Benzimidazole 2-trimethylsilyl

The N-bis-silylated o-phenylenediamine 1511 reacts with DMF at 120°C to give benzimidazole, in 97% yield, and dimethylamine and hexamethyldisiloxane 7, whereas reaction of benzaldehyde with 1511 gives only 29% 2-phenylbenzimida-zole 1513, because the intermediate benzimidazoline 1512 is only rather slowly dehydrogenated to 1513 [52]. Heating of N,N -bis(trimethylsilyl)ethylenediamine 1514 with DMF affords imidazoline 1515 and dimethylamine and HMDSO 7 ]52] (Scheme 9.32). The lactam 1516 cycHzes analogously with SiCU 57/triethylamine in 63% yield to give 1517 ]53]. 

The acyclic benzimidazole or benztriazole nucleosides were prepared by condensation of their trimethylsilyl derivatives with the alkylating agents... 

Die Oxidation von 1-Trimethylsilyl-benzimidazol mit Benzolselenylchlorid soil iiber einen pri-maren Angriff des Selen-Atoms am N-Atom erfolgen. Unter Abspaltung von Chlor-trimethyl-silan wird 2-Phenylseleno-benzimidazol (93% Schmp. 131-135°) erhalten401 ... 

Reine N-Alkylierung wird bei der Umsetzung von in situ hergestellten 1-Trimethylsilyl-478 Oder l-Tributylstannyl-benzimidazolen436,441 mit Elektrophilen beobachtet. Die N-Trimethylsilyl-benzimidazole lassen sich wasserfrei mit geschiitzten Acetalen selektiv N-alkylieren478. 

Eine effektive, reversible Schutzgruppe fur Benzimidazole ist l-Chlormethoxy-2-trimethylsilyl-ethan (SEM — Cl), das in Dimethylformamid zu l-[(2-Trimethylsilyl-ethoxy)-methoxy]-benz-imidazol [50% Sdp. 220°/0,2 Torr (26,7 Pa)] kondensiert. Die so geschiitzten Heterocyclen sind wesentlich weniger feuchtigkeitsempfindlich als die (l-Diethoxy-methyl)-Derivate (s.S.357). Man kann die SEM-Schutzgruppe in siedendem Tetrahydrofuran mit Tetrabutyl-ammonium-fluorid leicht wieder entfernen508. 

MePTZ = lO-methylphenothiazine 2,3-dpp = 2,3-bis (2-pyridyl)pyrazine 2,9-Me2-4,7-Ph2-phen = 2,9-dimethyl-4,7-diphenyl-l,10-phenanthrolme 2,9-Me2-phen = 2,9-dimethyl-1,10-phenanthroline 3,4,7,8-Me4-phen = 3,4,7,8-tet-ramethy 1-1,10-phenanthroline 4,4 - NH2 2-bpy = 4,4 -dia-mino-2,2 -bipyridine 4,4 -Me2-bpy = 4,4 -dimethyl-2,2 -bipyridine 4, 4 -Ph2-bpy = 4,4 -diphenyl-2,2 -bipyridine 4, 4 - Bu2-bpy = 4,4 -di-tert-butyl-2,2 -bipyridine 4,7-Me2-phen = 4,7-dimethyl-l,10-phenanthroline 4-MeOPh-HPh bpy = 4 -(4-methoxyphenyl)-6 -phenyl-2,2 -bipyridine 4-Me-phen = 4-methyl-1,10-phenanthroline 5,6-Me2-phen = 5,6-dimethyl-l,10-phenanthroline 5-Ph-phen = 5-phenyl-1,10-phenanthroline bimy = benzimidazol-2-ylidene biq = 2,2 -biquinoline bpy = 2,2 -bipyridine bpy-dvb-bpy = 1,4-bis[2-(4 -methyl-2,2 -bipyrid-4-yl)ethenyl]benzene bpy-pyrl = 4-(2-pyrrol-l-ylethyl)-4 -methyl-2,2 -bipyridine bpy-pyr2 = 4,4 -bis((3-pyrrol-l-ylpropyloxy)carbonyl)-2,2 -bipyridine BSA = bovine serum albumin BTA = bis(trimethylsilyl)acetylene chrysi = 5,6-chrysenequinone diimine COD = 1,5-cyclooctadiene DAB = 1,4-diaza-1,3-butadiene DFT = density functional theory dmb =1,8-diisocyano-/ -menthane dmb-tol = 4-methyl-4 -(iV-methyl-/ -tolylaminomethyl)-2,2 -bipyridine dmpe = l,2-bis(di-methylphosphino)ethane dmpm = bis(dimethylphosphino) methane dpmp = bis(diphenylphosphinomethyl)phenylphos-phine dppb = l,2-bis(diphenylphosphino)benzene dppe = l,2-bis(diphenylphosphino)ethane dpp-HCNN = 2,9-di-... 

Related to prototropy is silylotropy. At room temperature, solutions of 1-trimethylsilyl-benzimidazole show an average C NMR spectrum, but once the tautomerism is frozen the molecule loses its symmetry <83H(20)i7i3>. 

Transglycosylation of silylated 3 -azido-3 -deoxythymidines with silylated N -octanoyladenine [33], iV -palmitoylguanine [33] and benzimidazole [40] in acetonitrile and, in the presence of trimethylsilyl trifluoromethanesulfonate, afforded a mixture of the a and P anomers of the corresponding nucleosides of adenine, guanine and benzimidazole. 

One-pot S5mthesis of both 1,2-disubstituted benzimidazoles and quinoxalines has been carried out in water at room temperature with excellent yields [69]. In the presence of trimethylsilyl chloride, o-phenylenediamine gives benzimidazole with aldehyde and quinoxaline with a-bromoketone. Isotope-labeling experiment carried out in the reaction with benzaldehyde and o-phenylenediamine demonstrated the 1,3-hydride migration process during the formation of 1,2-disubstituted benzimidazoles (Scheme 47). 

SCHEME 47 On-water synthesis of 1,2-benzimidazole using trimethylsilyl chloride. 

---