Oxazoles,mesoionic

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Part A is devoted specifically to the synthesis, reactions, and spectroscopic properties of oxazoles and encompasses four chapters Chapter 1—Synthesis and Reactions of Oxazoles Chapter 2—Spectroscopic Properties of Oxazoles Chapter 3—Oxazole Diels-Alder Reactions and Chapter 4— Mesoionic Oxazoles. 

Mesoionic oxazolium-5-oxides 49 react with aminomalonic ester to give pyrrolidinones 50 as the major or exclusive products <99H(50)71> and the oxazolamine 51 is converted by sodium acetate in acetic acid into the hydantoin 52 <99JHC283>. The intramolecular Diels-Alder cycloaddition of the oxazole 53 and related compounds has been used as a route to substituted isoquinolines <99JOC3595>. ... 

Beide Formen sind iiber die 5-Hydroxy-oxazole (2) und die Anionen (3) miteinander verbunden. Als weitere tautomere Form ist daneben noch das Mesoion (4a) zu beriicksichtigen. 

The standard method of preparing anhydro-5-hydroxyoxazolium hydroxides (300) is by dehydration of iV-substituted a-acylamino acids, usually with acetic anhydride (equation 154) dicyclohexylcarbodiimide and trifluoroacetic anhydride have also been used. N-Acylglycines (299 R3=H) give rise to unstable mesoionic oxazoles which tend to dimerize (see Section 4.18.3.1.5(0) if such acids are treated with trifluoroacetic anhydride, stable trifluoroacetyl derivatives (300 R3 = CF3CO) are isolated. Numerous unstable betaines (300 R1, R = alkyl or aryl, R -H) have been generated by the action of triethylamine on the corresponding hydroperchlorates, prepared by the method shown in equation (151). 

The oxazole ring possesses less aromatic stabilization than a thiazole ring and is readily opened in many of its fused derivatives, especially in oxazolium salts. In the pyridazinium derivative (191) the oxazole ring is opened by oxygen, sulfur or carbon nucleophilic attack at the C-8a ring junction (77YZ422). In the mesoionic pyridine (192) an amine attacks at C-2, which is a pseudocarbonyl carbon atom (70JCS(C)1485). 

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

The mesoionic oxazol-5-one 245 is in equilibrium with an acylaminoketene 246, which undergoes a [2+2] cycloaddition reaction with diisopropylcarbodiimide to give the cycloadduct 247, mp 159-160 °C in 63 % yield. ... 

Oxazoles 1, benzoxazoles 2, oxazolium salts 3, and oxazole A -oxides 4 are fully conjugated compounds (Figure 1). In addition, the two mesoionic structures l,3-oxazolium-5-olates 5 and (l,3-oxazolium-4-olates) 6, commonly known as miinchnones and isomiinchnones, respectively, are also considered to be conjugated rings. There are five systems of hydroxyl-substituted oxazoles and they exist in their oxo forms the 2(3H)-, 2(5H)-, 4(5//)-, 5(2//)-, 5(4//)-oxazolones 7-11. Three forms of dihydrooxazoles are known 2,3-, 2,5-, and 4,5-dihydrooxazoles respectively 12-14. The fully saturated ring is called oxazoline 15. The monooxo derivatives are 2-oxazolidinone 16,4-oxazolidinone 17, and 5-oxazolidinone 18. The three variants of oxazolidinediones are 19-21 and the fully oxidized oxazolidi-netrione is 22. 

There are two common forms of mesoionic compound that belong to the oxazole ring system mlinchnones (1,3-oxazolium-5-olates) 86, named by Huisgen for the city Miinchen, and isomilnchnones (l,3-oxazolium-4-olates) 87 (Figure 4). These are highly versatile compounds which are often used as 1,3-dipoles in cycloaddition chemistry <2002HC(59)681>. 

References to reviews dating prior to 1982 may be found in the first edition of Comprehensive Heterocyclic Chemistry <84CHEC-I(6)177>. Since then, several comprehensive compilations of oxazole chemistry have been published, including the 45th volume in the series The Chemistry of Heterocyclic Compounds, edited by I. J. Turchi . There are chapters on monocyclic oxazoles, oxazolones, mesoionic oxazoles, the use of oxazoles and dihydrooxazoles in organic synthesis, as well as one covering the spectroscopy of oxazoles. A less extensive summary by... 

As in CHEC-I <84CHEC-I(6)177>, the naming and numbering of oxazole and its derivatives follow the convention of Chemical Abstracts. The fully conjugated compounds are called oxazoles (1), benzoxazoles (2), oxazolium salts (3), and oxazole A -oxides (4). Hydroxy-substituted oxazoles exist in the oxo form, and there are five representatives the 2QH)-, 2(SH)-, 4(5//)-, 5(2//)-, and 5(4//)-oxazolones, (5)-(9) respectively. There are two mesoionic structures, the anhydro-4-hydroxy-oxazolium hydroxides (10) and the 5-hydroxy analogues (11), the latter of which are also referred to as the munchnones. Compound (12) is named 4,5-dihydrooxazole instead of A -oxazoline or 2-oxazoline, which is commonly used in the general literature. The other dihydrooxazoles include the less common 2,3- and 2,5-dihydrooxazoles, (13) and (14), respectively. The fully saturated compound... 

Oxazole derivatives have been thoroughly studied and display a wealth of synthetic opportunities. The mesoionic miinchnones undergo 1,3-dipolar cycloadditions across the C(2)—C(4) positions. The 5(4H)-oxazolones have excited interest for a long time because they undergo fission of the C(5)—O bond to afford a-amino acids. Appropriately substituted dihydrooxazoles and oxazolidines are effective carriers of asymmetry, and they have only begun to be exploited in this role although numerous possibilities have been demonstrated. 

Y-Acylprolines, in a reaction with trifluoroacetic anhydride and catalytic base, rearrange to oxazoles via mesoionic oxazolium-5-olates (168) <93TL859>. The yields are good for N-benzoyl, N-cinnamoyl, and 7V-pivaloylprolines, but no oxazole is formed with N-acyl groups bearing a hydrogens on an sp carbon. A possible mechanism is shown in Scheme 78. 

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