Mass Spectroscopy of Natural Products 111-Mass Spectrometric Comparison of Lysergic Acid and 9,lO-Dihydrolysergic Acid J. Schmidt, R. Kraftt and D. Voigt Research Centre for Molecular Biology and Medicine of the Academy of Sciences of the GDR, Institute of Plant Biochemistry, 402 Halle/S., Weinberg 3, GDR
The influence of the 9,lO-double bond in the ergoline skeleton on the fragmentation behaviour of lysergic acid and 9,lO-dihydrolysergic acid is discussed. The main fragmentation pathways were determined using high resolution mass spectrometry and metastable ion studies. The 70 eV electron impact spectra are compared with the 12 eV electron impact spectra and the negative ion mass spectra (2-4 eV).
~
~~
INTRODUCTION In the last few years, several reports have appeared dealing with mass spectrometric investigations of ergoline derivatives.'-6 It was established, that the fragmentation processes of these compounds are greatly influenced by the sidechain at C-8, the double bond between positions 9 and 10, and the substituents at N-6.3 A comparison of the mass spectral behaviour of lysergic acid (1)and 9,lO-dihydrolysergic acid (2) should especially reflect the influence of the 9,lO-double bond.
(source temperature 160 "C, electron current 500 PA, accelerating voltage 8 kV). The high resolution mass measurements were obtained from a Varian MAT 71 1 for 1 and a JEOL JMS-D 100 for 2. The metastable ions occurring in the first field free region were measured on an AEI MS 902 by scanning the accelerating voltage with fixed electric sector voltage and fixed magnetic field' within a range of 4-8 kV and 2-8 kV ( m l e 127). The negative (2-4 eV) ion mass spectra were obtained on an electron attachment mass spectrograph ('Elektronenanlagerungsmassenspektrograph') of the Research Institute 'Manfred von Ardenne', Dresden, G D R (unheated ion source, inlet temperature 100 "C, electron current 10 mA, accelerating voltage 40 kV). The low energy electrons were produced in a low pressure plasma (discharge gas argon).8 The source pressure was lo-' Torr, the analyser pressure lop6Torr.
RESULTS AND DISCUSSION Using high resblution mass spectrometry and metastable ion studies, the important fragmentation pathways of these compounds have been studied. The main differences indicated by a comparison of the 70 eV and 1 2 eV E I spectra as well as the negative ion mass spectra (2-4 eV) are also discussed. The results should both provide a possibility of distinguishing between ring D saturated and unsaturated ergolines and be a basis for mass spectrometric investigations of lysergic acid and 9,lO-dihydrolysergic acid derivatives.
EXPERIMENTAL ~~
~~
~
~~
The 7 0 e V and 1 2 e V low resolution E I spectra were recorded using an AEI MS 902 mass spectrometer
t Central Institute of Molecular Biology, 1115 Berlin-Buch, Lindenberger Weg 70, GDR.
Scheme 1 shows the proposed fragment ions originating from the molecular ion of lysergic acid (1). These fragmentation processes include the ring D of the ergoline skeleton and the attached substituents in the N-6 and C-8 positions. The origin of ion a ( m / e 267) can be explained by a hydrogen loss at C-5 because the formation of immonium ions seems to be favoured.' Ion e ( m / e 225) is formed via a retro Diels-Alder p r o ~ e s s .This ~ reaction includes the loss of the N-6 methyl group. The corrected ion abundance ratio [M CHJ+/[M - C2H5N]+of 0.2 shows the predominance of the energetically favoured retro Diels-Alder reaction with respect to the loss of methyl (ion b ) . The ion at m / e 224 appears as a doublet with an abundance ratio 1JIf of 24.0. Here the COz elimination represents the main process. The loss of COZis thermally influenced in 1,but a quantitative estimation of this thermal influence is difficult under the given experimental conditions. The [M-l]+ ion is the parent ion of further fragmentations (Scheme 2). Loss of water leads to m / e 249
CCC-0306-042X/78/0005-0674$02.50 674 BIOMEDICAL MASS SPECTROMETRY, VOL 5,
NO. 12, 1978
@ Heyden & Son Ltd, 1978
MASS SPECTRA OF LYSERGIC ACID AND 9,lO-DIHYDROLYSERGIC ACID
(jj
1:
CO
COOH
-CH,
m / e 249 ( 1 1 Yo)
a, m i e
267 (21%)
m / e 221 (41%)
1
-CH~N
- H.1
H
COOH
Q -
E h - C H ,
a, m / e 267 (21%)
m*
-
m l e 192 (49%)
m / e 248 (1.7%) -COI
YOOH
m*
b, m / e 253 (3.3%)
1'
m l e 220 (16%) c, m / e
"a
250 (20%)
d, m / e 239 (2.0%)
YOOH
1' e, m / e 225 (20%)
m l e 205 (28%)
Scheme 2. Fragmentation pathways from the [M - l]+ ion of 1.
