Diazoacetic acid ethyl ester

Trimethyllead diazoacetic acid ethyl ester reacts with activated alkenes or acetylenes to provide organolead pyrazoles or pyrazolines197 ... 

The diazoacetic acid ethyl ester is prepared by the following reaction... 

Diazoacetic acid, ethyl ester 5 D1155—D1156... 

Fig. 14.23. Ring expansion of a cyclohexanone via addition of diazoacetic acid ethyl ester and subsequent [l,2]-rear-rangement.

SYNS DAAE DIAZOACETIC ACID, ETHYL ESTER DIAZOESSIGSAEURE-AETHYLESTER (GERMAN) EDA ETHOXYCARBOKYLDIAZOMETHANE ETHYL DIAZOACETATE... 

DIAZOACETATE (ESTER) SERINE see ASA500 DIAZO-ACETIC ACID ESTER with SERINE see ASA500 DIAZOACETIC ACID, ETHYL ESTER see DCN800 DIAZOACETIC ESTER see DCN800 N-DIAZOACETILGLICINA-IDRAZIDE (ITALIAN) see DC0800... 

This method is improved by using diorganoboron chlorides and organoboron dichlorides to react with diazoacetic acid ethyl ester at — 78°C. Nitrogen is evolved, and, after addition of methanol (at — 78°C), the acetic acid ethyl ester derivative can be isolated in 50-90% yield ... 

Ethyl diazoacetate diazoacetic acid ethyl ester) (254) Carbon chemical shift 438,... 

Fig. 4.15. Synthesis of KDO using ethyl diazoacetate as synthetic equivalent of the anion of glyoxylic acid ethyl ester [980].

It has been shown that the lead tetraacetate-mediated 1,2-aryl shift of various meta-substituted / -cyclohexyl aryl ketones, e.g. (10), results in excellent yields of the corresponding rearranged esters (11). A unique reaction, providing 3-hydroxy-2-arylacrylic acid ethyl esters (14), has been observed between aryl aldehydes and ethyl diazoacetate in the presence of the iron Lewis acid [rj — (C5H5)Fe(CO)2(THF)BF4], It appears that the enol esters are formed by an unusual 1,2-aryl shift from a possible intermediate (13), which in turn is formed from the reaction of the iron aldehyde complex (12) with ethyl diazoacetate (see Scheme 4). 

Follow-up chemistry of azetidyl ylide 94, which was obtained by hydrolysis of ylide 84, led to various pyrrolidines and pyrazoles [68]. The reaction with methyl oxalyl chloride gave a 4-triphenylphosphoranyhdene-pyrrolidine-2,3,5-trione 95, while treatment with ethyl diazoacetate afforded 4-anilido-3-triphenylphosphoran-ylidene-pyrazole-5-carboxylic acid ethyl ester 96 (Scheme 20). 

ETHYL DIAZOACETATE (Acetic acid, diazo-, ethyl ester)... 

The simple primary amines of the aliphatic series, then, do not form diazo-compounds because the reaction which would le, d to their formation only occurs at a temperature at which they are destroyed. The reactivity of the NH2-group can, however, be increased by a neighbouring carbonyl group. Thus we come to the case of the esters of the a-amino-carboxylic acids and of the a-amino-ketones. The ethyl ester of glycine can be diazotised even in the cold the diazo-compound which does not decompose under these conditions undergoes stabilisation by elimination of water and change into ethyl diazoacetate ... 

Hydrazine was first obtained by hydrolytic decomposition of bis-diazoacetic acid . The latter, a tetrazine derivative, is obtained from ethyl diazoacetate in the form of alkali salt by the (catalytic) action of strong alkali. Two molecules of the acid simply unite and, at the same time, the ester group is hydrolysed ... 

In the Sepracor synthesis of chiral cetirizine di hydrochloride (4), the linear side-chain as bromide 51 was assembled via rhodium octanoate-mediated ether formation from 2-bromoethanol and ethyl diazoacetate (Scheme 8). Condensation of 4-chlorobenzaldehyde with chiral auxiliary (/f)-f-butyl sulfinamide (52) in the presence of Lewis acid, tetraethoxytitanium led to (/f)-sulfinimine 53. Addition of phenyl magnesium bromide to 53 gave nse to a 91 9 mixture of two diastereomers where the major diasteromer 54 was isolated in greater than 65% yield. Mild hydrolysis conditions were applied to remove the chiral auxiliary by exposing 54 to 2 N HCl in methanol to provide (S)-amine 55. Bisalkylation of (S)-amine 55 with dichlonde 56 was followed by subsequent hydrolysis to remove the tosyl amine protecting group to afford (S)-43. Alkylation of (5)-piperizine 43 with bromide 51 produced (S)-cetirizine ethyl ester, which was then hydrolyzed to deliver (S)-cetirizine dihydrochloride, (5)-4. 

Other preparations of 2-iminothiazolidin-4-ones which are discussed in the review by Brown139 utilize the reactions of thiourea with a-hydroxy acids,146 ethyl diazoacetate,73 glycidic esters,74,147 cinnamic acid,148 unsaturated diacids (fumaric, maleic, and citraconic) or their esters or imides,149-152 and propiolic esters.153,154 There has been considerable controversy in the literature surrounding the propiolic ester synthesis since many workers have proposed that the products are 1,3-thiazines (see Section IV, B, 1). The pertinent papers in this controversy have been summarized by Cain and Warrener.155 Nagase158 has recently settled the argument in favor of the 2-iminothiazolidin-4-... 

Ethyl diazoacetate has been used extensively in the homologation of ketones to 3-keto esters. Lewis acid is required for the reaction (equation 23). ° There is a tendency for the least-substituted group to migrate, particularly if one group is fully substituted (equation 24). In a total synthesis of ( )-aplysin (20) this selective rearrangement was applied (Scheme 9), and a similar approach was used in a synthesis of (+)-hirsutic acid. Ethyl diazoacetate has also been used in the homologation of acyclic... 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

The most versatile carbene precursors are a-diazocarbonyl compounds such as diazoacetic acid esters because they are readily prepared, easy to handle and much more stable than ordinary diazoalkanes [10,38]. Nevertheless, one should always be aware of the potential hazards of diazo compounds in general [39],but if the necessary precautions are taken, they can be safely handled even on an industrial scale [18]. The most frequently used reagent is commercially available ethyl diazoacetate. Besides a-diazocarbonyl reagents, diazomethane [40,41 ] and a y-diazoacrylate derivative [42] have been used in enantioselective Cu-cata-lyzed cyclopropanations but the scope of these reactions has not been studied systematically. It has been shown in certain cases that diazo compounds can be replaced by other carbene precursors such as iodonium ylides, sulfonium yUdes, or lithiated sulfones [8,43],but successful applications of these reagents in enantioselective Cu-catalyzed reactions have not been reported yet. 

The catalyst was successfully applied to the production of S-2,2-dimethylcy-clopropanecarboxylic acid (Scheme 4). Reaction of ethyl diazoacetate with isobutylene in the presence of the R-catalyst gave the corresponding ethyl ester in 92% ee [10,22,31]. 

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