Organic Mass Spectrometry, 1971, Vol. 5, pp. 993 to 1002. Heyden & Son Limited. Printed in Northern Ireland

HETEROCYCLIC STUDIES-XXIV : * MASS SPECTRA OF SOME PTERIDIN-4(3H)-ONES AND

3-METHOXYPTERIDIN-4(3H)-ONES

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

Salford M5 4WT, Lancashire, England

(Received 13 January 1971 ; accepted 22 April 1971)

Abstract-Mass spectra of pteridin-4(3H)-one and all its mono-, di- and tri-C-methyl derivatives are recorded. Spectra of 3-methoxypteridin-4(3H)-one and four of its mono- and dimethyl derivatives are also recorded.

Pteridin-4(3H)-one fragments mainly by loss of CO and HCN in either order. Methyl substitution in the pyrazine ring leads to that ring fragmenting in preference to the oxygen bearing pyrimidine ring. Elucidation of fragmentation pathways was facilitated by changes in peak positions with changing methyl substitution patterns.

3-Methoxypteridin-4(3H)-ones fragment mainly through initial loss of CH20, but the ions so produced break down differently from isomeric molecular ions of pteridin-4(3H)-ones. Several fragmentation pathways are discussed.

THIS paper is concerned with the electron-impact induced fragmentation of 3-meth- oxypteridin-4(3H)-ones (I) and related pteridin-4(3H)-ones (11). The latter are also described as 4-hydroxypteridines, but like many substances loosely called hydroxy- heterocycles, they exist as equilibrium mixtures of hydroxy compounds and corre- sponding cyclic amide tautomers. When the ‘hydroxy group’ is in the tc- or y-position with respect to a ring nitrogen atom, the amide form is almost always dominant in the solid state and in solution.2 This is true of ‘hydroxypteridines’ including so called ‘4-hydroxypteridine’ (111; R1 = R2 = R3 = H) which is essentially pteridin-4C3H)- one (11; R1 = R2 = R3 = H).3

Mass spectra of several classes of heteroaromatic compounds containing cyclic amide groups have been published. These include pyridone~,~ pyrimidones,s quin- azolones,6 pyrid~pyrimidones,~ purinones? and ~ ter idones .~ The electron-impact induced breakdown of pteridin-4(3H)-one (11: R1 = R2 = R3 = H) has already been described briefly: but we now describe it in more detail, together with the fragmentation of all its mono-, di- and tri-C-methyl-derivatives (Fig. 1). The spectrum of one methyl derivative (11; R1 = R3 = H, R2 = Me) has been published.1°

An important pathway for the fragmentation of pteridin-4(3H)-one molecular ions (IV; R1 = R2 = R3 = H) was by loss of CO and then HCN (Scheme 1) to give peaks at m/e 120 (22%) and 93 (29%). The 2-methyl derivative (IV; R1 = Me, R2 = R3 = H) similarly lost CO and MeCN to yield ions a (R’ = Me, R2 = R3 = H) m/e 134 (13%) and b (R2 = R3 = H), m/e 93 (21%). Much smaller peaks were observed for loss of CO from the 6- and 7-methyl derivatives, while the 2,6-, 2,7- and 6,7-dimethyl and 2,6,7-trimethyl derivatives did not give appreciable [M - 28]+* peaks at all (Table 1).

Initial loss of a molecule of HCN or MeCN from the pyrazine ring was also clearly important (Scheme 2). In the compounds which contained at least one methyl group

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996 JIM CLARK, RUTH MAYNARD and C. SMITH

SCHEME 1

TABLE 1. METASTABLE TRANSITIONS IN SPECTRA OF PTERIDIN-4(3H)-ONES

Pteridin-Lt(SH)-one; 98.9(148 + 121), 97-3(148 --j. 120), 73.0(121 -+ 94), 72.1(120 -+ 93), 46.8(93 +