1.O, is included in these pathways. Subsequent fragmentation of ion e leads to m / e 154 representing a conjugated system. Expulsion of HCN from m / e 154 yields m / e 127. A similar process occurs in indole. Deuterium labelling experiments in indole showed that predominantly the C-2 hydrogen is eliminated in this reaction." While the ion at m / e 168 arises directly from ion g (Scheme 4) by loss of C3H6N (cleavage of bonds C5-N-6 and C-8-C-9), ion m / e 167 represents the result of a ring expansion described in an earlier paper.'
YOOH f, m l e 224 (2.8%)
1: 0 - C H ,
:1
co
1'
COOH
1'
-C2H5N
g, m l e 224 (68%)
E N - C H .
c, m / e
7 -
-
_c
250 (20%)
m / e 207 (18%)
e, m / e 225 (20%)
CiJW'JO -6 H 3 l
- C O O H l mr
h, m / e 223 (43%)
HCOOH
+
0 - C H ,
1:
k, m / e 222 (21%)
I
.
Scheme 1. Fragmentation of the molecular ion of 1. The loss of water is also influenced by a weak thermal effect.
and this ion should be the precursor of m / e 248, although such a step is energetically unfavourable. The subsequent fragmentations are supported by metastable ions. Scheme 3 shows the fragmentation processes of ions c and e (see also Scheme 1). The origin of the doublet at m / e 207, appearing with an abundance ratio of about @ Heyden & Son Ltd, 1978
m / e 235 (4.4%) - C O ~m*
m / e 180 ( 5 1 % ) -C2HzI m*
_.
H
Scheme 3. Fragmentation pathways of ions c and e of 1.
BIOMEDICAL MASS SPECTROMETRY,.VOL. 5,
NO. 12, 1978 675
J. SCHMIDT, R. KRAFT AND D . VOIGT
[MI? m/e 268 (100%) -co/ g, m/e 224 (68%)
h, m/e 223 (43%)
FOOH m/e 269 (6.4%)
Q-CH,
m/e 194 (14%)
m/e 168 (14%)
COOH I m/e 255 (2.1"A)
m/e 167 (26%) m/e 252 (1.2%)
Scheme 4. Origin of the ions at mle 194 and rnle 167 of 1.
The EI spectrum of 9,lO-dihydrolysergic acid (Fig. 2) shows fragment ions having decreased abundances compared with the spectrum of lysergic acid (Fig. 1). The molecular ion of 2 has an increased stability. Ions arising from the molecular ion of 2 are presented in Scheme 5. In contrast to 1, the loss of the N-6 methyl group is
mle 227 (0.7%)
m/e 226 (1.8%) 268 [ M I '
224
m/e 225 (5.2%)
L 250
100
I50
200
HCOOH
m/e 224 (3.2%)
7
+CHI
m/e
Figure 1. The 70 eV El spectrum of lysergic acid (1).
t6HgN02
m/e 144 (22%)
-7+
H Scheme 5. Fragmentation of the molecular ion of 2. The loss of water is also influenced bv a weak thermal effect.
q
-z Iml 50
100
200
I50
250
m /P
Figure 2. The 70 eV El spectrum of 9.10-dihydrolysergic acid (2).
