884
riiethyl:tniiiie5 ( 2 U nil. 1. The fiask was heated uiitil t h e tern-
perature of the cwitents reached about 210". The residue
(viscwus brown oil) was cwoled, dissolved in hot MC; ethanol.
decolorized with Xorit -4,and filtered. On cooliiig, 5.5 g. (56c; )
Is, 1n.p. 147-150", was obtained. TWU
rec,rystalli~atioiisfrom the same solverit raised the melting point
to 154-155° (short woolly rieedles).
.Inal. Calrd. for ClaH17SOj:C, 60.21 : H , 6.10: S , 5 . I ) l .
Foiiiid: C, 60.82; H, 6.30: N , 5.21.
N-Methyl-2-( 3,5-dimethoxy-4-hydroxyphenyl)succinimide
(IV).-The reartion was mrried out as for 111. From I (10 g.,
O.OX7 mole), IT: (6.4 g., FISC; ) \vas obtained as yellowish white
crystals, i i 1 . p . lS:<-lS6'. Two rec,rystallizatioiis, using S o r i t
A once for dec,i,li,ri;satir)ii, r:iiseti the melting point to lS6-lKin,
whit e crystals.
;lnal. C a l d . for C,,HiJO;: C, % . S i ; H, 5,156: S , 5.2s.
Foiilrd: C, 5S.67: H , 5.76: S , 5.15,
SI nthesis of Some Hydroxylamine DeriFatives
of Py rimidines and Purines'
Hecaiise of interest, i i i orotic' arid aiialogs iii this laboratory,Y
6-?;-hSdroxylamiiioiiracil ( I ) and iiwcil-6-hydroxamic acid (11)
have been synthesized. 6-4-Hydroxylamiiiopriririe ribonucleo-
side (111)was regarded as a n analog of adenosine, becarise 6-Kc'-
hydroxylamiiiopiiriiie3 is active as an analog of both adenine arid
hypoxanthine.
2,4-l)imet hoxy-6-c~hloropyriniidiiie~~~ failed t o react with
hydroxylamine; however, the demethylated derivative, 6-c:hloro-
iiracil,i rewted smoothly with hydroxylamine to give I. Com-
pound I1 was prepared from methyl orotate,8 whereas 111 was
prepared from 6-chloropiiriiie rihoriiic~leo~ide~ and hydroxyl-
amine.
Experimental Section'"
6-N-Hydroxylaminouracil (I).--A solution of K O H ( 11.2 g.,
0.2 mole) in ethanol (40 nil.) was added to a solution of hydroxyl-
amine hydrochloride (12 g., 0.17 mole) in boiling ethanol (200
nil.). The precipihted KC1 was filtered. 6-Chlorourac*i17
( 1 g., 0.007 mole) was added t o the soliition of hydro
The mixtiire was refliixed for 1 hr. and allowed to cool to room
iemperatiire with stirring ( 1 hr. j. T h e prodiicbt, which separated
as a solid, was washed with water and ethanol to give aiialytically
pure I (0.73 g., i4!;), m.p. 280" der., 264 r n M ( e 6250).
Anal. Calcd. for CJHJ,O~: C, 33.57, H, 3 . 5 2 ; N, 29.36.
Foiind: C, 33.56; H , 3 . 7 7 ; Ti,29.25.
Uracil-G-hydroxamic Acid (II).---A mixture of methyl orotatex
(1.25 g., 0.0074 mole), ?jH,OH. H C l ( l . 4 g., 0.02 mole), and water
(10 nil.) was cvoled t o 0". JI'ith stirring, S a O H (12.5 AY,3.6 ml.)
was added t o the mixtiire dropwise a t '3". The now clear solri-
( 1 ) This uork was suiiported l)y a grant (C.\-02817) from the S a t i o n a l
('ancer Institute. U. A . Public Health Service.
( 2 ) K . F:. Handschiimaclier. Cancer Res., 28, 6-13 (1963).
( 3 ) A . Qiner-Horolla and .II3endich.
. .I. A m . Chem. Soc., 80, 3932 (1858).
artorelli. .\. I,. Richer, P. K. Clianr, a n d G . .i.Fischer, Bio-
r.lrc.m. I'harmarol., 13,507 (196-1).
( 5 ) 11. .J. Fisher a n d T. 13. .Johnson. .J. , i m Clirm. Soi,., 54, 727 (1832).
(6) S. 1%. Greenliaum a n d W . I,. Holinep, ihid.. 76, 28Y9 ( 1 9 5 4 ) .
( 7 ) .T. P.H o r w i t z and .\. .J. Tomson, . I . Oru. Chem., 26, 3392 (1862).
(8) .I. .J. 1:os. h-. T u n g , and I . \\-empen. B i o c h e m . B i o p h y s . Acta. 23,
2!93 (l!IR7),
($1) I<. l<. Haker, K. Heirson, 11. . I . T l i o i i i a a , ani1 .I. .\. . J o l i n r t ~ n . J I . .
. I . (IVY. C I , W I . .aa, !m (IYS7).
(10) Aleltinp points were determined i n a capillary tulie i n B coppei block
a n d art. corrected. SIicroanalyses uwre performed by Schn-arzkopf Micro-
analytical Lalioratoriea. LVootlsiile. S . Y..a n d liy M i d u e s t hlicrolali. Inc.,
liiiliaiiaidis, Ind.
iioii \viis ;rtljiistcd Io pH 5 w i t h c.oiic*c.iitraietf I-ICI. ('riidr 11,
which separated niit as a yellow solid. W:LS recrystallized friini
water t o yield t h e monohydrate (1.2 g., XG";), n1.p. 250° dt,c. ..
