Azodicarboxylic esters

Similarly, no systematic study of the IR spectra of the pyridopyridazines has been recorded, but the spectra of the [2,3-d] derivatives have been discussed <68AJCl29l). The diones of this series have also been studied <69MI21501), and IR used to distinguish between the structure (303) and the possible isomeric formulation (304) <74JHC35l). The IR spectra of some of the azodicarboxylic ester adducts <79X2027) have been recorded, whilst in the benzo fused systems some problems with the structure of acyl derivatives in the pyridazino[4,5-6]quinoline series have been resolved with the help of IR spectroscopy <71BSF906, 72BSF1588). 

Amongst miscellaneous UV spectra recorded are those of alkylthio adducts of pyrido[3,2-c]pyridazine (78KGS1272), various pyrido[3,4-d]pyridazines (57AC(R)728) and several vinyl-pyridine-azodicarboxylic ester adducts (79T2027, 79KGS639). 

The other main source of various pyridopyridazines from pyridines are the [4 + 2] cycloaddition reactions, already mentioned (Section 2.15.8.3), between vinylpyridines and azodicarboxylic esters (79T2027, 79KGS639) or triazolidinediones e.g. 78KGS651). 2-Vinyl-pyridines gave reduced pyrido[3,2-c]pyridazines (370), 4-vinylpyridines gave [3,4-c] analogues, whilst 2-methyl-5-vinylpyridine furnishes a mixture of the [2,3-c] and [4,3-c] compounds. Yields are low, however, and these remain curiosities for practical synthetic purposes. 

When Diels and Alder published their famous paper in 1928, Diels had been working with related reactions for several years [6]. In 1925, Diels reported the reaction of azodicarboxylic ester (Et0C(0)2CN=NCC(0)0Et) with compounds containing a conjugated diene system. He found that addition of the azodicarboxylic ester occurs at the 1,4-position of the conjugated system as with cyclopentadiene and with butadiene. This work probably led to the famous Diels-Alder reaction. In 1927, Diels and his student Alder published a paper on the reaction of azodicarboxylic ester with styrene. 

Because of its great reactivity PTAD has found wide use in the interception of reactive, unstable dienes. For example, unstable isoindenes,226 3a//-indenes,146 1,3-divinylallenes,227 and benzene oxides228 have all been successfully trapped with PTAD. 4-(4-Bromophenyl)-l,2,4-triazole-3,5-dione (5, R = 4-Br—C6H4) is often used if the derivatives ai e required for X-ray structure determination.229 Azodicarboxylic esters have been used to trap tetra(trifluoromethyl)cyclobutadiene,230 and spiro[4.4]nonatetraene.231... 

The corresponding azodicarboxylic ester does the same thing H. Loebl, G. Stein, and J. Weiss, /. Chem. Soc., 1949,2074. 

In common with other azodicarboxylic acid derivatives, the uses of 4-phenyl-l,2,4-triazoline-3,5-dione are many. It undergoes a Diels-Alder reaction with most dienes11-14 and is, in fact, the most reactive dienophile so far reported.15 16 As with the formation of all Diels-Alder adducts the reaction is reversible, and in the case of the adduct with 3-j3-acetoxy-17-cyano-5,14,16-androstatriene, the reverse reaction can be made to proceed under especially mild conditions.14 An instance has also been reported of the dione photochemically catalyzing other retro Diels-Alder reactions.17 Along with the proven use of azodicarboxylic ester,18-18 the dione should be potentially important in the preparation of strained ring compounds. 

The [4 + 2]cycloaddition of 4,5-dicyano-l,3,2-diazaphospholes and acetylenes yields 1,2-azaphos-pholes (Chapter 3.15). Azodicarboxylic esters (R = Et, Pr ) give a 1,1-addition accompanied by a dimerization of the product (Scheme 32) [Pg.799]

Interaction of the mesoionic thiadiazolium salt (299 Ar = Ph) with hydrazine led to the formation of l,4-dihydro-6-hydrazino-l,2,4,5-tetrazine (300) (76KGS713). The reaction of salts (299) with azodicarboxylate esters was at one time thought to provide the mesomeric... 

Azobis(2,6-diphenylpyrylium-4-yl) and S, NR congeners, polarography, 60, 97 Azodicarboxylic esters cycloaddition to 2-azabuta-l,3-dienes,... 

Although the reaction of a carbon nucleophile with an azodicarboxylate ester to a derivative of a hydrazine acid was first reported in 192414a, it wasn t until 1986 that this reaction was used in stereoselective C —N bond-forming reactions and, as often happens in science, simultaneously by several groups15-18. 

The ene reaction of an azodicarboxylate ester was first observed in 196218-19 as a process competing with cycloaddition to dienes, but little additional work has been done on the ene reaction with simple alkenes. An elegant study in 1976 provided evidence for a concerted, suprafacial reaction between dimethyl azodicarboxylate and (S)-(Z)-l-deutero-4-methyl-l-phenyl-2-pentene (15) based on the direction and high level of chirality transfer observed20. 

Dichlorocarbene addition to azodicarboxylate esters, Phenyl(bromodichloro-mcthyl)mercury reacts with diethyl azodicarboxylate to give phenylmercuric bromide (98% yield) and a product (87% yield) which was found not to be the expected di-aziridine( I), but to have the structure (2). The same product is obtained by decarboxylation of CCIjCOONa in the presence of diethyl azodicarboxylate in refluxing 1,2-dimethoxyethane (69% yield). 

Azodicarboxylic esters are excellent dienophiles and they can also add to electron-rich double bonds as heterodienes. Adducts of both types have been used as intermediates in the synthesis of amino sugars. 

Azodicarboxylate esters are the reagents of choice for electrophilic N-amino amination leading to hydrazine derivatives. Besides Grignard reagents and alkyl or aryl lithium compounds,enolates and silyl enol ethersderived from ketones have been aminated by this method. In particular, di-r-butyl azodicarboxylate has been reacted with a variety of chiral enolates (Scheme I9)i03->o and chiral silyl ketene acetds (Schemes 20 and to afford a-hydrazino acid derivatives with high dia-... 

Alder, K., Pascher, F., Schmitz, A. Substituting additions. I. Addition of maleic anhydride and azodicarboxylic esters to singly unsaturated... 

Evans, D. A., Britton, T. C., Dellaria, J. F., Jr. The asymmetric synthesis of a-amino and a-hydrazino acid derivatives via the stereoselective amination of chiral enolates with azodicarboxylate esters. Tetrahedron 1988, 44, 5525-5540. 

Formal two-electron reduction of a-diketones, a-imminoketones, a-sulfoxyketones, and 2-butene-diones has been achieved by addition to dicarbonyl complexes, ( -CsRslzTilCO (R=H, Me), forming the corresponding titana-cycles (72 and 73, Scheme 13).49 Analogous reactivity is observed with azodicarboxylic esters 74. 

His academic research was focused to provide training for the 50 Ph.D. students who benefited from his tutelage. Work on the synthesis and reactions of azodicarboxylic esters that had been started at Goodyear was continued, p-dialkylaminoethyi esters of stericaily hindered alkyl-substituted benzoic acids were made that had longer local anaesthetic action than Procaine, and azo-nitrogen analogs of unsaturated acids and their derivatives were studied for potential... 

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