676 BIOMEDICAL MASS SPECTROMETRY, VOL 5,
NO. 12,
1978
realized predominantly by radical abstraction from the molecular ion. The corrected ion abundance ratio [M CH3]+/[M- C2H5N]+' of 4.0 supports this fact. The formation of ion m / e 144 can only take place via a rearrangement including a double hydrogen migration. Such a double hydrogen migration was also observed in the mass spectra of androstanes." In the present case three bonds must be broken (C-5-N-6, C-5-C-10 and C-10-C-11) and this reaction is made possible by a migration of a C-7 hydrogen to C-5 and a C-9 hydrogen @ Heyden & Son Ltd, 1978
MASS SPECTRA OF LYSERGIC ACID AND 9,lO-DIHYDROLYSERGIC ACID
'"1
I223
Table 1. Abundance ratios of some daughter ions produced by simple cleavage and rearrangement reactions at 70 eV and 12 eV Abundance ratio 1 2 70eV 12eV 70eV 12eV
191
50 0
IM -C,H,N]'/[N - COOH]' [M -CO,I+/[M- COOHI+ [M - HCOOHl+/[M - COOHI+ [M - &HsN021f/[M - COOHI'
.c
0 al
a
0.7 21.0 2.8
0.2 1.5 0.4
0.2 0.3 4.4
0.5 7.7 27.0
0 100
I50
200
250
m/e
m / e 225 (5.2%)
1
Figure 3. The 2-4eV negative ion mass spectrum of lysergic
- ~ 2 ~ m*q
acid (1).
N-CH,
7
- HCOOH
[M-l]+
-C3H40;
m / e 269 (6.4%)
to C-11 via a 4-membered mechanism. It may be concluded that this step presumes a saturated ring D system. Therefore, the appearance of an m / e ion 144 represents a possibility of distinguishing between ring D saturated and unsaturated ergoline derivatives. This ion has been also observed in mass spectra of other ring D saturated ergolines, e.g. in ~ l a v i n e s . ' . ~ The influence of the 9,lO-double bond in the ergoline skeleton is also shown in the formation of an ion at m / e 182, which is formed by abstraction of the carboxylic group from m / e 227. A similar reaction occurs in 1 ( m / e 225 -+m / e 180). However, the resulting shift of the corresponding peak to m / e 182 is not clear evidence for a saturated system, because an isobaric ion is observed in the mass spectra of N-6-demethyl lysergic acid derivatives.' In contrast to 1 the stable aromatic systems at m / e 167 and m / e 154 arise directly from the [M-l]+ ion (Scheme 6). The ion at m / e 197 is formed both from the [M- l]+ ion by loss of C3H402 (cIeavage of bonds N-6-C-7 and C-8-C-9) and m / e 225 by loss of C2H4. Corresponding processes in 1 are not observed. In general the 70 eV and 12 eV E I spectra show the same fragmentation pattern. The relative abundances of all fragment ions are decreased in the low eV EI spectra. However, comparison of daughter ion abundances due to a simple cleavage reaction at 70 eV and 12 eV (Table 1) indicates that rearrangement processes are favoured energetically in the low voltage region. Lower activation
IOC
269[M-l]-
-z
0)
c
V 0 3
$? 51 j
I
225
I44
100
150
194
200
I 250
m/e
Figure 4. The 2-4eV negative ion mass spectrum of 9,lO-dihydrolysergic acid (2).
@ Heyden &Son Ltd, 1978
m / e 167 (15%)
g - C H 3
m*
m / e 154 (27%)
-HCN
I
m*
m / e 127 (l0'/0)
Scheme 6. Fragmentation pathways from the [M - 11' ion of 2.
energy processes dominate at low eV.I2A comparison of the abundance ratio [M - COz]+/[M-HCOOH1+ at 12 eV shows a remarkable difference between 1 (9.4) and 2 (0.06). The formation of ion m / e 144 in 2 (see Scheme 5) represents the main process at 12 eV (S.OYO). This fact indicates a rearrangement reaction requiring a very low activation energy (see also Table 1). The 2-4 eV negative ion mass spectra of lysergic acid and 9,lO-dihydrolysergic acid (Figs. 3 and 4) show remarkable differences. Both 1 and 2 form an [M- 11ion. While this ion represents the base peak in 2, its abundance in 1 is relatively low (31%). An important reaction in the negative ion fragmentation of both compounds is loss of the carboxylic group appearing in 1 as the base peak and in 2 with an abundance of 34%. The main skeleton fragment ions also occur in the 2-4 eV negative ion mass spectra, but some of these ions are shifted by one mass unit towards lower masses. If one compares the described mass spectra of 1 and 2 it can be stated that the molecular ion of the ring D saturated system is characterized by an increased stability. This fact should have consequences for the mass spectral fragmentation of correspondingly more complicated ergoline derivatives.