~j:H,2 274 nip ( e i420). It was recrystallized twicse from w:i~c'r t o
give the analytical sample.
.lnal. Calrd. for CsHb?j'j30a.H20 Isample dried :it (jOo ( 0 . 1
m n i . ) J : C, :i1.75: H, 3 . 7 3 ; 4, 2 2 . 2 2 . Foiiiid: C', 31.72: H, :{.!)!I:
S, 22.2!). Calrd. for CaHjS301[sample dried at 120" (0.1 m m . ) ] :
C', :$5.10: H,2.95: K , 24.56. Fourid: C', i35.22: H. :3.15: S .
'4.87.
6-N-Hydroxylamino-S-B-u-ribofuranosylpurine (111). -TI) :I
iiiirie hydrorhloride (0.7 y., 0.01 iiiole) in
boiling ethanol (10 nil.) \vas added a solutioii of K O H (0.56 g . .
0.01 m i l e ) in ethsnol ( 3 nil,), The precipitated KCI was filtered.
6-Chloro-Y-~-u-rihc~fiiraiiosyl~~iriiieg~" (0.2% g., 0.002 mol(,),
dissolved i i i ethanol (20 rnl.), x a s added 10 t he strliitioii I I ~
N H 2 0 H . T h e miit lire w:is refluxed for 1 hr. : i ~ i d1 heii i'oili'e1i-
trated in canto at 41'. The residiie (412 nig.) was rctcryst:illizetl
from hot ethariol to yield the piire prodiict (21111 nig., 7 0 ' ; i , 1 1 1 . p
I<),\' (le(,.,A::! X 2 . > nip ( e 16,700). T h e arinlyticxl snnlplp \$-:IS
tl o r i w more from ethanol.
i l d . for CIl,H,3N10s:C, 42.40: H , 4.t;:;: N. 24.72.
F o i i I l k C', 42.42: H. 4 , 7 7 : S , 24.94.
Quinoxaline Sulfonamides
The developmelit of the field of c*heiiiottierapy has inore r~
caently led to a reneaed interest iii t.he yiiiiioxaliries i i i c.oiiiiecTion
with their poteiitial values as phariiiac.eiiticals.'-" JVe havr
synthesized some halogenat.ed qilinoxalirie siilfoiianiides i i i view
of the reported effect nf c8hloriiiratoms o i i the activity of qriiii-
t ixalii ies .e
Sulforiamides 1 1 1 1 cwiideiisitioii n.ii ti 2,:i-dic.hlori)cliiiiiii~aliiic.
iiiing the procedure of \Tolf, et ul.,: gave disrllfoiianiide deriv:r-
tives when 2 nioles of sdfoiiarnide was rised, and a inixtiire o f
predominantly miino- and sniall ainoriiits of tlisii1foii:Lrnitles
when 1 mole of siilfonsmide was employed. The reactinii of
sulfanilamide and 2,3-dirhloraqiiiiit,zalirie coilfirmed the findings
of Wolf and c~1-workers7 arid Plat t arid Sharpx that thc free aniiiio
groiip does riot take part iri cwndeiisatioii.
2,3-l)ichloroqiiiuc,xaliiie on reartioil with beiizaniide i i i dif-
ferent ratios gave urily 2,3-dibeiizaiiiitio(iiiioxaline wider similar
conditions. Acei,ainidr, o i l heatiiig with dic~hloroc~i~iriosaliii~
:it 130" or refluxing iii ethanol, afforded a inktiire of products.
with or withoiit, c,liloriiie. Interaction of sodamide with di-
chloroquinoxaliiie iii boiliug toliieiie either in a stoichiometric
ratio or with an excess gave a mixtiire of uiiideiitifiable products.
Experimental Section
2,3-Dihydruxycjiiiilo.ualiiieg (915,; I, white needles, m.p. 6 2 0 " :
%,3-dichloroquiiiosaliiie1O( 7 5 % ) , colorless shining long needles,
(1) R.SI. Iclieson. .J. C/t?m. S O < , . .4 7 3 1 (19,j(iJ.
(2) 0. Gawron, a n d 1'. E. dpoerri. .I. A m . Chem. Sor., 67, 51.4 (191.5).
(3) R . 13. Alizzoni arid P. E. Apoerri, ibtd., 67, 16.52 il94,5).
(-1) K. I'fistcr, 111, . \ . 1'. Siillivan, .1. Tllpijlaril, and Xf. Tislder. i/jid.,
73, 4955 (1951).
( 5 ) J. Weijlard atid A l . 'I'i~liler, r. S . Patent 2.404.1UY ( . J n I > l l i , l!HOl;
Chem. d b s t r . , 40, 6100 (19-16).
(6) A . F. Crowthcr. 1'. H . >. Ciiril, I). (:. I)a\-ev, and (:. 4. S t a r e ) , J .
(''hem, S u r . . 1260 (19-19).
( i ) 1'..J. Wolf, I<. Pfister, 111, 11. 11. Beutal, K . AI.\Vilson, ('. .4, 11oliin*on,
and J. R. Stevens. J . .Am. C h e m . S o r . , 71, 6 (1Y49).
(8) 13. C . P l a t t a n d T. 11. Sharp, J . Chem. Sor., 2129 (1948).
19) 11. '1.Phillips. i b i d . , 1143 (19313: 2383 (1928).
( I O ) 0. Hinsbera ani1 .I. P d l a k . Be(..,29, 584 (18061.
November 1965 KEW COMPOUSDY

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