Aldehydes imidoyl chlorides

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

The solid-phase synthesis of the 2(lff)-pyrazinone scaffold is based on a Strecker reaction of commercially available Wang amide linker with appropriate aldehyde and tetramethylsilyl (TMS) cyanide, followed by cyclization of a-aminonitrile with oxalyl chloride resulting in the resin linked pyrazinones. This approach allows a wide diversity at the C-6-position of pyrazinone scaffold (Scheme 35, Table 1). As it has been shown for the solution phase, the sensitive imidoyl chloride moiety can easily undergo an addition/elimination reaction with in situ-generated sodium methoxide affording the resin-linked... 

Stannous chloride is used most frequently for the reduction of nitro compounds [177, 178, 179] and of quinones [180, 181], It is also suitable for conversion of imidoyl chlorides [182] and of nitriles [183] to aldehydes, for transformations of diazonium salts to hydrazines [184], for reduction of oximes [f[Pg.30]

Heteropolyacids Hi4[NaPsW29MoOno] and H3PMO12O4 have been shown to be efficient catalysts for consecutive condensation of aldehydes with 5-aminopyrazole -carboxamide and cyclization into pyrazolo[3,4-t4pyrimidines <2007MI1467>. The reaction of ethyl 5-acylaminopyrazoles with hexachloroethane and triphenylphosphine in the presence of a base has been recently reported to afford an imidoyl chloride that reacted in situ with ethylamine yielding an amidine in 71% yield that cyclized readily in DMF in the presence of potassium carbonate to yield pyrazolopyrimidines in 65% yield <2007TL3983>. 

A more direct access to imidoyllithiums was to perform the lithiation of imidoyl chlorides 72 with lithium and substoichiometric amounts of naphthalene at low temperatures so that intermediates 73 were generated (Scheme 19)65,81. Aldehydes, ketones and acyl chlorides have been used as electrophilic reagents to afford imines 74 or the corresponding ketones, depending on the hydrolysis conditions. 

Amides have been converted into imidoyl chlorides and then reduced to aldimines with LiAlH(OBu ).3, as in Scheme 15. Although not claimed as a synthesis of aldehydes, the aldimines can be hydrolyzed to aldehydes quite readily. Interestingly, the authors say that an excess of the reducing agent can be used because further reduction to the amine requires 24 h, whereas the first stage to the aldimine requires only 30 min at -78 C. 

As in the previous chapter, the material will be organized according to substrate category, starting with the carboxylic acids themselves and then moving on to the various derivatives. The methods have been placed generally in sections corresponding to the immediate precursors of the aldehydes. Thus, the hydrolysis of Reissert compounds appears under amides as opposed to acyl chlorides, and the Sonn-Muller appears under imidoyl chlorides and not amides. 

One of the classical reductive aldehyde syntheses is the Sonn-MUller reduction of imidoyl chlorides. The method is closely related to the Stephen reduction described in the previous section. As shown in Scheme 16, substrates (53) may be prepared either by the treatment of anilides with phosphorus pentachloride or sulfinyl chloride, or less usually via the Beckmann rearrangement. They are... 

Table 13 Aldehydes Synthesized by the Reduction of Imidoyl Chlorides using SnCh (Sonn-Miiller) or CrCb ...

Finally, treatment of amides with phosphorus oxychloride gives Vilsmeier complexes, which are often formulated as A-alkylated imidoyl chlorides (59). Irrespective of their precise nature, it has been found that they can be converted very efficiently to aldehydes by reduction with zinc followed by aqueous work-up (Scheme 17). Although the method has only been used for benzaldehyde and a number of chlorinated and brominated analogs, the yields reported are consistently high (87-97%). ... 

It is known that nitrilium salts can be prepared by alkylation of nitriles , via the reaction of imidoyl chlorides with Lewis acids as well as by Beckmann rearrangement of oximes . The application of nitrilium salts in organic synthesis is summarized in a number of reviews " . In this connection it is appropriate to mention another three-component one-pot synthesis of 5,6-dihydro-4. -l,3-oxazines 40 based on the reaction of aldehydes with iV-tcr/-butylnitrilium salt 41 which, however, proceeds without the participation of Af-acyliminium ions . The reaction is carried out by mixing the aliphatic or aromatic aldehyde, tcrt-butyl chloride and Lewis acid (SbCljjSnC ) in benzonitrile solution (equations 16 and 17). 

Sohn and Muller458 have allowed ethereal hydrogen tetrachlorostannate(n) to react with imidoyl chlorides, obtaining thereby good yields of aldehydes in... 

