Methyloxazoles

NMR data for 4-methyloxazole have been compared with those of 4-methylthiazole the data clearly show that the ring protons in each are shielded. In a comprehensive study of a range of oxazoles. Brown and Ghosh also reported NMR data but based a discussion of resonance stabilization on pK and UV spectral data (69JCS(B)270). The weak basicity of oxazole (pX a 0.8) relative to 1-methylimidazole (pK 7.44) and thiazole (pK 2.44) demonstrates that delocalization of the oxygen lone pair, which would have a base-strengthening effect on the nitrogen atom, is not extensive. It must be concluded that not only the experimental measurement but also the very definition of aromaticity in the azole series is as yet poorly quantified. Nevertheless, its importance in the interpretation of reactivity is enormous. 

Diphenyloxazole gave only the product of the condensation between the aromatic rings without transposition, while 2,4-diphenyloxazole did not react appreciably [77JCS(P1)239]. However, some important information about the mechanism was obtained when 2-phenyloxazole and 2-phenyl-5-methyloxazole were irradiated with a monochromatic light at 294 nm at 24°C. In both cases, the only... 

Table 7. Optically Active 4,5-Dihydro-4,4-dimethyl-2-(2-hydroxyalkyl)oxa7oles pre. pared from 4,5-Dihydro-4,4-dimetliyl-2-(4-melhylphenylsulfinyl)methyloxazoles and Aldehydes...

C4H5NO 693-93-6) see Pyridoxine 4-methyloxazole-S-carboxamide (C5H4N2O2 4866-00-6) see Pyridoxine 2-methyi-4-(oxiranylmethoxy)-ltf-indole (Ci.H.jNOa 62119-47-5) see Bopindolol Mepindolol (2S-7ranj)-(2-methyl-4-oxo-3-azetidinyl)carbamic acid 1,1-dimelhylethyl ester (C9H14N2O3 80582-03-2) see Aztreonam... 

The chlorination of the antibacterial sulfonamide sulfamethoxazole was initiated by N-chlorination of the primary amine. Further reaction of the A,A-dichlorinated compound resulted in the final production of 3-amino-5-methyloxazole and 1,4-benzoquinone-imine (Dodd and Huang 2004). 

By lithiation of 4-methyloxazole with n-BuLi and subsequent quenching with trimethyltin chloride, Dondoni et al. prepared 2-trimethylstannyl-4-methyloxazole [18], which was then coupled with 3-bromofuran to provide the expected furylthiazole. 

In 1987, Yamanaka s group described the Pd-catalyzed reactions of halothiazoles with terminal acetylenes [22a]. Submission of 4-bromo- and 5-bromo-4-methyloxazoles to the Sonogashira reaction conditions with phenylacetylene led to the expected internal acetylenes. 

Amino-3-methylisoxazole, 1502 2-Amino-4-methyloxazole, 1500 5-Amino-3-methylthio-l,2,4-oxadiazole, 1192 Ammonium A-nitrosophenylaminooxide, 2399 2-Aza-l,3-dioxolanium perchlorate, 0898 Azoformaldoxime, 0815 Bis(l-benzo[d]triazolyl) carbonate, 3598 Bis(l-benzo[d]triazolyl) oxalate, 3629 Bis(trifluoromethyl) nitroxide, 0638 2-/er/-Buty 1-3 -phenyloxaziridine, 3406 Calcium bis(O-hydroxylamide). 3930 Calcium hydroxide O-hydroxylamide, 3929... 

Tandem heterocycles are formed by posttranslational conversion of oligopeptide sequences consisted of serine, cysteine and threonine. A striking example of tandem heterocycles is telomestatin (Figure 7.2), a nanomolar telomerase inhibitor, which contains eight heterocycles. In its biosynthesis, five serines were converted to five oxazoles, two threonines to two methyloxazoles and one cysteine to one thiazoline [25]. 

However, unlike the situation seen with 2-methyloxazole and 1,2-di-methylimidazole where side-chain metalation predominates, lithiation at C-5 can still be the predominant mode of reaction in certain cases, due to the stronger activating effect of the sulfur atom. The nature of the substituent at C-4, the type of electrophile employed, the temperature of the reaction, and the type of base used can all affect the product ratio (74JOC1192). 

Diels-Alder reactions.2 This vinyl sulfone has been used as an acetylene equivalent in a new synthesis of vitamin Be. Thus 1 undergoes a Diels-Alder reaction with 4-methyloxazole (2) to give a pyridoxine derivative (3) with elimination of mcthanesulfinic acid. The product is converted into the vitamin (4) in three simple steps. 

Oxazoles may be similarly prepared in good yields. Thus, 5-ethoxy-4-methyloxazole (173) was obtained by treating ethyl 2-formamide propionate (172) with phosphorus pentoxide in chloroform at 55°C (72JCS(P1)909,914). Known collectively as the Robinson-Gabriel synthesis, these cyclodehydrations can be effected by sulfuric acid or anhydrous hydrogen fluoride (cf CHEC 4.18). 

Scheme 8 Synthesis of a Peptide-Based 5-Methyloxazole from a Dipeptide Containing a Threonine Residue via an Oxidation-Cyclodehydration Sequence 631...

Methyl 2-[(5)-l-(Benzyloxycarbonylamino)ethyl]-5-methyloxazole-4-carboxylate (33) 1 1 TEA (4.1 equiv) and a soln of 32 ( 3 mmol, 1 equiv) in dry CH2C12 (lOmL) were added sequentially to a stirred soln of Ph3P (2.0 equiv) and I2 (2 equiv) in dry CH2C12 (40 mL) at rt under N2. The mixture was stirred until TLC analysis indicated that the reaction was complete, concentrated, purified by flash chromatography (silica gel, EtOAc/petroleum ether) to yield the desired product 33 yield 66% mp 125.5-126 °C (colorless needles, EtOAc/petroleum ether) [a]D165 -34.4 (c 1.0, CHCI3). 

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