Diazomethane reaction with alcohols

Methylation. The reaction with diazomethane has often been used for differentiating the acidic groups (28, 35, 38, 45, 46, 69). Diazomethane reacts, in general, with carboxylic acids, forming methyl esters which are easily hydrolyzed by dilute hydrochloric acid. With phenols, ethers are formed which are stable to hydrolysis. Alcohols are methylated only if catalysts are present, e.g., BF, ZnClj (70), or HjO (71). As Garten et al. 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Selective reduction of 530 with DIBAL gave a mixture (1 3) of the allylic alcohols 531 and 532 via preferential delivery of hydride to the unsaturated carbonyl function from the exo face. The allylic alcohol 531 was then converted to the allylic ether 533 by reaction with diazomethane in the presence of anhydrous aluminum chloride, whereas the major allylic alcohol 532 was converted to... 

What is the structure of the alcohol which upon reaction with diazomethane will yield VH-a as the product ... 

For GC analysis, the salts of the lowest molecular weight acids present in ozonation products subjected to base-promoted hydrolysis have been converted to their benzyl esters by reaction with benzyl bromide (Bonnet et al. 1989). The salts of all acids produced have commonly been converted to the free acids, usually with the aid of a cation exchange resin. The acids have then been converted to methyl esters by reaction with diazomethane (Bonnet et al. 1989) or, more often, have been converted to trimethylsilyl (TMS) esters (Matsumoto et al. 1986, Taneda et al. 1989, Habu et al. 1990). Trimethylsilylation has the major advantage that alcoholic and phenolic hydroxyl groups are simultaneously converted to TMS ethers, thus greatly facilitating GC analysis. 

A number of atypical reactions of enamines have been developed. For example, hydroboration-oxida-tion affords stereochemically defined, vicinal amino alcohols (equation 26). Similarly, enamines have been shown to undergo reaction with diazomethane to form substituted cyclopropanes. These materials can be further transformed to a alkylated ketones by thermolysis followed by hydrolysis (equation 27). ... 

Pete and coworkers [1000, 1001] have irradiated a,P-ethylenic esters of enantiopure alcohols, and the intermediate dienols that form are protonated either with AyV-dimethylethanol at -35°C in hexane [1001] or with i-PrOH or terf-BuOH [1000], The chiral auxiliaries are diacetoneglucose 1.48 or (S)-ethyl lactate 2.1 (R = Me, R = Et), or better yet the corresponding add (Figure 4.9). The cleavage of the chiral auxiliary is accomplished by treatment with PhCH20H/Ti(0/-Pr)4 or by mild hydrolysis. After the subsequent reaction with diazomethane, nonracemic benzyl or methyl a-alkylated-P.y-unsaturated esters are obtained with high enantiomeric excesses (Figure 4.9). 

Surface oxides on graphite undergo the reactions typical of carboxylic acids, phenols and alcohols. Methylation with diazomethane or dimethylsulfate, silanization of—OH groups by reaction with halosilanes, formation of acyl chlorides by reaction with thionyl chloride, further reactions of these acyl chlorides, neutralization of acidic surface groups with different bases, ion exchange and more special reactions are used to characterize surface oxides on carbon and to modify their properties for technical applications . 

Methylation of Heteroatoms. The most widely used feature of the chemistry of diazomethane is the methylation of carboxylic acids. Carboxylic acids are good substrates for reaction with diazomethane because the acid is capable of protonating the dia-zomethane on carbon to form a diazonium carboxylate. The car-boxylate can then attack the diazonium salt in what is most likely an Sn2 reaction to provide the ester. Species which are not acidic enough to protonate diazomethane, such as alcohols, require an additional catalyst, such as Boron Trifluoride Etherate, to increase their acidity and facilitate the reaction. The methylation reaction proceeds under mild conditions and is highly reliable and very selective for carboxylic acids. A typical procedure is to add a yellow solution of diazomethane to the carhoxylic acid in portions. When the yellow color persists and no more gas is evolved, the reaction is deemed complete. Excess reagent can be destroyed by the addition of a few drops of acetic acid and the entire solution concentrated to provide the methyl ester. 

