Diazoacetate

CROTYL DIAZOACETATE (Acetic acid, diazo-, trans-2-butenyl ester) 

Submitted by C. John Blankley, Frederick J. Saoter, and Herbert O. House  

The p-toluenesulfonylhydrazone of glyoxylic acid chloride. Caution Since hydrogen chloride and sulfur dioxide are liberated during this reaction, it should be conducted in a hood. To a suspension of 50.2 g. (0.21 mole) of glyoxylic acid / -toluenesulfonyl-hydrazone in 250 ml. of benzene is added 30 ml. (49 g. or 0.42 mole) of thionyl chloride (Note 5). The reaction mixture is heated under reflux with stirring until vigorous gas evolution has ceased and most of the suspended solid has dissolved (about 

S hours is required, Note 6). The reaction mixture is then cooled immediately (Note 6) and filtered through a Celite mat on a sintered-glass funnel. After the filtrate has been concentrated to dryness under reduced pressure, the residual solid is mixed with 40-50 ml. of anhydrous benzene, warmed, and the solid mass is broken up to give a fine suspension. This suspension is cooled and filtered with suction. The crystalline product is washed quickly with two portions of cold benzene to remove most of the residual colored impurities, and then the remaining crude acid chloride is transferred to a flask for recrystallization. 

The combined benzene filtrates from this initial washing procedure are concentrated under reduced pressure, and the washing procedure with benzene is repeated to give a second crop of the crude acid chloride which is transferred to a flask for recrystallization. 

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Supplement XXV, 2nd 1936 3458-3793 Hydroxy-indanthrene, 102. Carboxylic acids Diazoacetic acid, 109. 

Analysis The carbene synthon is easy it can be ethyl diazoacetate NiCHCOiEt. The diene can be made by the Wittig reaction from a familiar aUylic bromide (TM 31). 

The reaction of cyclohexene with the diazopyruvate 25 gives unexpectedly ethyl 3-cyclohexenyl malonate (26), involving Wolff rearrangement. No cyclo-propanation takes place[28]. 1,3-Dipolar cycloaddition takes place by the reaction of acrylonitrile with diazoacetate to afford the oxazole derivative 27[29]. Bis(trimethylstannyl)diazomethane (28) undergoes Pd(0)-catalyzed rearrangement to give the A -stannylcarbodiimide 29 under mild conditions[30]. 

The thiepin system 31 is formed quantitatively by ring expansion of the diazoacetate derivative 30 via carbene formation catalyzed by 7r-allylpalladium chloride and its intramolecular insertion[31], The 4-diazomethyl-4//-pyrane 32 is expanded to the oxepine 33 in quantitative yield with the same catalyst[32]. 

Hydrazine [302-01-2] (diamide), N2H4, a colorless liquid having an ammoniacal odor, is the simplest diamine and unique in its class because of the N—N bond. It was first prepared in 1887 by Curtius as the sulfate salt from diazoacetic ester. Thiele (1893) suggested that the oxidation of ammonia (qv) with hypochlorite should yield hydrazine and in 1906 Raschig demonstrated this process, variations of which constitute the chief commercial methods of manufacture in the 1990s. 

From Diazo Compounds via 1,3-Dipolar Cycloaddition. This method has been utilized widely in heterocychc chemistry. Pyrazohne (57) has been synthesized by reaction of ethyl diazoacetate (58) with a,P-unsaturated ester in the presence of pyridine (eq. 12) (42). 

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

Decomposition of the diazoacetic ester (548) to the keto carbene (549) is promoted by copper(II) trifluoromethanesulfonate. In the presence of nitriles, 1,3-dipolar addition to the nitrile occurred giving the oxazole (550) (75JOM(88)ll5) (see also Section 4.03.8.1). 

Since 1,3-dipolar cycloadditions of diazomethane are HOMO (diazomethane)-LUMO (dipolarophile) controlled, enamines and ynamines with their high LUMO energies do not react (79JA3647). However, introduction of carbonyl functions into diazomethane makes the reaction feasible in these cases. Thus methyl diazoacetate and 1-diethylaminopropyne furnished the aminopyrazole (620) in high yield. 

Azulene (2) A mixture of 2-isopropyl-4,7-climethylindane 1 (200 g, 1.91 mol) and ethyl diazoacetate (50 g, 0.5 mol] was heated for 1 h at 130°C. Vacuum distillation and recovery ol 1 (160 g) gave a brown residue which was heated with 40% NaOH (40 mL) and EtOH (200 mL). The unreacled ester was extracted with Et20 and the aqueous solution was acidified to obtain crude 2, which after distillation afforded 24 g ol 2(52%), bp t60-185°C/ 2mm. 

Diazoacetic esters are potentially explosive and therefore must be handled with caution. They are also toxic and prone to cause development of specific sensitivity. A well-ventilated hood should be used for the entire procedure. 

Traces of acid must be eliminated before the diazoacetate solution is concentrated. 

Higher temperatures should be avoided because of the explosive character of ethyl diazoacetate. The product should be placed in dark brown bottles and kept in a cool place. It should be used as soon as possible. 

Etliyl diazoacetate has been prepared from sodium nitrite luid ethyl glycinatc hydrochloride in the presence of diethyl filler. The present [irocedure utilizes the unique ability of... 

Benzoylphenyidiazomethane 2 Butan-l-yl diazoacetate t-Butyl diazoacetate t-Butyl-2-diazoacetoacetate Diazoacetonitrile 2-Diazocyclohexanone Diazocyclopentadiene 1 -Diazoindine... 

By choice of fluorinating agent, either hydrofluorination [6, 98, 99] or halo fluorination [6, 99] of ethyl diazoacetate is realized (equation 26)... 

Alkyl diethylphosphononuoroacetates have been used extensively in ol fi-nanon procedures [69], principally forming the ffJ-a-fluoro-a.P-unsaturated esters with very high stereoselectivity [70] (equation 61) (Table 22). Preparation of the ethyl diethylphosphonofluoroacetate from ethyl fluoroacetate has obviated the necessity to prepare ethyl bromofluoroacetate from bromine fluoride and ethyl diazoacetate [71],... 

In addition to the reactions descubed m the prcpaiation diazoacetic ester unites with misaturatecl acids andfoims cyclic compounds. Fumaric cstei, for example, combines in the following way —... 

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. ... 

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