Intermediate imidoyl chlorides

The use of DMF to accelerate the formation of acid chlorides from carboxylic acids has been reviewed previously,4 and is believed to occur via an imidoyl chloride intermediate.5... 

There are many heterocyclic molecules in which 1,3,4-thiadiazoles are fused to other ring systems. For example, Molina et al. developed a procedure for building a thiadiazole ring on to a properly substituted imidazole moiety (Scheme 29). Reaction of l-amino-2-methylthio-4-phenylimidazole (161) with triphenylphosphine dibromide in dry benzene furnished the 2-methylthio-4-phenyl-l-triphenylphosphoranylidenamino imidazole (162) in a 95% yield. With aroyl chlorides at elevated temperature, this gave the 2-aryl-6-phenylimidazo[2,l-Z ][l,3,4]thiadiazoles (164) in yields between 50% and 70% via the imidoyl chloride intermediate (163) which could be isolated and shown to cyclize to the thiadiazole. The method developed for the imidazole ring was also applicable to the thiadiazolotriazine ring system <88H(27)1935). 

Methanamide salts, [RNH=CHNRCHClj]Cl or [RNH=CHNRH]C1, are produced (in the absence of added base) as a result of the reaction of RNHCHO with the imidoyl chloride intermediate [1040],... 

The classical example of this type of reaction is the v. Braun method of degradation, by which a secondary amine can be transformed into a primary amine, and finally into ammonia, via the imidoyl chloride intermediates. This reaction has been used for the structure elucidation of alkaloids. Although degradative studies are not conducted to any extent today due to the convenience of spectral methods, the v. Braun elimination is still used in organic synthesis to prepare nitriles as well as alkyl halides. 

The reaction of N-alkyl-N -arylmethyloxamides XXV with phosphorus pentachloride to yield l-alkyl-2-aryl-5-chloroimidazoles (XXVI) proceeds via imidoyl chloride intermediates ( " ). 

Reaction with Amino Derivatives. Methyl A (jO-toluenesul-fonyl)carbamate serves as an electrophilic partner in the suhstitu-tion reaction with amines and afforded a good yield of sulfonylurea derivatives. The sulfonylurea derivatives so obtained were converted into carboxamidine derivatives in moderate yields via the imidoyl chloride intermediates, which are prepared by chlorination using phosphorus pentachloride in chlorobenzene and showed high reactivity with a broad range of amines (eq 4). 

Synthesis of Imidazoles and Imidazole-Like Cores. The synthesis of imidazoles starting from resin-bound amino acids usually involves the linkage of adjacent amine groups of a peptide bond through the treatment of phosphoryl chloride. The phosphoryl chloride plays the role of the dehydration reagent in the conversion of an in situ formed imidoyl chloride intermediate to the desired imidazole scaffold. 

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. 

Detailed mechanistic studies by Fodor demonstrated the intermediacy of both imidoyl chlorides (6) and nitrilium salts (7) in Bischler-Napieralski reactions promoted by a variety of reagents such as PCI5, POCI3, and SOCh)/ For example, amide 1 reacts with POCI3 to afford imidoyl chloride 6. Upon heating, intermediate 6 is converted to nitrilium salt 7, which undergoes intramolecular electrophilic aromatic substitution to afford the dihydroisoquinoline 2. Fodor s studies showed that the imidoyl chloride and nitrilium salt intermediates could be generated under mild conditions and characterized spectroscopically. Fodor also found that the cyclization of the imidoyl chlorides is accelerated by the addition of Lewis acids (SnCU, ZnCh), which provides further evidence to support the intermediacy of nitrilium salts. ... 

The reaction of imines with thiohydrazides gives 1,3,4-thiadiazole via a thioacylimidohydrazine intermediate. The imidoyl chloride 148 when treated with the IV-phenyl thiosemicarbazide 149 gave the 1,3,4-thiadiazole hydrochloride 150 (Equation 53) <2002MI1241>. 

Two synthetic pathways to [l,2,4]triazolo[l,5- ]quinoxalines are shown in Scheme 54. Transformation of 430 to 433 was described by Katritzky et al. <2002JOC3118>. The ring-closure reaction proceeded via a very complicated pathway in relatively low yield (25-31%). The first intermediate is the imidoyl chloride 431 which, when treated with... 

Diazoamides also give triazoles, on heating or by treatment with base. Reaction of the diazoamide (9) with phosphorus pentachloride gave a 5-chlorotriazole derivative through an intermediate imidoyl chloride (Scheme 23). ... 

When thionyl chloride was used instead of POCl3, the intermediate imidoyl chlorides 14 were isolated in yields higher than 60% (89KGS120). On being reduced in aqueous Na2S205 at 60-80°C, they readily eliminate... 

The replacement of the halogen in the imidoyl chloride by an azide group with subsequent cyclization of the intermediate imidoyl azide 150 into 1,5-disubstituted tetrazole 5 can be performed under PTC conditions < 1996S 1428>. This procedure avoids contact with HN3 solutions and also removes the problem of the low solubility of HN3 salts in organic solvents. It is important that in this procedure the losses due to hydrolysis of imidoyl chlorides... 

The substitution of the halogen in the cyclic imidoyl chloride, like 2-chloropyridine, with azide leads to the intermediate formation of an imidoyl azide 497 that further undergoes cyclization into a fused tetrazole 14 (Scheme 61) <2004SOS(13)861>. 

Both cyclic imidoyl chlorides and cyclic imidoyl bromides have been used as starting materials for generating and further cyclization of intermediate imidoyl azides into the corresponding fused tetrazoloazines. Thus, treating 4-methyl-3,5,6-tribromopyridazine with NaN3 in a mixed solvent (THF-DMSO) at room temperature led to 3,5-diazido-4-methyl[l,5- ]tetrazolopyridazine 502 (45% yield) <20040BC1782>. 

Graubaum and co-workers described the reactions of chlorothioformates 102 with 5-aminothiatriazole 90. Depending on the reaction conditions different products are formed. In the presence of a base, the main product is the trithiadiazapentalene 101, but in the absence of a base the dithiazolinimine hydrochlorides 100 are obtained (Scheme 23) <1989M997, 1990JPR208>. Thus, the reactivity of chlorothioformates is intermediate between that of acid chlorides and imidoyl chlorides. 

Scheme 13). A possible mechanistic pathway involves imidoyl chloride and nitrilium cation intermediates. A similar reaction of A.A/ -diacetyl-1,2-diaminobenzene and phosphoryl chloride with the 2,2 -diindolyl-methane 12 did form the macrocycle 46, but only in a very low yield12 (Scheme 13). 

Imidoylstannanes 69 can be prepared by reaction of imidoyl chlorides 68 with tri-organostannyllithiums at —78 °C. The transmetallation with methyllithium gave the corresponding imidoyllithiums 70. The reaction of these intermediates with different electrophiles gave, after hydrolysis, the corresponding imines or ketones 71 (Scheme 18)80. 

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. 

In basic conditioas, the adducts which form when secondary enaminones or enaminosulfones react with diethoxycarbonyl- or benzylethoxycarbonyl-1-diazene cyclize to 2-imidazolones [29]. The transient intermediates which form when oximes react with imidoyl chlorides undergo [3,3]-sigmatropic... 

Another reaction which proceeds through an intermediate amidine is that in which 4-foimylimidazoles are made from 5-aminopyrimidine and an N-substituted imidoyl chloride in the presence of phosphoryl chloride. Once the intermediate amidine has formed, the pyrimidine ring opens up. Yields, however, are rather low ( 25%) [45]. 

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