Diazo compounds diazomethane

The simplest diazo compound, diazomethane, undergoes loss of nitrogen in the gas or solution phase to yield a divalent carbon compound, methylene ... 

Alkylation with Diazo Compounds Diazomethane or diazoethane are commonly used as diazo compounds. The reactions of these alkylating agents proceed smoothly only with AN containing electron-withdrawing groups (EWG) adjacent to the a-C atom (4-6) (Scheme 3.3). 

The parent of the diazo compounds, diazomethane, CH2=N=N, has been mentioned before in connection with ylide reactions for ring enlargement (Section 16-4A) and the preparation of methyl esters from acids (Table 18-7). It is one of the most versatile and useful reagents in organic chemistry, despite the fact that it is highly toxic, dangerously explosive, and cannot be stored without decomposition. 

Diazoalkane decomposition. Surprisingly, tetraphenylethylene is almost as efficient as various copper catalysts for decomposition of diazoalkanes to car-benoids. For example, diazomethane and cyclohexene in the presence of this catalyst react to form norcarane in 15 5% yield with copper catalysis the yield of norcarane is 24%. Cyclopropanations have been observed with this hydrocarbon catalyst with a variety of diazo compounds diazomethane, a-diazoacetophenone, and diazofluorene. Diphenyldiazomethane, however, is converted mainly into benzophenone azine, (C5H5)2C=NN=C(C6Hs)2. 

Diethylamine acetate Pyridiniiim salt T etramethylammonium acetate, Tetraethyl-ammonium-Piperidinium acetate Isoxazolium salts Trialky loxonium salt Amidinium salts Ketenimines Diazo compounds Diazomethane, Phenyl-diazomethane K-methy Idiazotate Hexamethylenetetramine Azo compounds Azodicarboxamide ROOC-N N-COOR A zodiisobuty ronitrile T riazenes Azidinium salts p-Nitrobenzene-diazonium sulfate Sulfanilic acid, diazotized... 

Decomposition of diazo compounds to carbenes is a quite general reaction. Examples include the simplest diazo compound, diazomethane, as well as diaryl diazomethanes and diazo compounds in which one or both of the substituents is an acyl group. The inability to synthesize the required diazo compound is sometimes a limitation on the method. The low-molecular-weight diazoalkanes are toxic and unstable, and are usually prepared and used in situ rather than isolated. The simple aliphatic diazo compounds are synthesized from derivatives of the corresponding amine. All the common precursors of diazomethane, for example, are derivatives of methylamine. The details of the base-catalyzed decompositions vary somewhat from... 

Esters can be prepared by acid-catalyzed esterification or by reaction of the acid chloride with the alcohol. In small-scale syntheses, it is often more convenient to prepare the ester by reaction of the carboxylic acid with the appropriate diazo compound. Diazomethane is routinely used for making methyl esters, but more highly substituted esters can be prepared if the corresponding diazo compound is available. Benzhydryl esters, for example, are readily prepared from carboxylic acids by reaction with diphenyldiazomethane ... 

Pyrrolidinium acetate Piperidinium -Isoxazolium salts Trialky loxonium salt Amidinium salts Ketenimines Benzaldoxime Hy dr azobenzene Diazo compounds Diazomethane, Phenyl-diazomethane Ethyl diazoacetate K-methyldiazotate Hexamethylenetetramine Azo compds., Azobenzene Acylazo compds. Azodicarboxamide ROOC-N N-COOK Azodiisobutyronitrile Triazenes Diazonium fluoro-borates... 

Diazo compounds —N2 Organic diazo compounds metal diazo compounds Diazomethane diazoacetonitrile lithium diazomethanide... 

Diazo Compounds. Diazomethane reacts immediately with 1 dissolved in diethyl ether in a regioselective manner to give 2,5-dihydro- 1,3,4-thiadiazole (17) as a relatively stable sohd. This confound is a superior precursor of the reactive thiocarhony 1 5-methylide (8, eq 9) as it smoothly eliminates nitrogen at 45 °C. In the absence of an appropriate interceptor, thiirane 9 is formed. In the presence of electron-deficient dipolarophiles, diverse five-membered spiro-heterocycles (18) are formed via 1,3-dipolar cycloaddition (eq 9).22.23 Representative examples of dipolarophiles leading to 18 in high yield are DMAD, TV phenyl maleinimide, chloral, dimethyl azodicarboxylate, adamantanethione, as well as 1.21... 

