Organic Magnetic Spectrometry, 1971, Val. 5. pp. 447 to 452. Heyden & Son Limited. Printed in Northern Ireland

HETEROCYCLIC STUDIES-XXII. * MASS SPECTRA OF SOME 3-HYDROXYPTERIDIN-CONES

JIM CLARK and C . SMITH Department of Chemistry & Applied Chemistry, University of Salford,

Salford M.5 4WT, Lancashire, England

(Received 21 December 1970 : accepted 2 February 1971)

Abstract-Mass spectra of 3-hydroxypteridin-4-one and five of its mono- and di-methyl derivatives are recorded. Fragmentation of the non-methyl compound (I; R' = RZ = RS = H) occurred mainly by successive losses of NO, CO, HCN and HCN. Changes in m/e values of the major peaks with methyl-substitution pattern in the derivatives were consistent with the proposed fragmentation pattern. Several minor fragmentation pathways were also observed but all involved an initial loss from the oxygen containing ring.

THIS paper reports the low resolution mass spectra and probable fragmentation pat- terns of six 3-hydroxypteridin-4-ones. The compounds are potentially tautomeric but are believed to exist predominantly as N-hydroxypteridinones (I) rather than hydroxy-N-oxides (II).2 They are therefore essentially cyclic hydroxamic acids, a class of compounds whose mass spectra have received little a t tent i~n.~ The few reports made so farso* reveal no consistent mode of fragmentation for compounds of this type.

Spectra of our 3-hydroxypteridinones (I) are recorded as line diagrams (Figs. 1 and 2). The molecular ion gave the base peak in all cases. The molecular ion of the simplest compound (111, R1 = R2 = R3 = H), m/e 164, clearly fragmented mainly by successive losses of NO, CO, HCN and HCN (Scheme 1) to give ions of m/e 134 (4579, 106 (5%), 79 (29%) and 52 (27%), which are conveniently represented as (a to d; RI- = R2 = R3 = H). All steps were confirmed by appropriate metastable peaks. The fact that the first lcss of HCN involved the carbon atom originally at posi- tion 2 of the pteridine molecule was confirmed by the shift of the m/e 79 peak to m/e 93 in the 6- and 7-methyl isomers (I; RI- = R3 = H, R2 = Me and I ; R1 = R2 = H; R3 = Me) but not in the 2-methyl isomer (I; R1 = Me; R2 = R3 = H) where the peak was still at m/e 79. Similarly the corresponding peak in the 6,7- dimethyl compound (I; R1 = H, R2 = R3 = Me) was at m/e 107 but only m/e 93 in its 2,7-dimethyl isomer (I; R1 = R3 = Me, R2 = H). The effect of methyl sub- stitution on the m/e 52 peak was also consistent with the above fragmentation path.

Ions (b) sometimes lost a hydrogen atom or else breakdown of ions (a) occurred by loss of CHO (Scheme 2) instead of CO (Scheme 1) because three of the compounds gave ions (e) at m/e 105 ( e ; R1 = R2 = R3 = H), m/e I19 (e ; R1 = Me, R2 = R3 = H) and m/e 133 (e; R1 = R3 = Me, R2 = M) of about 5% relative intensity. These lost RCN (R = H or Me) and the molecule expelled must have included the sub- stituent originally at position 2 because the resulting ions (f) had mje 78 (lo%), 78 (lo%), and 92 (5%) showing losses of HCN, MeCN and MeCN respectively. Another minor fragmentation pathway for ions (a) seemed to be loss of MeCN or HCN from the pyrazine ring but this was apparent only in the spectra of compounds with at least one methyl group in that ring. Thus the 6- and 7-methyl and 6,7- and

* For part XXI, see Ref. 1. 447

448

1641 JIM CLARK and C. SMITH

60 - c - ..--

40 -

.

20 -

2 134

66 79 44 52

93

i,l / I , i l l , j , I , I , , I / , ,

148

I ~ r i -1

60 - c - ..--

40 -

.

20 -

2 134

66 79 44 52

93

i,l / I , i l l , j , I , I , , I / , ,

148

I ~ r i -1

100 -

80 -

60 - Y - C ...-

40 - 2

loo^ 80 ( c )

I ? ! P 178 ( b )

79

120 148 52

178

20 - 93

i l l , 1 4 1 , /Ill I 1 i , I I, , I ~

162

1 I

I, ---r--l

I t 1 c FIG. 1 . 70 eV mass spectra of 3-Hydroxypteridin-4(3H)-ones : (a) 3-Hydroxypteridin- 4(3H)-one (I; R' = RZ = R3 = H); (b) 3-Hydroxy-2-rnethylpteridin-4(3H)-one (I; R1 = Me, R2 = R3 = H). , (c) 3-Hydroxy-6-rnethylpteridin-4(3H)-one (I;

R1 = R3 = H, RS = Me).

Heterocyclic studies-XXII

192

80

60 I

w E -4

40 162 d

93

134 20

1 76 107

I 1111 I I I I/ I I It I * / , I

449

I

40 60 80 100 120 140 160 180 200 itt/fe

43 60 80 100 120 140 160 180 200 itiic

FIG. 2. 70 eV mass spectra of 3-Hydroxypteridin-4(3H)-ones : (a) 3-Hydroxy-7- metliylpteridin-4(3H)-one (I; R' = R2 = H, R3 = Me); (b) 3-Hydroxy-2,7-dimethyl- pteridin-4(3H)-one (I; R' = R3 = Me, R2 = H); (c) 3-Hydroxy-6,7-dimethylpter-

idin-4(3H)-one (I; R1 = H, RZ = R3 = Me).