Acknowledgements We thank Professor Dr M. Hesse, Institute of Organic Chemistry, University of Zurich, Switzerland for recording the high resolution mass data of compound 1 and Dr W. Ihn, Central Institute of Microbiology and Experimental Therapy of the Academy of Sciences of the GDR, Jena, German Democratic Republic, for recording these data for compound 2.
BIOMEDICAL MASS SPECTROMETRY, VOL. 5, NO. 12, 1978 677
J. SCHMIDT, R. KRAFT AND D. VOIGT
REFERENCES 1. M. Barber, J. A. Weisbach, B. Douglas and G. 0. Dudek, Chem. lnd. (London) 1072 (1965). 2. Y. Nakahara and T. Niwaguchi, Chem. Pharm. Bull. 19,2337 (197 11. 3. T. Inoue, Y. Nakahara and T. Niwaguchi, Chem. Pharm. Bull. 20, 409 (1972). 4. D.Voigt, S. Johne and D. Groger, Pharmazie 29,697 1974). 5. J. Vokoun, P. Sajdl and Z. Rehacek, Zenfralbl. Bakferiol.; Abt. 2 129,499 (1974). 6. J. Vokoun and Z. Rehacek, CoUecf. Czech. Chem. Commun. 40, 1731 (1975). 7. M. Barber, W. A. Wolstenholme and K. R. Jennings, Nature (London)214,664 (1967). 8. M. von Ardenne, K. Steinfelder and R. Tummler, Elektronenanlagerungsmassenspekfrographie organischer Subsfanzen, p. 22 Springer-Verlag, Berlin (1971).
678 BIOMEDICAL MASS SPECTROMETRY, VOL 5, NO. 12, 1978
9. H. Budzikiewicz, C. Djerassi and D. H. Williams, Mass Spectrometry of Organic Compounds, p. 9 Holden-Day, San Francisco (1967). 10. J. C. Powers, J. Org. Chem. 33, 2044 (1968). 11. H. Grote and G. Spiteller, Org. Mass Spectrom. 11, 1297 (1976). 12. D. H. Williams and I. Howe, Principles of Organic Mass Spectromefry, p. 51. McGraw-Hill, London (1972).
Received 18 April 1978
@ Heyden & Son Ltd, 1978
@ Heyden & Son Ltd, 1978
The influence of the 9,lO-double bond in the ergoline skeleton on the fragmentation behaviour of lysergic acid and 9,lO-dihydrolysergic acid is discussed. The main fragmentation pathways were determined using high resolution mass spectrometry and metastable ion studies. The 70 eV electron impact spectra are compared with the 12 eV electron impact spectra and the negative ion mass spectra (2-4 eV).
~
~~
INTRODUCTION In the last few years, several reports have appeared dealing with mass spectrometric investigations of ergoline derivatives.'-6 It was established, that the fragmentation processes of these compounds are greatly influenced by the sidechain at C-8, the double bond between positions 9 and 10, and the substituents at N-6.3 A comparison of the mass spectral behaviour of lysergic acid (1)and 9,lO-dihydrolysergic acid (2) should especially reflect the influence of the 9,lO-double bond.
(source temperature 160 "C, electron current 500 PA, accelerating voltage 8 kV). The high resolution mass measurements were obtained from a Varian MAT 71 1 for 1 and a JEOL JMS-D 100 for 2. The metastable ions occurring in the first field free region were measured on an AEI MS 902 by scanning the accelerating voltage with fixed electric sector voltage and fixed magnetic field' within a range of 4-8 kV and 2-8 kV ( m l e 127). The negative (2-4 eV) ion mass spectra were obtained on an electron attachment mass spectrograph ('Elektronenanlagerungsmassenspektrograph') of the Research Institute 'Manfred von Ardenne', Dresden, G D R (unheated ion source, inlet temperature 100 "C, electron current 10 mA, accelerating voltage 40 kV). The low energy electrons were produced in a low pressure plasma (discharge gas argon).8 The source pressure was lo-' Torr, the analyser pressure lop6Torr.
