Imidazoles, 2,5-dihydro-1-hydroxy

Methoxy derivative was obtained from 2-(4,5-dihydro-l//-imidazol-2-yl)-7-hydroxy-8-methyl-2,3-dihydro-5//-pyrido[l,2,3- /e]-l,4-benzoxazin-5-one with methyl tosylate in DMF in the presence of K2CO3 at 50 °C for 1 h (99EUP894796). 

The reaction of 2-aminobenzyl alcohol 376 with 2-chloro-4,5-dihydroimidazole afforded [2-(4,5-dihydro-177-imidazol-2-ylideneamino)phenyl]methanol hydrochloride 377, which upon treatment with carbon disulfide gave l-(477-3,l-benzoxazin-2-yl)imidazolidine-2-thione 378 (Scheme 71). The assumed reaction mechanism involved the initial formation of the dithiocarbamate 379, which underwent intramolecular nucleophilic addition to furnish the unstable thiazetidine 380. By nucleophilic attack of the hydroxy group on the carbon atom of the thiazetidine ring, thiocarbamate derivative 381 was formed, which gave the final 3,1-benzoxazine 378 by an intramolecular cyclocondensation with the evolution of H2S <2006H(68)687>. 

Bei Verwendung von Formaldehyd als Aldehyd-Komponente wurden mil mehreren unter-schiedlichen a-Hydroximino-ketonen keine Imidazol-3-oxide, sondern 2-Hydroxy-imidazo-le erhalten, die als tautomere 2-Oxo-2,3-dihydro-imidazole vorliegen71b. 

Synthesen unter Einsatz von Harnstoffen oder Thioharnstoffen fiihren mit a-Hydroxy-ketonen zu 2-Hydroxy- bzw. 2-Mercapto-imidazolen, die, wenn einer der beiden Reste R1 oder R2 oder beide ein H-Atom sind, als tautomere 2-Oxo-2,3-dihydro-116-119 (s.a. Bd. VIII, S. 166) bzw. 2-Thiono-2,3-dihydro-imidazole vorliegen120,121. 

Aus a-Dicarbonyl-Verbindungen und Amidinen bilden sich zunachst 4,5-Dihydroxy-4,5-dihydro-imidazole, die isoliert werden konnen127 128. Setzt man eine disubstituierte a-Dicarbonyl-Verbindung und statt des Amidins ein Guanidin-Derivat ein, so erhalt man unter Abspaltung eines Aquivalents Wasser 4,5-disubstituierte 2-Amino-4-hydroxy-4H-imidazole, die in vielen Fallen ebenfalls isoliert werden konnen129,130 ... 

Beide Produkte konnen zu IH-Imidazolen umgesetzt werden. Wenn mindestens einer der beiden Reste R1 bzw, R2 ein H-Atom ist, lagern sich die 4,5-Dihydroxy-4,5-dihydro-imidazole sau-rekatalysiert in 5-Hydroxy-imidazole um127. Die Synthese gelingt auch im Eintopfverfahren ohne Isolierung der 4,5-Dihydroxy-4,5-dihydro-imidazol-Zwischenstufe131 (s.a. Bd. VII/4, S. 154-155). 

Dagegen tritt bei 2-Amino-4,5-diphenyl-4-hydroxy-4H-imidazol keine Umlagerung ein, da kei-ne Methyl-Gruppe vorhanden ist. Es wird stattdessen in konz. Salzsaure zu 2-Amino-4,5-di-hydroxy-4,5-diphenyl-4,5-dihydro-imidazol hydratisiert129. Mit Methanol/Salzsaure erhalt man 2-Amino-4,5-dimethoxy-4,5-diphenyl-4,5-dihydro-imidazol129 ... 

Durch Kondensation von Glycin-estern mit Carbonsaure-ester-imiden und Aldehyden bei an-schliebender katalytischer Hydrierung der primar gebildeten 4-Alkyliden-5-oxo-4,5-dihydro-imidazole erhalt man 4-substituierte 5-Hydroxy-imidazole (Bd. E5/1, S. 518, 519). 

Phosgen266 bzw. Ammoniumhydrogencarbonat267 als Cl-Baustein liefern 4,5-Dicyan-2-hydr-oxy)- bzw. 5(4j-Aminocarbonyl-4(5)-cyan-2-hydroxy-imidazole die beide in der tautome-ren Form als 2-Oxo-2,3-dihydro-imidazole vorliegen. 

Oxo-2,3-dihydro-l,3-oxazole konnen mit Isocyanaten in Ausbeuten von 80-90% zu Harn-stoff-Derivaten umgesetzt werden. Diese lagem sich saurekatalysiert in Ausbeuten von 44-97% (meistens iiber 90%) in die entsprechenden 1-Alkyl-2-hydroxy-imidazole um388 ... 

