Carbodiimide intermediates

An aza-Wittig reaction-cycloaddition reaction sequence was utilized for the synthesis of pyridotriazines 94. Treatment of iminophosphorane 92 with phenylisocyanate leads to the formation of the corresponding carbodiimide intermediate, which with another molecule of isocyanate affords 94 in [4+2] heterocycloaddition reactions (Equation 13) <1997T16061>. 

In view of the importance in biochemical processes of pteridines such as folic acid, methotrexate, L-biopterin, and leucettidine <1996CHEC-II(7)679>, synthetic routes to fused pteridines continue to occupy considerable attention. Imidazo-fused pteridines have now been prepared from 3-aminopyrazine-2-carboxamides via carbodiimide intermediates. If the amido-nitrogen in the starting compound is further substituted, as in the scheme, the... 

Another general route to 5,10-dihydro[l,2,4]triazolo[5,l-b]quinazolines via the electrocyclization of an azino carbodiimide intermediate has been described (94S1057). The key iminophosphorane, a benzophenone-1-[(triphenylphosphoranylidene)amino]ethylidenehydrazone, was easily prepared in a Kirsanov-variant first applied by Bayless and Zimmer (68TL3811). It consists of the reaction of triphenylphosphine/iodine/trieth-ylamine with benzophenone 1-aminoethylidenehydrazone (94SI057). 

An interesting variation of this quinoxaline synthesis is outlined by the synthesis of sydnoquinoxalines shown in Scheme 103. The starting material is phenylsydnone 288 with an iminophosphorane group in an o-position. With isocyanate or isothiocyanate carbodiimide intermediates 289 are formed by an electrophilic aromatic substitution at the sydnone ring (4 position), the 4-(arylamino)sydno[3,4-a]quinoxalines (290) are obtained (91S745). 

AT-Substituted amidines 74 are transformed via the carbodiimide intermediate 75 into urea derivatives 76 as shown in Scheme 34 [141]. This reaction has been performed with a variety of aliphatic and aromatic substituents and in addition to (diacetoxyiodo)benzene 3 other hypervalent iodine compounds can also be used for this rearrangement. Phenyl substituted amidines 74 (R = Ph) can lead to cyclized products of type 77. 

A particular case of a photochemical strategy towards functionalized benzimidazoles regards the synthesis of 2-acylamino derivatives 70, which can be obtained from irradiations in methanol of 3-(o-amino)phenyl-l,2,4-oxadiazoles 68. In this reaction, a photolytic cleavage of the ring O—N bond, followed by migration of the aryl substituent, leads to the carbodiimide intermediate 69, a precursor of the benzimidazole nucleus (Scheme 12.20) [47]. 

Other intramolecular cyclization reactions involving arylcarbodiimides with an ortho vinyl group to form 2-aminoquinolines and pyrido[2,3-b]indoles are listed in Table 3.1. The latter reactions involve a [2-1-4] cycloaddition in which the carbodiimide intermediate acts as an azadiene and the bond of the ortho vinyl group acts as the dienophile. Calculated transition states for electrocyclization and cycloaddition reactions show that the mode of reaction depends on substituents, stereoelectronic, eutropic and steric factors." ... 

The reaction of cyclic iminophosphoranes 7 with isocyanates produces a carbodiimide intermediate 8, which was characterized as the corresponding urea 9. ... 

Covalent immobilization of enzymes increases their stability while lowering their activity. Also, their storage stability is notably higher. The synthesis of arginine from citrulline, ATP and argenino-succinate synthetase may involve a carbodiimide intermediate. ... 

An aza-Wittig reaction utilizing isocyanates leads to ferrocene-containing imidazolones. Thus, condensation of P-ferrocenylvinyliminophosphorane 1377 with isocyanates provides the carbodiimide intermediate 1378, which can then be reacted with various amines to give the imidazolones 1379 in good yields (Scheme 356) <1996TL7829> (see Section 4.02.9.2(i)(b)). 

Quinazolines have also been prepared by the reaction of a polystyrene-bound phosphoranimine and isocyanates, followed by an intramolecular cyclization of the carbodiimide intermediate 4-Ferrocenylidene-l-aminoimidazolone derivatives have been obtained from p-ferrocenyl-a-azidoacrylates and isocyanates followed by condensation of the resulting carbodiimidoester with hydrazines " In a Staudinger/ aza-Wittig process and in the presence of PPh3, bimetallic ferrocenyl oxazole derivatives (23) - (26) have been formed by the reaction of a-... 

Ahmed et al. [140] reported the synthesis of thiazolo[5,4-d]pyrimidines from p3uimidines without 5-amino or 5-nitro substituents. The reaction between 5-bromo-4-thioxo-p3mmidi-nones and dimethylcyanamide affords carbodiimide intermediates, which is a very fast... 

Before Raap, Gaponik et al. [37] improved the synthesis reported by Stolle et al. [38]. By reacting thiosemicarbazide with lead oxide and sodium azide in a CO2 atmosphere, a carbodiimide intermediate is formed and reacts in situ with HN3 to lead to 1,5-DAT (Fig. 10). Unfortunately, this reaction leads to large amounts of lead azide as the side-product, which makes this synthesis problematic for an industrial scale. 

Synthesis of Imidazolones. In general, the synthesis of imadazolones is achieved by the treatment of resin-bound amino acids with isocyanates or isothiocyanates to form the corresponding ureas and thioureas that then undergo an oxidation reaction resulting in a carbodiimide intermediate. Mukaiy ama s reagent or other oxidative reagents are employed. The carbodiimide intermediate is treated with primary or secondary amines to form the imidazolone scaffolds. 

This methodology has also been used for the preparation of several alkaloids (Scheme 15.14). Syntheses of the marine alkaloids, isonaamine A (67a), dorimidazole A (67b) and pieclathridine A (67c), have been described by aza-Wittig reactions of phosphazenes 63 with tosyl isocyanate, followed by addition of amine 65 to the carbodiimide intermediate 64 and subsequent intramolecular cyclization of compound 66. 

The first parallel solid-phase 1,3,5-triazino-annulation S5mthesis has been achieved by Hoesl et al. [28]. Aza-Wittig reaction of an iminophosphorane generated in situ from a resin-bound 2-aminobenzimidazole (under Mitsunobu conditions) resulted in the formation of a highly reactive carbodiimide intermediate, which subsequently underwent intramolecular heterocyclization to afford the corresponding triazinobenzimidazoles (Scheme 7). 

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