By a similar process, von Braun and Rudolph459 obtained unsaturated aldehydes from the imidoyl chlorides derived from anilides of <%,/ -unsaturated acids the reaction proceeds by way of the Schilf bases, which are then hydrolysed to the aldehydes. 

The aldehyde XXXIII was converted by phosgene into the vinylogous imidoyl chloride XXXIV which was condensed with 4a-methylhexahy-drocarbazole XXXV in the presence of base to give the product XXXVI isolated and characterized as its yellow crystalline perchlorate. A series of related compounds was also prepared am I the properties and spectra of the whole group of substances gives strengtJ i to the assigned structures. 

Beckmann rearrangement of ketoximes to synthesize aldehydes. Thus, 4-chlorobenzophenone oxime (LXI) was treated with phosphorus pentachloride and the obtained imidoyl chloride (LXII) was reduced to the corresponding azomethine (LXIII), which on hydrolysis afforded 4-chlorobenz-aldehyde (LXIV) in high yield. 

Imidoyl chlorides are also intermediates in the Gattermann aldehyde synthesis and in the Houben-Hoesch ketone synthesis. The former reaction uses hydrocyanic acid, hydrogen chloride, and aluminum chloride as the catalyst, while in the latter reaction nitriles, hydrogen chloride, and zinc chloride are used. Hoesch in 1915 assumed that the nitriles combine with hydrogen chloride to form imidoyl chlorides, which undergo electrophilic substitution reaction with a wide variety of substrates. Stephen verified Hoesch s hypothesis by reacting phenylbenzimidoyl chloride with resorcinol, and he obtained the intermediate anil CLIX, which can be hydrolyzed to the corresponding ketone (CLX). 

The synthesis of aldehydes from imidoyl chlorides via reduction and hydrolysis of the azomethine has been demonstrated by Sonn and Muller who used stannous chloride as the reducing agent. 

Reaction sequence employed to convert aromatic anilides to aldehydes. Treatment of the anilide with phosphorus pentachloride generates the imidoyl chloride, which is reduced to the imine with a mixture of stannous chloride and hydrochloric acid. Subsequent hydrolysis yields the aldehyde ... 

Denmark has described several chiral bis-phosphoramides as Lewis base activators of weak Lewis acid SiCL and demonstrated their ability to mediate an enantioselective Passerini-type reaction. Catalytic bis-phosphoramide 36 and stoichiometric SiCU, in the presence of a proton scavenger (Htinig s base), promoted the formation of a-hydroxyamides with remarkably good enantioselectivity and yield. A variety of aromatic and unsaturated aldehydes and aryl, alkyl, and functionalized alkyl isocyanides proved to be useful and effective starting materials. High yields of Passerini products were attributed to the production of imidoyl chloride 37, which reduced the prevalence of the nitrilium intermediate and prevented the addition of a second equivalent of isonitrile. 

Lewis acid catalysis serves for the Passerini-type reaction of aldehydes with isocyanides forming a-hydroxyamides. The catalytic system consisting of SiCU and (107) provides high yield and good to excellent enantioselectivity for the addition of t-butyl isocyanide to a wide range of aldehydes [167]. The amide product is formed from the imidoyl chloride intermediate (110) by hydrolysis (Scheme 9.78). Treatment of the intermediate product with methanol followed by hydrolysis gives a-hydroxyesters with the retention of enantioselectivity. 

The synthesis of analogous iminoacyl complexes by isonitrile insertion into linear alkyl-zirconocene chlorides is also known. In an overall regiospecific hydrocyanation of alkenes, iminoacyls 21 derived from tBuNC or Me3SiCN (as the Me3SiNC isomer) may be treated with I2 to rapidly generate an imidoyl iodide and subsequently the nitrile 22 (Scheme 3.6) [22], Less hindered iminoacyl complexes (e. g. R = Bu, Cy) may be hydrolyzed to afford aldehydes 23 [23]. 

Reaction of nitriles with dry hydrogen chloride in anhydrous ether or in an ether-chloroform mixture affords imidoyl chlprides which are reduced by stannous chloride to products that afford aldehydes on hydrolysis. The method seems to be generally applicable only to aromatic and heterocyclic aldehydes the activity of the stannous chloride used for the reduction seems to be the most important factor in the reaction.580 2-Naphthaldehyde has been synthesized580 in 95% yield by this method, and 4-methyl-5-thiazolecarbaldehyde in 40% yield.581... 

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