RESULTS AND DISCUSSION Using high resblution mass spectrometry and metastable ion studies, the important fragmentation pathways of these compounds have been studied. The main differences indicated by a comparison of the 70 eV and 1 2 eV E I spectra as well as the negative ion mass spectra (2-4 eV) are also discussed. The results should both provide a possibility of distinguishing between ring D saturated and unsaturated ergolines and be a basis for mass spectrometric investigations of lysergic acid and 9,lO-dihydrolysergic acid derivatives.
EXPERIMENTAL ~~
~~
~
~~
The 7 0 e V and 1 2 e V low resolution E I spectra were recorded using an AEI MS 902 mass spectrometer
t Central Institute of Molecular Biology, 1115 Berlin-Buch, Lindenberger Weg 70, GDR.
Scheme 1 shows the proposed fragment ions originating from the molecular ion of lysergic acid (1). These fragmentation processes include the ring D of the ergoline skeleton and the attached substituents in the N-6 and C-8 positions. The origin of ion a ( m / e 267) can be explained by a hydrogen loss at C-5 because the formation of immonium ions seems to be favoured.' Ion e ( m / e 225) is formed via a retro Diels-Alder p r o ~ e s s .This ~ reaction includes the loss of the N-6 methyl group. The corrected ion abundance ratio [M CHJ+/[M - C2H5N]+of 0.2 shows the predominance of the energetically favoured retro Diels-Alder reaction with respect to the loss of methyl (ion b ) . The ion at m / e 224 appears as a doublet with an abundance ratio 1JIf of 24.0. Here the COz elimination represents the main process. The loss of COZis thermally influenced in 1,but a quantitative estimation of this thermal influence is difficult under the given experimental conditions. The [M-l]+ ion is the parent ion of further fragmentations (Scheme 2). Loss of water leads to m / e 249
CCC-0306-042X/78/0005-0674$02.50 674 BIOMEDICAL MASS SPECTROMETRY, VOL 5,
NO. 12, 1978
@ Heyden & Son Ltd, 1978
MASS SPECTRA OF LYSERGIC ACID AND 9,lO-DIHYDROLYSERGIC ACID
(jj
1:
CO
COOH
-CH,
m / e 249 ( 1 1 Yo)
a, m i e
267 (21%)
m / e 221 (41%)
1
-CH~N
- H.1
H
COOH
Q -
E h - C H ,
a, m / e 267 (21%)
m*
-
m l e 192 (49%)
m / e 248 (1.7%) -COI
YOOH
m*
b, m / e 253 (3.3%)
1'
m l e 220 (16%) c, m / e
"a
250 (20%)
d, m / e 239 (2.0%)
YOOH
1' e, m / e 225 (20%)
m l e 205 (28%)
Scheme 2. Fragmentation pathways from the [M - l]+ ion of 1.
1.O, is included in these pathways. Subsequent fragmentation of ion e leads to m / e 154 representing a conjugated system. Expulsion of HCN from m / e 154 yields m / e 127. A similar process occurs in indole. Deuterium labelling experiments in indole showed that predominantly the C-2 hydrogen is eliminated in this reaction." While the ion at m / e 168 arises directly from ion g (Scheme 4) by loss of C3H6N (cleavage of bonds C5-N-6 and C-8-C-9), ion m / e 167 represents the result of a ring expansion described in an earlier paper.'
YOOH f, m l e 224 (2.8%)
1: 0 - C H ,
:1
co
1'
COOH
1'
-C2H5N
g, m l e 224 (68%)
E N - C H .
c, m / e
7 -
-
_c
250 (20%)
m / e 207 (18%)
e, m / e 225 (20%)
CiJW'JO -6 H 3 l
- C O O H l mr
h, m / e 223 (43%)
HCOOH
+
0 - C H ,
1:
k, m / e 222 (21%)
I
.
Scheme 1. Fragmentation of the molecular ion of 1. The loss of water is also influenced by a weak thermal effect.
and this ion should be the precursor of m / e 248, although such a step is energetically unfavourable. The subsequent fragmentations are supported by metastable ions. Scheme 3 shows the fragmentation processes of ions c and e (see also Scheme 1). The origin of the doublet at m / e 207, appearing with an abundance ratio of about @ Heyden & Son Ltd, 1978
m / e 235 (4.4%) - C O ~m*
m / e 180 ( 5 1 % ) -C2HzI m*
_.
H
Scheme 3. Fragmentation pathways of ions c and e of 1.
