5-methyl-4- oxazole

Sindler-Kulyk and co-workers " investigated direct formylation of 4-methyl-oxazole 3 and 4,5-dimethyloxazole 611 as a means to prepare analogues that could be further elaborated in their synthesis of vitamin Bg (Scheme 1.166). They isolated a 1 1 mixture of 4-methyl-5-oxazolecarboxaldehyde 609 and 4-methyl-2-oxazole-carboxaldehyde 610 in low yield from 3. Similarly, 611 afforded 4,5-dimethyl-... 

Heptadecenyl)-2-imidazoline-1-ethanol. See Oleyl hydroxyethyl imidazoline 2-(8-Heptadecenyl )-4-methyl-2-oxazol I ne-4-methanol. See Methyl hydroxymethyl oleyl oxazoline... 

Methyl-4-(1 -hydroxy-1 -methylethyl) benzene. See Tri methyl benzyl alcohol Methyl hydroxymethyl oleyl oxazoline CAS 14408-42-5 EINECS/ELINCS 238-387-5 Synonyms 2-(8-Heptadecenyl)-4-methyl-2-oxazol i ne-4-methanol 2-Oxazol i ne-4-methanol, 2-(8-heptadecenyl)-4-methyl-Classification Substituted heterocyclic compd. Empirical C22H41NO2 Uses Antistat in cosmetics... 

The formation of methyl-oxazole compounds was also described by Wang et al. [34] utilizing an analog of the keto-enol intermediate (22) described in Sect. 2.1.1, Scheme 2. Scheme 11 shows the synthesis of compound 57 which exhibits anti-tubulin activity of 7.7. iM [34], In addition, a range of oxazole COX-2 inhibitors has been reported by Hashimoto et al. [55] employing similar chemistry. 

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. 

DBU (3mL, 20 mmol) was added to methyl 2-[(benzyloxycarbonylamino)oxazolidine-4-carboxylate (2.8 g, 9.6 mmol) in CQ4/MeCN/Py (2 3 3). After 3 h at rt, the solvent was extracted with 0.5 M HC1 and the aqueous phase reextracted with EtOAc (2 x). The EtOAc phase was washed with brine, dried (MgS04), and the solvent removed. Chromatography (silica gel, EtOAc/hexane 1 1) afforded methyl 2-[(benzyloxycarbonylamino)methyl]oxazole-4-carboxylate yield 0.94 g (33%). The oxazole ester (0.29 g, lmmol) was dissolved in dioxane (15 mL) and NaOH (0.12 g, in 5mL H,0) was added. The mixture was stirred at rt for 1 hr. The soln was neutralized with 10% aq KHS04 to pH 6, and the dioxane was removed. The soln was acidified to pH 3 and taken to dryness. The residue was crystallized (EtOAc/ hexane) yield 0.24 g (90%). 

Quibell and co-workers39 at Peptide Therapeutics used a 5-(hydroxy-methyl)oxazole scaffold 44 to prepare a range of oxazole libraries on HEMA-grafted, glycine-derivatized Gears (a small Crown design). The... 

A mixture consisting of the Step 6 product (0.081 mmol), 5-phenyl-2-methyl-oxazole-4-ethanol mesylate (0.11 mmol), and K2C03 (3.61 mmol) dissolved in 3 ml DMF was stirred 12 hours at 80°C, filtered, and then concentrated. The residue was purified by chromatography using hexane/EtOAc, 3 1, and the product isolated in 36% yield as a light brown solid. 

The directed metalation of aromatic systems that was discussed in Section 2.1.3.3 has one ramification that was not mentioned there the directed lithiation of an o-methyl group. Although the resultant species is formally a resonance-stabilized anion, and therefore covered in Volume 2 of this series, we mention it here for consistency with the other topics covered. In particular, the examples that have appeared in recent years involve substrates having a methyl ortho to a tertiary amide. Intentional use of such a directed lithiation has been used in the synthesis of the isocoumarin natural products hydrangenol and pyllodul-cin.137,138 Interestingly, the directed metalation of 5-methyl-oxazoles and -thiazoles occurs in preference to deprotonation at a 2-methyl group (azaenolate) (Scheme 33). ... 

The ammonium formate in formic acid procedure has rendered possible the first preparation of isomeric 4,5-disubstituted oxazoles.03101 Bredereck, Gompper, and Reich101 have reported the anomalous behavior of certain long-chain a-bromo ketones a single a-bromo ketone on reaction with ammonium formate in formic acid gives a mixture of two isomeric oxazoles. Refluxing of a-bromo ketones or of a-chloro-/3-keto esters with ammonium acetate in acetic acid results in the formation of substituted 2-methyl-oxazoles.40 102 Ethyl a-chloroacetoacetate on heating with ammonium carbonate or formamide in formic acid yields 4-methyloxazole-5-carboxylic ester.40 103... 

Infrared spectra of 4-methyloxazole and 2,4-dimethyloxazole for the gaseous and liquid states, and of liquid 2-n-hexy 1-5-methyl oxazole, have been measured at room temperature between 4000 and 600 cm-1. A comparison with the spectra of oxazole and considerations of the rotational envelopes has allowed a plausible assignment of the absorption bands with reasonable success.261 Examination of the infrared spectra in the solid state of 2,4-dimethyl-, 2-methyl-4-phenyl-, and 2-methyl-4,5-diphenyl-oxazolcs, and various benzoxazoles shows regularities in the 1660-1500 cm-1 region. Absorption bands at 1660-1600 cm-1 and 1585-1500 cm-1 have been assigned to the vibrations arising from the heterocyclic ring system.262... 

