Photochemical Decarboxylation of Orotic Acid
J . Org. Chem., Vol. 44, .Yo. 13, 1979 2133
hasis of physical and spectrciscopic properties. T h e residual tar from the reaction \vas not inve Kinetic Study. A pur ple of .V,,V-dibromo-cu-aminoisoliutyrcitiitrile (0.8:11g. 0.0034 mol) was dissolved in 15 m L of methylene chloride. A n aliquot (0.20 mL1 was analyzed iodometrically for positive hromine with (i.008 N Na$3~O,jsolution. T h e solution was transferred tci a .iO-niI. round-bottom flask (magnetic stirrer, ice bath. and drying tutie!, I n a heparate vial. recrystallized nitrosobenzene (0,:367 g. 0,I)O:U t n i i l i MX dissolved in I O mI, of methylene chloride anti c~hilledtci il "('. At'ter eyuilihration. the time was recorded and the iiilution of' nitrciscrhen as added in one portion to the vigo r o u ~ l >stirred hiilution c r t ihronioamine. Progress of'the reaction a t 0 "C was tollo\ved I rving the progressive color change: (lark preen, light liro\vti. cirange. and I'inally red. I'pon development ot'a pronciunced led color. 0.20-rn1, aliyucits of reaction mixture v.we quickly ithdra\r-ti a n d titrated iodometrically. T h e process was reIiratrd ~ v e r1~3'- 3 1inin until the y tor pcisitive Iiromine was rvithiti ( i f t h e initial value ladjusted tor dilution with 1 0 mI, o f n i > ( i l l i t ion!. Hy thih method. reaction time \vas estimated tr~is~rlieii~erie ( 1 h. Purt1ii.r titration ( 1 2 h i (it'diqwitb revealed i i r i atldititrnal tlccrcaie in poiit i\-e Iiromitie. ..\c.cirrding t o t lit> > a m e prcicedure. the .\ -dil)rotnoamine (0.41() 2. (i.iici169 m o l i [\a. re,ic,tett with tiitroscihenzene 10.181 g) in 2,: mI, III' nnrthylene cliliiri(lc~.Estimated t t i t a l reaction time was 5.2: 11. I)uplic,ate r u n s w i ~ hwacticiti mixtures initially O.U0:180 (25 mI,1 and i1.ti0182 mol 1 2 511.1 , I i n 110th htarting tnaterialh required 6.00 and :.%! h . rv~pectivvl>. 1 ~ 1 1 coiiiiileticrti. ,
52128-65-6; ~~'-cyclohesyl-,~'-phenyldiazene .V'-oside. 5212:3-66-7; ,V-butyl-,V'-phenyldiazene S'-oxide, 52123-78-1: .V-tieopentyl-~V'oI~ntyl-.\'-plieiiyldiazene phenyldiazene .Y'-oxide. 69XIr5-25-4: 5-2:3-5; 'V-carhethox? phenyldiazene .Y'-cixide. tosyl-.V'-phenyldiazene ,\'-ciside. 6(il%-94-5: nitro6-96-9: .V - iiso b u t yroni t rilo i- AV'-t tart - t i t i t yld iaze ne .\"-oxide. 69815-27-6: 2-methy1-2-nitrcrs~i~~ro~~aiie. 91 7-95-ij: .V,.Vdit)romo-c\-aminoisohut).ronitrile, 6908:3-9:i-h: c~-aminoisohutyronitrile hydrochloride. 51)846-:36-1: ,V..\-dihronio-rc'l.t-),utvlamitie. t5165r5-:16-8:.V..~'-dibromo-l-methyl-l-hiity~j)entylaniine. 6908:3-91-9: -ditircimo-tt~rt-t,ct!-initie. 6908:1-95-0: .Y..Y-dilirotnciiso~,rc,py amine, 55877-,59-:1: .V,.V-dib rhesylatnine. (j8277-7-4-7: .Y,,Y-dibromobutylamine. 68277-tiil~r~itiiririe~iI,ent?.larnitie. 6908:3-97-2: .V..V-ditir~imois~ihu ditircimocarhatnate. 51066-0~~-9: ide. 21819-10-1,
References a n d Notes
