Nitrones imidazole

Imidazole nitrones 127 reacted with dimethyl acetylenedicarboxylate to yield imidazo[l,5-fc]isoxazoles 128, which in the presence of base afforded imidazoles 129 <00TL5407>. Chiral imidazoline nitrone 130 participated in a [3+2] cycloaddition reaction with various dienophiles to furnish imidazoisoxazoles 131 <00SL967>. A convenient synthesis of AyvyV -trisubstituted ethylenediamine derivatives from 2-methyl-2-imidazoline has been reported <00SC3307>. Dehydrogenation of 1,3-di- and 1,2,3-trisubstituted imidazolidines afforded l//-4,5-dihydroimidazolium salts <00SC3369>... 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

Bis(oxazolinyl)pyridine-Ce(IV) triflate complex 78 catalyzed the enantioselective 1,3-DC of acyclic nitrones with a, 3-unsaturated 2-acyl imidazoles. For example, C-phenyl 7V-benzyl nitrone reacted with 77 in the presence of 78 to give the adduct 79 with excellent diastereo-and enantioselectivity. Isoxazolidine 79 was then converted into P -hydroxy-P-amino acid derivatives by hydrogenation of the N-0 bond in the presence of Pd(OH)2/C and cleavage of the 2-acyl imidazole with MeOTf in MeCN <06OL3351>. 

Enantio-pure five-membered cyclic nitrones (154) and (155) were formed in a one-pot synthesis from the corresponding lactols (152) and (153) as the result of their reactions with unsubstituted hydroxylamine and by (a) subsequent treatment with MsCl and NaOH (Scheme 2.55) (310a) or by (b) subsequent treatment with TBDMSC1,12, TPP, imidazole, and tetrabutylammonium fluoride (TBAF) (310b). 

A strictly dehned region of chemical shifts of C2, C4, and C5 atoms in A-oxides of 4A-imidazoles allows to dehne clearly the position of the A-oxide oxygen atom (102). Chemical shifts of the a-C nitrone group in a-N-, O-, and S-substituted nitrones are located in the region of 137 to 150 ppm (388, 413). On the basis of 13C NMR analysis of 3-imidazoline-3-oxide derivatives, the position of tautomeric equilibria in amino-, hydroxy-, and mercapto- nitrones has been estimated. It is shown that tautomeric equilibria in OH- and SH-derivatives are shifted toward the oxo and thioxo forms (approximately 95%), while amino derivatives remain as amino nitrones (413). In the compounds with an intracyclic amino group, an aminonitrone (A) - A-hydroxyaminoimino (B) tautomeric equilibrium was observed (Scheme 2.76), depending on both, the nature of the solvent and the character of the substituent in position 2 of the heterocycle (414). 

Unlike the 4H- imidazoles (219), (223), (224) electrochemical oxidation of the nitrone group in 4-R-3-imidazoline-3-oxides (228), (230-232), as in a-PBN and DMPO is of irreversible nature. Therefore, the formation of radical cations... 

Determination of electrochemical oxidation potentials and electrochemical reduction of 13 p-phosphorylated acyclic nitrones shows that phosphorylated compounds have a clear anodic shift of potentials of both, oxidation (Ep 1.40 to 2.00 V versus SCE in CH3CN) and reduction (Ep—0.94 to —2.06 V). This is caused by a strong electron-acceptor influence of the diethoxyphosphoryl group (430). In contrast, a reversible one-electron oxidation of azulene nitrones (233) (Scheme 2.80) occurs 0.6 V below the Ep potential of PBN, that is at the value one observes the oxidation of AH -imidazole-1,3-dioxides (219) (428, 429). In other words, the corresponding RC (234) is 14 kcal more stable than the RC of PBN. Although the EPR spectrum of RC (234) was not recorded, RC (236) from dinitrone (235) turned out to be rather stable and gave an EPR spectrum (170). 

Oxaziridines, 6-oxa-l,4-diazabicyclo[3.1.0]hex-3-enes (245) and their 4-oxides (246), obtained in the photolysis of 4H -imidazole-3-oxides (223) and 1,3-dioxides (219), underwent a quick thermal isomerization to the starting nitrones. Further... 

For the first time, the possibility of carrying out preparative inverted spin trapping was demonstrated by the oxidative methoxylation of heterocyclic nitrones derived from AH -imidazole-1,3-dioxide (219) (Scheme 2.79) (513, 514). 

