Alcohols with diazo ketones

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

Rearrangement of the diazo ketone, with loss of nitrogen, in the presence of suitable reagents and a catalyst (colloidal silver, silver oxide, or silver nitrate in the presence of ammonia solution). An acid is formed In the presence of water, an amide results when ammonia or an amine is used, and an ester is produced in the presence of an alcohol ... 

Esters of the homologous acids are prepared by adding silver oxide in portions rather than in one lot to a hot solution or suspension of the diazo ketone in an anhydrous alcohol (methyl, ethyl or n-propyl alcohol) methanol is generally used and the silver oxide is reduced to metallic silver, which usually deposits as a mirror on the sides of the flask. The production of the ester may frequently be carried out in a homogeneous medium by treating a solution of the diazo ketone in the alcohol with a solution of silver benzoate in triethylamlne. 

Ethyl a-naphthylacetate is prepared as follows. To a solution of 10 g. of the diazo ketone in 150 ml. of ethanol at 55-60°, add a small amount of aslurry of silver oxide, prepared from 10 ml. of 10 per cent, aqueous silver nitrate and stirred with 25 ml. of ethanol. As soon as the evolution of nitrogen subsides, introduce more of the silver oxide and continue the process until all the slurry has been added. Reflux the mixture for 15 minutes, add 2-3 g. of decolourising carbon, filter and evaporate the alcohol on a water bath. Distil the residue and collect the ethyl a-naph-thylacetate at 176-178°/ 1 mm. the yield is 9 g. 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Diazo ketones are relatively easy to prepare (see 0-112). When treated with acid, they add a proton to give a-keto diazonium salts, which are hydrolyzed to the alcohols by the SnI or Sn2 mechanism.456 Relatively good yields of a-hydroxy ketones can be prepared in this... 

The bicyclic product 59 proved not to be derived from diazo ketone 58. It may arise from the reaction of diazenyl ketene intermediate 53 with diazomethane via the postulated 2-[2-methyl-2-(phenyldiazenyl)propyl] cyclopropanone intermediate 60 and its subsequent isomerization to the bicyclic product 59 (Scheme 14). The formation of the diazenyl ketene intermediate 53 has been made plausible by carrying out the reaction in the presence of an excess of isobutyl alcohol to afford isobutyl 3-methyl-3-[(E)-phenyldiazenyl]butanoate (61) in a competing addition. 

Certain aryl-substituted a- and /S-amino Intones have been successfully reduced to amino alcohols by catalytic hydrogenation over palladium, platinum, or nickel catalysts. Cleavage of the carbon chain sometimes occurs during catalytic hydrogenation of /S-amino ketones. Fair yields of the amino alcohols ate obtained in these cases by reduction with sodium amalgam in dilute acid or aluminum amalgam and water. /S-Amino aldehydes from the Mannich reaction (method 444) are reduced in excellent yields to amino alcohols by lithium aluminum hydride or by catalytic hydrogenation over Raney nickel. Lithium aluminum hydride reduces diazo ketones to 1-amino-2-alkanols (93-99%)- ... 

Improved procedures for the rearrangement of diazo ketones have been developed- In one of these, the readily hydrolyzable benzyl ester is formed by heating the diazo ketone with benzyl alcohol in the presence of a tertiary amine. ... 

Carboxylic acids can be converted to esters with diazo compounds in a reaction essentially the same as lO-II. In contrast to alcohols, carboxylic acids undergo the reaction quite well at room temperature, since the reactivity of the reagent increases with acidity. The reaction is used where high yields are important or where the acid is sensitive to higher temperatures. Because of availability diazomethane (CH2N2) " is commonly used to prepare methyl esters, and diazo ketones are common. The mechanism is as shown in 10-11. 

In an earlier chapter, we saw how to reduce the carbon chain by one methylene unit using the Hunsdiecker reaction. The opposite of this, namely the extension of the carbon chain by one unit, may be achieved with the Amdt-Eistert synthesis. In the first step, an acyl halide is treated with diazomethane to form the a-diazo ketone. This is then treated with water and silver oxide. The resultant product is the free acid. If an alcohol is used instead of water, then the related ester is formed. Suggest what is the pathway for this reaction. 

The Wolff rearrangement of six- and five-membered a-diazocycloalkanones has been extensively applied to the synthesis of highly strained frameworks. The rearrangement of an (x-diazo-cyclobutanone was reported from 2-diazo-3,4-bis(diphenylmethylene)cyclobutanone (1). The diazo ketone (1) was prepared by treatment of the 3,4-bis(diphenylmethyl-ene)cyclobutane-l,2-dione tosylhydrazone with alumina in 95% overall yield from the corresponding cyclobutanedione. Irradiation in the presence of water, alcohols and aniline afforded 1-carboxy-, 1-alkoxycarbonyl- and 1-phenylcarbamoyl-substituted 2,3-bis(diphenyl-methylene)cyclopropanes 2, respectively, in 13-87% yields. Thermal decomposition in aqueous dioxane afforded the cyclopropanecarboxylic acid 2 (X = OH) in 52% yield. ... 

Nucleophilic addition of Ti(IV)-enolates of diazo ketone (136) to cycloheptanone (186) affords alcohol 187 which, on further dehydration with trifluoroacetic anhydride gives a,P-unsaturated carbonyl compounds (188 189) in 58% yield.84... 

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