2.3- Dihydro-l//-imidazo

The 2,3-dioxo-6-thioxo-2,3,5,6-tetrahydro-l/7-imidazo[l,2-A]pyrazole 393 and 5,6-dioxo-2,3-dihydro-l//-imidazo[l,2- ]-imidazole 395 were synthesized by condensation of the respective 5-amino-3-thioxo-2,3-dihydro-pyrazole 392 and 2-aminoimidazoline 394 compounds with either oxalyl dichloride or diethyl oxalate in moderate to poor yields (Equations 178 and 179) <1995JPR472, 2002EJM845>. These cyclizations can suffer from various side reactions such as expulsion of CO, polymerization, or formation of open-chain products. To solve these problems, reagents such as oxalic acid bis-imidoyl- and bis-hydrazoylchlorides 397 and 400 as well as 2,3-dichloroquinoxalines 403... 

When simple substituted benzimidazoles such as 2-azidomethyl benzimidazole are employed, their iminophosphoranes (148) react with isocyanate to give carbodiimide 149. The free NH group of the imidazole can intercept the carbodiimide intermolecularly. Thus, upon addition of a second equivalent of isocyanate, cyclization affords 2,3-dihydro-l//-imidazo[l,5-a]benzimidazole 150 (Scheme 59) (89T1823 94S1197). 

According to Eq. (17), a series of 2,3-dihydro-l//-imidazo[l,5-/7]pyr-azole derivatives (46) were obtained (78JOC4841). They were investigated as structural analogues of histamine. 

The reactions of ethyl 2,4-dimethylpyrrole-3-carboxylate with a number of primary amines and an excess of formaldehyde lead to the formation of 2,3-dihydro-l//-imidazo[l,5-a]pyrroles. The reaction of cyclohexylamine, which, as indicated in the foregoing section, would not be expected to yield a product involving two pyrrole nuclei, does result in the formation of the dihydroimidazopyrrole in 70% yield as shown in Scheme 6. ... 

Trialkyl-2,3-dihydro-l//[l,4]diazepino[2,3-/]quinolines 109, obtained from the reaction of 5,6-diaminoquinoline with ketones, on treatment with acid or under thermal conditions afforded solely the 2-methyl-3//-imidazo[4,5-/]quino-line 110. However, no change was observed when diazepinoquinolines were treated... 

Dihydro-l/7-imidazo[l,2-a] l,3,5 benzotriazepin-5(67/)-ones 6a-d and the Analogous -benzotriazepine-5(6//)-thiones 6e-j General Procedure 378... 

Addiert man Aryl-isocyanate an Triphenyl-phosphan-(2-benzimidazolyl-methylimin) (I), so erhalt man 2-Aminocarbony 1-1 -arylimino-2,3-dihydro-lH-benz-imidazole)(IlI). Die Entstehung der Produkte wird iiber ein Carbodiimid-Zwischenprodukt II interpretiert520. 

Step 2 5-(p-Chlorophenyl)-5-Hydroxy-2,3-Dihydro-5H-Imidazo[2,l-a]Isoindole - l-(p-Chlorophenyl)-3-ethoxy-lH-isoindole (1 g), 2 g of ethyleneimine hydrotetrafluoroborate moistened with methylene chloride (containing approximately 0.66 g of dry salt) is refluxed in 25 ml of absolute toluene for 2 hours in an atmosphere of nitrogen. The resulting mixture is poured into 2 N sodium carbonate solution (25 ml) and extracted with ether. The ether solution is contacted with air for 6 days at room temperature to give the desired product. The crude material is recrystallized from acetone/hexane (1 1) to give 5-(p-chlorophenyl)-5-hydroxy-2,3-dihydro-5H-imidazo[2,l-a]isoindole MP 198° to 199°C. 

Treatment of pyrrole 231 and indole 233, bearing the benzotriazol-l-yl moiety (Bt) as leaving group, with isocyanates (Ar, THE, DBU, reflux, 5-7 h) gives high yields of 2,3-dihydro-l/7-pyrrolo[l,2- ]imidazoles 232 (71-95%) (Equation 56) and l/7-imidazo[l,5- ]indoles 234 (79-87%) (Equation 57), respectively <2004JOC9313>. The same conditions when... 

The formation of a heterocyclic system by intramolecular elimination of the ort/m-fluorine atom of an aromatic ring was demonstrated by the reaction of pentafluorobenzoyl chloride with 2-imidazolidinethione or 2-mercaptoimidazole, forming 6,7,8,9-tetrafluoro-2,3-dihydro-5//-imidazo-[2,1 -6][l,3]-benzothiazin-5-one (yield 54%) and 6,7,8,9-tetrafluoro-5//-imidazo[2,l-6][l, 3]benzothiazin-5-one (yield 48%) (94JOC7688) (Scheme 166). 

A new and efficient anionic domino process of 3-aminoisoxazoles with oxaldiimidoyl dichlorides, involving cleavage of the isoxazole ring besides cyclisation reactions, provided a regioselective access to 2,4-dihydro-l//-imidazo[43-b)quinoxalines 33 <01EJO2257>. 

This nitrile synthesis can be applied equally well to aliphatic and aromatic carboxamides. It is also applicable to the production of 7-chloro-3-cyano-2,3-dihydro-l-methyl-2-oxo-5-phenyl-li-f-l,4-benzodiazepine 1451, which is not accessible using the usual strongly acidic dehydrating agents [1100]. 1451 is produced as an intermediate in a synthesis of imidazo[5,l-c]benzodiazepine-l,4 1452 by dehydration of the carbaldoxime 1450 with triphenylphosphine/tetrachloromethane in 76% yield [1102]. 

The phosphoric acid having a 2,4,6-triisopropylphenyl moiety (223) has been found to be an effective catalyst for the intramolecular cascade imidization-nucleophilic addition-lactamisation reaction of methyl 2-formylbenzoates (220) with N -allqrlethane-1,2-diamines (221) (Scheme 59). Thus, medicinally interesting chiral 2,3-dihydro-lH-imidazo[2,l-a]isoindol-5(9Z>//)-ones (222) have been obtained with high yieids (89-94%) and excellent enantioselectivities (80-96% ee). ... 

Of the classical Hofmann, Curtius, Lossen and Schmidt degradations, only a rare example of the first is known, hypobromite converting 4,7-diamino-2-phenyl-6-pteridinecar-boxamide (208) into 8-amino-2,3-dihydro-6-phenyl-l//-imidazo[4,5-g]pteridin-2-one (209 equation 64) (63JOC1203). 

Diazadienes have been used in organic synthesis for the preparation of various heterocyclic compounds. Alkylation of 1,3-diazadienes 207 and the benz-fused analog 210 at the nitrogen atom by aryl acyl bromides provided the iV-alkyl amidinium bromides 208 and 211, which underwent annulation to the 2,3-dihydro-imidazo[2,l-A]thiazole 209 and imidazo[2,l- ]benzothiazoles 212, respectively (Equations 92 and 93) <2001S741, 2002J(P1)741>. 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

---