fragmentation patterns in the electron-impact mass spectra

8/12/2019 Fragmentation Patterns in the Electron-Impact Mass Spectra

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Chromone Studies. Part 12.1 Fragmentation Patterns in the

Electron-impact Mass Spectra of

2-(N,N-Dialkylamino)-4H-1-benzopyran-4-ones and

-naphthopyran-4-ones

Perry T. Kaye* and Isaiah D.I. Ramaite#

Department of Chemistry, Rhodes University, Grahamstown, 6140 South Africa.

Received 23 October 2002; revised and accepted 26 February 2003.

ABSTRACT

The major electron-impact mass fragmentation patterns exhibited by 2-(N,N-dialkylamino)-4H-1-benzopyran-4-ones and

-naphthopyran-4-ones have been explored using a combination of low-resolution, high-resolution and B/Elinked-scan data.

KEYWORDS

2-Aminochromones, 2-amino-4H-1-benzopyran-4-ones, mass spectrometry, fragmentation patterns.

Chromone (4H-1-benzopyran-4-one) derivatives are widely dis-tributed in nature and many exhibit interesting biologicalactivity.2 The synthetic bischromone derivative, sodium cromo-glycate, is used in the treatment of bronchial asthma,3 whilevarious 2-aminochromones have been shown to exhibitanti-platelet acitivity.4 As part of an ongoing study of chromonederivatives, we have examined the influence of substituents on,amongst others, C(2)N rotational barriers in N,N-disubstituted2-aminochromones5 and the basicity of 2-(N,N-dimethylamino)

analogues.6 In this communication we discuss the results of amass spectrometric study of a series of variously substitutedN,N-disubstituted 2-aminochromone derivatives112.

We have reported the use of several established methods toaccess the title compounds112(Scheme 1).5 Thus, the 2-(N,N-dimethylamino) derivatives15,11 and 12 were convenientlyobtained from the correspondingo-hydroxyacetophenones13,following the method reported by Morris et al.7 Compounds1and 68 were prepared using the approach of Bantick andSuschitzky,8 involving reaction of 2-ethylsufinyl-4H-1-benzo-pyran-4-one 15 (obtained, in turn, from the thiolactone 14) witheach of the secondary amines dimethylamine, diethylamine,piperidine and pyrrolidine. Treatment of methyl salicylate

precursors 16 with thelithium enolate ofN,N-dimethylacetamide,and cyclization of the resulting intermediates 17 mediated bytrifluoromethanesulfonic anhydride,7 afforded the 2-amino-chromones1and9, while the parent system1and the methoxyanalogues 5 and 10 were obtained from the (N,N-dimethyl-carbamoyl)acetate ester18and the corresponding phenols19.9

The electron-impact (E.I.) mass fragmentation patterns exhib-ited by the N,N-disubstituted 2-aminochromone derivatives112 were studied using a combination of low-resolution,high-resolution and B/E linked-scan data. The fragmentationpathways proposed for the parent system, 2-(N,N-dimethyl-amino)-4H-1-benzopyran-4-one 1, are outlined in Scheme 2,while Table 1 summarizes them/zand relative abundance datafor the corresponding fragments for compounds112.

Themolecular ion1a (m/z 189;Scheme2) isalsothe basepeak

a patternexhibited bymost of thecompoundsexamined, reflect-ingthe stabilityof thehighlydelocalizedsystems 112.Nofewerthan five distinct fragmentations of the molecular ion may beidentified (cf. Paths IV; Scheme 2). In path I [1a 1b (m/z 174)],loss of a methyl radical affords an even-electron species, formu-lated as an iminium cation. This fragmentation appears to becommon to all of the 2-(N,N-dimethylamino) derivatives (15and 912). In fragmentations supported by the linked-scandata,the diethylamino analogue 6 loses methyl and ethyl radicalsfrom the molecular ion (Scheme 3), presumably to afford thecorresponding iminium cations6b(m/z202) and6m(m/z188).Subsequent elimination of ethylene from the iminium cation 6bwould then account for the iminium cation6n(m/z174).

The 2-piperidino- and 2-pyrrolidino derivatives (7 and 8,respectively) each lose an -hydrogen atom to give the corre-sponding cyclic iminium cations 7o and 8o (Scheme 4). The2-piperidino system7also loses a methyl radical to afford, it issuggested, a ring-contracted fragment 7bidentical to 8o. A veryweak peak atm/z200 (


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Short Communication P.T. Kaye and I.D.I. Ramaite, 26

S. Afr. J. Chem., 2003, 56, 2529,

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Scheme 1Reagents and conditions:i, BF3OEt2, Et2O;ii, [Cl2C=NMe2]

+ Cl, Cl(CH2)2Cl;iii, MeOH, 50 C;iv, K2CO3, EtI, (CH3)2CO;v, MCPBA, Cl(CH2)2Cl;vi, R2NH (i.e.R

1H);vii, LDA, THF;viii, MeCONMe2;ix, Tf2O, CH2Cl2;x, POCl3, C6H5Cl;xi, NaOAc, H2O, 9095C.

Scheme 2E.I. mass fragmentation pathways for 2-(N,N-dimethylamino)-4H-1-benzopyran1, all of which are supported by B/Elinked-scan data. Accurate

masses (m/z) are followed, in brackets, by calculated masses.


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Table 1 Selected peaks (m/z), followed, in brackets, by percentage relative abundance from the E.I. mass spectra of the 2-(N,N-dialkylamino)-4H-1-benclassified according to ion typesal(Scheme 2).

