1.1- Enediamines conjugated

AH-SOD hexamethyl-enediamine-conjugated super- AST aspartate aminotransferase... 

Enediamines, also known as ketene A/,iV-acetals or ketene aminals, are members of the enamine family. They can be divided into simple 1,1-enediamines1,2 and conjugated... 

In contrast to enamines1,2, the chemistry of 1,1-enediamines have been only briefly studied although the earliest reports3,4 of such compounds may date back to the 1940s. This has been partly due to the relative difficulty of the synthesis of simple 1,1-enediamines 1 in earlier years. A convenient method for the preparation of conjugated... 

In this chapter we will survey the chemistry of 1,1-enediamines. Their structural and physical properties will be first reviewed in Section II. We will see that their reactivity is critically dependent on their structures. Simple and conjugated or acyclic and cyclic 1,1-enediamines may lead to substantially different results and the correlation between structure and reactivity will be discussed. Spectroscopic characteristics will also be displayed in this section. Preparative methods of 1,1-enediamines will be summarized in Section III, which is arranged in order of importance of the methods and their scope of applicability. The reactions of 1,1-enediamines are presented in Sections IV-VI. Emphasis will be placed on the synthetic applications of these versatile synthons in the construction of heterocyclic compounds. 

In the ultraviolet spectrum simple 1,1-enediamine 3 absorbs at 227 nm18 while the conjugated enediamine 8 shows two absorption bands at longer wavelengths of 240 and 320 nm29. The mass spectra of 1,1-enediamines display M and M-l ions and the molecular ion is usually the most abundant peak in the spectra of conjugated en-ediamines18,29. 

The olefinic chemical shift (<5) of a number of acyclic and cyclic, simple and conjugated 1,1-enediamines are listed in Tables 1 and 218,29,38-44. These values reflect... 

In general, the reaction of ketene dithioacetals and amines serves well to prepare the conjugated 1,1-enediamines. 

The reaction of amines and ketene acetals was used as a main synthetic approach to 1,1-enediamines in earlier years72. Both simple and conjugated 1,1-enediamines can be obtained by this route. Displacement reaction of ketene acetal 34 with two equivalents of piperidine furnishes 1,1-dipiperidinoethene (35) in 62% yield (equation 9)73. Primary amines and ammonia react with 34 to give amidine derivatives. Cyano-74 and trifluor-oacetyl-substituted enediamines75 have been synthesized from the corresponding ketene acetals in good to excellent yields (e.g. equation 10). 

Nair and Desai113 described another synthetic route to conjugated cyclic 1,1-enediamines such as 8. Condensation of cyclic thiourea component 101 with arylacyl bromide furnishes arylacylmethylisothioureas 102, which are converted to products 8 when treated with triphenylphosphine in the presence of base (equation 35). 1,1-Enediamines having other diamine moieties are obtained similarly. Although this... 

Conjugated 1,1-enediamines undergo alkylation with alkyl halides at a slower rate than nonconjugated ones, and heat is usually required. Unlike the case of simple... 

Different modes of reaction are known for the reaction of 1,1-enediamines with electrophilic acetylenes. Simple 1,1-enediamines undergo cycloaddition reaction which will be discussed in Section V.A119, whereas conjugated 1,1-enediamines act as nucleophiles towards activated acetylenes. 

Meyer and coworkers125 have reported the condensation reaction between conjugated 1,1-enediamines and aldehydes. Acyclic 1,1-enediamines 160 react with aldehydes in a 2 1 ratio to give 2,6-diamino-4,5-dihydropyridine-3,5-dicarboxylates (161) with elimination of water and amine (equation 59). 

Conjugated 1,1-enediamines react with halogens smoothly to afford / -carbon haloge-nated amidinium salts85. Elimination of hydrogen halide then converts the amidinium salts to /Mialogenated 1,1-enediamines 188 (equation 75)148,149. 

A Mannich reaction of conjugated 1,1-enediamines has been reported 151-153. Cyclic 1,1-enediamines react readily with formaldehyde and primary amines to give the fused heterocycles 191 (equation 78)152,153. The reaction proceeds through the Mannich reaction, which is then followed by condensation between the amino groups and formaldehyde. 

In this section, we will discuss the few, but interesting, cycloaddition reactions156 of 1,1-enediamines. These cycloadditions provide a useful synthetic approach to a variety of complex compounds, and reflect the differences between 1,1-enediamines and en-amines on the one hand, and between simple and conjugated 1,1-enediamines on the other. 

A [2 + 2] cycloaddition reaction between simple 1,1-enediamine and a sulfonyl chloride was also observed157-159. In the presence of a base, 1,1-dimorpholinoethy-lene (154) reacted with methanesulfonyl chloride (199) in ether or in tetrahydrofuran to give 3-morpholinothietane 1,1-dioxide (200) in good yield (equation 83). However, the reaction takes a different course in chloroform, leading to the conjugated 1,1-enediamine 201. Other reactants than 154 and 199 did not form cycloaddition products under the same conditions160. 

In contrast to the cycloaddition of simple 1,1-enediamines, the reaction between conjugated 1,1-enediamines and nitrile oxides proceeds at a slower rate and the yields of products 222 are low (equation 92)172,173. 

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