Imidoyl chloride, reactions with

The ketimine 736 is prepared by the reaction of the imidoyl chloride 735 with organotin reagents[604,605]. 

Based on the properties of ionic hquids in high-temperature microwave-enhanced reactions, the authors chose l-butyl-3-methylimidazolium tetraflu-orophosphate ([bmimjPFe) as the suitable ionic liquid (Scheme 23). The addition of 0.15 mmol of [bmimjPFe to a reaction in 2.0 mL of DCF was found to increase the reaction rate dramatically and a set-temperature of 190 °C was reached in a mere 1 min, while the reactions programmed at 190 °C, in the absence of the ionic liquid, reached only 170 °C in 10 min. The reactions were finished in a mere 18-25 min of irradiation time, including the hydrolysis of the sensitive imidoyl chloride moiety with water. The formed bis-lactams were isolated in good yield and purity. 

Pyrimidinamine derivatives 446 were produced by Ti -mediated reaction of imidoyl chlorides 444 with cyanamides 445 (equation 189). 

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. 

The reaction of imidoyl chlorides 8 with sodium azide in diglyme solution gives high yields of trifluorosulfonylcarbodiimides 9, which are unstable and undergo di- and trimerization reactions on standing. ... 

Reaction of aryl nitrilium ions (40) or imidoyl chlorides (41) with benzonitrile produced the nitrilium species (42), which underwent Friedel-Crafts reaction yielding the quinazoline system (43 Scheme 17). Generation and cyclization of nitrilium species using Friedel-Crafts reagents has since found widespread favor in heteroaromatic synthesis and such procedures have been reviewed in detail. An illustration of its use for a nonbenzenoid aromatic system is given in equation (31). ... 

Mixed anhydrides (234 equation 126) are formed in the reaction of silver benzoate with imidoyl chlorides. Imidoyl chlorides react with alcohols or phenols in the presence of base (alkoxide, tertiary amine) to give imidates, e.g. (235 equation This method is especisdly useful for the... 

In the first of a series of new reactions, Meerwein heated JV-phenylbenz-imidoyl chloride (56) with acetonitrile and aluminum chloride to obtain 4-methyl-2-phenylquinazoline (see 1). He postulated that the nitrilium salt (57) (not isolated) was the intermediate. Aromatic nitriles could also be used. The imidoyl chloride could be replaced by a mixture of benzanilide and thionyl chloride other Lewis acids could replace the aluminum chloride. The solvent could be tetrachloroethane, nitrobenzene, or an excess of the nitrile. Best reaction temperatures ranged from 90° to 160°C and yields were usually excellent. Imidate esters, e.g., PhNC(Ph)OEt, could replace the imidoyl chloride.41... 

Dimethylisoquinolines (161) are obtained in a one-pot reaction by treatment of the oximes (159) with phosphorus pentachloride. Beckmann rearrangement is followed by cyclization of the resulting imidoyl chloride (160) with phosphorus pentoxide (Scheme 65). ... 

Hydrolysis of the intermediate imidoyl ester hydrochlorides (LXXXVI) affords the corresponding carboxylic acid esters (22.101.109,145 p j. example, reaction of the imidoyl chloride LXXXVII with excess alcohol affords the carboxylic acid ester LXXXVIII in high yield ( ). 

Pd-catalyzed and microwave-enhanced Heck reaction of an imidoyl chloride derivative with boronic acid derivatives also furnished 4-aryl-substituted pyrrolo[3,2-c]quinoline 764 in a straightforward manner and in good yield. Subsequently, this group further developed a similar synthetic method to construct 4-alkyl-substituted pyrrolo[3,2-c]quinoline 766 (Scheme 4.223) using penten-2-one 765 as starting material. " ... 

The intramolecular attack of a nitrilium ion is a key step in the Meerwein quinazoline synthesis. A recent example of this reaction can be seen in the synthesis of 4-(A -dimethylamino)-2-arylquinazolines, as demonstrated below. Treatment of imidoyl chloride 39 with NJ -dimethylcyanamide (40) followed by TiCU results in the formation of intermediate 41. Mechanistically, after the production of the likely intermediate nitrilium ion 41, the Houben-Hoesch reaction occurs to give quinazoline 42. A related procedure has been utilized for the synthesis of... 

