121s
'rREAT
B.
Vol. (i.5
JOHNSON
[CVNTKIUUTION FROM 11lE L)QPAKTMEN 1 U P C l i t M I S l R Y , Y A L E LrNIVERSITY]
Chlorination' of 2,4-Diketotetrahydropyrimidinesby Action of a Mixture of Superox3;' and Hydrochloric Acid BY
1'KE.IT
In our study of halogenation technique to be used in an investigation dealing with the chemistry of nucleotides and nucleosides, i t became necessary to develop a method for the chlorination of pyrimidines, which would function in the absence of free chlorine and a t a low temperature. In this paper the author will present some of the preliminary results obtained in a solution of this problem. I t is well known that the presence of hydrochloric acid accelerates the speed of decomposition of hydrogen peroxide into oxygen arid water. This simple decomposition, which involves a low concentration of chlorine, has been studied quantitatively by Maass and Hiebert? and Livingstone and Bray,j who obtained results supporting a unimolecular change a t 25'; and more recently by Budge,6 who studied the speed of decomposition over temperature ranges of 23, 30 and 35". Maass antl Hiebert postulated that the mechanism of this reaction or change might be represented by Lhc primary formation of a coniplc\; molecule, H20yHCl, ant1 interpreted the j i l t vr mediate chatigcs of the decomposition exprciwd bclow in equations a, b and r ( 1 ) (1) a b c
-+ H,O + HOC1 + HLOL+HJO + 0.+ HC1 + IICl +11 0 C1
H20,HCl
HOC1 HOC1
-
~
R . JOHNSONz ! 2 , SH---CO
kG ~;
CH+
KE-CH I
NH-CO kO
I
cCl--+ II
NH-CH
I1
"-TO
CO
:
CCln
I
NH-CHOH I11
'l'his interesting change is accomplished accordirig to our present technique by bubbling chlorine gas freely into a suspension of uracil I in water, or by oxidizing this pyrimidine with potassium chlorate in hydrochloric acid solution. Both methods of operating are productive of excellent yields of the hexahydropyrimiciine 111, but are conducted under experimental conditions which are unfavorable for our present research. The author finds that superoxo12 mixed with strong hydrochloric acid provides an ideal reagent for bringing about such changes as expressed in Equation (,2). The transformation to the hexahydropyrimidine derivative I11 is accomplished at ordinary temperature, and chlorine is introduced into the respective pyrimidine molecule at ]losition-5 with production of quantitative yields ) i the desired 3,($-diketohexahydroxypyrirnidinc, m(1 it1 very pure condition. In other words, iiascent chlorine gas or potassium chlorate, or any inorganic salt of this nature, are unnecessary for accomplishing these transformations. Results typifying some interesting changes brought about by the application of this technique with different pyrimidines studied in our preliminary research are recorded in Table I. (
Accepting this interpretation a5 true, we have here theoretically an ideal chlorinating medium Experimental Part for the smooth conversion of ",Ci-diketotetrahiV.dro-411 these reactions reported in Table I are conducted a t pyrimidines into the characteristic 3,;i-aisubstituted 2,6-diketohexahydropyrimidine combina- ordinary temperature, and the yields of the reaction prodtions. This change is illustrated by the quaiititn- uct s are practically quantitative. No secondary reactioiis are met with t o complicate the results. The general tive conversion of uracil I into S,G-diketo-5,3-di- nicthod of operating is very simple and is as follows: One chloroxyhexahydropyrimidine I11.* 5-Chloroura- grain of the pyrimidine is finely pulverized and stirred into IO cc. of cold superoxol. S o reaction apparently results. cil I1 is an intermediate product of this reaction. ( l j Researches on l'yrimidinen, Cl,XXT.lll, 12) Merck 30% hydrogen peroxide. ( 3 ) l h i s research \vas partially supported by ii grant froni t h e Research Committee of the Council 011 Pharmarr antl Cherniitry. .lmerican Medical Association ( G r a n t KO. -423) (1) Maass and Hiebert, THISJOURNAL, 46, 290 (192-11. ( 5 ) Livingstone and Bray, ibid., 47, 2060 (101T)). (ti) Budge. ibid., 64, 1769 (1032). $ 7 ) I t is also known t h a l reaction c i/. r-cvursihli.. I F I L : . .i