Paper 30. Chemistry of K H a i o Compounds. Postdoctoral Fellow, 1977- 1978 V. Nelson, A . Serianz. and P Kovacic, J. Org Chem.. 41, 1751 (1976) F. R . Sullivan, E. Luck, and P Kovacic. J. Org. Chem., 39,2967 (1974). R. C. Zawalski and P. Kovacic, Synth. Commun . 8, 549 (1978). J. W. Mellor, " A Comprehensive Treatise on Inorganic and Theoretical Chemistry". Longmans. Green and Co., New York. 1922, p 245. J. H. Boyer. ' The Chemistry of the Nitro and Nitroso Groups", Part I. H. Feuer. Ed.. Interscience. New York, 1969. pp 284-285 P Kovacic. M. K. Lowery, and K. W. Field. Chem Rev.. 70, 639 (1970). M. Anbar, S. Guttmann, and R. Rein, J . A m Chem. Soc.. 81, 1816 (1959): L. Farkas, M.Lewin. and R. Bloch. bid.. 71, 1988 (1949): M. Anbar and R. Acknowledgment. Acknowledgment is made to the donors Rein. bid., 81, 1813 (1959). of the Petroleum Research Fund, administered by the P. A. S. Smith, "Open Chain Nitrogen Compounds' \/oI. 2, W. A. Benjamin, American Chemical Society. for support of this research. LVe New York. 1966, Chapter 13. p 373. (ai F. D. Lewis and W. H Saunders, Jr.. Nitrenes". W. Lwowski. Ed.. lnthank Piotr Starewicz. .Jay LVrobel. and .John Speier for asterscience, New York, 1970, pp 82. 86: (b) P. A . S. Smith. ;bid., p 103. sistance and Paul Karges for some of the microanalyses. T. Fuchigami, T Nonaka. and K. lwata. J. Chem. Soc , Chem Commun.. 951 (1976). 2-1: 3, 41718-2.5-6: 1, W. Gottardi. Monatsh Chem.. 105, 61 1 (1974). '307-(11-7: 7, 14925-8:3-8:8,69083-994: D.Carr, T P Seden. and R . W. Turner, Tetrahedron Lett., 477 (1969). [a) G A . Russell. E. J. Geels. F. J Smentowski. K.-Y Chang, J. Reynolds, 1 1 , 17:{-:14-7: .\-iisohutyronitrilo,and G. Kaupp. J Am. Chem. Soc.. 89,3821 (19671. (b) ref 7, pp 160 and Iiut~i-,Y'-pheiiyldi161 t i u t y l ~ ~ e n t y l ) - . ~ ' - p h e n - (16) P Kovacic and S S Chaudhary Org Synth 48. 4 (19681 -.Y'-phenyldiazene .Y'- (171 T A Kling. R E White and P Kovacic. J Am Chem Soc 94. 7416 Iisicii.. (i!98 15.2 i ;: .\ -ii[ri,riil)yl-.\"-~heiiyldiazeni. .\'-oxide. (1972) jrt-
Chemical Evolution. 33. Photochemical Decarboxylation of Orotic Acid, Orotidine, and Orotidine 5'-Phosphate .J. P. Ferris* and P. C. .Joshi l l e p a r t m e n t of
Chemistry. Rensselaer Poi? tcchriic In,titute, Tro?,,.Vel[. k'ork 12181 Receiced October 19. I978
Orotic acid. orotidine. a n d orotidine 5'-phosphate are photochemically converted to uracil. uridine, and uridine ,5'-phosphate in chemical yields of 13, 45, and 23%, respectively. T h e chemical yields for uracil and uridinr formarespectively. T h e chemical yield of uracil increases 2.5-fold when the orotic acid tion a r e 1.6 X IO-: and 1.7 X concentration is decreased IO-fold, indicating t h a t bimolecular reactions limit the uracil yield. T h e reaction proceeds from the singlet excited state as shown hy the absence of quenching by paramagnetic ions and the absence of sensitization by benzophenone and acetone. T h e F e ( I I 1 i - and Cu(I1)-promotedphotochemical formation of uracil from orotic acid proceeds in up to l P 0 yield. Small amounts of harbituric acid are also observed. X plausible pathway for t h e prebiological formation of uracil and its derivatives from HCIV via orotic acid and its derivatives is discussed
Hydrogen cyanide is considered to have been a likely starting material for the synthesis of biomolecules on t h e primitive Earth.' I t is formed in a variety of primitive Earth simulation experiments, and it is present in interstellar space. Dilute aqueous solutions of H C N condense to give oligomers which in turn undergo hydrolytic decomposition t o purines, pyrimidines, and amino acids. I n addition, two of the compounds formed by the hydrolysis of H C N oligomers, 4-aminoimidazole-5-carboxamideand orotic acid (la), are intermediates in the contemporary biosynthesis of purine and 0022-3263/79/1944-2133$01.00/0
