double bonds in imines, hydrazones, oximes, nitrones, azines, and substituted diazomethanes can be cleaved, yielding mainly ketones, aldehydes and/or carboxyHc acids. Ozonation of acetylene gives primarily glyoxal. With substituted compounds, carboxyHc acids and dicarbonyl compounds are obtained for instance, stearoHc acid yields mainly azelaic acid, and a smaH amount of 9,10-diketostearic acid. 

Benzyl chloromethyl ketone has been prepared by the reaction of diazomethane with phenylacetyl chloride. The method of Clibbens and Nierenstein, in which one equivalent of diazomethane is added to the acyl chloride and the chloromethyl ketone obtained directly, could not be duplicated by Bradley and Schwarzenbach or by the submitters. 

The more important methods of preparation of diazomethane include those from nitrosomethylurea, nitrosomcthylurethane, N-nitroso-/3-methylaminoisobutyl methyl ketone, and 1-methyl-l-nitroso-3-nitroguanidine. ... 

The addition of diazomethane to a,/l-unsaturated ketones, e.g., benzalace-tone and benzalacetophenone, results in A -pyrazolines (16) which decompose thermally to the conjugated ketones (17). Cyclopropane formation is not observed in this instance. 

With -3-ketones, i.e., (11), diazomethane addition proceeds with attack at the A -bond leading to stereospecific formation of [2a,la-c]-A -pyrazolines (12). 

Addition of diazomethane to the A -17-ketone (20) proceeds from the -face of the molecule to give (22) in high yield after cleavage of the intermediate pyrazoline (21). ° ... 

Nelson and Scliut investigated the reaction of 5a-cholestanone (lb) with diazomethane in a search for a direct, one-step preparation of A-homo ketones. Using a large excess of diazomethane generated in situ from A-methyl-nitrosourea with potassium hydroxide in ether-methanol at 0°, 5a-cholestanone (lb) is converted into the 7-membered ring homolog (3b) as the predominant product. Both theoretically possible A-homo ketones can be expected with an unsymmetrically-substituted cyclohexanone such as 5a-cholestanone (lb). 

It is recommended that Nelson and Schut s diazomethane procedure be considered first for preparing saturated A-homo-4-ketones, or enlarging cyclic ketones in general, rather than the Tiffeneau procedure, because fewer steps are involved, isolation and purification are operationally simpler, and the overall yield is often better. 

A valuable extension of the diazomethane reaction for the preparation of A-homosteroids was discovered by Johnson, Neeman and Birkeland " who found that a,j5-unsaturated ketones are homologated by reaction with diazomethane in the presence of either fluoroboric acid or boron trifluoride. The main product is formed by the insertion of a methylene group between the carbonyl group and the unsaturated a-carbon to give a / ,y-unsaturated ketone. 

B-Homosteroids have also been prepared by acid-catalyzed reaction of diazomethane with a,/5-unsaturated ketones. 3/ -Hydroxycholest-5-en-7-one acetate (57) reacts with diazomethane in the presence of concentrated fluoroboric acid, boron trifluoride etherate or aluminum chloride to give 3yS-hydroxy-B-homo-cholest-5-en-7a-one acetate (67). The 7a-keto group is reported to be chemically less reactive than an 11-keto group. 

B-norketone (119) by enlarging ring A with diazomethane to give A-homo-B-norketone (120). Wolff-Kishner reduction of (120) gave hydrocarbon (118) identical to the product from ketone (116a). 

What evidence is there for the individual reaction steps The add-base reaction (Eq, 2) has the characteristics of a Broensted equilibrium, as has been shown in the case of diazomethane-benzoic acid (in toluene). Further evidence for this is provided by the reactions of diazoacetic ester and diazo ketones. The occurrence of free, mobile diazonium cations is also supported by the fact that solutions of diazomethane in methanol show greater conductivity than solutions of pure solvent. ... 

The reactions of diazomethane with heterocycles containing a ketonic grouping in the ring do not differ, in principle, from those of alicyclic ketones (see footnotes 3 and 177) ring expansion and the formation of epoxides compete. In general, ring expansion is the more important reaction for example, tetrahydropyran-4-one (99) is converted to l-oxacycloheptan-4-one (100) (60%) and 4,4 -epoxy-4-methyltetrahydropyran (101) (23%). ... 

In a first step, the carboxylic acid 1 is converted into the corresponding acyl chloride 2 by treatment with thionyl chloride or phosphorous trichloride. The acyl chloride is then treated with diazomethane to give the diazo ketone 3, which is stabilized by resonance, and hydrogen chloride ... 

The hydrogen chloride thus produced can in turn react with the diazoketone to yield a a-chloro ketone. In order to avoid this side reaction, two equivalents of diazomethane are used. The second equivalent reacts with HCl to give methyl chloride. ... 

Diazomethane reacts with ketonic compounds according to the reactions to give epoxides and homologated ketones. If the ketone employed is cyclic, only a single... 

The well-known reaction leading to ring expansion of cyclic ketones has been applied to derivatives of oxo sugars in an attempt to develop a new route to novel deoxy sugars. By treatment with diazomethane both a five-membered (42) and a six-membered (26) sugar ring have been expanded by insertion of a methylene group. 

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. 

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