Imidoyl chloride synthesis

Another synthesis avoids the isolation of 6-APA and starts directly with penidllin G. Reaction with chloromethyl pivalate gives its pivaloyloxymethyl ester. This reacts with PCI5 to an imidoyl chloride which may be solvolyzed with propanol. The add chloride of (R)-... 

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... 

The imidoyl chloride functionality of 44 enabled synthesis of a novel 5-HT ligand 46 with a pseudo-amidine structure via palladium-catalyzed cross-coupling (Equation 4) <1999TL8109>. 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

The smooth hydrolysis of imidoyl chlorides provides access to carbonam-ides from iminophosphoranes via an aza-Wittig reaction, without the occurrence of free acid or amino functions. This is of special advantage in the synthesis (Scheme 32) of sensitive substrates such as )8-lactam antibiotics (60) (77H719, 79JOC4393). 

The iminophosphorane 177 available from methyl azido(phenylhydrazo-no)acetate by a Staudinger reaction represents an ideal starting material for the synthesis of l//-l,2,4-triazoles (180). Two synthetic routes are possible (Scheme 68). The first is the reaction of iminophosphoranes with halides via isolable A-acylphosphonium salts (178), and imidoyl chlorides (179), leading to triazoles. The other approach involves the less reactive anhy-... 

One particular advantage of this method is that the lachrymatory 3-chlorovinyl ketones may be produced in situ by the acylation of an alkyne. This route has been further extended to the synthesis of azapyrylium salts from an alkyne and the imidoyl chloride (651) and to diazapyrylium compounds from nitriles (Scheme 258) (65CB334). 

Cycloaddition of bis(imidoyl chloride) 94 with the dianion of ethyl thioglycolate 93 allowed the synthesis of 2,3-diiminothietane 95 in 30% yield (Equation 30) <1999CC2439>. The thietane 95 was easily isolated by column chromatography. 

Beckert and co-workers reported the synthesis of 1,2-diazetidine derivatives 246 by the reaction of bis-imidoyl choloride 244 with amidrazone 245 <2002H(57)1257>. The product underwent decomposition during the isolation. Thus, they carried out the isolation at lower temperature to furnish 246a (38%) and 246b (48%). On the other hand, reaction of hydrazine 247 with bis-imidoyl chloride 244 gave 1,2-diazetidines derivatives 248 (Scheme 37). Some of the structures were confirmed by X-ray crystallography (Section 2.13.3.1) The reaction is expected to proceed via the formation of a C-N bond with the displacement of a chlorine atom. 

As in the Skraup quinoline synthesis, loss of two hydrogen atoms is necessary to reach the fully aromatic system. However, this is usually accomplished in a separate step, utilising palladium catalysis to give generalised isoquinoline 6.14. This is known as the Bischler-Napieralski synthesis. The mechanism probably involves conversion of amide 6.12 to protonated imidoyl chloride 6.15 followed by electrophilic aromatic substitution to give 6.13. (For a similar activation of an amide to an electrophilic species see the Vilsmeier reaction, Chapter 2.)... 

Disubstituted tetrazoles 751 are most often prepared by the cyclization of imidoyl azides 750. The traditional method for generation of imidoyl azides 750 consists of treating the appropriate imidoyl chlorides 749 with HN3 or NaN3 (Scheme 323) numerous other methods for the synthesis of imidoyl azides and their cyclization to tetrazoles have also been reported . 

Wesding M, Livinghouse T (1987) Acybiitrilium Ion Cyclization in Heterocycle Synthesis. A Convergent Method for the Preparation of 2-Acylpyrrolines via the Intramolecular Acylation of Silyloxyalkenes with a-Keto Imidoyl Chlorides. J Am Chem Soc 109 590... 

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. 

---