Diazomethane protonation

Azolinones are protonated on oxygen in strongly acidic media. O-Alkylation of 2-azolinones can be effected with diazomethane thiazolinone (486) forms (487). Frequently O- and iV-alkylation occur together, especially in basic media where proton loss gives an ambident anion. 

Compound Time at room temperature Diazomethane per cent protonation At C At N UAIH4 per cent protonation At C At N ... 

The determination of position of protonation by reaction with diazomethane was performed as follows The enamine was treated at —70° with ethereal hydrogen chloride and the suspension of precipitated salt was treated with diazomethane and allowed to warm slowly to —40°, at which temperature nitrogen was liberated. The reaction with lithium aluminum hydride (LAH) was carried out similarly except that an ether solution of LAH was added in place of diazomethane. The results from reaction of diazomethane and LAH 16) are summarized in Table 1. 

One of the most important applications of diazomethane depends on its ability to replace a mobile hydrogen atom by a methyl group. In comparison with other methylation agents, diazomethane occupies a rather special place this is, in part, because only rather strongly acidic protons are replaced. Because of the simple method of working up the reaction mixture, the reaction is especially well applicable for sensitive compounds and for small amounts. If tautomeric or potentially tautomeric compounds are treated with diazomethane, two... 

The general equation (1) for the methylation of a sufficiently acidic compound Z—H with diazomethane show s that the reaction formally takes place in two steps. Diazomethane docs not itself contain a methyl group, thus the first step, Eq. (2), must involve the loss of a proton from Z—-H and that it is taken up by diazomethane to give the corresponding cation CHa—which is the actual methylating agent ... 

The reaction occurs in two steps (1) protonation of diazomethane by the carboxylic acid to yield methyldiazonium ion, CH3N2+, plus a carboxylate ion and (2) reaction of the carboxylate ion with CH3N2+. 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

The Lewis acid-Lewis base interaction outlined in Scheme 43 also explains the formation of alkylrhodium complexes 414 from iodorhodium(III) meso-tetraphenyl-porphyrin 409 and various diazo compounds (Scheme 42)398), It seems reasonable to assume that intermediates 418 or 419 (corresponding to 415 and 417 in Scheme 43) are trapped by an added nucleophile in the reaction with ethyl diazoacetate, and that similar intermediates, by proton loss, give rise to vinylrhodium complexes from ethyl 2-diazopropionate or dimethyl diazosuccinate. As the rhodium porphyrin 409 is also an efficient catalyst for cyclopropanation of olefins with ethyl diazoacetate 87,1°°), stj bene formation from aryl diazomethanes 358 and carbene insertion into aliphatic C—H bonds 287, intermediates 418 or 419 are likely to be part of the mechanistic scheme of these reactions, too. 

C and 15N NMR chemical shifts were calculated for protonated diazomethane [CH3N=N]+ and the cyanodiazonium ion [N=CN=N] +. 142 For the C-protonated diazomethane, which is more stable than N-protonated species, the IGLO-HF calculated 13C NMR chemical shift of 54.1 ppm agrees with the experimental value of 44.5 ppm. 15N NMR chemical shifts were calculated as 237.9 and 379.9 ppm. 

Further studies on 1,3-dipolar addition reactions of diazophosphonates have been recorded,122 and work on 2-diazo-l-hydroxyalkylphosphonates also continues.123 The ester (155 R = H) reacts with esters of acetylenedicarboxylic acid without liberation of nitrogen to give stereoisomeric C-phosphorylated pyrazolines, which can be decomposed with both phosphorus-carbon and carbon-carbon bond fission, affording mixtures containing dimethyl acetylphosphonate, dimethyl hydrogen phosphonate, and tri(alkoxycarbonyl)pyrazolines. In the reaction between the same diazophosphonate and diazomethane, the latter conceivably acts as a basic catalyst for proton transfer in a series of steps which includes phosphonate-phosphate isomerization. The importance of a labile proton is demonstrated by the fact that the ester (155 R = Me) does not react in the manner described above. 

Most electrophilic carbene complexes with hydrogen at Cjj will undergo fast 1,2-proton migration with subsequent elimination of the metal and formation of an alkene. For this reason, transition metal-catalyzed cyclopropanations with non-acceptor-substituted diazoalkanes have mainly been limited to the use of diazomethane, aryl-, and diaryldiazomethanes (Tables 3.4 and 3.5). 

The main drawback to this reaction is the toxicity of diazomethane and some of its precursors. One possible alternative is the use of alkyltriazenes as reactive alkylating agents.52 Alkyltriazenes are readily prepared from primary amines and aryldiazonium salts.53 The triazenes, on being protonated by the carboxylic acid, generate a reactive alkylating agent that is equivalent, if not identical, to the alkyldiazonium ions generated from diazoalkanes. 

In recent years, modification of zeolites, such as HZSM-5, by phosphoric compounds or metal oxides has been extensively studied, but little information is available on the modification of zeolites by diazomethane, which is an excellent methylating agent for protonic acidic sites. It is capable of entering into the small pores of zeolites because of its small molecular size and linear molecular structure. Yin and Peng (1,2) reported that the acidity and specific surface area of the inorganic oxide supports (AljOs, SiOj) and zeolite catalysts... 

Attempts to generate thiocamphor (5)-methylide (44) by the addition of diazomethane to thiocamphor and subsequent N2-elimination from the [3-1-21-cycloadduct 43 led to enethiol ether 45 via a 1,4-H shift (Scheme 5.17). The formation of an unstable intermediate 43 was proposed on the basis of the proton nuclear magnetic resonance ( H NMR) spectrum of the crude mixture. The postulated intermediate 44 could not be intercepted by dipolarophiles or methanol, and did not undergo electrocyclization to give the corresponding thirrane (41). 

Alkylations of NH azapentalenes are carried out not on the neutral molecule, but on the corresponding anion. Methylations are usually performed with iodomethane or methyl sulfate on the silver salt,61 or, more frequently, on the sodium salt. Methylations with diazomethane may also be included since Gompper404 has shown that initial proton abstraction to give the methylating agent CH3N is involved. Scheme 16... 

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