Pyrroles, 45-8 5- oxazole

In 1972, van Leusen, Hoogenboom and Siderius introduced the utility of TosMIC for the synthesis of azoles (pyrroles, oxazoles, imidazoles, thiazoles, etc.) by delivering a C-N-C fragment to polarized double bonds. In addition to the synthesis of 5-phenyloxazole, they also described reaction of TosMIC with /7-nitro- and /7-chloro-benzaldehyde (3) to provide analogous oxazoles 4 in 91% and 57% yield, respectively. Reaction of TosMIC with acid chlorides, anhydrides, or esters leads to oxazoles in which the tosyl group is retained. For example, reaction of acetic anhydride and TosMIC furnish oxazole 5 in 73% yield. ... 

The preparation of 3-vinylpyrroles was investigated utilizing the Horner-Wads worth-Emmons reaction with 3-formyl-lV-tosylpyrrole <06S1494>. The intramolecular acylation of pyrrole-2-Weinreb amides provided access to novel indolizinone derivatives <06T6182>. The amidation of pyrrole-2-carbonyl chloride was utilized as a key step in the preparation of pyrrole-oxazole analogue 90 of the insecticide Pirate <06S1975>. 

A parallel synthesis of novel pyrrole-oxazole analogues of the insecticide Pirate was performed through the dehydration of acylaminoketones with POCl3<06S1975>. 

The kinetics and product distributions of ozonolysis of vinylcyclohexane and methylene cyclohexane have been investigated.162 Steric hindrance of the cyclic substituent largely offsets electronic effects hi determining the rate of reaction. The main products of ozonation of catechols were quinones, while catechol acetals gave rise to compounds with an opened benzene ring.163 The ozonolysis of azoles such as pyrroles, oxazoles, and imidazoles has been reviewed.164... 

These reactions can lead to the formation of numerous heterocyclics associated with meat flavor as described by Vernin and Parkanyi (57), including furans, thiophenes, pyrroles, oxazoles, imidazoles, thiaz-oles, pyrans, pyridines, pyrazines, cyclic sulfides and polysulfides. 

Furan—> thiophene or pyrrole oxazole or various mesoionics —> furan, thiophene, or pyrrole... 

Nearly 1000 compounds have so far been identified in the volatile constituents of meat from beef, chicken, mutton and pork (6). The largest number of volatiles has been determined in beef and these were representative of most classes of organic compounds. Hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids, esters, lactones, ethers, sulfur and halogenated compounds as well as different classes of heterocyclic substances (Figure 1) namely furans, pyrldlnes, pyrazines, pyrroles, oxazol(in)es, thiazol(in)es, thiophenes were present in cooked meat flavor volatiles as shown in Table I. Many of these compounds are unimportant to the flavor of meat and some may have been artifacts (16). 

Only one thiophene has been reported to undergo (2 + 2)-cyclo-addition with carbonyl compounds, viz., 2,5-dimethylthiophene.210 In this reaction, too, only one type of isomer (180) was obtained, in 50-60% yield. N-Benzoyl-l//-pyrrole reacted with two molecules of ketone to give cycloadduct 181.211 Similarly, JV-acyl-1//-indoles reacted with certain ketones to produce adducts 182.212 The lack of reactivity of other heterocycles, such as 1//-pyrroles, oxazoles, and isoxazoles, has been attributed to a quenching effect on the excited ketone of the non-bonded electrons on the heteroatom.212... 

Imidazole, colourless crystals, mp 90°C, bp 256°C, is soluble in water and other protic solvents, but only sparingly soluble in aprotic solvents. Imidazoles have high melting and boiling points when compared to pyrrole, oxazole and thiazole because the imidazole molecule is a donor as well as an acceptor of hydrogen bonds, and only intermolecular hydrogen bridges can be formed. 

Kondensation zwischen der Carboxylgruppe und Hydroxy-, Mer-capto-, Amino- oder reaktionsfahigen Methylengruppen unter Ausbil-dung von Pyrrol-, Oxazol- oder Thiazolringen. 

Ohta and co-workers carried out extensive studies on intermolecular arylation of various heterocycles (furan, thiophene, pyrrole, oxazole, thiazole, A-methylimi-dazole, benz[fe]oxazole, benzo[i>]furan, and benzo[ ]thiophene) with mainly chlo-ropyrazines as heteroaryl halides using Pd(PPh3)4 and AcOK [3]. 

A domino sequence comprising a cycloaddition and subsequent cycloreversion step can often find a more general application in organic synthesis, especially in the formation of aromatic compounds such as furans or pyrroles. Oxazole moieties as electron-deficient dienes often serve as the crucial reactive centers which cycloadd to a triple bond and eliminate a nitrile upon cycloreversion. If the first step is intramolecular, the impelling enthalpy preserved in the stability of the formed CN function is additionally accompanied by a positive entropy when the nitrile, sometimes volatile, leaves the substrate. In an older example from 1984 [10], Jacobi and coworkers devised a scheme for the preparation of a highly substituted furan on their synthetic way to paniculide A. An intramolecular Diels-Alder reaction was followed by the critical extrusion of volatile acetonitrile, furnishing the bicycle 8 in 94% yield (Scheme 6.2). 

More than 100 aroma compounds have been identified in roasted coffee, including such important flavor contributors as furan derivatives, pyrazines, pyrroles, oxazoles, and acids (list AND hOrhammer). ... 

Loughlin, WA, Muderawan, I.W., Mcaeaiy, MA, Volter, K.E., and King, M.D. (1999) Studies towards the synthesis of phorbazoles A-D Formation of the pyrrole oxazole skeleton. Aust. J. Chem., 52, 231-234. Radspieler, A. and Liebscher, J. (2001) Total synthesis of phorbazole C. Tetrahedron, 57, 4867-4871. 

The 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

Modification of reaction schemes leading to furans, thiophenes and pyrroles by incorporation of a heteroatom into the substrate provides ready access to imidazoles, thiazoles, oxazoles, dithioles, oxathioles, etc. Incorporation of two heteroatoms into the substrates... 

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. ... 

Van Leusen and co-workers also demonstrated the utility of dilithio-tosylmethyl isocyanide (dilithio-TosMIC) to extend the scope of the application. Dilithio-TosMIC is readily formed from TosMIC and two equivalents of n-butyllithium (BuLi) in THF at -70"C. Dilithio-TosMIC converts ethyl benzoate to oxazole 14 in 70% yield whereas TosMIC monoanion does not react. In addition, unsaturated, conjugated esters (15) react with dilithio-TosMIC exclusively through the ester carbonyl to provide oxazoles (16). On the other hand, use of the softer TosMIC-monoanion provides pyrroles through reaction of the carbon-carbon double bond in the Michael acceptor. 

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. 

Keywords furans, pyrroles, thiophenes, phospholes, oxazoles, pyrones, pyr-idones, oxazinones, high pressure... 

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