4.5- dimethyl-2- oxazole

The photoisomerizations of this type appear to be quite general, but the yield of the oxazoles varies considerably. Thus ultraviolet irradiation of 3,5-dimethylisoxazoIe in methanol gives an 80% yield of 2,5-dimethyl-oxazole.176 1,2-Benzisoxazoles (112) similarly rearrange to benzoxazoles together with some substituted o-hydroxybenzonitriles as by-products.176... 

Oxazoles.—Formation. ci)-Diazoacetophenone reacts with benzonitrile in the presence of trifluoromethanesulphonic acid to give 2,5-diphenyloxazole (514). Bi-, ter-, and quater-oxazoles have been synthesized from a-metallated isocyanides thus lithiobenzyl isocyanide (PhCHLiNC) and dimethyl oxazole-3,4-dicarboxylate afford compound (515). Stable methylene-oxazolines (516 R = Me or Ph) are obtained by heating the iminesHN=C(Ph)OCHRC=CH. The fluorinated oxazoline (518) results from the action of benzonitrile on the oxiran (517), and also from the reaction of bis(trifluoromethyl)carbene with the benzoylimine (CF3)2C=NCOPh/ Treatment of 2-acylamino-l-aryl-alkan-l-ols (519) under the conditions of the Pictet-Gams reaction, i.e. with phosphorus pentoxide in boiling toluene or xylene, results in cis- and trans-2-oxazolines (520), rather than isoquinolines, as claimed previously. The spiro-oxazolines (521 R = Me or Ph) are formed when the lithiated di-isocyanide CN—CH2CH2CHLi—NC is treated with acetone or benzophenone, respec-tively. ... 

In the homogeneous eatalysis domain, veiy recently Jia et al. examined the homogeneous eatalytie ability of one of their newly synthesised complexes [ (DMOX)CdCl 2(/t-Cl)2] (8) (DMOX = 4,5-dihydro-2-(4,5-dihydro-4,4-dime-thyloxazol-2-yl)-4,4-dimethyl-oxazole), for direct C-N crosscoupling of amine with aryl halide. The results point out that Cd(ii) complex 8 shows significant catal5dic activity in C-N crosscoupling of amines with aryl halide (Scheme 17.4). 

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

C3NO 0 — N — — 2,2 -p-Phenylenebis(5-phenyloxazole) 2-(4-pyridyl)oxazole 2,4-dimethyl-5-(p-nitrophenyl)oxazole 2-oxazolidinone ... 

In 1909, Robinson demonstrated the utility of acylamidoketones as intermediates to aryl-and benzyl-substituted 1,3-oxazoles through cyclization with sulfuric acid. Extension of sulfuric acid cyclization conditions to alkyl-substituted oxazoles can give low yields, for example 10-15% for 2,5-dimethyl-l,3-oxazole. Wiegand and Rathbum found that polyphosphoric acid can provide alkyl-substituted oxazoles 4 in yields equal to or greater than those obtained with sulfuric acid. Significantly better yields are seen in the preparation of aryl- and heteroaryl-substituted oxazoles. For example, reaction of ketoamides 5 with 98% phosphoric acid in acetic anhydride gives oxazoles 6 in 90-95% yield. ... 

The reaction of 78 with phosphorus pentasulfide in xylene gives the corresponding 2-oxazolethione, which also forms the iV -methyl product with dimethyl sulfate and 4,5-diphenyl-2-methyhnercapto-oxazole in 98% yield on treatment with silver oxide-methyl iodide. 

Phenylacetylamino-2-methyl-propanol5 Zu einer Losung von 0,5 g (2,46 mMol) 5-Oxo-4,4-dimethyl-2-benzyl-4,5-dihydro-1,3-oxazol in einem Gemisch von 15 ml THF, Athanol und Wasser (1 1 1) werden unter Riihren in kleinen Portionen 0,05 g (1,3 mMol) Natriumboranat gegeben. Man laBt 20 Stdn. bei 20° stehen, siiuert an, cngt ein, extrahiert mit Diathylather, trocknet, entfernt die Solventien i.Vak. und kristallisiert den Riickstand aus Diathylather Ausbeute 0,47 g (91% d.Th.) F 75-76°. 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

Dimethoxyphenyl)-4,4-dimethyl-2-oxazoline Oxazole, 2-(2,3-dimethoxyphenyl)-4,5-dihydro-4,4-dimethyl- (9) (57598-32-0)... 