Compd R1 R2 R3 R4 R5 a b c d e f g

1 NMe2 H H H H 189a 174a 161a 160a 148 a 147 a 146a 12

(100) (20) (9) (7) (8) (16) (62) (1

2 NMe2 H H Br H 267a,b 254b 241b 240b 228b 227 b 226b 20

(60) (10) (5) (3) (4) (10) (37) (

3 NMe2 H H F H 207a 192 179 178 166 165 164 1

(100) (18) (6) (5) (9) (17) (47) (1

4 NMe2 H H Cl H 223a,c 208c 195c 194c 182 c 181 c 180c 15

(100) (20) (11) (5) (30) (17) (52) (

5 NMe2 H OMe H H 219a 204a 191 190 178 177 176 1

(100) (23) (4) (7) (26) (7) (26) (

6 NEt2 H H H H 217a 202a,d d d d 147 a 146a 12

(100) (58) (3) (3) (4

7 Piperidino H H H H 229 a 214a e e e 147 a 146a 1(100) (20) (6) (15) (2

8 Pyrrolidino H H H H 215 a 200a e e e 147 a 146a 1(100) (


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Retro-Diels-Alder (RDA) fragmentations are common inchromone systems11 and are exemplified by the [RDA + H]+

fragmentation1a 1h(m/z121; Path V); subsequent loss of Hand CO, with concomitant ring-contraction, then leads to thecyclopentylidene ketene species 1l (m/z 92). The ketene frag-ments 1i and 1l could also beformed directly fromthe chromoneradical cation1gviaknown RDA and [RDA CO] fragmenta-tions,11 respectively.

Thefragmentationpatterns illustratedfor the parent system 1in Scheme 2 are all supported by the B/Elinked-scan data and

appear to be representative, with a few exceptions, of the entireseries of compounds examined (Table 1). Not surprisingly, themethoxy derivatives5and10exhibit additional fragmentationsassociated with characteristic12 fission of theO-methyl ether link(Scheme 5).

Experimental

The preparation and characterization of the 2-(N,N-dialkyl-amino)chromones 112 have been reported previously.5

Low-resolution mass spectra were obtained on a Hewlett-


S. Afr. J. Chem., 2003, 56, 2529,

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Scheme 3Fragmentations exhibited by compound6, all of which are supported byB/Elinked-scan data.

Scheme 4Fragmentations exhibited by compounds7and8, all of which are supported byB/Elinked-scan data.

Scheme 5Additional fragmentations exhibited by the methoxy analogues5and10, all of which are supported by B/Elinked-scan data.


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Packard 5988A mass spectrometer, while high-resolution andB/E linked-scan data were obtained on Kratos MS80RF orVG70-SEQ Micromass double-focusing instruments (CapeTechnikon Mass Spectrometry Unit).

Acknowledgements

The authors thankthe Deutscher Akademischer Austauchdienst(DAAD)and theNational Research Foundation (NRF) for bursa-ries (to I.D.I.R.), Rhodes University and the NRF for generousfinancial support and Mr A. Sonemann and Dr P. Boshoff forobtaining the low- and high-resolution data, respectively.

References

1 Part 11.C.A. Gray, P.T. Kayeand A.T. Nchinda,J. Chem.Res., 2002,321.

2 G.P. Ellis,Chromenes, Chromanones and Chromones,Wiley, New York,1977, p. 1 ff.; J. Staunton, in Comprehensive Organic Chemistry (D.Bartonand W.D.Ollis,eds.), vol.4, Pergamon, Oxford,1974, p. 659 ff.;

J.A. Lpez, W. Barillas, J. Gomez-Laurito, G.E. Martin, A.J. Al-Rehaily,M.A. Zemaitis and P.L. Schiff,J. Nat. Prod.,1997,60, 24.

3 J.S.G. Cox, J.E. Beach, A.M.J.N. Blair, A.J. Clarke, J. King, T.B. Lee,

D.E.E. Loveday, G.F. Moss, T.S.C. Orr, J.T. Ritchie and P. Sheard,Adv. Drug Res.,1970,5, 115.

4 J. Morris, D.G. Wishka, A.H. Lin, W.R. Humphrey, A.L. Wiltse, R.B.Gammill, T.M. Judge, S.N. Bisaha, N.L. Olds, C.S. Jacob, C.L. Bergh,M.M. Cudahy, D.J. Williams, E.E. Nishizawa, E.W. Thomas, R.R.Gorman, C.W. Benjamin and R.J. Shebuski,J. Med. Chem., 1993,36,2026.

5 P.T. Kaye and I.D.I. Ramaite,J. Chem. Res. (S),1997, 414.6 P.T. Kaye,A.T. Nchinda, L.V. Sabbagh and C. McCleland,J. Chem. Res.,

2000, 237.

7 J. Morris, D.G. Wishka and Y. Fang,J. Org. Chem., 1992,57, 6502.

8 J.R. Bantick and J.L. Suschitzky,J. Heterocycl. Chem., 1981,18, 679.

9 A.Ermili, A.Balbi, M.Di Braccio and G.Roma, Farmaco. Ed. Sc., 1977,32, 713.

10 R.M.Silversteinand F.X.Webster, Spectrometric Identificationof OrganicCompounds,6th edn., Wiley, New York, 1998, p. 30.

11 P.J. Brogden, C.D. Gabbutt and J.D. Hepworth, in ComprehensiveHeterocyclic Chemistry(A.J. Boulton and A. McKillop, eds.), vol. 3,Pergamon, Oxford, 1984, p. 613.

12 S.F. Dyke, A.J. Floyd, M.Sainsbury andR.S. Theobald,An Introductionto Organic Spectroscopy,Penguin, London, 1971, p. 188 ff.


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fragmentation patterns in the electron-impact mass spectra

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