Heterocyclics oxazoles

In NRPs and hybrid NRP-PK natural products, the heterocycles oxazole and thiazole are derived from serine and cysteine amino acids respectively. For their creation, a cyclization (or Cy) domain is responsible for nucleophilic attack of the side-chain heteroatom within a dipeptide upon the amide carbonyl joining the amino acids [61]. Once the cyclic moiety is formed, the ring may be further oxidized, to form the oxazoline/thiazoline, or reduced, to form oxazolidine/thiazolidine (Figure 13.20). For substituted oxazoles and thiazoles, such as those... 

Oxazoles are well-investigated compounds. The occurrence, uses, and synthesis of oxazole derivatives have been the subjects of extensive reviews.5 The heterocyclic oxazole unit is seen with various substitution-patterns in a large number of naturally occurring compounds. Furthermore, oxazoles serve as synthetic intermediates leading to many other systems.5 6 7 In this context, oxazoles have seen, for example, numerous applications as "2-azadiene" components in 4+2 cycloadditions with several types of dienophiles. Further transformations of the products then lead to a number of other nitrogen- or oxygen-containing heterocyclic products.6... 

Synthesis of heterocycles. Oxazoles can be prepared in high yield by the reaction of TosMIC with carbonyl compounds.2 Thus 5-phenyloxazole (2) can be obtained in 91 % yield by the reaction of benzaldehyde with TosMIC and K2C03 in refluxing methanol... 

Derivatives of ketones—including oximes, imines, and hydrazones— have served as precursors to oxazoles, although many examples of such conversions are described for steroidal and other fused ring systems. A few examples of steroidal and fused heterocyclic oxazoles and monocyclic analogs are described in this section. 

Brunner and co-workers and Bami and co-workers described examples of fused or heterocyclic oxazoles prepared using PPA (Scheme 1.127). Heating picolinic acid and 3-amino-2-naphthol in PPA afforded 2-(2-pyridyl)naphtho[2,3-d] oxazole 466 directly. Similarly, 2-(nitrophenyl)oxazolo[5,4-fe]pyridines 468, precursors to heterocyclic azo dyes, were prepared from 467. These authors... 

Mercaptoselenazoies with Q to C,o cyclic hydrocarbon substituents in the 4-position have been mentioned as giving negative images from photosolubie emulsions (38. 39). Equally cited are other heterocycles such as thiazole. oxazole, or imidazole. 

Comparative studies have been undertaken between different heterocyclic series, especially the azoles, thiazoles. oxazoles. imidazoles, and selenazoles. In a large number of these studies, the heterocycles are condensed w ith aromatic nuclei. 

Selenium heterocycles receive far less mention in the literature than do such homologs as oxazole, thiazole, or imidazole. In fact, preparative methods of selenium heterocycles are much more limited than for the other series, mainly because of manipulatory difficulties arising from the toxicity of selenium (hydrogen selenide is even more toxic) that can produce severe damage to the skin, lungs, kidneys, and eyes. Another source of difficulty is the reactivity of the heterocycle itself, which can easily undergo fission, depending on the reaction medium and the nature of the substituents. 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

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. 

In general, the solubility of heterocyclic compounds in water (Table 33) is enhanced by the possibility of hydrogen bonding. Pyridine-like nitrogen atoms facilitate this (compare benzene and pyridine). In the same way, oxazole is miscible with water, and isoxazole is very soluble, more so than furan. 

Isoxazotes are readily reduced, usually with concomitant ring fission (e.g. 262 — 263). They behave as masked 1,3-diketones 79AHC(25)147). 1,2-Benzisoxazoles are easily reduced to various products (Scheme 28) (67AHC(8)277). Chemical or catalytic reduction of oxazoles invariably cleaves the heterocyclic ring (Scheme 29) <74AHQ 17)99). For similar reactions of thiazoles, see Section 4.02.1.5.1. 

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... 

Ring transformations heterocyclic compounds reviews, 1, 70 Ring-chain tautomerism polyheteroatom six-membered rings, 3, 1056 Ripariochromene A synthesis, 3, 751, 755 Robinson-Gabriel synthesis oxazoles, 6, 216... 

Acyloins are useful starting materials for the preparation of a wide variety of heterocycles (e.g., oxazoles and imidazoles ) and carbocyclic compounds (e.g., phenols ). Acyloins lead to 1,2-diols by reduction, and to 1,2-diketones by mild oxidation. 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

Dewar and Turchi carried out similar rearrangements of secondary and tertiary alkyl and aryl oxazole-4-carboxamides (5a-e) to the corresponding secondary and tertiary 5-aminooxazoles (6a-e). For example, they realized yields > 90% when the amide nitrogen is part of a heterocyclic ring system. 

Selenazole is the selenium-containing compound in the series of heterocyclic 5-membered ring azoles with two different hetero atoms, of which the first two members are oxazole and thiazole. The numbering of the ring system is according to the scheme given (1). 

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

In this section coverage follows the general order of Part I [93AHC (57)271] in that heterocycles fused to furan will precede those fused to thiophene and pyrrole fused oxazoles will precede fused thiazoles, etc. 

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. 

Selenazole is a 5-membered heterocycle of the azole series, containing two heteroatoms. Other members of this group include thiazole and oxazole, whose chemistry is more developed because of their easier access and lower toxicity. The numbering of the heterocyclic system is as follows ... 

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