Pyrazoles are formed when the diazo compounds react with alkynes or with functionalized alkenes, viz. the enols of /3-diketones. Pyrazolenines (353 Section 4.04.2.2.1) are isolated from disubstituted diazomethanes. Many pyrazoles, difficult to obtain by other methods, have been prepared by this procedure, for example 3-cyanopyrazole (616) is obtained from cyanoacetylene and diazomethane (7iJCS(C)2i47), 3,4,5-tris(trifiuoromethyl)pyrazole (617) from trifluorodiazoethane and hexafluoro-2-butyne (8lAHC(28)l), and 4-phenyl-3-triflylpyrazole (618 R =H) from phenyltriflylacetylene and diazomethane (82MI40402). An excess of diazomethane causes iV-methylation of the pyrazole (618 R = H) and the two isomers (618 R = Me) and (619) are formed in a ratio of 1 1. 

The addition of diazo compounds generally leads to three membered tings, although in special cases, linear adducts with an intact diazo group [110] or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and aziridines [112,113,114] Aziridines are obtained exclusively on reaction of certain polyfluorinated acyl imines with diazomethane [115]... 

In this review an attempt is made to discuss all the important interactions of highly reactive divalent carbon derivatives (carbenes, methylenes) and heterocyclic compounds and the accompanying molecular rearrangements. The most widely studied reactions have been those of dihalocarbenes, particularly dichlorocarbene, and the a-ketocarbenes obtained by photolytic or copper-catalyzed decomposition of diazo compounds such as diazoacetic ester or diazoacetone. The reactions of diazomethane with heterocyclic compounds have already been reviewed in this series. ... 

Thus it is not surprising that three-membered rings with two hetero atoms were mentioned in the literature at an early stage. For example, at the turn of the century, nitrones, hydrazones, and aliphatic diazo compounds were all formulated with three-membered rings (I, 2, 3). Later the three-membered ring structures for these compounds became questionable. The structure of the aliphatic diazo compounds was studied very intensively. For diazomethane no clas-... 

Whereas the utility of these methods has been amply documented, they are limited in the structures they can provide because of their dependence on the diazoacetate functionality and its unique chemical properties. Transfer of a simple, unsubstituted methylene would allow access to a more general subset of chiral cyclopropanes. However, attempts to utilize simple diazo compounds, such as diazomethane, have never approached the high selectivities observed with the related diazoacetates (Scheme 3.2) [4]. Traditional strategies involving rhodium [3a,c], copper [ 3b, 5] and palladium have yet to provide a solution to this synthetic problem. The most promising results to date involve the use of zinc carbenoids albeit with selectivities less than those obtained using the diazoacetates. 

Compounds containing the neutral (formally zwitterionic) group =N2 attached by one atom to carbon are named by adding the prefix diazo- to the name of the parent compound (Rule 931.4), e.g., diazomethane, ethyl diazoacetate. Diazo is a so-called characteristic group appearing only as a prefix in substitutive nomenclature. Chemical Abstracts and Beilstein indexing of diazo compounds is analogous to that mentioned above for diazonium ions and salts, but Diazo compounds is not... 

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... 

Carboxylic acids can be converted to esters with diazo compounds in a reaction essentially the same as 10-15. 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, the diazo compounds most often used are diazomethane (for methyl esters) ... 

The reaction of diazo compounds with amines is similar to 10-15. The acidity of amines is not great enough for the reaction to proceed without a catalyst, but BF3, which converts the amine to the F3B-NHR2 complex, enables the reaction to take place. Cuprous cyanide can also be used as a catalyst. The most common substrate is diazomethane, in which case this is a method for the methylation of amines. Ammonia has been used as the amine but, as in the case of 10-44, mixtures of primary, secondary, and tertiary amines are obtained. Primary aliphatic amines give mixtures of secondary and tertiary amines. Secondary amines give successful alkylation. Primary aromatic amines also give the reaction, but diaryl or arylalkyl-amines react very poorly. 

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. 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

Alkali metal salts of diazomethane are very explosive when exposed to air in the dry state, and should be handled, preferably wet with solvent, under an inert atmosphere. See other diazo compounds... 

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. 

In 1986, Pfaltz et al. introduced a new type of pseudo C2-symmetrical copper-semicorrin complex (68) as the catalyst (Scheme 60).227 228 The complexes (68) are reduced in situ by the diazo compound or by pretreatment with phenylhydrazine to give monomeric Cu1 species (69), which catalyze cyclopropanation. Of the semicorrin complexes, complex (68a) (R = CMe2OH) showed the best enantioselectivity in the cyclopropanation of terminal and 1,2-disubstituted olefins.227,228,17 It is noteworthy that complex (68a) catalyzes cyclopropanation, using diazomethane as a carbene source, with good enantioselectivity (70-75% ee).17... 

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