Earliest synthesis

The earliest synthesis method, which involves a ring-opening polymerization of a cyclic chlorophosphazene followed by replacement of the chlorine atoms in the polymer by organic groups, is the most extensively developed route to the preparation of poly(organophosphazenes). It is summarized in reaction sequence (3). 

The earliest synthesis of characterized diboron compounds was the preparation of B2C14 by Stock,1 using an electric discharge between zinc electrodes immersed in liquid BC13. Many discharge procedures have been reported for the synthesis of B2C14.21 26 Structures of some halogenated diboranes, 1, 2, and 3 are shown in Fig. 1. Diborane(6) 3 (or diboron hexahydride) has been reviewed.27 31... 

The unique structure of anatoxin-a, and its potential as a pharmacological tool, has inspired many different chemical syntheses of anatoxin-a and analogs. The earliest synthesis, in 1977, used (—)-cocaine as starting material [23]. Subsequently, there... 

The earliest synthesis of imidazole was achieved by Debus from glyoxal, formaldehyde and ammonia (Scheme 70), and many of the classical methods of Imidazole synthesis were based on this general type of reaction. Initially, most syntheses utilized a-diketones, but in the 1930s it was shown that a-hydroxy ketones could serve equally well provided that some oxidizing agent (e.g. ammoniacal copper(II) acetate, citrate or sulfate) was incorporated in the reaction mixture. Further improvement used ammonium acetate in acetic acid as the nitrogen source. 

Many of the classical methods grew out of the earliest synthesis of imidazole, which was achieved in 1858 by Debus [1] when he allowed glyoxal, formaldehyde and ammonia to react together. Although the earliest modifications of this method used a-diketones or a-ketoaldehydes as substrates [2, by the 1930s it was well established that a-hydroxycarbonyl compounds could serve equally well, provided that a mild oxidizer (e.g. ammoniacal copper(ll) acetate, citrate or sulfate) was incorporated [3. A further improvement was to use ammonium acetate in acetic acid as the nitrogen source. All of these early methods have deficiencies. There are problems associated with the synthesis of a wide range of a-hydroxyketones or a-dicarbonyls, yields are invariably rather poor, and more often than not mixtures of products are formed. There are, nevertheless, still applications to the preparation of simple 4-alkyl-, 4,5-dialkyl(diaryl)- and 2,4,5-trialkyl(triaryl)imidazoles. For example, pymvaldehyde can be converted quite conveniently into 4-methylimidazole or 2,4-dimethylimidazole. However, reversed aldol reactions of pyruvaldehyde in ammoniacal solution lead to other imidazoles (e.g. 2-acetyl-4-methylimidazole) as minor products [4]. Such... 

The earliest synthesis of the pyrido[l,2-a]pyrazine ring system involved the reaction of chelidonic acid (77) and ethylenediamine to give the... 

The earliest synthesis of members of these analogs (617) involved reaction of aldose sugars (34) with L-cysteine (39JBC601 53MI1 75LA1637 76-LA450) or 2-aminoethanethiol (61CB225) (Scheme 162). 

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