Oxazoles 5-hydroxy

Treatment of the oxazole (699) with ammonia converts it into 5-hydroxy-4,6-dimethyl-pyrimidine (700) and homologues may be made similarly 60CB1998). 

Hydroxy-imidazoles, -oxazoles and -thiazoles (484 Z = NR, O, S) can isomerize to 2-azolinones (485a). These compounds all exist predominantly in the azolinone form and show many reactions similar to those of the pyridones. They are mesomeric with zwitterionic and carbonyl canonical forms e.g. 485a 485b Z = NR, O, S). 

The 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

Thieno[3,4-d]oxazole-3a(4H)-carboxylic acid, dihydro-2-methyl-synthesis, 6, 1020 Thieno[2,3-d Joxazoles synthesis, 6, 990 Thieno[3,2-g]pteridine structure, 3, 284 lH-Thieno[3,4-c]pyran-2-ones synthesis, 4, 1032 Thienopyrazines synthesis, 4, 1022-1024 Thieno[2,3-6]pyrazines, 4, 1023 electrophilic substitution, 4, 1024 Thieno[3,4-6]pyrazines, 4, 1024 Thieno[3,4-c]pyrazole, 4,6-dihydro-3-hydroxy-carbamates... 

In 1949, Comforth showed that preparation of 2,5-disubstituted oxazoles was not limited to diaryloxazoles through condensation of aldehydes (benzaldehyde, n-hept-aldehyde) with a-hydroxy-amides (lactamide). The intermediate oxazolidone 13 were converted into oxazoles 14 on warming with phosphoryl chloride. ... 

Wipf and Miller have reported side-chain oxidation of 3-hydroxy amides with the Dess-Martin periodinane, followed by immediate cyclodehydration with triphenylphosphine-iodine, which provides a versatile extension of the Robinson-Gabriel method to substituted oxazoles. Application of this method was used to prepare the oxazole fragment 10 in 55% overall yield from 3-hydroxy amide 8. 

Chelated oxo structures were assigned to 5-hydroxy-4-acyl-l,3-oxazoles on the basis of their NMR spectra, the preference being given to the con-former 249a with a six-membered chelate ring (Scheme 86) (75BSB845). 

Low yields of 5-acyl-2,3-dihydropyrrolo[2,l-Z ]oxazoles (37) were obtained by treatment of 2-acyl-5-nitropyrrole (35) with ethylene oxide. Better yields are reported starting from hydroxy derivative 36a or its acetate 36b using sodium hydride in THE The presence of an acyl group at the position 2 was found necessary for the cyclization (Scheme 5) (71JCS(C)2554). 

Metalation of 4,5-dihydro-2-[(7 )-sulfinylmethyl]oxazoles (e.g., 2) with butyllithium at -90 C and reaction of the chiral azaenolates with aldehydes furnishes the hydroxyalkylated sulfinylox-azole derivatives 3 which are desulfurized to give the 4,5-dihydro-2-(2-hydroxyalkyl)oxazoles 4. The corresponding 3-hydroxy acids 5 are obtained by acidic hydrolysis in 60-85% overall yield and 26-53% ee31. 

The anions of 2-(arylsulfinylmethyl)oxazoles can be added to aldehydes to give 2-(l-aryl-sulfinyl-2-hydroxyalkyl)oxazoles which have been transformed into /1-hydroxy acids. With lithium bases, the enantioseleetivity could be increased to 50%. The use of a more chelating counter ion, such as magnesium, lowered the optical yields44. 

Methyl-2-phenyl-4-athoxycarbonyl-l,5-dihydro-l,3-oxazol wird je nach Menge Li-thiumalanat entweder selektiv zum Alkohol reduziert oder man erhalt unter Ringspaltung 2-Benzylamino-3-hydroxy-butandiol-(1,3) (s. S. 347). 

Bei —0,15 bis -0,4 V entsteht 3-Hydroxy-(naphtho-[ ,2-c]-oxazol) bzw. I-Hydr-oxy- (naphtho-[2,l-c]-l,2-oxazol) aus l-Nitro-2-aminocarbonyl- bzw. 2-Nitro-l-amino-carbonyl-naphthalin5 ... 

Analog reagieren 3-Nitro-2-aminocarbonyl- und 8-Nitro-l-aminocarbonyl (bzw. carboxy)-naphthalin5 zum 1 -Hydroxy-(naphtho-[2,3-c -1,2-oxazol) bzw. 8-Amino-naphthalin-1 -carbonsaure-lactam ... 

Bis-[ ( benzo-1,3-oxazol) -yl-(2)-thio]- 343 Bis-[1,4- (bzw. 3,4]-dihydro-naphthy[-(2)-oxy]- 588 Bis-[dimethylamino]- 345 Bis-[4-dimethyIamino-phenyl]- 346 Bis-[4-hydroxy-phenyl]-(2-carboxy-phenyl)- 167 Bis-[4-methoxy-phenyl]-dideutero- 346 Bis-[4-methyl-phenyl]-Bis-f 2-methyl-thiiranyl-(2)]- 570 Bis-[naphthyl-(2)-oxy]- 588 Bis-[naphthyl-(2)-thio]-... 

CN (lip,16(i)-21-(acetyloxy)-9-fluoro-ll-hydroxy-2 -methyl-5 H-pregna-l,4-dieno[17,16-d]oxazole-3,20-dione... 