Hydroxyamino-imidazole werden in Wasser unter Umlagerung der Hydroxy-Gruppe und Addition von Wasser in 2-Amino-4,5-dih,ydroxy-4,5-dihydro-imidazole umgewan-delt1247 ... 

Die Carbonyl-Absorptionen der 2-Oxo-2,3-dihydro-benzidimidazole finden sich in einem wei-ten Bereich (von 1770-1675 cm- x)39, zu den Infrarot-CO-Banden acylierter 2-Hydroxy-benz-imidazole s.668. 

Die Umsetzung von 2-Acylamino-3-phenyl-propansaure-amiden mit Natrium-hypobromit verlauft iiber 2-Oxo-2,3-dihydro-imidazole, die in geringen Ausbeuten unter Ringspaltung und einer IIofmann-Rcaktion zu 2-Hydroxy-l,3,4-oxadiazolen518,556 557 reagieren ... 

The treatment of N-(2-hydroxyethyl),N-(4-fluorophenyl)-4-benzyloxy-3-methoxypyridine-2-carboxamides with a mixture of polystyryldiphe-nylphosphine, imidazole, and I2 in CH2C12 at ambient temperature overnight yielded 9-methoxy-2-(4-fluorophenyl)-3,4-dihydro-l H,8H-pyrido [l,2-fl]pyrazine-l, 8-diones (06WOP2006/066414). When N-(2-hydro-xyethyl),JV-(4-fluorophenyl)-4-benzyloxy-3-methoxy-6-bromopyridine-2-carboxamides was heated in HBr-AcOH solution (38%) at 100 °C for overnight 6-bromo-9-hydroxy-2-(4-fluorophenyl)-3,4-dihydro-lH,8H-pyrido [l,2- ]pyrazine-l,8-diones were the products. 

The oxo derivative prepared in step (a) or the hydroxy derivative prepared in step (b) is hydrogenated in 2 N hydrochloric acid in the presence of 10% palladium on carbon at 70°C. When the uptake of hydrogen ceases, the reaction mixture is filtered and made alkaline. The product is extracted with methylene chloride which is washed with water, dried and evaporated to dryness. From the residue, which is the product as base, is made the hydrochloride of 4(5)-(2,3-dihydro-2-ethyl-lH-inden-2-yl)imidazole using dry hydrogen chloride in ethyl acetate. It has melting point 211-215°C. 

The betaine anhydro-2-hydroxy-8-methyl-4-oxo-3 -phenyl-4//- imidazo[2,1 -b ][ 1,3]thi-azinium hydroxide undergoes thermal rearrangement to 2,3-dihydro-7-hydroxy-2-methyl-5-oxo-6-phenyl-3(2H),5H-pyrrolo[l,2-c]imidazolethione. A process involving an initial fission of the 1,2-bond and electrophilic ring closure of the resultant ketene intermediate into the 4-position of the imidazole nucleus is most likely involved in the rearrangement (equation 67) (80JOC2474). 

Benzofurazan 4,5-Diamino- E8c, 704 (Imidazol-Ringspalt.) Furo 2,3-d pyridazin 4-Hydrazino-E16a, 718 (C1->NC1-NH2) Pteridin 2-Hydroxy-3,4-dihydro-IV/lc, 331... 

Aminonitrone-A -hydroxyaminoimine tautomerism in 2-substituted l-hydroxy-4,4,5,5-tetramethyl-4,5-dihydro-l//-imidazole 140 is considered to be an acid-base equilibrium with the ratio between the forms dictated by the ratio of their acidity constants. A substituent with a positive mesomeric and/or inductive effect stabilizes the nitrone form 140A more effectively than the A-hydroxyaminoimino form 140B (Scheme 35) <2004JST(697)49>. ... 

Substituted l-oxo-4,4,5,5-tetramethyl-4,5-dihydro-17/-imidazoles 1548 have been prepared from Af-hydroxy imidazoline 1547, as shown in Scheme 399 <2004JST(697)49>. 

Dihydro-7-norfalloil-1H-imidazole-1-ethanol. 4,5-Dihydro-7-nortall oil-IH-imidazole-l-ethanol EINECS 263-171-2 1-(2-Hydroxyethyl)-2-(tall oil alkyl)-2-imidazoline 1H-lmidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs. 2-lmidazoline, 1-(2-hydroxyethyl)-2-(tall oil alkyl)- Miramine TOC 2-Nortall oil-1 H-imidazole-1-ethanol, 4,5-dihydro- 2-(Tall oil alkyl)-1-(2-hydroxyethyl)-2-imidazoline Tall oil hydroxy-ethyl imidazoline. 

Two syntheses from an imidazole nucleus have been developed (Scheme 9). By reaction between imidazole and acrolein, 6,7-dihydro-5-hydroxy-5//-pyrrolo[l,2-o]imidazole (61) has been obtained in moderate yield, probably from initial Michael adducts and further cyclization <87JHC56l>. The second synthesis shows an example of intramolecular cyclization, from compound (62) to give (63) <86TL323>. 

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