Dimethoxybenzoyl chloride Benzoyl chloride, 2,3-dimethoxy- (9) (7169-06-4) 2-Amino-2-methyl-1-propanol 1-Propanol, 2-amino-2-methyl- (8,9) (124-68-5) 2,2 -Dimethoxy-6-(4 ,4 -dimethyloxazolinyl)biphenyl Oxazole, 2-(2 ,6-dimethoxy[1,1-biphenyl]-2-yl)-4,5-dihydro-4,4-dimethyl- (9) (57698-39-7)... 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

Lithiated 2-alkyl-4,5-dihydro-l,3-oxazoles (363) react with nitrones in high stereoselectivity to give initially 1,6-dioxa -2,9-diazaspiro [4.4] nonane (364). Upon further treatment with oxalic acid it is quantitatively converted to 4,4-dimethyl-2-( 1 -methyl-2-phenylvinyl)-4,5-dihydro-1,3-oxazole (365) (diastereo-meric mixture E/Z = 9 1) with elimination of tert-buthylhydroxylamine (Scheme 2.157) (598, 599). 

In the model studies toward the total synthesis of dimethyl sulfomycinamate, Kelly et al. successfully carried out the Stille couplings of oxazolyl triflate 18 with an array of organostannanes [19, 20]. Thus, 2-aryl-4-oxalone 17 was transformed into the corresponding triflate 18, which was then coupled with 2-trimethylstannylpyridine under the agency of Pd(Ph3P)4 and LiCl to provide adduct 19. The couplings of triflate 18 with phenyl-, vinyl- and phenylethynyl trimethyltin all proceeded in excellent yields. Unfortunately, application to the more delicate system in the natural product failed and the oxazole moiety was installed from acyclic precursors. 

When l-[diazo(methoxycarbonyl)acetyl]-2-oxopyrrolidine derivative 231 was treated with Rh2(pfm)4 (pfm = per-fluorobutyro amidate) in the presence of W-phenylmaleimide, none of the desired dipolar cycloadduct was formed but instead the acidic proton at C-3 in the isomiinchnone intermediate 232 was transferred, and the fused oxazoli-dinone 3-oxo-2,3,5,6-tetrahydropyrrolo[2,l- ]oxazole-2,7-dicarboxylic acid dimethyl ester 233 was isolated in 77% yield (Scheme 33) <1997JOC6842>. 

Interestingly, deprotonation of the 3-oxo-pyrrolo[l,2-f]oxazole 277 with r-BuLi at —78°C took place at the C-5 position. Addition of an electrophile provided the substituted products 278 in good yields. Stannyl and silyl chlorides, dimethyl sulfate, ketones, and benzaldehyde were successfully used as electrophiles. A significant feature of this lithiation-substitution reaction is the generally high Ar-diastereoselectivity only single diastereomers of products were isolated (Scheme 41) <2001JA315>. 

The rhodium acetate complex catalyzed the intramolecular C-H insertion of (/ )-diazo-fR)-(phenylsulfonyl)acet-amides 359 derived from (f )-amino acids to afford in high yield the 6-benzenesulfonyl-3,3-dimethyl-7-phenyl-tetrahydro-pyrrolo[l,2-c]oxazol-5-one 360 (Equation 63) <2002JOC6582, 2005TL143>. 

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... 

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>. 

A new heterocyclic system, 3 ,4-dihydro-3//-benzo[4,5]imidazo[l,2-f]oxazol-l-one 462, was synthesized by reaction of 4,4-dimethyl-5-methylene-l,3-dioxolan-2-one with o-phenylenediamine in the presence of copper bromide as catalyst in carbone dioxide at 60-80 °C under high pressure (Equation 217) <1999CHC216>. 

Trapping of the intermediate acyl nitrile ylide with dimethyl acetylenedicar-boxylate leads to pyrroles in low yields (< 18%) [1250]. Representative examples of the preparation of oxazoles with carbene complexes are listed in Table 4.18. 

Oxazole, 2-4-dimethyl-5-acetyl Sd Hu" Oxazole, 2-4-dimethyl-5-ethyl Sd Hu" Oxazole, 2-5-dimethyl Sd Hu" ... 

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