Oxazoles, 2-alkyl-4,5«dihydro

Similar alkylations may be effected on oxygen. l-(2-Chloroethyl)imidazolidin-2-one (312) when treated with potassium hydroxide or sodium hydride underwent ring closure to the tetrahydroimidazo[2,l-6]oxazole (313) (57JA5276). This approach can be used for the preparation of bicyclic hydantoins and the corresponding dihydro derivatives of (313) using the mesylate of (312) and NaH (77JHC5U, 79JMC1030). 

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). 

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>. 

Conjugate addition to (35 ,7a/ )-3,7a-dihydro-3-phenyl-l//,5f/-pyrrolof1,2-r ]oxazol-5-onc (8) yields the saturated -substituted bicyclic lactams 9 with complete diastereoselectivity13. Treatment of the latter with 2.2 equivalents of lithium diisopropylamide in tetrahydrofuran at — 78 °C, followed by alkylation with a haloalkane, furnishes the a,/i-dialkylatcd products 10 with excellent selectivity (d.r. >98.5 1.5, determined by H and 13CNMR)13. In this case the major diastereomer has the cw-relationship between the newly introduced substituent (R2) in the pyrrolidine ring and the fused oxazolidinc ring rcsiduc13. 

Each desired enantiomer of 3-substituted dihydro-2(3.//)-furanones and 3-substituted tetrahydro-2//-pyran-2-ones was prepared starting either from 4,5-dihydro-2-(m-trimethylsilyloxy)oxazoles and alkylating with the corresponding alkyl halide, or by reversing the order of alkyl group introduction. Upon hydrolysis with dilute hydrochloric or sulfuric acid, 2-substituted cyclic lactones were obtained in 40-75% overall yield and 60-86% enantiomeric excess20. 

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 ... 

Die aus Hydroximino-malonsaure-amid-nitriloxid (in situ durch Thermolyse eines Furoxans in Xylol/DMF hergeslelll)164 mil Olefinen zuganglichen 3-(Aminocarbonyl-hydrOximino-mc-thyl)-4,5-dihydro-l,2-oxazole lagern sich bei den Reaktionstemperaturen zu 4-Aminocarbo-nyl-3-(2-hydroxy-alkyl)-furazanen urn164, lft5 ... 

Intramolekularer Ersatz einer Methoxy-Gruppe durch eine Amino-Gruppe erfolgt bei der Einwirkung von Lithium-diisopropylamid auf 2-[3-(co-Amino-alkyl)-2-methoxy-phe-nyl]-4,4-dimethyl-4,5-dihydro-l,3-oxazol in Tetrahydrofuran. Auf diese Weise lassen sich erhalten4 ... 

Treatment of aromatic carboxaldehyde (diaminomethylene)hydrazones (105) with hot acetic anhydride or benzoyl chloride affords l,4-diacyl-3-acylamino-5-ary 1-4,5-dihydro- 1H-1,2,4-traizoles (106) in 75-95% yields. In contrast, when the 4-pyridine analog of 105 was employed, the unusual hemianimal triazole derivative (107) was obtained. The structures of the novel compounds were determined by spectral methods and in several cases by x-ray structural analysis. Mechanistic considerations are discussed [95M733]. The oxazole-1,2,4-triazole (108) was prepared by cyclization of the corresponding oxazolecarbonyl-thiosemicarbazide with bicarbonate, alkylation at the sulfur and oxidation to the sulfoxide with MCPBA [95JHC1235]. 

The primary adducts (156) and (157) of oxazoles with alkenes and alkynes, respectively, are usually too unstable to be isolated. An exception is compound (158), obtained from 5-ethoxy-4-methyloxazole and 4,7-dihydro-l,3-dioxepin, which has been separated into its endo and exo components. If the dienophile is unsymmetrical the cycloaddition can take place in two senses. This is usually the case in the reactions of oxazoles with monosubstituted alkynes with alkenes on the other hand, regioselectivity is observed. Attempts to rationalize the orientation of the major adducts by the use of various MO indices, such as 7r-electron densities or localization energies and by Frontier MO theory (80KGS1255) have not been uniformly successful. A general rule for the reactions of alkyl- and alkoxy-substituted oxazoles is that in the adducts the more electronegative substituent R4 of the dienophile occupies the position shown in formula (156). The primary adducts undergo a spontaneous decomposition, whose outcome depends on the nature of the groups R and on whether alkenes or alkynes have been employed. 

Oxo-3-alkyl-4-alkyliden-4,5-dihydro-l,2-oxazole als cyclische O-Acyl-oxime wer-... 

In 2-Stellung substituierte 4,5-Dihydro-l,3-oxazole unterscheiden sich als maskierte Carbonsauren in ihrer Reaktivitat stark von den freien Carbonsauren. So kondensieren die 2-Alkyl-Derivate unter Jod- oder Saurekatalyse glatt mit aromatischen Aldehyden zu den 2-(l-Alkyl-2-aryl-vinyl)-Derivaten II, die nach hydrolytischer Spaltung in sehr guten Aus-beuten 3-Aryl-propensauren liefern427 ... 

Gemische a,/ - und / ,y-ungesattigter Carbonsauren erhalt man bei der Umsetzung lithiierter 2-Alkyl-4,5-dihydro-l, 3-oxazole mit Carbonyl-Verbindungen (vgl. Tab. 

Die asymmetrische Synthese von 3-Alkyl-alkansauren gelingt durch Umsetzung des chira-len 4-Methoxymethyl-2-methyl-5-phenyl-4,5-dihydro-l,3-oxazols mit racemischen sek, Alkylhalogeniden, da ein Enantiomer bevorzugt reagiert62 ... 

Bei wasserunloslichen Oxiranen wird bei 0° bis pH 2 angesauert und mit Pentan/Ether (1 1) iiberschiissiges Oxiran extrahiert. AnschlieBend wird die waBr. Phase mit Natronlauge neutralisiert und mit Ether extra-hiert. Die nach dem Abziehen des Ethers erhaltenen 4,4-Dimethyl-2-(3-hydroxy-alkyl)-4,5-dihydro-l,3-oxazole werden mit 50 ml 3 N Salzsaure 15-20 Min. in der Hitze hydrolysiert, mit Ether extrahiert, getrocknet und eingeengt. Zur weiteren Reinigung werden die Lactone destilliert. 

Peanut flavor. The aroma of roasted peanuts is mainly due to thermally formed flavor compounds. Major constituents include pyrazines, e.g., methyl-, 2,5-dimethyl-, trimethyl-, and 2-ethyl-3,5(6)-dimethyl-pyrazine, as well as pyrroles, thiophenes, oxazoles, and thiazoles, e.g., 2-isopropyl-4,5-dimethylthiazole (CgHijNS, Mr 155.26), also contributing to the typical P. f. Also important are alkyl-substituted dihydro-4//-... 

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