66), 37.1(121 +67). 2-Methylpieridin-4(3H)-one; 112q162 -+ 135), 110.8(162 -+ 134), 105.0(107 + 106), 90.4(162 4

121), 848(135 -+ 107), 72.1(120 -+ 93), 71.1(119 + 92), 65.4(135 -+ 94), 64.5(134 + 93), 52.4(119 + 79), 46.8(93 + 66). 6-Methylpteridin-4(3H)-one; 1125(162 + 135), 105.0(107 + 106), 86.4(135 + lOS), 94.8(135 + 107), 59.8(107 + SO), 35.2(80 -+ 53). 7-Methylpteridin-4(3H)-one; 105.0(107 ---t 106), 90.4(162 -+ 121), 85.4(134 + 107), 73.0(121 -+ 94), 59.8(107 +SO), 37.1(121 + 67). 2,6-Dimethylptev~~ifz-4(3H)-one; 126.1(176 -+ 149), 119.0(121 ---f 120), 105.0(107 -+ 106), 98.3(149 + 121), 78.3(149 + lOS), 59.8(107 +SO), 59.3(108 + 67). 2,7-Dimethylptevi-4(3H)-one; 124.4(176 -+ 148), 105.0(107 -+ 106), 1033(176 + 135), 84.8(135 +

107), 65.4(135 -+ 94), 59.8(107 + SO). 6,7-Dirnethylpteuidin-4(3H)-one; 105.0(107 --f 106), 103.5(176 -+ 135), 86.4(135 + lOS), 84.8(135 -+

107), 59.8(107 -+ SO). 2,6,7-Trimethylpteri~i~-4(3H)-one; 119.0(121 + 120), 116.8(190 + 149), 98.3(149 + 121), 79.8- (149 -+ 109), 78.3(149 -+ lOS), 59.3(108 -+go), 35-2(80 + 53).

SCHEME 2

Heterocyclic studies-XXIV 997

in the pyrazine ring this process was probably dominant and was probably important in all cases. Furthermore, the molecule of RCN originated fairly specifically from the 7,8-positions to give ion c. Thus pteridin-4(3H)-one, its 2- and 6-methyl and its 2,6- dimethyl derivative showed strong [M - 27]+- peaks with relative intensities of 36, 18, 87 and 48 %, whilst its 7-methyl, 2,7-dimethyl and 2,6,7-trimethyl derivatives showed [M - 41]+- peaks with relative intensities of 100, 44 and 100%. Ions c lost either a CO molecule to give ions d or a further molecule of RCN. When the latter occurred the RCN molecule included the 2-substituent because the 2-methyl compound lost MeCN (after HCN), the 7-methyl compound HCN (after MeCN) and the 6-methyl compound HCN (after HCN). Corresponding losses were observed for the di- and tri-methyl compounds. A suggested mechanism for formation of the resulting ions e is shown in Scheme 2. There was no evidence for successive losses of RCN from the 7,8- and 5,6-positions where these could have been distinguished from the losses from the 7,8- and 2,3-positions just discussed.

The separate fates of ions b and d could not usually be determined with certainty because, given suitable substitution patterns, they had identical mle ratios and may even be interconvertible. Loss of HCN from b or d occurred in most cases and loss of MeCN was sometimes apparent. Alternatively loss of a hydrogen atom occurred in all cases where the ions contained a methyl group. Ions e fragmented by loss of CO, HCN or MeCN.

Our spectrum of 4-hydroxypteridine is essentially the same as that publishedg except that the relative intensities of the [M - 271 and [M - 281 peaks are reversed and the very intense mle 44 peak (base peak) observed by the previous workers was not present in our spectrum. This peak may arise from a volatile impurity because we noted a fairly strong mle 44 peak for a short time after the sample was introduced on the direct insertion probe. mle 44 was also the base peak in the published spec- trum of 6-methylpteridin-4(3H)-onelo but no such peak was apparent in our spectrum.

