Lossen

Of the classical Hofmann, Curtius, Lossen and Schmidt degradations, only a rare example of the first is known, hypobromite converting 4,7-diamino-2-phenyl-6-pteridinecar-boxamide (208) into 8-amino-2,3-dihydro-6-phenyl-l//-imidazo[4,5-g]pteridin-2-one (209 equation 64) (63JOC1203). 

Z-Ecgonine, CgHigOgN. HjO. This substance was first obtained I Lossen as the final basic hydrolytic product of the action of acids c cocaine, and is obtainable in like manner from several of the alkaloii occurring with cocaine (see above). It crystallises from dry alcohol i monoclinic prisms, m.p. 198° (dec.), 205° (dry), [a]n — 45-4°, is soluble i water, sparingly so in alcohol, insoluble in most organic liquid Eegonine forms Salts with bases and acids the hydrochloride crystallis... 

Hygrinc, Cj Hj ONj. This, the second fraction of Lossen s hygrine, decomposes when distilled imder atmospheric pressure, but boils at... 

In the Lossen reaction a hydroxamic acid derivative (usually an 0-acyl derivative) is deprotonated by base, and rearranges via migration of the group R to give an isocyanate 2. Under the usual reaction conditions—i.e. aqueous alkaline solution—the isocyanate reacts further to yield the amine 3. The Lossen reaction is closely related to the Hofmann rearrangement and the Curtins reaction. 

The Lossen reaction is of limited importance in synthetic organic chemistry one reason for that is the poor availability of the required hydroxamic acid derivatives. Some hydroxamic acids are even unreactive." ... 

Lossen Statius (Ref 4, p 104) by treating 5-phenyltetrazole with nitric acid (d 1.5g/cc). 

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 ... 

Rearrangement of hydroxamic acids and acyl halides (Lossen)... 

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). 

As early as 1899, 8tieglitz proposed a tetrahedral intermediate for the hydrolysis of an imino ether to an amide. Thns it was clear qnite early that a complicated overall transformation, imino ether to amide, would make more sense as the result of a series of simple steps. The detailed mechanism proposed, althongh reasonable in terms of what was known and believed at the time, wonld no longer be accepted, but the idea of tetrahedral intermediates was clearly in the air. 8tieglitz stated of the aminolysis of an ester that it is now commonly snpposed that the reaction takes place with the formation of an intermediate prodnct as follows referring to work of Lossen. (Note that the favored tautomer of a hydroxamic acid was as yet unknown.)... 

Treatment of the sulphonate esters of N-phosphinyl-hydroxylamines with a strong base such as methoxide often results in a Lossen-like rearrangement. Thus with methoxide in methanol,... 

Attempts to initiate formation of a nitrene, and its rearrangement to the iminooxo-phosphorane 80, by subjecting l-chloroamino-2,2,3,4,4-pentamethylphosphetane 1-oxide to a-elimination with sodium methoxide proved unsuccessful48). In contrast, however, the phosphorylhydroxylamides 88 rearrange in the presence of tert-butyl-amine to the heterocumulene 89 and then add base to give the phosphonic diamides 90 (>90%)49). The reaction is reminiscent of the well-known Lossen degradation. 

---