Oxazole, structure

Proline has been often used in reactions with aldehydes to form 1-oxo perhydropyrrolo[l,2-f]oxazole structures <1998J(P1)3777, 2004PNA5839>. These compounds were used for the asymmetric synthesis of proline derivatives which are present in natural products or analogs (Scheme 49) <2005T10018, 2005TA2075, 2006JOC97>. 

The fully saturated oxazolidine (31), its three monooxo derivatives, 2-oxazolidinone (32), 4-oxazolidinone (33) and 5-oxazolidinone (34), and the three oxazolidinediones (35)-(37) complete the list of oxazole structures. Oxazolidinetriones (38) have not been reported. 

The principal systems described with a pyrrolo[l,2-c]oxazole structure are the perhydro-l-oxo, -3-0X0, and dioxo derivatives. Reactivity of these types of compound is based on the carbonyl chemistry. 

Proline and some derivatives have been condensed with several aldehydes to give in each case a single stereoisomer with the l-oxoperhydropyrrolo[l,2-c]oxazole structure (240). These compounds have been used for asymmetric synthesis <83JA5390,85HCA155, 85T603). 

When considering the retrosynthesis (see 5.10), it must be borne in mind that the oxazole structure combines the functionalities of an imido ester (C-2) and of an enediol ether (C-4 and C-5). Retrosynthetic considerations can then move in two directions (FII) by analogy to furan-thiophene-pyrrole. 

Munchone is another mesoionic compound formed by a reaction similar to that for sydnone (R. Huisgen, University of Munich, hence its name ). Here, a C=0 unit takes the place of N=0 on nitrogen of a glycine derivative (Scheme 7.29). The ring formed has the dipolar 1,3-oxazole structure (7.27). 

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. 

A multiply bonded nitrogen atom deactivates carbon atoms a or y to it toward electrophilic attack thus initial substitution in 1,2- and 1,3-dihetero compounds should be as shown in structures (110) and (111). Pyrazoles (110 Z = NH), isoxazoles (110 Z = 0), isothiazoles (110 Z = S), imidazoles (111 Z = NH, tautomerism can make the 4- and 5-positions equivalent) and thiazoles (111 Z = S) do indeed undergo electrophilic substitution as expected. Little is known of the electrophilic substitution reactions of oxazoles (111 Z = O) and compounds containing three or more heteroatoms in one ring. Deactivation of the 4-position in 1,3-dihetero compounds (111) is less effective because of considerable double bond fixation (cf. Sections 4.01.3.2.1 and 4.02.3.1.7), and if the 5-position of imidazoles or thiazoles is blocked, substitution can occur in the 4-position (112). 

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

Thieno[3,4-d]oxazole-3a(4H)-carboxylic acid, dihydro-2-methyl-synthesis, 6, 1020 Thieno[2,3-d Joxazoles synthesis, 6, 990 Thieno[3,2-g]pteridine structure, 3, 284 lH-Thieno[3,4-c]pyran-2-ones synthesis, 4, 1032 Thienopyrazines synthesis, 4, 1022-1024 Thieno[2,3-6]pyrazines, 4, 1023 electrophilic substitution, 4, 1024 Thieno[3,4-6]pyrazines, 4, 1024 Thieno[3,4-c]pyrazole, 4,6-dihydro-3-hydroxy-carbamates... 

It has been shown recently that 4-arylidene-2-phenyl-5-oxazol-ones react with diazoalkanes at the exocyclic double bond to give compounds of type 52a. The proton magnetic resonance spectra of these compounds support the cyclopropyl structure. 

Chelated oxo structures were assigned to 5-hydroxy-4-acyl-l,3-oxazoles on the basis of their NMR spectra, the preference being given to the con-former 249a with a six-membered chelate ring (Scheme 86) (75BSB845). 

The structure of the two oxazoles 30 and 32 was proved by mass spectrometry (69JOC999). 

The similarity of the ultraviolet spectrum of 4,5-diphenyloxazol-2-one (91) with those of both alternative methyl derivatives preclude application of the spectral comparison method to the elucidation of their structures, but the fluorescence spectra of these compounds indicate that 91 exists in the oxo form. ° Infrared data for a number of substituted oxazol-2-ones support this conclusion. ... 

A comparison of MP2/6-31G structural parameters of 1,2-oxazole 19 (isox-azole) and 1,3-oxazole 20 with microwave data is provided by Kassimi et al. (Scheme 16) [96JPC8752]. The general agreement is excellent. The same authors investigated dipole moments, quadrupole moments, octopole moments, and dipole polarizabilities of 19 and 20 together with several oxadiazoles and oxatriazoles [96JPC8752, 99JPC(A) 10009]. For the mean polarizability of these species, they found the approximative formula... 

DPT calculations confirmed the experimental findings that 2-ZnCl-l,3-oxazole 21 prefers a closed-ring structure while the corresponding 2-Li-l,3-oxazole 22 is not stable and prefers an acyclic structure (Scheme 17) [98CEJ814]. NBO analyses showed that the orbital of the C—M (M = Li, Zn) bond is -hybridized in the Zn... 

Hayashi et al. [18] have synthesized two diastereoisomers of 2,2 -bis[4-(alkyl)oxazol-2-yI]-l,T-binaphthyl,bis(oxazoline) derivatives possessing both binaphthyl axial chirality and carbon centered chirality (structures 9 and 10, Scheme 5). 

The mass spectra of azolides are not very specific, since they depend to a large extent on the structures of the respective acyl groups. Flash vacuum pyrolyses of azolides has been studied for 1-acyl-1,2,4-triazoles and benzotriazolides by tandem mass spectrometry (MS/MS). 461 Rearrangements of triazolides resulted in the formation of oxazoles. 471... 

---