The change in fragmentation pathway with methyl substitution in the pyrazine ring was much more marked than expected and may be associated with the ability of the electron donating methyl groups to stabilise a positive charge on the pyrazine ring rather than the oxygen containing pyrimidine ring.

3-Methoxypterid~~-4(3H)-ones (Fig. 2). Few spectra of N-alkoxy derivatives of the amide forms of hydroxy-heterocycles have been published.ll Such compounds (e.g. I) are essentially esters of cyclic hydroxamic acids. Spectra of some 3-hydroxy- pteridin-4-(3H)-ones (V), which are the cyclic hydroxamic acids from which the present esters are derived, were published recently.12

The molecular ion of each of the five N-methoxy derivatives (VI) lost a molecule of formaldehyde, presumably as shown in Scheme 3, to yield an intense ion which was probably a hydroxypteridine ion (f). The latter broke down in several ways. Loss of CO was always important [(f) + (g)] and was followed by loss of two or more molecules of HCN or MeCN. Variations in the relative intensities of [M - 85]+. and [M - 99]&. ions with the methyl substitution pattern indicated that the origin of the first of these RCN molecules was not highly specific but involved both the 2- and 7- positions of the pteridine nucleus to give ions i o r j , some of which had already been encountered in the breakdown of pteridones (above).

Loss of CO from the hydroxypteridine ions (f) could also be preceded by loss of HCN or MeCN, particularly in the compounds which had at least one methyl

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Heterocyclic studies-XXIV

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substituent on the pyrazine ring. The loss occurred fairly specifically from the 7,8- positions of the pteridine nucleus, since the 6-methyl compound (f; R1 = R3 = H, R2 = Me) lost HCN to give an ion h (R1 = H, R2 = Me), m/e 135 (43%) but the 7- and 6,7-dimethyl derivatives (5 R1 = H, R3 = Me, R2 = H or Me) lost MeCN to give ions h (R1 = H, R2 = H or Me) at m/e 121 (31 %) and m/e 135 (loo%), respectively. The 2-methyl derivative (f; R1 = Me, R2 = R3 = H), however, lost MeCN appreciably from the 1,2-position to yieId an ion mle 135 (19%) and the

tVI) *J-CO

SCHEME 3

Heterocyclic studies-XXIV 1001

parent compound (f; R1 = R2 = R3 = H) may lose HCN from the corresponding position.

All fragmentations of the N-niethoxypteridines described so far were initiated by loss of CH,O from the molecular ion but initial loss of 31 amu (CH,O-) was also apparent in two cases.

3-Methoxypteridin-4(3H)one, its 6- and 7-methyl, and its 6,7-dimethyl derivative all gave intense peaks at mle 58 (54 to 100%) but the corresponding peak was at mle 72 (100%) in the 2-methyl compound. The fragment k , which clearly contains the 2-substituent, may arise as shown in Scheme 4. Analogous peaks at mle 56 and 42 were present in the spectra of 3-liydroxypteridin-4(3H)ones with and without a 2- methyl substituent.12

SCHEME 4

Comparison of the spectra of the 3-methoxypteridinones (Table 2) with those of the pteridinones reveals that some of the hydroxypteridine ions (f), produced as intermediates in the fragmentation of the methoxy compounds, break down quite

TABLE 2. METASTABLE TRANSITIONS IN SPECTRA OF 3-METHOXYF'TERIDIN-4(3H)-ONES

3-Metltoxypieridin-4(3H)-one; 123.1(178 + 148), 97.3(148 + 120), 72.1(120 + 93), 46.8(93 + 66). 3-Mefhoxy-2-methylpteridin-4(3H)-one; 136.7(192 + 162), 110.8(162 + 134), 90.4(162 + 121). 3-Methoxy-6-methylpteri~i~-4(3H)-one; 136.7(192 + 162), 1125(162 + 135), 110-8(162 + 134), 85.4(134 + 107), 59.8(107 + 80). 3-Methoxy-7-1i:ethylter~~in-4(3H)-one; 136.7(192 + 162), 110-8(162 + 134), 90.4(162 + 121), 85.4(134 + 107), 74.0(122 + 9 3 , 59.8(107 + 80); 48.7(95 + 68). 3-IVlethoxy-6,7-dirnethylpteridin-4( 3H)-one; 1 50.4(206 + 176), 1245 (1 76 + 148), 103.6( 1 76 + 135), 85.4(134 + 107).