An interesting case of an alcohol reacting with diazomethane at a rate competitive with a carboxylic acid has been reported (eq 15). In this case, the tertiary structure of the molecule is thought to place the alcohol and the carboxylic acid in proximity to each other. Protonation of the diazomethane by the carboxylic acid leads to a diazonium ion in proximity to the alcohol as well as the carboxylate. These species then attack the diazonium ion at competitive rates to provide the methyl ether and ester. No reaction is observed upon treatment of the corresponding hydroxy ester with diazomethane, indicating that the acid is required to activate the diazomethane. 

CHR) , formed, e g. from the reaction of diazomethane and alcohols or hydroxylamine derivatives in the presence of boron compounds or with metal compounds. Poly-methylene is formally the same as polyethene and the properties of the various polymers depend upon the degree of polymerization and the stereochemistry. 

An ethereal solution of diazomethane free from alcohol may be prepared as follows such a solution is required, for example, in the Amdt-Eistert reaction with acid chlorides (compare Section VI,17). In a 100 ml. longnecked distilling flask provided with a dropping funnel and an efficient downward condenser, place a solution of 6 g. of potassium hydroxide in... 

Alkylation of A-4-thiazoline-2-one may yield O-R or N-R derivatives according to experimental conditions. With diazomethane in ethanol O-raethylation takes place (29. 36. 214). N-Methylation is reported when a basic solution of A-4-thiazoline-2-one reacts with methyl iodide or dimethylsulfate (21, 29, 215, 216), Reaction of l-chloro-2-dimethyl-aminoethane with the sodium salt of 4 R-A-4-thiazoline-2-one (91) in alcohol, first claimed to yield the aminoalkylether (217, 218), was shown after infrared investigation to give the N-substituted derivative (92) (107), even when R Ph (Scheme 45). More probably the site of reaction in... 

Heating the adduct of ethylene oxide and sulfur dioxide with primary alcohols in the presence of alkaH hydhdes or a transition-metal haHde yields dialkyl sulfites (107). Another method for the preparation of methyl alkyl sulfites consists of the reaction of diazomethane with alcohoHc solutions of sulfur dioxide (108). 

Thus, the acidity oi a lactam is evidently not a reliable quantity for predicting the course of the methylation. The acidity gives information only as to the reaction velocity. In this connection the reaction course of isomethylreductone (6) is illuminating, " With diazomethane in ether containing 1 mole of water, the enolraethyl ether (7) is formed. However, if water is present only in traces, then the alcoholic hydroxyl group is selectively attacked to give 8. 

Diazomethane is a yellow gas that is toxic and explosive but that may be handled safely in solution in ether. It reacts immediately with an acid to liberate nitrogen and form the methyl ester. Its reaction with alcohols to form methyl esters requires catalysis by a Lewis acid. The procedures illustrate the use of this reagent as a methylating agent (see Chapter 17, Section III, for preparation of diazomethane). 

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... 

In studies on l-diazo-2-ketosulfones, Shioiri et at. found that the thermal decomposition of benzoyl(sulfonyl)diazomethanes 6 with benzyl alcohol in acetonitrile also gave two products.<82CPB526> One is the 4-sulfonyloxazole 7 whereas the other product 8 results from rearrangement and reaction with the alcohol. The ratio of products varies with the nature of the sulfone substituent with the benzyl group giving highest yields of oxazole (Scheme 5). 

A series of reactions with gases have been selected for the rapid quantification of many of the major products from the oxidation of polyolefins. Infrared spectroscopy is used to measure absorptions after gas treatments. The gases used and the groups quantified include phosgene to convert alcohols and hydroperoxides to chloroformates, diazomethane to convert acids and peracids to their respective methyl esters, sulfur tetrafluoride to convert acids to acid fluorides and nitric oxide to convert alcohols and hydroperoxides to nitrites and nitrates respectively. 

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