Diaryl or arylalkyl imidoyl chlorides react with the acyltetracarbonylferrate anions (67) at room temperature in CH2CI2 to give the mesoionic l,3-oxazol-5-ones (68) in isolated yields of 37—65%. The anion (67) is generated in the normal way by reaction of [Fe(CO)s] with sodium amalgam followed by reaction with the appropriate acid chloride at -30 °C. The mesoionic compounds (68) are useful intermediates since they react with alcohols to give a-amino-acids and undergo a variety of cycloaddition reactions to form new heterocycles. 

Disubstituted tetrazoles 24 are obtained by reaction of imidoyl chlorides 26 with... 

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)-... 

In a later paper Speziale and Smith 109) investigated the reaction of trivalent phosphorus compounds with N-monosubstituted a-trichloro-acetamides and a-trichloroacetamide. The products were imidoyl chlorides (129) and dichloroacetonitrile (130), respectively. The intermediacy of enamines (131) was assumed. For the monosubstituted amides the enamine... 

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. ... 

When sulfuryl chloride was used in this reaction instead of POCI3 or PCI3, imidoyl chlorides 17 were isolated as the products (89KGS120). By reduction of 17 with Na2S205 aryl methyl tellurides 18 are formed which readily eliminate a molecule of methyl chloride to give 2-arylbenzotellurazoles 12 (R = Ar) in 40-65% yields. 

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]. 

For example, the sensitive imidoyl chloride moiety at the C-3 position of the pyrazinone scaffold is known to vmdergo Stille reactions with a variety of tetraaryltin reagents, generating the corresponding 3-substituted pyrazi-nones (Scheme 10) [26]. Furthermore, the transition-metal-catalyzed stannyl-ation at the C-3 position is also documented in the hterature, in view of cross-couphng with a variety of alkyl and (hetero)aryl hahdes [26]. However, this strategy is completely restricted to the C-3 position, while the Cl atom of C-5 position was found to be inert under these conditions. 

When a blank reaction was run by purging the solution of pyrazinone (Scheme 22, pyrazinone b) in o-DCB with ethylene gas and irradiating it at 190 °C for 100 min, only a mere 53% conversion of the starting material was observed. Microwave-enhanced hydrolysis of the sensitive imidoyl chloride moiety of the cycloadduct using aqueous NaOH resulted in a yield of only 12%. However, the situation changed dramatically when the vial was pre-pressurized with ethylene gas at 5 bar. The reaction was completed after 30 min of microwave irradiation at 190 °C, and the hydrolyzed product was isolated in 87% yield. The reaction could be completed in a mere 10 min when carried out at 220 °C at an increased ethylene pressure of 10 bar, or in 20 min at 190 °C at 10 bar ethylene pressure. 

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... 

It has been shown that the imidoyl chloride moiety of 2(lff)-pyrazinones can imdergo an easy addition/elimination reaction with alkyl amines [24], while reactions with anilines proceed under harsher conditions. Ullmann coupling [109-113] of 2(lff)-pyrazinones with substituted anilines could open the way to the libraries of physiologically active compounds useful in inhibiting HIV replication [7]. Polymer-bound pyrazinone was successfully... 

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

Imidate esters can also be generated by reaction of imidoyl chlorides and allylic alcohols. The lithium anions of these imidates, prepared using lithium diethylamide, rearrange at around 0°C. When a chiral amine is used, this reaction can give rise to enantioselective formation of 7, 8-unsaturated amides. Good results were obtained with a chiral binaphthylamine.265 The methoxy substituent is believed to play a role as a Li+ ligand in the reactive enolate. 

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>. 

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

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>. 

The synthesis of 1,3-selenazoles from A -phenylimidoyl isoselenocyanates has been reported. N-phenylimidoyl isoselenocyanates 94 are prepared from N-phenylbenzamides 92. Treatment of 92 with thionyl chloride affords N-phenylbenzimidoyl chlorides 93, which yield imidoyl isoselenocyanates 94 on reaction with potassium isoselenocyanate. The imidoyl isoselenocyanates 94 were transformed into selenoureas 95 with either ammonia or primary or secondary amines. Reaction of 95 with an activated bromomethylene compound such as bromoacetophenone in the prescence of a base gave the 1,3-selenazole 97 via the salt 96 <00HCA1576>. 

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... 

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