Rearrangement, Lossen

Benzenesulfonyloxy-1 //-pyrrolo[3,4-/>]quinoxaline-1,3(2F/)-dione (591) gave //-phenyl-3-(A( -phenylureido)-2-quinoxalinecarboxamide (592) (PI1NH2, PhH, 20°C, 6 h 82% the mechanism probably involved Lossen rearrangement at an intermediate stage but remains unprove) A(-p-tolyl-3-(A( -p-tolyl-ureido)-2-quinoxalinecarboxamide (87%) was made similarly using p-toluidine. ... 

The 0-acyl derivatives of hydroxamic acids give isocyanates when treated with bases or sometimes even just on heating, in a reaction known as the Lossen rearrangement. The mechanism is similar to that of 18-13 and 18-14 ... 

Figure 11. Isokinetic relationship for the Lossen rearrangement of dihydroxamic acids (208), in the log kj versus log k, plot, real (full line) and apparent (broken line) relations.

The amidase from Rhodococcus erythopolis strain MP50 was nsed to selectively convert racemic 2-phenylpropionamide into 5 -2-phenylpropiohydroxamate. This was converted into the isocyanate by Lossen rearrangement and then by hydrolysis to S-( )-phenylethyl-amine (Hirrlinger and Stolz 1997). 

The Lossen rearrangement of an hydroxamic acid under basic conditions is a variant of the Hofmann reaction in which the aroyloxy group fills the role of the bromine.314... 

The neutral alkali metal salts of benzohydroxamic acids have been found to undergo an unprecedented rearrangement to A(,A( -diarylureas. 2 side reaction, producing /9-alanine derivatives by way of a Lossen rearrangement, has been observed to accompany the hydrolysis of alkyl succinimidyl carbonates in basic aqueous buffers (see Scheme 97). The development of a modified Lossen rearrangement, whereby... 

Originally, the Lossen rearrangement specifically referred to the conversion of a hydroxamic acid to an amine with the loss of carbon dioxide ... 

R-C(=0)-NH0H RNCO RNHCOOH RNH2 + CO2. A thio-Lossen rearrangement has been proposed to occur spontaneously for the product generated by the action of myrosinase on sinigrin. ... 

SOLVENT-SEPARATED ION PAIR SOLVENT-SHARED ION PAIR TIGHT ION PAIR LOSSEN REARRANGEMENT LOW-BARRIER HYDROGEN BONDS (Potential Role in Catalysis)... 

Lossen rearrangement has been used in the synthesis of compounds with pharmacological interest as an alternative to the explosive Curtins rearrangement as in the synthesis of ONO-6818 ° (554) (equation 247). 

Determination of pectic structures by specific degradation of pectins, via a carbodiimide 556 mediated Lossen rearrangement on alkaline hydrolysis of galacturonic acid residues 555, was reported (equation 248). 

To improve the product yields in Lossen rearrangement, mesyloxycarbamates have been used as alternative reagents . The use of A-acyl-O-mesylhydroxamic acids (558) avoids the competing formation of self-condensation by-products (560). These are obtained from the accumulation of isocyanate (559) before complete consumption of the hydroxamic acid (557) as observed in the classical Lossen rearrangement (equation 249). 

The migration of the 0-r-butoxy group with concomitant generation of the 0-t-butoxy isocyanate 562 was observed in the Lossen rearrangement of 561 induced by base deprotonation " (equation 250). 

Chandrasekhar and colleagues used Af-acyl-Af, 0-bis(ethoxycarbonyl)hydroxylamines in a similar procedure to prepare amines. Aromatic Af-hydroxyimide derivatives were used by Marzoni and Varney " and Giitschow " to synthesize benz[crf]indol-2(l//)-one and 1-benzoxazin-4-one derivatives, respectively, via Lossen rearrangements. Both Af-benzyloxy and A-mesyloxy derivatives were used. 

The hydroxamate anion 566 is invoked as intermediate in the formation of urea 568 from the iV-tosylated /3-lactam 564 by a Lossen rearrangement in the presence of a secondary amine 565 (equation 252). Apparently, attack of amine in an S/v2 fashion at the C(4) carbon of the /3-lactam 564 opened the ring to form hydroxamate anion 566, which then initiated a facile Lossen rearrangement to isocyanate 567 trapped with another molecule of base to give 568. 

To improve the scope of the Lossen rearrangement, other structural analogous substrates to hydroxamic acids have been tested. Af-Phosphinoylhydroxylamines are the phosphorus analogues of hydroxamic acids and, when suitably activated, they undergo a Lossen-Uke rearrangement in the presence of base. 

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