450 JIM CLARK and C. SMITH

I O€I

rrii

(R = Me or H) (C)

(4 SCHEME 1

(4 (f) SCHEME 2

2,7-dimethyl compounds exhibited peaks at m/e 107 (14%), 107 and 121 (8 and 9%), 121 (5%) and 121 and 135 (4 and 7%).

All the spectra showed substantial peaks at m/e 44 or 58 but not both. Since it was only the 2-methyl- (I; R1 = Me, R2 = R3 = H) and 2,7- dimethyl (I; R1 = R3 = Me, R2 = H) derivatives which showed the m/e 58 peak the m/e 58 ions must include the 2-substituent. The m/e 44 and 58 ions, which are probably RIC=NOHf (h ; R1 = H or Me) or isomers, may be formed as indicated in Scheme 3.

( 1 2 )

SCHEME 3

Heterocyclic studies-XX11 451

A cleavage similar to (9) + (11) but with charge retention on the opposite fragment may also proceed, with formation of [M - MI+* or [M - 581'. ions (i or)). Although no metastable peak for this transition was observed, metastable peaks corresponding to further losses of 2HCN to give [M - 71]+ and [M - 98]+. ions were observed in the spectrum of 3-hydroxypteridin-4-one. Corresponding [M - 58]+., [M - 851' and [M - 112]+* ions occurred in the spectrum of its 2-methyl derivative (1; R1 = Me, R2 = R3 = H) but the process appeared unimportant in conipounds substituted in the pyrazine ring. The likelihood that the loss of 44 or 58 a.m.u. is made up of succes- sive losses of OH. and HCN or MeCN, as suggested for the [M - 58]+- peak given by 3-hydroxy-2-methyl-pyrido [3,2-d]pyrimidin-4-one (IV),4 is diminished by the virtual absence of [M - OH]+ peaks in the present spectra [except for mle 175 (13 %) in the spectrum of the 6,7-dimethyl derivative (I; R1 = H, R2 = R3 = Me)]. This conclusion was supported by the continued absence of an [M - OH]+ peak when the spectrum of one of the compounds (I; R1 = R2 = R3 = €I) was run at 15 eV.

The low intensities of [M - 161 and [M - 171 peaks in the present spectra are noteworthy. Had the N-oxide form (11) of the compounds been important, substantial [M - 16]+. peaks might have been e~pected.~ In any case 3-hydroxy-2-methyl- pyrido [3,2-d]pyrimidin-4-one (IV),4 which is closely related to the present compounds, gave an [M - 161-t. peak with a relative intensity of 99 % compared with 4 to 10 %

r- l+.

(IV)

for the present compounds. Loss of an oxygen atom from the N-hydroxypteridones should give species equivalent to molecular ions of 4-hydroxypteridines (V) or their tautomers (VI) which, by analogy with hydroxy-pyridines ,6 -quinolines,' -quinazo- lines ,8 -pyridopyrimidines* and other hydroxypteridines ,9 would be expected to lose CO and then two or more molecules of HCN or MeCN depending on the methyl substitution pattern, Metastable peaks in the relevant positions do indicate such losses from the [M - 16]+* ions of compounds with at least one methyl group in the pyra- zine ring. Only one of the present compounds (I; It1 = H, R2 == Rs = Me) gave an appreciable [M - 17]+ peak.

EXPERIMENTAL Mass spectra were determined on an AEI MS-12 spectrometer with an ionising voltage of 70 eV,

trap current 100 PA, and accelerating voltage 8 kV. Samples were introduced into the source, which was maintained at ZOO", on a direct insertion probe.

Acknowledgements-We thank Mrs Ruth Maynard for assistance in measuring spectra and pre- paring line diagrams.

452 JIM CLARK and C. SMWH

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Baxter, and G. A. Swan J. Chem. Soc. (C) 2446 (1967), R. A. Abramovitch, R. T. Coutts and N. J. Pound, Chem. and Ind. (London) 1871 (1971); R. T. Coutts and K. W. Hindmarsh, Org. Mass. Spectrom. 2, 681 (1969); R. T. Coutts and K. W. Hindmarsh, O r - . Mass Spec- rrom. 3, 105 (1970).

4. I. R. Gelling, W. J. Irwin and D. G. Wibberley, J. Chem. Soc. (23) 513 (1969). 5. T. A. Bryce and J. R. Maxwell, J . Chem. SOC. (0) 206 (1965). Y . Morita, Chem. Pharm. Bull.

6. R. Lawrence and E. S . Waight, J. Chem. Soc. ( B ) 1 (1968). 7. D. M. Clugston and D. B. McLean, Can. J. Chem. 44,781 (1966). 8. T. 3. Batterham, A. C. K. Triffett and J. A. Wunderlich, J. Chem. SOC. (23) 892 (1967). 9. T. Coto, A. Tatematsu and S. Matsuura, J. Org. Chem. 30,1844 (1965).

14,426 (1966).

10. W. B. Wright and J. M. Smith, J. Am. Chem. SOC. 77,3927 (1955).