Imidoyl chloride

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

Conversion of CA into cyanuric chloride [108-77-0] (C1CN)3 by PCl is another example of reaction at carbon (78). Cyanuric chloride as an imidoyl chloride reacts as an acid chloride, unlike chloroisocyanurates. 

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 group of compounds is represented by A-methyl-2,5-diphenyl-l-aza-6-oxa-6fl-tellurapentalene 94 which was prepared in low yield (11%) by coupling an imidoyl chloride 95 with a tellurenyl chloride 96 in acetonitrile solution containing 2,6-lutidine (87MI2). 

In the presence of BuLi l-amino-2-methylpyridinium iodide and imidoyl chloride 74 yielded 2-(substituted amino)-3-(substituted imino)-3//-pyr-ido[l, 2-ft]pyridazine 75 (01JHC205). 

Unlike alk-2-enylbenzonitrile ylides. which on thermolysis yield isolablecyclopropa[c]isoquino-lines, the thiophene analogs 2 and 5, generated from the respective imidoyl chloride, 1 and 4, cyclize directly to thienoazepine 3 and 6, respectively.40... 

Treatment of dibenzo[A,/][l, 5]diazocine-6,12(5//,l l/7)-dione (2) with phosphorus pentachlor-ide transforms the amide functions into imidoyl chloride moieties.57... 

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. 

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. 

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. 

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>. 

Bis-imidoyl chloride 187 reacts with A -methyl imidazole 188 to give bis-cationic diimidazo[l,2- 2, T-c]pyrazine 189 (Equation 46) <2006T731>. The charges are believed to be delocalized over the ring system. 

Conversion of cephalosporin 71 to the imidoyl chloride, followed by treatment with base in the presence of DEAZD gives a novel spiro 0-lactam (72), again via nitrile ylid cycloaddition.116... 

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>. 

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... 

Imidoylstannanes, R13SnCR2=NR3, can be prepared from the reaction of stannyllithium compounds with the corresponding imidoyl chlorides (C1CR2=NR3 R2 and R3 = aryl),163 or, more generally, from the reaction of an acylstannane with an amine.164 The imidoylstannane can then be reduced to an a-aminostannane (Equation (49)).165... 

The imidoyl phosphate can be obtained from the imidoyl chloride and the silver or organic salts of a phosphate ... 

The first derivative (4) of aminomethylenemaionates (1) was prepared in 13% yield by Just through the reaction of diethyl sodiomalonate and imidoyl chloride (3) in diethyl ether (1885CB319, 1885CB2623). Disubsti-tuted malonate (5) was also isolated from the reaction mixture in 9% yield. 

Imidoyl chlorides of toluidines and naphthylamines were also applied (1886CB979). To avoid the formation of the disubstituted malonates, 2 mol of sodiomalonate was reacted with 1 mol of imidoyl chlorides (1886C B979). 

From Imidoyl Chlorides and in Vilsmeier-Haack and Similar Reactions... 

Shah and Heeramaneck improved the yields (30-45%) of 318 when mixtures of imidoyl chlorides (317), diethyl malonate, and diethyl sodio-malonate in 1 1 1 molar ratio were reacted in toluene at reflux temperature for 2 hr (36JCS428). This modification was later applied by others too (46JA1272 49J1C171). Diethyl (naphthylamino)phenylmethylenemal-onates (319) were also prepared in 18% and 30% yields by starting from N-( 1- and 2-naphthyl)imidoyl chlorides (37JCS867). 

The sodium salt of diethyl malonate was reacted with imidoyl chlorides (320) in boiling toluene for 4 hr, or in DMF at ambient temperature for 1-3.5 hr, to give l-(arylamino)-2,2,2-trifluoroethylidenemalonates (321) in 51-99% yields (80EUP12639). 

Diethyl malonate was reacted with imidoyl chloride (322) in DMF in the presence of sodium hydride at 95-100°C for 30 min to give methylthio(2-trifluoromethylphenylamino)methylenemalonate (323) in 40% yield (84FRP2532939). 

Seka and Fuchs reacted imidoyl chlorides (1 mol) (327) with diethyl sodiomalonate (1.4-2.5 mol) in diethyl ether in an autoclave at 80-150°C for 16-35 hr and obtained 2-ary 1-4-hydroxyquinoline-3-carboxylates (328) in 26-38% yields (31M52). 

In a Vilsmeier-Haack-Amold reaction, A/,Ar-disubstituted amino-methylenemalonates (329) were prepared in good yields from the sodium derivative of diethyl malonate or from diethyl malonate in the presence of triethylamine in benzene or toluene at a temperature below 20°C with imidoyl chlorides, which were prepared in situ from N./V-disubstituted formamides and phosphoryl chloride (63BRP917436). Instead of diethyl malonate, diethyl ethoxymagnesiummalonate could also be used (63 BRP917436). 

Imidoyl chlorides (1679) were reacted with dimethyl malonate in THF in the presence of sodium hydride at room temperature to give aminometh-ylenemalonates (1680) in 67-82% yields (89TL4821). The 4-methylphenyl derivative of 1680 (R = 4-MeC6H4) was cyclized by heating in cumene at 200°C to afford 4-hydroxy-2-trifluromethylquinoline-3-carboxylate (1681) in 66% yield. 

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