[CONTRIRUTIOS FROM
THE
DEPARTMENT OF BIOCHEMISTRY, ~JSIVERSITT O F CALIFORSIA, BERKELEY 4, CALIF.]
Periodate Oxidation of Hydroxylamine Derivatives. BY THOMAS EMERY X
~ DJ.
Products, Scope and Applicationl.''
B. NEILANDS +
RECEIVEDMARCH3 , 1960 Periodate was found t o cleave primary and srcondary hydroxamic :tcids very rapidly to yield n carboxylic acid and an oxidized derivative of hydroxylamine. S-substituted ( z . e . , secondary) hydroxamic acids and N-methylhydroxylamine gave on periodate oxidation an intensely ultraviolet-absorbing substance. From S-ii~eth~-lh!.droxylamine,cis-nitrosomethane dimer was isolated in good yield. The effectiveness of IlJ-droxylamine as a carboxyl-blocking reagent was tested by conversion of K-hydroxysuccinamic acid t o methyl S-h?-dros!-~uccinulnateand subsequent periodate oxidation of the latter t o methylhydrogensuccinic acid.
In a communication concerning the structure of may have general applicability for the synthesis of the ferrichrome compounds we reported3a reaction cis-nitrosoalkane dimers. From the latter, the of periodate with hydroxamic acids. It was con- trans isomers are obtained very easily.6 The yield cluded that periodate rapidly and quantitatively is very good, the starting materials are readily cleaves these substances to liberate the acyl group available and the need for special apparatus is as the free acid. In this paper we wish to describe eliminated. The adaptation of the reaction to the structural (a) the oxidation product of the hydroxylamine moiety and (b) the use of hydroxylamine a s a car- study of complex hydroxamic acids of natural oriboxyl-blocking reagent. gin is self evident. After periodate oxidation the Both K-methylacethydroxamic acid and K- acyl part is separated by ether extraction and the inethylhydroxylamine yielded, on periodate oxida- hydroxylamine moiety identified after catalytic tion, material with a very strong absorption band hydrogenation t o the corresponding amine. A a t 264 mp. Since K-methylhydroxylamine is read- search of the literature reveals the existence of sevily available, it was utilized as the starting material eral naturally-occurring iron-binding compounds of for the preparation of the ultraviolet-absorbing microbial origin which are very likely hydroxamic compound. The latter, which was obtained as a acids. The structures of nocardamine7 and mycowhite, crystalline solid, was shown to be cis-nitroso- bactina already have been determined. Lye esmethane dimer (I). tablished that the former reacts with periodate to give the characteristic absorption peak. Since g r i ~ e i n ,terregens ~ factor lo and coprogenl' have ferrichrome-like activity and all bind ferric ion, it appears probable that these, too, are N-substioL I Lo tuted hydroxamic acids. Terregens factor, noCompound I was characterized by ultraviolet ab- cardamine and ferrichrome all show a similar reaction with periodate. The other compounds have sorption properties, positive diphenylamine-sulfuric acid test, reduction to methylamine and by not been tested. The immediate appearance of the conversion to the trans isomer following simple intense ultraviolet absorption band of the nitroso dissolution in chloroform. Dimer I was prepared dimer after periodation is a simple and sensitive for the first time by Gowenlock and Trotman" test for an N-alkyl hydroxylamine or an N-substithrough the pyrolysis of t-butyl nitrite, and it has tuted hydroxamic acid. In order to examine the effectiveness of hydroxylvery recently been reported5 as a minor product in the photolysis of azomethane and nitric oxide. amine as a carboxyl-blocking reagent, succinic anPrevious attempts to prepare nitrosoalkane dimers hydride was converted successively to methplhydroby oxidation of the iV-substituted hydroxylamines gensuccinic acid,12 N-hydroxysuccinamic acid13 have failed, presumably because of a rapid tautom- and methyl N-hydroxysuccinamate. The latter, erism of the nitroso compounds to the oximes. which was obtained as a clear oil, was oxidized with Possibly the oxidation with periodate succeeds periodate in the usual way to give methylhydrogenthrough the formation of an intermediate similar to succinic acid in satisfactory yield. Under the conditions used for the above synthethat which occurs in the oxidation of glycols and which forces the alkyl radicals into the cis configura- sis, diazomethane apparently did not react with tion. The reaction with X-substituted hydroxamic the hydroxyl of the hydroxamic function to any apacids may proceed through a similar mechanism, preciable extent. Xlthough the experiments rehut in this case the product was not isolated and ported here do not exclude the passibility of an N the configuration o f the dinier was not establishctl. niethylation, the latter event would have no i n i p r .llthough no attempt was made to use as starting ( I ? ) n G. Gi,wenlc,ck a n d J T r o t m a n , .I. f'h?vi. S C ~ C1670 ,, (l$J5lil ( 7 ) A . Stoll, J. R e n z and A Brack. IJrl,, ( ' h i i r i A r l o , 3 4 , 8H2 ( I 9 2 1 1 material alkyl hydroxylaniities other than S( 8 ) G. A . Snow, J . C ' h ~ i n ..Coc , 2588 11451\. tnethylhydroxylamine. it appears that the reaction (9) IC. A . Kuehl, hI U . Riqhop, I,. Chaiet xnrl K. I'olkcrs, 'I'HI? ( I1 Abstracted from t h e ductoral dissertation of T h r m a i ICmeiy, University of California, Berkeley, 19ii0. ( 2 ) This research was sustained h y a grant f r o m the O t i c r , of S a v a l Research ( 3 ) T Emery and J . B. Seilnndi, THISJ O U R N I . . 82, :(lis8 (19Ii0) i< B. > C; Gowenlock a n d J. T r o t m a n , .I. Chiiii. .?or., 1140 (19.3) 1,;) J . C,. C a l t e r t . S S Thcbrna. anrl P. I. H a n s t , 'I'HIS J , , I ~ R \ , \ I , , 82, 1 ,t IO601 .
73, 1770 (1931) (10) A I . 0 Burton, F J Soivden anrl A . G I,ockheari, ( ' i i i i J . Bioc i i r n i . ~ h ~ , 32, . ~400i u ~ 9 . w~ . i l l ) C. Pidacks, .4. R . Whitehill, I,. A I , F'rue.;,. i: U'. Hesqeltine. H 1.. Hutchings, N . Riihonc,, and .I. H . William.;, T H TJ O~I I R N Z I , 1 5 . tiOfi.1 i i 4 S : i ) 12) A \:?i!ht,rmi- itncl ,I 1 S
