Diazoacetic ester, hydrolysis

Pfau-Plattner azulene synthesis. Formation of azulenes by ring enlargement of indanes on addition of diazoacetic ester, hydrolysis, dehydrogenation, and decarboxylation of the resulting acid. 

The copper-catalyzed decomposition of diazoacetic ester in the presence of pyrrole was first described in 1899 and later investigated in more detail by Nenitzescu and Solomonica. Ethyl pyrrole-2-acetate (13), the normal product of electrophilic substitution, was obtained in 50% yield and was degraded to 2-methylpyrrole. Similarly iV -methylpyrrole with two moles of diazoacetic ester gave, after hydrolysis, the 2,5-diacetic acid (14) while 2,3,5-trimethylpyrrole gave, after degradation, 2,3,4,5-tetramethylpyrrole by substitution of ethoxycarbonylcarbene at the less favored )3-position. Nenitzescu and Solomonica also successfully treated pyrroles with phenyl-... 

Jackson and Manske described the decomposition of diazoacetic ester with indoles to give, after hydrolysis, the 3-acetic acid and some 1,3-diacetic acid no product of 2-substitution was found (see also ref. 49). Diazoacetone and diazopyruvic ester similarly gave the 3-sub-stituted indoles.Badger et al. have also examined the reaction of iV -methylindole, as well as of indole, with diazoacetic ester. Again only the 3-substituted product resulted and no evidence was obtained for addition. 

The specific rate of the hydrolysis of diazoacetic ester N2CHC00C2H5 + H20 => H0CH2C00C2H5 + N2 varies with the hydrogen ion concentration as follows ... 

Hydrazine salts have been prepared by the action of hypochlorites on ammonia1 or urea 2 by the hydrolysis of salts of sulfohydrazimethylene disulfonic acid 3 by the hydrolysis of triazoacetic acid 4 by the reduction of diazoacetic ester 5 by the reduction of nitroguanidine followed by hydrolysis 6 by the reduction of the nitroso derivatives of hexamethylene tetramine 7 by the reduction of nitrates or nitrites with zinc in neutral solution 8 by the action of sodium bisulfite on hyponitrous acid... 

Indolizine-l-acetic acid has been prepared by reaction of 3-benzoylindolizine with diazoacetic ester followed by basic hydrolysis <68AC(R)1206). 

The methods of preparation of i. ost cyclojro-par.e acids involve first the preparation of tAie cyclic ester and subsequent hydrolysis to the free acid. That such hydrolysis did not change tne cyclic structure has been seen to be true ir. all tne cases tnus iar examined i o exceptions to tnis rule will now be studied,ior tney are botn 1,1,2,3 compounds. Aconitic ester and diazoacetic ester give by the usual reactions a cyclopropane ester as follows ... 

A shorter method has been used to prepare indolizine-1-acetic acid (88) by reaction with diazoacetic ester followed by base hydrolysis and acidification.139... 

The reaction is carried out at ambient temperature and nearly complete enantioselectivity (>99%) is observed for mono- and 1,1-disubstituted olefins with diazoacetates. With all copper catalysts, the transkis selectivities in the cyclopropanation of mono-substituted olefins are only moderate. The transkis ratio depends, in this case, mainly on the structure of the diazo ester rather than the chiral ligand (eq 2). It increases with the steric bulk of the ester group of the diazo compound. With the BHT ester, the more stable trans isomer is formed with selectivities up to >10 1. The steric hindrance usually prevents ester hydrolysis, but the BHT group can be removed by reduction with LiAlHj. The trans isomer is even enriched by the reduction procedure because the cis isomer reacts more slowly. 

Interesting niiro derivatives of diazomethane were obtained by Schollkopf and co workers. Thus Schollkopf and Markusdi 1210] described nitrodia o-methane which was obtained from r-butyl diazoacetic ester by nitration with N2OS followed by hydrolysis (54) sec also Chapter I. p. 30 ... 

Hydrazine salts have been prepared by the action of hypochlorites on ammonia (1) or urea (2) by the hydrolysis of salts of sulfohydrazimethylene disiilfonic acid (3) by the hydrolysis of triazoacetic acid (4) by the reduction of diazoacetic ester (5) by the reduction of nitroguanidine followed by hydrolysis (6) by the reduction of the nitroso derivatives of hexamethylene tetramine (7) by the reduction of nitrates or nitrites with zinc in neutral solution (8) by the action of sodium bisulfite on hyponitrous acid followed by reduction (9) by the reduction of K2S03N202 (10) by the action of ammonia on dichlorourea (11) by the reduction of nitrosoparaldimin (12) by the action of copper sulfate on ammonia at high temperatures (13) by the reduction of methylene diisonitrosoamine (14) by the hydrolysis of the addition product of diazoacetic ester and fumaric or cinnamic esters (15). 

Decarbonylation of cyclopropene acids. In a study of the synthesis of methyl sterculate (6) from methyl stearolate (1), Gensler et al.1 were unable to repeat the apparently straightforward synthesis based on addition of the Simmons-Smith reagent described in 1, 1021-1022. They were also unable to eifect addition of methylene generated by cuprous bromide decomposition of diazomethane. However, the reaction of (1) with diazoacetic ester in the presence of copper bronze, followed by hydrolysis, gives the cyclopropene diacid (2) in 70-90% yield. 

Ring expansion (1, 369-370 6, 252-253). The ring expansion of ketones to the next higher homolog with ethyl diazoacetate requires hydrolysis and decarboxylation of the intermediate 8-keto ester, a step that is sometimes troublesome. Baldwin and Landmesser have used benzyl diazoacetate and allyl diazoacetate as alternative reagents. The benzyl jS-keto esters are cleaved and decarboxylated on hydrogenation both benzyl and allyl keto esters are reduced by sodium in liquid ammonia to ketones. 

The first chemical synthesis of azulene was reported by Pfau and Plattner in 1937. Their synthesis takes advantage of the ring enlargement of indane 133 on addition of diazoacetic ester to give cycloheptatriene 135. This compound is converted into azulene via a three-step sequence hydrolysis, dehydrogenation, and decarboxylation of the resulting acid. 

Steinkopf and Augestad-Jensen in 1922 reported the reaction of diazoacetic ester with thiophene and the hydrolysis of the adduct (10) to an acid, m.p. 107°, of unknown identity. Pettit has used this adduct in the synthesis of the thiapyrylium cation (10->11 12). The same adduct (10) was obtained by photolysis of diazoacetic ester... 

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. 

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... 

Reaction with trialkyIhoranes.14 Ethyl diazoacetate reacts with trialkylboranes with loss of nitrogen to give, after hydrolysis, the homologated ethyl ester ... 

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