pyrimidine nucleotides, respectively. Primitive life forms may have had enzymes for the utilization of these compounds for nucleic acid synthesis once the supply of preformed purines and pyrimidines was exhausted.3 Probably t h e first enzymes were not very efficient and only enhanced the rates of chemical processes modestly over t h a t of the rate in the absence of an enzyme. I t is likely that the same chemical processes also occurred under primitive Earth conditions in the absence of enzymes. T h e chemical conversion of 4-aminoimidazole-5carboxamide to purines under primitive Earth conditions has C 1979 American Chemical Society
2134
Ferris a n d Joshi
J . Org. Chem., Vol. 44, No. 13, 1979
Table I. Photochemical Conversion of Orotic Acid to Uracil
irradiation time, h
concn, M
x 6.4 x 65x 6.4 x
4
x x 6.4 x 6.5 x 6.1x 6.4 x 6.4 x
6.4 6.;i
24 36 48 60
10-5
0.25 3.9
10-4
0.45
10-5 10-4
7.8 1.1 12.7
2.2
10-4 10-5
11.3
10-5
3.6 6.7
10-4
4.7
10-4
4.9
10-4
3.3
10-4
already been described.4 In this paper we describe the formation of uracil, uridine, and uridine 5'-phosphate from t h e corresponding orotate derivatives under plausible prebiological condition?." Results and Discussion
Orotic acid and its derivatives undergo a facile photochemical decarboxylation. At first it was thought that the photochemical decarboxylation of orotic acid was a new reaction, but careful scrutiny of the literature revealed that iiracil formation had been suggested previously but not proved.6 This is probably because lop3 M orotic acid is con-
0
R 1
1
18.6 37.8 44.9 37.9 31.6
R 2
a,R=H b, R = 1 - r i b o f u r a n o s y l c . R = 1 - r i b o f u r a n o s y l 5 -phosphate
verted to the dimer (a O.l)i much faster than it is converted to uracil ( @ l(I-j).j T h e photodecarboxylation of orotidine and orotidine 5-phosphate has not been previously reported. T h e decarboxylation of orotidine to uridine constitutes a formal structure proof of orotidine.8 T h e rate of formation of -c 0.02) is 1000 times faster than the uridine from orotidine rate of formation of uracil. Bimolecular reactions decrease the yield of decarboxylated products as shown by our observation that the chemical yield of uracil goes from .5 to 13%when the orotic acid concentration to 6 X 10-5 M (Table I). I n addiis decreased from 6 X tion, the chemical yields of decarboxylation products from orotidine ( l b ) and orotidine 5-phosphate ( I C ) , substances which do not undergo efficient p h ~ t o d i m e r i z a t i o nare , ~ 5-10 times greater than that of uracil from orotic acid (Tables I1 and 111).In principle, the yield of uracil (2a) from orotic acid ( l a ) should be equivalent to the yield of uridine (2b) from orotidine ( l b ) since there is photoequilibrium between orotic acid and its p h o t ~ d i m e rThe . ~ equilibrium was detected in the present work by the formation of uracil on irradiation of orotic ,acid photodimtAr. A fraction of the orotic acid present a t equilibrium should be cleanly photolyzed t o uracil, but t h e
0.7 1.3 3.9
~~
20
6 ,5 X 10-' 12
yield of photoproducts, % uridine uracil
trace
6.5 X 10-i 6.4 x 10-4 6.5
irradiation time, h
yield, oh
6.4 X 2
Table 11. Photochemical Decarboxylation of Orotidine
5.6 C
'
1.3
Table 111. Photochemical Decarboxylation of Orotidine 5'-Phosphate
yield. "u irradiation time, h
uridine 5'-phosphate
1
7.3 14 22 23
2 3 4
uracil trace 1
2 2 :i
orotic acid
.,
1
90% of the light a t wavelengths