BIOMEDICAL MASS SPECTROMETRY,.VOL. 5,
NO. 12, 1978 675
J. SCHMIDT, R. KRAFT AND D . VOIGT
[MI? m/e 268 (100%) -co/ g, m/e 224 (68%)
h, m/e 223 (43%)
FOOH m/e 269 (6.4%)
Q-CH,
m/e 194 (14%)
m/e 168 (14%)
COOH I m/e 255 (2.1"A)
m/e 167 (26%) m/e 252 (1.2%)
Scheme 4. Origin of the ions at mle 194 and rnle 167 of 1.
The EI spectrum of 9,lO-dihydrolysergic acid (Fig. 2) shows fragment ions having decreased abundances compared with the spectrum of lysergic acid (Fig. 1). The molecular ion of 2 has an increased stability. Ions arising from the molecular ion of 2 are presented in Scheme 5. In contrast to 1, the loss of the N-6 methyl group is
mle 227 (0.7%)
m/e 226 (1.8%) 268 [ M I '
224
m/e 225 (5.2%)
L 250
100
I50
200
HCOOH
m/e 224 (3.2%)
7
+CHI
m/e
Figure 1. The 70 eV El spectrum of lysergic acid (1).
t6HgN02
m/e 144 (22%)
-7+
H Scheme 5. Fragmentation of the molecular ion of 2. The loss of water is also influenced bv a weak thermal effect.
q
-z Iml 50
100
200
I50
250
m /P
Figure 2. The 70 eV El spectrum of 9.10-dihydrolysergic acid (2).
676 BIOMEDICAL MASS SPECTROMETRY, VOL 5,
NO. 12,
1978
realized predominantly by radical abstraction from the molecular ion. The corrected ion abundance ratio [M CH3]+/[M- C2H5N]+' of 4.0 supports this fact. The formation of ion m / e 144 can only take place via a rearrangement including a double hydrogen migration. Such a double hydrogen migration was also observed in the mass spectra of androstanes." In the present case three bonds must be broken (C-5-N-6, C-5-C-10 and C-10-C-11) and this reaction is made possible by a migration of a C-7 hydrogen to C-5 and a C-9 hydrogen @ Heyden & Son Ltd, 1978
MASS SPECTRA OF LYSERGIC ACID AND 9,lO-DIHYDROLYSERGIC ACID
'"1
I223
Table 1. Abundance ratios of some daughter ions produced by simple cleavage and rearrangement reactions at 70 eV and 12 eV Abundance ratio 1 2 70eV 12eV 70eV 12eV
191
50 0
IM -C,H,N]'/[N - COOH]' [M -CO,I+/[M- COOHI+ [M - HCOOHl+/[M - COOHI+ [M - &HsN021f/[M - COOHI'
.c
0 al
a
0.7 21.0 2.8
0.2 1.5 0.4
0.2 0.3 4.4
0.5 7.7 27.0
0 100
I50
200
250
m/e
m / e 225 (5.2%)
1
Figure 3. The 2-4eV negative ion mass spectrum of lysergic
- ~ 2 ~ m*q
acid (1).
N-CH,
7
- HCOOH
[M-l]+
-C3H40;
m / e 269 (6.4%)
to C-11 via a 4-membered mechanism. It may be concluded that this step presumes a saturated ring D system. Therefore, the appearance of an m / e ion 144 represents a possibility of distinguishing between ring D saturated and unsaturated ergoline derivatives. This ion has been also observed in mass spectra of other ring D saturated ergolines, e.g. in ~ l a v i n e s . ' . ~ The influence of the 9,lO-double bond in the ergoline skeleton is also shown in the formation of an ion at m / e 182, which is formed by abstraction of the carboxylic group from m / e 227. A similar reaction occurs in 1 ( m / e 225 -+m / e 180). However, the resulting shift of the corresponding peak to m / e 182 is not clear evidence for a saturated system, because an isobaric ion is observed in the mass spectra of N-6-demethyl lysergic acid derivatives.' In contrast to 1 the stable aromatic systems at m / e 167 and m / e 154 arise directly from the [M-l]+ ion (Scheme 6). The ion at m / e 197 is formed both from the [M- l]+ ion by loss of C3H402 (cIeavage of bonds N-6-C-7 and C-8-C-9) and m / e 225 by loss of C2H4. Corresponding processes in 1 are not observed. In general the 70 eV and 12 eV E I spectra show the same fragmentation pattern. The relative abundances of all fragment ions are decreased in the low eV EI spectra. However, comparison of daughter ion abundances due to a simple cleavage reaction at 70 eV and 12 eV (Table 1) indicates that rearrangement processes are favoured energetically in the low voltage region. Lower activation
IOC
269[M-l]-
-z
0)
c
V 0 3
$? 51 j
I
225
I44
100
150
194
200
I 250
m/e
Figure 4. The 2-4eV negative ion mass spectrum of 9,lO-dihydrolysergic acid (2).
