Five-membered oxazole

Intermediate three-membered rings have never been detected in the cycloaddition reaction and a direct route to the five-membered rings is probable in most cases. For example, benzoyl nitrene adds to triple bonds and in contrast to the addition to nonpolar double bonds, a five-membered oxazole is obtained (Sch. 22) [21,38]. An azirine intermediate is not detected, however it cannot be excluded that the three-membered ring containing a 7i-bond rearranges rapidly giving rise to the oxazole. 

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

The distinction between these two classes of reactions is semantic for the five-membered rings Diels-Alder reaction at the F/B positions in (269) (four atom fragment) is equivalent to 1,3-dipolar cycloaddition in (270) across the three-atom fragment, both providing the 47t-electron component of the cycloaddition. Oxazoles and isoxazoles and their polyaza analogues show reduced aromatic character and will undergo many cycloadditions, whereas fully nitrogenous azoles such as pyrazoles and imidazoles do not, except in certain isolated cases. 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

Ring expansion of five- to six-membered rings such as oxazole —> pyridine derivatives via a Diels-Alder reaction is a well-established procedure. However, the conversion of a six-membered heterocycle into a five-membered ring system has not been exploited to any great extent, and those systems that have been studied usually involve a cationic species. 

A Hiickel model used for calculating aromaticity indicated that the isoxazole nucleus is considerably less aromatic than other five-membered heterocycles, including oxazole and furan. SCF calculations predicted that isoxazole is similar to oxazole. Experimental findings are somewhat difficult to correlate with calculations (79AHC(25)147). PRDDO calculations were compared with ab initio values and good agreement for the MO values was reported... 

Oxazole is a five-membered aromatic heterocycle. Would you expect oxazoie to be more basic or less basic than pyrrole Explain. 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

The alkylation of the G-H bonds occurs even in the CH=N moiety of five-membered heteroaromatic compounds such as thiazoles, benzimidazoles, and oxazoles (Equation (25)).26,26a This intermolecular alkylation without chelation assistance is very interesting. 

The carbonylation of imidazole derivatives with several olefins takes place in high yields with the aid of an Ru3(CO)i2 catalyst.112,112a The carbonylation occurs exclusively at the a-position to the sp2 nitrogen (Equation (85)). A wide range of olefins can be utilized in this reaction, and a variety of functional groups are compatible under the reaction conditions. The (/i-H)triruthenium clusters such as 12 are proposed as a key species in this carbonylation reaction. Other five-membered A-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can be used for the carbonylation reactions, where the carbonylation takes place at the a-C-H bond to the sp2 nitrogen. 

Silicon protection is also commonly used to direct lithiation chemistry in five-membered heterocycles. For example, oxazoles , thiazoles and Ai-alkylimidazoles ° ° lithiate preferentially at C-2, where the inductive effect of the heteroatoms is greatest. If C-2 is blocked, lithiation occurs at C-5, where there is no adjacent lone pair to destabilize the organolithium. Functionalization of these heterocycles at C-5 can therefore be achieved by first silylating C-2, reacting at C-5 and then removing the silyl group. The synthesis of 666 illustrates this sort of sequence (Scheme 258) °. ... 

Diketo oxime 43 (Scheme 27) find extensive use in organic synthesis. These compounds are useful building blocks in five-membered heterocyclic chemistry. These oximes can be used for the synthesis of pyrroles , thiazoles , oxazoles and pyrazoles . The diketo oxime 43 was synthesized in high yield by addition of an aqueous solution of sodium nitrite to a 0°C solution of 1-benzoylacetone 42 in AcOH . ... 

It is evident from the structure of the oxazol-5(4//)-one, also sometimes called an azlactone or oxazolinone, why it is so susceptible to epimerization. Removal of the a-proton generates a five-membered ring with six n-electrons, an aromatic system according to the Hiickel 4n + 2 rule (Scheme 5). 

The UNCAs are ideal activated intermediates for the study of intrinsic rates of racemization. Epimerization can occur only via the direct abstraction mechanism, because the five-membered ring structure precludes formation of an oxazol-5(4//)-one. In addition, the UNCA maintains its structural integrity during the epimerization process. A report by Rom off129 describes two simple methods for the measurement of intrinsic rates of racemization under a wide variety of reaction conditions utilizing UNCAs as the prototypical activated intermediates. 