C22H2XO3 14135-32-1) see Betamethasone 17a-hydroxy-16P-methyl-5p-pregn-9(ll)-ene-3,20-dione (C22H32O3 13656-78-5) see Betamethasone 21-hydroxy-2 -methyl-5p//-5a-pregn-9(ll)-eno[17,16-d]-oxazole-3,20-dione acetate (ester)... 

Rapi, G. et al., J. Chem. Soc., Chem. Comm., 1982, 1339-1340 Oxidative rearrangement of the oxazole to 4-hydroperoxy-5-hydroxy-4-methylimidazolidin-2-one in presence of iron(II) catalysts at ambient temperature may become explosive if not controlled effectively. 

Application of the Ritter reaction conditions on y-hydroxy-a,P-alkynoic esters, 102, produced ethyl 5-oxazoleacetates 103 or y-A-acylamino-P-keto ester 104 by reaction with aryl or alkyl nitriles respectively. The y-A-acylamino-P-keto ester 104 can also be transformed into oxazole derivatives using an additional step involving POCI3 <06TL4385>. 

The group of Janda has presented a microwave-mediated oxazole synthesis utilizing /3-ketoestcrs bound to a novel polymeric resin [57]. The desired polymer support was prepared by transesterification reactions of tert-butyl /f-ketoesters and hydroxy-butyl-functionalized JandaJel resin and subsequent standard diazo transfer. The resulting a-diazo /f-ketoesters were employed for the synthesis of an array of oxa-zoles (Scheme 7.41). 

A hydroxy group can be introduced on this bicyclic system as a nucleophile. The pyrrolo[l,2-c]oxazole system can be hydroxylated at the 7a-position to produce in good yield the corresponding 7a-hydroxypyrrolo[l,2-c]oxazole. The diastereoselectivity of this nucleophilic addition is total, with attack at the iminium ion on the face hindered by the phenyl group at C-3. <2002TL463, 2004JOC7558, 2006TA53>. 

Chiral hydroxy benzimidazole 267 was dialkylated with dibromomethane or benzaldehyde dimethyl acetal to form benzo[4,5]imidazo[l,2-f]oxazoles 268 and 269 (Equation 118) C1997TA1491, 1998TA2245>. After removal of the BOC group and formylation of the liberated amine, formylaminomethylthiazole cyclized in phosphoryl chloride to... 

From Nocardia strains several closely related compounds (nocobactins, formo-bactin, amamistatins) were isolated that contain three typically Fe " binding sites, two hydroxamate units, and ahydroxyphenyloxazole stmcture (cf. Sect. 3.2 below). The C-terminus is A-hydroxy-cyc/o-Lys bound to a long chain 3-hydroxy fatty acid, whose hydroxy group is esterified by A -acyl-A -hydroxy-Lys, the a-amino group of which is bound to 2-o-hydroxyphenyl-5-methyl-oxazole-4-carboxylic acid (Table 4). For the amamistatins the configuration of the cyclic lysine was determined as L, the open one as d, and that of C-3 of the fatty acid as (S). The involvement in the iron metabolism was not investigated. 

Oxazol-4-ones (Anhydro-4-hydroxy-l,2-oxazolium Hydroxides) (367)... 

Trimethyloxazole 257 undergoes photochemically induced [2 + 2] cycloaddition with aromatic and aliphatic aldehydes to provide bicyclic oxazolines 258 with excellent regiochemical and stereochemical control. Diastereoselec-tivities from 75-99% can be achieved, which is the first reported example of a Paterno-Biichi reaction involving an oxazole. The oxetane cycloadducts can be hydrolyzed to a-amino-(3-hydroxy ketones. Other oxazoles have not been evaluated to determine if they undergo the photochemical cycloaddition (Scheme 8.71). 

Als Nebenprodukte entstehen oft 1,3-Oxazole (vgl. Bd. E8a, S. 903, 911). a-Hydroxy- und a-Acetoxy-ketone liefern die entsprechenden 1,3-Oxazole sogar als Hauptprodukte42,43. Aus 3-Brom-l-oxo-l-phenyl-butan erhalt man mit Ammoniumformiat in Ameisensaure 4-Ethyl-5-phenyl-imidazolin 75% Ausbeute. Dagegen entsteht aus dem isomeren l-Brom-2-oxo-l-phenyl-butan unter analogen Reaktionsbedingungen das entsprechende 1,3-Oxazol in iiber 70% Aus-... 

Die Umsetzung von 5-Acetyl-2-amino-l,3-oxazol mit sekundaren Aminen fiihrt zu Gemischen aus 4(5)-Acetyl-2-dimethylamino-imidazolen (32-62%) und 2-Dimethylamino-5-hydroxy-4-methyl-pyrimidinen (15-44%)387 ... 

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 ... 

So erhalt man bei der Reaktion von 3-Hydrazinocarbonyl-5-methyl-l,2-oxazol mit Phosgen als vermutliches Zwischenprodukt 3-(2-Chlorcarbonyl-hydrazinocarbonyl)-5-methyl-l,2-oxa-zol, das beim Erhitzen zu 2-Hydroxy-5-( 5-methyl-l, 2-oxazol-3-yl)-2-oxo-2,3-dihydro-1,3,4-oxa-diazol (32% Schmp. 225-226°) cyclisiert139 ... 

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