Carbon-13 magnetic resonance studies have been made on 4-methyl-oxazole and its onium ions.270-276-279 The 13C-H coupling constants are... 

Cyclization of 275 to a 5-[(phenylsulfonyl)methyl]oxazole 276 could be accomplished in good to excellent yield by treatment with base. Examples of oxazoles prepared using this methodology are shown in Table 1.21. 

Hojo and co-workers " described a novel synthesis of 4-aryl-5-(trifluoro-methyl)oxazoles 331, starting from aldehyde tert-butyl(methyl)hydrazones (Scheme 1.89). Triiluoroacetylation of a tert-butyl(methyl)hydrazone 327 yields 328 that cyclizes to a 4,5,5-trisubstituted oxazoline 329 upon refluxing in toluene in the presence of silica gel. Dehydration of 329 was then accomplished in two steps using POCI3 and a base to generate the 4-aryl-5-(trifluoromethyl)oxazoles 331. 

Storr and co-workers at ICI reported the first example of an oxazole-o-quinodimethane in 1990 (Scheme 1.207). FVP of 5-[[(p-chlorobenzoyl)oxy]-methyl]-4-methyloxazole 750 generated oxazole-o-quinodimethane 751. Trapping 751 with thiophenol gave rise to a mixture of 4-methyl-5-[(phenylthio)methyl]ox-azole 752 and 5-methyl-4-[(phenylthio)methyl]oxazole 753, whereas reaction of 751 with sulfur dioxide produced 4,6-dihydro-thieno[3,4-d]oxazole 5,5-dioxide... 

Trifluoromethyl)furan 147 was prepared in 67% yield by heating 4-methyl-oxazole 5 and 3,3,3-trifluoropropyne in toluene at 180°C for 13 h (Fig. 3.44). Metalation of 147 at the 2 position with n-butyllithium and subsequent reaction with aldehydes gave 3-(trifluoromethyl)-2-furyl carbinols 148. ... 

Alkoxyoxazoles have also proven to be valuable heterodienes in the synthesis of highly substituted furans and biologically active natural products via oxazole-aUtyne Diels-Alder reactions. Thus the synthesis of a synthon for the DEF ring system of fredericamycin began with the cycloaddition of 5-ethoxy-4-methyl-oxazole 8 with enyne ester 149 (Fig. 3.45). This reaction proceeded in 24 h in refluxing toluene to afford a 65% yield of the 2-ethoxyfuran 150. Furan 150 was then converted to the isoquinoline 151 in six steps. ... 

In 1988, Vedejs and Fields prepared 3-thiazolines from 5-methoxy-2-methyl-oxazole 249 and a series of thioaldehydes, generated in situ from their cyclopenta-diene adducts. Thus heating 249 and thioaldehyde 250 in a sealed tube at 140°C for 48 h afforded a 95% yield of 251 as a 1 1 mixture of diastereomers (Fig. 3.74). The unactivated oxazole, 5-methyl-2-phenyloxazole was unreactive under the same conditions. A Diels-Alder mechanism was proposed for this reaction but no intermediate Diels-Alder adduct was observed. A nitrile ylide pathway was discounted, since these reactions proceed at room temperature if the thioaldehyde is generated photolytically and oxazoles do not form nitrile ylides under those conditions. Thioformaldehyde, thioacetaldehyde, thiobenzaldehyde, and thioace-tone all successfully underwent similar reactions to provide thiazohnes. 

Regenerable, ion-supported (diacetoxyiodo)benzenes promoted the formation of 5-aryl-2-methyl oxazoles from acetophenones and acetonitrile in the presence of CF3SO3H with excellent yields and purity (13T2961). A procedure for the synthesis of oxa(thia)zol-3-yl methyl alcohols 135 started from 3-oxetanone 133 and (thio)amides 134.The reaction proceeds under microwave irradiation and acid catalysis (13CEJ9655). 

Oxazoles (283) heated with phosphorus pentasulfide can be converted to thiazoles. In this manner, Keyer and Brooker obtained 2-methyl-5-phenylthiazoles (10), Ri = Me, R2 = H, R3 = Ph in 85% yield (Scheme 152) (389). 

Oxazoles are easily cleaved. 2,5-Dialkyl-l,3,4-oxadiazoles (159) in aqueous solution with acid or base give hydrazides (if suitable substituents are present, further reaction can occur see Section 4.02.3.5.1). 3-Methyl-l,2,4-oxadiazole (160) is easily hydrolyzed to acetamidoxime (61CKL)292). 

In general, methyl groups in the 4- and 5-positions of imidazole, oxazole and thiazole do not undergo such deprotonation-mediated reactions, even when the ring is cationic. 

Methyl groups on C-linked phenyl attached to oxazoles, isoxazoles and oxadiazoles react with benzylidineaniline to give stilbene derivatives (Scheme 51) <78AHC(23)l7l). 

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