differently from molecular ions produced from corresponding pteridinones (IV). The fact that CO loss was always important in the former but sometimes negligible in the latter may be due to a different location of the charge or a different energy distribution in the respective ions but it could also be due to the ions having different tautomeric forms as indicated by structures IV andf.

EXPERIMENTAL

Spectra were measured on an AEI MS-12 single focusing mass spectrometer with 70 eV ionising electrons, 8 kV accelerating voltage and 100 p A trap current. Samples were introduced on a direct insertion probe into an ion source maintained at 200". Compounds were prepared by published methods; pteridin-4(3H)-one,13 2-methyIpteridin-4(3H)-0ne,1~ 6-methylpteridin-4(3H)-0ne,1~ 7- methylpteridin-4(3H)-one,15 2,6-dimethyIpteridin-4(3H)-0ne,*~ 2,7-dimethylpteridin-4(3H)-0ne,~~ 6,7-dimethylpteridin-4(3H)-0ne,'~ 2,6,7-trimethylpteridin-4(3€€)-0ne~~ and 3-methoxypteridin-4(3H)- 0ne.1~

1002 JIM CLARK, RUTH MAYNARD and C. SMITH

R E F E R E N C E S 1. Part XXIII, J. Clark and F. S. Yates, J. Chem. SOC. (C) 2475 (1971). 2. A. R. Katritzky, Advan. Heterocyclic Chem. 1, 341 (1963). 3. D. J. Brown and S. F. Mason, J. Chem. SUC. 3443 (1956). 4. G. Spiteller and M. Spiteller-Friedmann, Monutsh. Chem. 93,1395 (1962); R. Lawrence and E. S.

5. T. Nishiwaki, Tetrahedron 22, 3117 (1966); 23, 1153 (1967). 6. T. J. Batterham, A. C. K. Triffett and J. A. Wunderlich, J. Chem. SOC. (B) 892 (1967). 7. I. R. Gelling, W. J. Irwin and D. G. Wibberley, J. Chem. Sue. (B) 513 (1969). 8. G. Spiteller and M. Spiteller-Friedmann, Monutsh. Chem. 93, 632 (1962). 9. T. Goto, A. Tatematsu and S. Matsuura, J. Org. Chem. 30, 1844 (1965).

Waight, J. Chem. SOC. (B) 1 (1968).

10. A. Tatematsu, T. Goto and S. Matsuura, Nippon Kuguku Zusshi 87, 1226 (1966). 11. J. B. Bapat, D. St.C. Black and R. F. S. Brown, Advan. Heterocyclic Chenz. 10, 199 (1969). 12. J. Clark and C. Smith, Qrg. Muss Spectrom. 5, 447 (1971). 13. A. Albert, D. J. Brown and H. C. S. Wood, J. Chem. SOC. 2066 (1956). 14. A. Albert and C. F. Howell, J. Chem. SOC. 1596 (1962). 15. A. Albert, D. J. Brown and G. Cheeseman, J. Chenz. SOC. 4219 (1952). 16. J. Clark and G. Neath, J. Chem. SOC. (C) 1112 (1966). 17. A. Albert, D. J. Brown and G. Cheeseman, J. Chem. SOC. 471 (1951). 18. J. W. Daley and B. E. Christensen, J. Am. Chem. SOC. 78,225 (1956). 19. J. Clark and C. Smith, J. Chem. SOC. (C) 2777 (1969).