In addition to the oxidative alkoxylation of 4H -imidazole and oxazolidine derivatives, the reaction was also used with other cyclic aldo-nitrones such as DMPO, derivatives of 3-imidazoline-3-oxide (228-232) (506), and derivatives... 

Oxidative Animation of Nitrones to a-Amino-Substituted Nitroxyl Radicals Similar to the oxidative methoxylation reaction, oxidative animation of 4H -imidazole TV-oxides, in amine saturated alcohol solutions, give stable nitroxyl (282), nitronyl nitroxyl (283), imino nitroxyl (284) and (285) radicals with the amino group at the a-carbon atom of the nitroxyl group (Scheme 2.107) (520, 521). The observed influence of substituents on the ratio of animation products at C2 and C5 atom is close to the ratio observed in the previously mentioned oxidative methoxylation reaction. It allows us to draw conclusions about the preference of the radical cation reaction route. 

Oxidative Fluorination of Nitrones to a-Fluorosubstituted Nitroxyl Radicals Formation of nitroxyl radicals by the radical cation route was observed in reactions of various nitrones with xenon difluoride in dry methylene chloride (520, 523). In this reaction, more than 40 nitrones, including 4H -imidazole N,N -dioxides (219), 4H -imidazole TV-oxides (223) and (224), 2H -imidazole N -oxides (225), 2H -imidazole TV,TV-dioxides (226), 3,3,5,5-tetramethylpyrroline N -oxide (TMPO), derivatives of 3-imidazoline-3-oxides (231) and (232), have been examined. ESR spectra of nitroxyl radicals containing one or two fluorine atoms at a-C have been registered (Scheme 2.108) (523). In the case of... 

A diastereoselective dipolar cycloaddition of chiral nitrone 80 with alkene dipolarophiles afforded imidazo[ 1,2-3]-isoaxazole (Scheme 9). The conversion via N-O reduction of this ring system with Raney-Ni in methanol gave the corresponding pyrrolo[l,2-A imidazole in 66% yield. The structure has been confirmed by X-ray diffraction crystal stmcture analysis <2000SL967>. 

The reaction of nitrone 99 with dimethyl acetylenedicarboxylate (DMAD) at room temperature in CH2CI2 gave a colorless crystalline product that has been identified as trimethyl 3,3-dimethyl-l-phenyl-377-pyrrolo[l,2-f]imidazole-5,6,7-tricarboxylate 100. A mechanism explaining this transformation has been reported (Equation 13) <2001RCB882>. 

Heating compounds 190 in acetonitrile, at reflux, gives the cyclic nitrones 187 (R1 = Ph) (unreported yields), but imidazoles 192 are produced when R1 = H (Scheme 6) <2004SPL553>. 

Cycloaddition of nitrones (e.g. 166, equation 107) to alkoxyaUtenes proceeds in high yield with complete diastereoselectivity, giving 1,2-isoxazolidines of type 167. Similar reactions have been reported for vinyl ethers , vinyl acetate , enamines , vinyl imidazoles , enamides, vinyl sulfones and vinyl sulfides . Since the resultant 1,2-oxazolidines of type 167 and its analogs can be hydrolyzed under acidic conditions, this reaction may also be considered as an approach to O-unsubstituted N-alkylhydroxylamines . 

Imidazole synthesis. A new synthesis of 4,5-diarylimidazoles (2) involves reaction of catalytic amounts of aqueous elhanolic K.CN with N-methyl-C-aryl nitrones (1), prepared by condensation of aryl aldehydes with N-methyl-hydroxylamine. The reaction involves an intermediate cyanoimine (n). 

Similar reactions have been carried out with variously substituted pyrroline 1-oxides, imidazole 1-oxides, isoxazoline N-oxides (nitronic esters) and 3,4-diazacyclopentadienone AT-oxides in combination with a large variety of alkenic and alkynic dipolarophiles, aryl isocyanates, aryl isothiocyanates and N- sulfinylamines, leading to pyrrolidinoisoxazoles, pyrrolo[l,2-6][l,2,4]oxadiazoles, pyrrolo[2,l-d][l,2,3,5]oxathiadiazoles, isoxazolo[2,3-b ]isoxazoles and isoxazolo[l, 2-6 ]pyrazoles. 

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