Oxazole and Isoxazole. These are five-membered ring heterocycles containing oxygen and a nitrogen. Two common forms are oxazole (1,3-oxazole) and isoxazole (1,2-oxazole), both of which undergo aromatic hydroxylation. 

Azadiene 132, containing electron-donor and -acceptor substituents, has been shown by Gomper and Heinemann [81 AG(E)296] to be a suitable precursor of several five-membered rings by acid-catalyzed cyclization reactions (Scheme 33). Thus, oxazole 133 (86%), thiazole 134 (85%), and imidazoles 135 (22-38%) were obtained upon reaction of 132 with aqueous HC1, HC1/H2S, and RNH2 HC1, respectively. 

Oxazole, imidazole and thiazole systems contain a five-membered ring and two hetero-atoms, one of which is a nitrogen atom. The hetero-atoms are separated by a carbon atom in the ring. The second hetero-atoms are oxygen, nitrogen and sulphur for oxazole, imidazole and thiazole systems, respectively. 

The heteroaryl Heck reaction is an efficient tool for the introduction of other five membered heteroaromatic systems too (for more details see Chapter 6.4.). Chloropyrazines reacted readily with oxazole to give the coupled product (7.57.), consisting solely of the 5-oxazolyl isomer.77 Extension of the reaction to imidazole led to a similar observation,78 and the expected 5-pyrazyl-imidazole derivative was isolated in acceptable yield. Reactions using thiophene as the masked olefin gave similar results. Under forcing conditions the 2,5-diarylation of fiiran was also observed.77... 

Five-membered Rings Imidazoles, Oxazoles, Thiazoles, Dithiolium Salts and Derivatives 568... 

Other five-membered heterocycles such as thiophenes, thiazoles and oxazoles have been successfully annellated in the anthraquinone series. For example, the yellow dye (12) may be prepared from 2,6-diaminoanthraquinone by condensation with benzotrichloride and sulfur. Similarly, the six-membered heterocycles acridines, quinoneazines, pyrazines, acridones and pyrimidines are frequently incorporated (B-52MI11201). In fact, the best known of the anthraquinone vat dyes are indanthrone (13) and flavanthrone (14). The former anthraquinoneazine, a beautiful blue, which was the first such structure to be manufactured on a large scale, may be prepared by alkali fusion of 2-aminoanthraquinone at 220 °C (27MI11200). Treatment of 2-aminoanthraquinone in nitrobenzene with antimony pentachloride yields the yellow flavanthrone (14), the structure being confirmed by Scholl (07CB1691). Both indanthrone and flavanthrone and their derivatives have attracted considerable commercial attention. 

Frequently, five-membered heterocyclic systems have provided the C(3)N(4)C(5)C(6) fragment in 1,2,4-triazine syntheses. For instance, the oxazol-5-one (586) reacts with hydrazines to give, via open-chain intermediates (587), the l,2,4-triazine-3,6-diones (588)... 

Five-Membered Ring Heterocycles with Two Hetero Atoms Imidazoles, Benzimidazoles, 1H-pyrazoles, Oxazoles, Isoxazoles, Thiazoles, and Indazoles... 

The azoles (oxazole, imidazole, and thiazole) are five-membered aromatic heterocycles that have two heteroatoms in the ring. One of the heteroatoms in each of these heterocycles is an sp2-hybridized nitrogen that contributes one electron to the 6n aromatic system and has a basic nonbonded lone pair. The other heteroatom (oxygen, nitrogen, or sulfur) contributes two electrons to the 6n system. The imidazole skeleton is present in the amino acid histidine. The thiazole ring occurs in thiamin (vitamin B. ... 

The < a/o-peroxides of aromatic oxygen-containing five-membered heterocycles such as furan and oxazole are actually ozonides (1,2,4-trioxolanes), and by a reverse dipolar [3+2] cycloaddition they can be a source of carbonyl oxides. 

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