5-Hydroxy-4- imidazolidines

Dioxo-3-alkyl-imidazolidine werden mit Lithiumalanat in der Hitze zu 3-A1-kyl-imidazolidinen reduziert z.B. 2,4-Dioxo-3-methyl-5-phenyl-imidazolidin zu 7-Methyl-4-phenyl-imidazolidin (43% d.Th.) bei 23° und inverser Zugabe wird dagegen (vgl. S. 252) 2-Hydroxy-l-methyl-4-phenyl-imidazol (66% d. Th.) erhalten, das sich unter energischen Bedingungen zum 7-Methyl-4-phenyl-imidazol (25 % d. Th.) reduzieren laftt3 ... 

Auch cyclische Acyl-thioharnstoffe vom 4-Oxo-2-thiono-imidazolidin- bzw. -te-tra(hexa)hydro-pyrimidin-Typ lassen sich selektiv an der Carbonyl-Gruppe zu den ent-sprechenden 2-Thiono- (mit Lithiumalanat) bzw. 4-Hydroxy-2-thiono-Verbindun-gen (mit Alkalimetallboranat) reduzieren z. B. ... 

Die erhaltenen Hydroxy-thiono-imidazolidine gehen leicht unter Wasser-Abspaltung in 2-Mercapto-imidazolc tiber, die durch entsprechende Arbeitsvarianten auch direkt erhalten werden konnen. 

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

Nitrone cycloaddition reactions with alkynes have been widely used for the synthesis of imidazolidine nitroxides (736) and (737), containing chelating enam-ino ketone groups (821). Different heterocyclic systems were obtained, such as 3-(2-oxygenated alkyl)piperazin-2-ones (738) (822), also compounds containing the isoxazolo[3,2-i]indole ring system (739) (823) and a new class of ene-hydroxylamino ketones- (l )-2-( 1-hydroxy-4,4,5,5-tetraalkylimidazolidin-2-ylidene)ethanones (740) (824) (Fig. 2.46). 

K. Ienaga, K. Nakamura, A. Ishii, T. Taga, Y. Miwa, F. Yoneda, The Stepwise Mammalian Oxidation of the Hydantoin l-Methyl-imidazolidine-2,4-dione into Methylimi-dazolidinetrione via 5-Hydroxy-l-methyl-imidazolidine-2,4-dione , J. Chem. Soc. Perkin Trans. 1 1989, 1153-1156. 

Resting cells of bacterium Stenotrophomonas maltophilia CGMCC 1.1788 catalyze the stereoselective hydroxylation at position C12 of imidacloprid (IMl) in the imidazolidine ring to form (R)-5-hydroxy IML Under acidic conditions, 5-hydroxy IMI is converted into olefin IMl (Figure 12.2), which exhibits about 19 times more insecticidal efficacy than IMI against horsebean aphid imago. 

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>. 

Durch Umsetzung von 2-Hydroxy-l,3,4-oxadiazolen mit Amino-carbonsauren sind 5-substi-tuierte 3-Acylamino-2,4-dioxo-imidazolidine bequem zuganglich739. Aus 1,2-Diamino-benzol und 2-Hydroxy-5-phenyl bzw. 2-Mercapto-5-phenyl-1,3,4-oxadiazol crhalt man in guten Ausbcuten 2-Oxo- bzw. 2-Thiono-2,3-dihydro-benzimidazol1M> ... 

Mit 2-Formyl-pyridin entstehen 2-Amino-4-(2-pyridyl)-5-hydroxy-1,3-oxazole7,8, die ebenfalls zu Ami-nosauren verseifbar sind1. 3- und 4-Formyl-pyridine ergeben nur die entsprechenden 2,4-Dioxo-5-[3-(bzw.4)-pyridyl]-imidazolidine. 

Masked chiral a-hetero substituted carboxylic acid enolates have also shown utility in dia-stereoselective additions to nitroalkenes. For example, derivatives of a-hydroxycarboxylic acids, e.g. l,3-dioxolan-4-ones (187) a-amino acids, e.g. 1,3-imidazolidin-4-ones (188) and a-amino-fi-hydroxy-carboxylic acids, e.g. methyl 1,3-oxazolidin-4-carboxylates (189) and methyl l,3-oxazolin-4-carboxy-lates (190), have been employed.1S0a Further, diastereoselective additions of chiral (3-hydroxyesters (191), via the enediolates, to nitroalkenes (40) afford predominant anr/ -P-hydroxyesters (192 Scheme... 