@ Heyden &Son Ltd, 1978
m / e 167 (15%)
g - C H 3
m*
m / e 154 (27%)
-HCN
I
m*
m / e 127 (l0'/0)
Scheme 6. Fragmentation pathways from the [M - 11' ion of 2.
energy processes dominate at low eV.I2A comparison of the abundance ratio [M - COz]+/[M-HCOOH1+ at 12 eV shows a remarkable difference between 1 (9.4) and 2 (0.06). The formation of ion m / e 144 in 2 (see Scheme 5) represents the main process at 12 eV (S.OYO). This fact indicates a rearrangement reaction requiring a very low activation energy (see also Table 1). The 2-4 eV negative ion mass spectra of lysergic acid and 9,lO-dihydrolysergic acid (Figs. 3 and 4) show remarkable differences. Both 1 and 2 form an [M- 11ion. While this ion represents the base peak in 2, its abundance in 1 is relatively low (31%). An important reaction in the negative ion fragmentation of both compounds is loss of the carboxylic group appearing in 1 as the base peak and in 2 with an abundance of 34%. The main skeleton fragment ions also occur in the 2-4 eV negative ion mass spectra, but some of these ions are shifted by one mass unit towards lower masses. If one compares the described mass spectra of 1 and 2 it can be stated that the molecular ion of the ring D saturated system is characterized by an increased stability. This fact should have consequences for the mass spectral fragmentation of correspondingly more complicated ergoline derivatives.
Acknowledgements We thank Professor Dr M. Hesse, Institute of Organic Chemistry, University of Zurich, Switzerland for recording the high resolution mass data of compound 1 and Dr W. Ihn, Central Institute of Microbiology and Experimental Therapy of the Academy of Sciences of the GDR, Jena, German Democratic Republic, for recording these data for compound 2.
BIOMEDICAL MASS SPECTROMETRY, VOL. 5, NO. 12, 1978 677
J. SCHMIDT, R. KRAFT AND D. VOIGT
REFERENCES 1. M. Barber, J. A. Weisbach, B. Douglas and G. 0. Dudek, Chem. lnd. (London) 1072 (1965). 2. Y. Nakahara and T. Niwaguchi, Chem. Pharm. Bull. 19,2337 (197 11. 3. T. Inoue, Y. Nakahara and T. Niwaguchi, Chem. Pharm. Bull. 20, 409 (1972). 4. D.Voigt, S. Johne and D. Groger, Pharmazie 29,697 1974). 5. J. Vokoun, P. Sajdl and Z. Rehacek, Zenfralbl. Bakferiol.; Abt. 2 129,499 (1974). 6. J. Vokoun and Z. Rehacek, CoUecf. Czech. Chem. Commun. 40, 1731 (1975). 7. M. Barber, W. A. Wolstenholme and K. R. Jennings, Nature (London)214,664 (1967). 8. M. von Ardenne, K. Steinfelder and R. Tummler, Elektronenanlagerungsmassenspekfrographie organischer Subsfanzen, p. 22 Springer-Verlag, Berlin (1971).
678 BIOMEDICAL MASS SPECTROMETRY, VOL 5, NO. 12, 1978
9. H. Budzikiewicz, C. Djerassi and D. H. Williams, Mass Spectrometry of Organic Compounds, p. 9 Holden-Day, San Francisco (1967). 10. J. C. Powers, J. Org. Chem. 33, 2044 (1968). 11. H. Grote and G. Spiteller, Org. Mass Spectrom. 11, 1297 (1976). 12. D. H. Williams and I. Howe, Principles of Organic Mass Spectromefry, p. 51. McGraw-Hill, London (1972).
Received 18 April 1978
@ Heyden & Son Ltd, 1978
@ Heyden & Son Ltd, 1978
