Oxazole derivatives, synthesis

A.B. Reddy, R.V. Hymavathi, G.N. Swamy, A new class of multi-substituted oxazole derivatives synthesis and antimicrobial activity, J. Chem. Sci. 125 (2013) 495-509. 

Bossio R, Marcaccini S, Pepino R (1991) Synthesis of isocyanides and related compounds. Synthesis of oxazole derivatives via the Passerini reaction. Liebigs Ann Chem 1107-1108... 

Thermal synthesis of 2-substituted phenanthroxazoles and related compounds by cyclization of O-methyl o-quinone oximes with compounds ArCH2Y (Ar = aryl, hetaryl Y = H, OH, Cl, Br, OAc, SH, COR, NH2) or with amines (PhCHiNMej, PhNHMe, PhNMe2) has been described. Cyclization of a-oxooximes in the system alkyl halide or sulfate/DMF/K2C03 also leads to oxazole derivatives . 

The hydrolysis of the Schiff base 63 is an acid-catalyzed reaction initiated by the protons liberated during the anodic oxidation. A successful synthesis could be achieved in an undivided cell. The starting compound 63 was oxidized at the anode, and the liberated protons were reduced at the cathode the solution did not become too acidic. This reaction was applied to the oxidation of 3-arylidenamino-4-hydroxycoumarin, which gave the expected 1,3-oxazole derivatives.78 The mechanism of the conversion 63 -> 64 involves... 

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... 

For a closely related method for the synthesis of a-substituted a-amino acids via rearrangement of allyloxy-substituted oxazoles (derived from At-benzoyl-protected a-amino acids) see p 3448. For the synthesis of substituted 2-aminopent-4-enals by Claisen rearrangement of substituted (l-methyl-3-oxahexa-l,5-dienyl)amines see ref 85. 

The oxazole derivative 237 is a key component for the synthesis of cell permeable phosphatase inhibitors calyculins A and B and it is prepared via coupling of alkylamino oxazole 235 and -/V-protected acid 236.87... 

The catalytic oxidative system H/oxidant has also been applied for the synthesis of the following heterocyclic systems 2-imidazolines 134 by the oxidative coupling of benzaldehydes with ethylenediamines [113], benzimidazoles 135 by a similar oxidative coupling reaction of phenylenediamines with aromatic or aliphatic aldehydes [109] and oxazole derivatives 136 by the oxidative coupling of p-ketoesters with benzylamines (Scheme 4.70) [114]. 

This reaction was first reported by Schollkopf and Schroder in 1971 It is the formation of a 2-unsubstituted oxazole derivative by the condensation of an a-metalated isocyanide with an acylating reagent. Therefore, this reaction is known as the Schollkopf oxazole synthesis or Schollkopf reaction. ... 

Azomethine Ylide Precursor. The azide is readily converted into a precursor of azomethine ylides (eq 3). Reactions of the ylides with carbon-carbon multiple bonds and carbonyl group are used in a synthesis of pyrroline and oxazole derivatives (eq 4). ... 

Oxazoles are also obtained by the reaction of a-halogenoketones (78) with primary amides (the Bliimlein-Lewy synthesis), and this method is particularly appropriate for oxazoles containing one or more aryl groups as in (79). Formamide may also be used in this process, resulting in a free 2-position in the oxazole, and when a urea derivative (80) is used, 2-aminooxazoles (81) are formed (80ZOR2185, 78IJC(B)1030, 78JIC264). Numerous applications of these procedures are described in Chapter 4.18. 

Kondrat eva pyridine synthesis. This methodology to pyridine rings continues to be applied in total synthesis. An approach to the antitumor compound ellipticine 34 ° makes use of a Diels-Alder reaction of acrylonitrile and oxazole 32 to form pyridiyl derivative 33. Addition of methyllithium and hydrolysis transforms 33 into 34. 

Oxazol-4-ones 132 have been prepared by Trost and co-workers via a microwave-assisted cyclocondensation of bromo imides in the presence of NaF [86]. These products where then employed for a Mo-catalyzed asymmetric synthesis of Q -hydroxycarboxylic acid derivatives 134 (Scheme 47). 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

A microwave assisted Comforth rearrangement of oxazole-4-carboxamides 106 efficiently afforded 5-aminooxazole-4-carboxylates 107. This procedure was applied to the formal synthesis of a natural antibiotic derived from pseudomonic acid <06TL4698>. 

Scheme 15 shows the synthesis of an oxazole 63a and thiazole 63b derivative, accomplished by Yokooji et al. [59]. They employed arylation using tertiary phosphines and bromobenzene with CS2CO3 in xylene to form these compounds. 

The synthesis of 3-H-oxazol-2-ones was described by Nam et al. [69]. The substituted benzoin 89 was formed from the coupling of 3,4,5-trimethoxy-benzaldehyde 18 with 3-nitro-4-methoxybenzaldehyde, Scheme 22. Reaction with PMB-isocyanate and subsequent cyclization gave the protected oxazolone derivative 90. The PMB group was removed by reflux in TFA and reduction of the nitro-group was performed using Zn to give the combretoxazolone-aniline 91. 

There has been no report on this kind of compound in the literature for the period concerned. The perhydro derivatives were, on the contrary, well-studied for several years and applied in a variety of routes for the total synthesis of natural products or to produce optically active derivatives, mainly following the Meyers protocol <1984JA1146>. Only two examples of dihydropyrrolo[2,l- ]oxazoles are available and one example of a tetrahydro derivative is described. 

Pyrrolo[ 1,2-c]oxazolc itself was used for further elaboration of more complex molecules. The main members of this family that are used as intermediates in organic synthesis are the 3-oxo and 5-oxo perhydro derivatives. One can find also a number of 1,3-dioxo, 3,5-dioxo, 3,7-dioxo, and 5,7-dioxo perhydropyrrolo[l,2-r ]oxazoles that were prepared and/ or converted into another valuable compounds. 

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>. 

Ring cleavage of the bicyclic dihydro-oxazolo [3,4-c]oxazol-3-one 111 derived from D-serine was realized by action of boron trifluoride-acetic acid complex leading to the oxazolidinone 112, a useful building block for the synthesis of... 

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