2044
The Journal of Organic Chemistry
Powers
The Mass Spectrometry of Simple Indoles James C. Powers1 Contribution No. 2089 from the Department of Chemistry, University of California at Los Angeles, Los Angeles, California
90024
Received, October 2, 1967
The mass spectra of a variety of substituted indoles have been examined and the major fragmentation routes ascertained. Indole loses HCN and H2CN upon electron impact; the position of the hydrogen lost was established by examination of the spectra of deuterated indoles. Indoles substituted with methyl groups in the 1 ions due to the formation of azaazulenium ions. benzene ring give intense N-Methylindóle could be CH$ ion. Considerable distinguished from other isomers since it was the only methylindole to give an M scrambling was shown to take place upon electron impact of ary lindóles since loss of CH2N was an important fragment in the spectra of a variety of arylindoles. Indoles substituted with a methoxyl group in the 6 position could be distinguished from either the 5 or 7 isomer because of a more intense M CH3 ion and a less intense molecular ion. The mass spectra of several indole aldehydes, ketones, and carboxylic acid are discussed. Indole2- and 7-earboxylic acid derivatives show an “ortho effect” and can be differentiated from other isomers. From an examination of the spectra of several disubstituted indoles, it was concluded that one substituent preferentially directed the fragmentation. A scheme was derived which allows the prediction of which substituent this would be. Oxindoles can be characterized by the presence of a benzazetinium ion in their mass spectra. —
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Mass spectroscopy has become exceedingly important in the chemistry of natural products, and in particular, the chemist working with indole alkaloids is fortunate in being able to draw upon the wealth of information which is available due to the elegant work of Biemann and his coworkers at M.I.T. and Djerassi and his coworkers at Stanford on the mass spectra of these complex molecules.2 In contrast, the chemist or biochemist who is working with less complex indolic molecules is
unable to draw upon such a backlog of experience to aid in unraveling their mysteries. Simple indoles, although widely distributed in both the plant and animal kingdoms,3 have been neglected by the mass spectrosThis study was begun copist except for a few cases.4 in order to reverse this neglect. Indole.—The mass spectrum of indole has been reported.6 The molecular ion (m/e 117, base peak) loses HCN and H2CN to give strong peaks at m/e 90 (relative abundance 40%) and 89 (24%). These peaks are shifted one mass unit in the spectrum of 3-deuterioindole showing that Hc is not involved in either fragmentation. The loss of HCN involves both Ha and Hb. The spectrum of 1-deuterioindole is con5·6
The m/e 89 peak is not shifted in the spectrum of 1-deuterioindole indicating that most of the deuterium is lost with the H2CN fragment. No smaller fragment ions contained deuterium. Further fragmentation of indole gives rise to C5H3+ (m/e 63). This is partially shifted to m/e 64 in the spectrum of 3-deuterioindole and 1,3-dideuterioindole. This demonstrates that H0 and probably C-3 of indole are partially retained in this fragment. Methylindoles.—The mass spectra of a series of 11 alkylindoles including 2-methyl- and 3-methylindole have been investigated by Beynon and and Williams.6 The spectra of the remaining methylindoles have been determined and the data are presented in Table I. The spectra of 4-, 5-, 6-, and 7-methylindoIe are sur1 peak is the base peak in prisingly similar; the all cases. The similarity of the spectra is good evidence for the formation of a common intermediate in the fragmentation of these methylindoles. This is best represented as the azaazulenium ion l8 in analogy with the formation of tropylium ion from alkylbenzenes. This ion then sequentially loses HCN and two C2H2. —
Chart I
sistent with loss of 79% HbCN and 21% HaCN with transfer of the other hydrogen to the fragment ion.7 (1) Department of Biochemistry, University of Washington, Seattle, Wash. 98105. (2) (a) K. Biemann, “Mass Spectrometry: Organic Chemical Applications,” McGraw-Hill Book Co., Inc., New York, N. Y., 1962; (b) H. Budzikiewicz, C. Djerassi, and D. H. Williams, “Structure Elucidation of Natural Products by Mass Spectrometry,” Vol. 1, Holden-Day, Inc., San Franciscso, Calif., 1964. (3) B. B. Stowe in L. Zechmeister, Ed., “Fortschritte der chemie organise her Naturstoffe,” Vol. 17, Springer-Verlag, Vienna, 1959. (4) Mass spectroscopy has been invaluable in the structure determination of several naturally occurring indoleacetic acid and tryptophan derivatives. A. B. Lerner, J. D. Case, K. Biemann, R. V. Heinzelman, J. Szmuszkovicz, W. C. Anthony, and A. Krivis, J. Amer. Ckem. Soc., 81, 5264 (1959); J. C. Sheehan, P. E. Drummond, J. N. Gardner, K. Maeda, D. Mania, S. Nakamura, A. K, Sen, and J. A. Stock, ibid., 85, 2867 (1963); M. S. v. Wittenau and H. Els, ibid., 85, 3425 (1963). (5) J. H. Beynon and A, E. Williams, Appl. Spectrosc., 13, 101 (1959); 14, 27 (1960); J. H. Beynon, “Mass Spectroscopy and Its Application to Organic Chemistry,” Elsevier Publishing Co., Amsterdam, 1960, pp 397-403. (6) Catalog of Mass Spectra Data, American Petroleum Institute Research Project 44, Carnegie Institute of Technology, Pittsburgh, Pa., spectra no. 623.
Yn
-HCN
C7H5+, m/e 89
3, m/e 116 (7) The calculation of the isotopic distribution in fragments from a labeled compound is beset with several pitfalls (ref la, Chapter 5), and these numbers should be considered approximate. 1 (8) The mass spectrum of 7-methylbenzofuran has an intense (49%) peak. This has been postulated to have an oxonium ion structure analogous to 1. R. I. Reed and W. K. Reid, J. Chem. Soc., 5933 (1963). —
Mass Spectrometry
Vol. S3, No. 5, May 1968
m/e
1- ß»
131 130 116 103 102
100 83
Table I Mass Spectra of Methylindoles 2-Me6·1 3- ß« 4-Meá
of
Simple Indoles
2045
5-Me”
6-Me/
7-Me»
85 100
69 100
76 100
79 100
77 100
100
17
15
16
15
5
8
7
10 5
11
7 11
3 4
1 1
2
28
2 21
1
19 10 5 7
15
16
20
16 4
8
5
3
4 8
2 4
3
11
3 5
78
11
90 89 77 65 63
22 12 11
8
51
1
81.60
Metastable
130
peaks
130
68.20 116
103
-*
57.50
89
—
6
81.60
103
-*
9 7
5
130
—
77
57.50 103
Registry numbers
are as
77
—
follows:
»
603-76-9;
6
95-20-5;« 83-34-1;
j
16096-32-5;
·
614-96-0;
>
h
3420-02-8;» 933-67-5.
See
ref 5.
Table II Mass Spectra of Arylindoles
HCN
M M M
C6H6
-
-
-
-
M
-
-
-
-
2-C.H.V
1-C.Hj»
m/e
M+ M M M M
3-C.Hs'
3.(2-Py)