The optically pure bis-naphthalene ortho-methoxy amide 117 cyclized to the l,4-diazepin-5-one 118 in 86% yield and with >95% ee upon refluxing in ethylenediamine for 5 h to provide the first axially chiral 1,4-diazepine derivative (Scheme 64) <2000SL1616>. This example of a type g ring closure in which the leaving group is MeOH, proceeded in lower yield with an ot/ o-hydroxy substituent, with product distribution largely redirected toward an imidazolidine derivative in which the ethylenediamine reacted solely with the ester. In the structurally simpler salicylic acid ester series, activation of the phenol as the trifluoromethanesulfonate facilitated the SnAr reaction <1995TL7595>. 

The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho- aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols. 

Reagents 32c and 32e arc imidazolidines and oxazolidines characterized by sufficient reactivity of the X—CH2—N moiety for pixxlucing substrate aminomethylation. Indeed, when analogous, more stable cyclic derivatives are formed (e.g., 25), the Mannich reaction does not take place. Compounds 32c and 32e are used for synthesizing Mannich bases bearing a further amino or hydroxy functional group in the amine moiety, as depicted in the example reported below for product 37 (Fig. 21).- ... 

Imidazolidin 2,5-Dioxo-4-hydroxy-4-methyl- E14a/2, 440 (R-CO-COOH + H2N-CO-NH2) Imidazol-3-oxid... 

Hydroxy-ethoxy)-ethyl- E8c, 7 (Glyoxal + CH20/NH3/Amin) Imidazolidin 1,3-Diacetyl- IV/lc, 312 1,3,4-Oxadiazol 3-Acetyl-2-ethyl-2-methyl-2,3-dihydro- E14a/2, 701 (R — CO — O — C—N=N — C-Cyclisier.)... 

Cinnoline 5,6-Dimethoxy-4-hydroxy- E9a, 693 [2-Ac—4,5-(OR)2 —aniiin/HN02] Imidazolidin 2-Oxo-l-phenoxy-carbonyl- E4, 1086 (NH -r COOR)... 

Amino-3-methoxy-2-(3-pyridyl-methylen-amino)-E15/2, 1809 [(NC)2CH-NH2 + R-CHO] Azetidin 3-Azido-4-(4-methyl-phenyl)-2-oxo- E16b, 371 (Nj-C-CO-Cl + Imin) Furazan 4-(Anilinomethylen-amino)-3-methyl- E8c, 673 (NH2 -> N=CH —NH —Ar) Hydrazin l,2-Bis-[2-pyrrylme-thylen]- -1-oxid X/2, 121 1 H-(Imidazo 1,2-a]-l,3,5-benzotriaze-pin), 10-Hydroxy-2,3-dihydro E9d, 476 [1 -(2-NH2 — Ar) — 2-imino — imidazolidin/COCl2) Imidazo[4,5-f indazol 5,6-Dimethyl-... 

Imidazolidin 3,4-Dimethy]-2-oxo-l-phenyl- E4, 376 (Umamidier.) lH-lndazol l-Butyl-3-hydroxy- E8b, 791 (Ar—NR —CO —Cl 4-NaN3)... 

Imidazolidin 3-(4-Chlor-phenyl)-l,5-dimethy -5-ethyl-4-hydroxy-2-oxo- E14a/2, 429 (Oxo - OH)... 

Imidazolidine-2-thiones (or 2-ones) have been shown by NMR studies to exist entirely in these forms rather than as the possible 2-mercapto-(or 2-hydroxy-)2-imidazoIines (80CS(15)193). The thione structure for benzimidazolinethiones is supported by UV, IR and dipole moment measurements. In addition, an X-ray study of l-(j8-D-ribofuranosyl)benz-imidazoline-2-thione confirms its thione (59) rather than the thiol (60) structure (Scheme 19). 

Sodium borohydride converts 4//-imidazole N-oxides into 1-hydroxy-imidazoline or -imidazolidine derivatives. Under the same conditions 1,3-dioxides form 1,3-dihydroxy-imidazolidines (76CHE1280). 

When l-hydroxy-3-imidazoline 3-oxides (263) are treated with HCl they dehydrate forming imidazole 3-oxides (Scheme 153) (73CHE1175). Reduction of 4//-imidazole N-oxides with borohydride leads to either 1-hydroxy-imidazolines or -imidazolidines, depending on the position of the oxide function. Under the same conditions 4//-imidazole 1,3-dioxides give 1,3-dihydroxyimidazolidines (76CHE1280). The 4iT-imidazole AT-oxides are prepared by heating 5,5-disubstituted l-acyloxy-3-imidazoline 3-oxides in vacuo. 

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