collision-induced dissociations of enolate negative ions. deprotonated cyclohexanones

International Journal of Mass Spectrometry and Zon Processes, 79 (1987) 267-285 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands

267

COLLISION-INDUCED DISSOCIATIONS OF ENOLATE NEGATIVE IONS. DEPROTONATED CYCLOHEXANONES

MARK J. RAFTERY and JOHN H. BOWIE

Department of Organic Chemistry, University of Adelaide, Adelaide, South Australia 5001 (Australia)

(First received 6 July 1987; in final form 11 August 1987)

ABSTRACT

The retro reaction of the cyclohexanone enolate ion is specific, involving loss of ethene from the 3,4 (4,5) positions. Similar reactions occur for all alkyl-substituted cyclohexanone enolates. 3-Substituted cyclohexanones form two enolate ions and, in these cases, the predominant retro reaction is that in which the larger olefin is eliminated. Loss of H, is the major fragmentation of all cyclohexanone enolate ions. There are two losses of H,, from the 3,4 and 3,6 positions with the former being the more pronounced. 3Alkylcyclohexanone enolates also lose RI-I (R is the 3-alkyl substituent); there are two discrete mechanisms directly analogous to the losses of H,. 3Substituted cyclohexanones undergo a unique reaction which involves two specific proton transfers; for example, the 3-methylcyclohexanone ion + MeCOCH; +C,H,, with the two transferring protons coming from the methyl group and the 4 position. 2Substituted cyclohexanone ions also undergo retro reactions and loss of H,, but when the substituent > Et, characteristic elimination of an olefin (with proton transfer from the 1’ position) occurs from the side chain.

INTRODUCTION

Enolate negative ions may be produced from alkyl ketones with HO- in a chemical ionization source of a mass spectrometer [l]. Collision-induced fragmentations of ketone enolate ions have been explored in several labora- tories [2-lo]; such data provide structural information [ll-131 and funda- mental information concerning ion behaviour [ll-131. The basic fragmentations of alkyl enolate ions are illustrated by reference to heptan-4-one. The losses of methane and ethene are the major decomposition channels of the heptan-4-one enolate ion and the reaction pathways are shown in Eqs. (1) and (2) *. In the stepwise process (l), steps a and b are both rate-determining, while in reaction (2), step c is rate-determining [7].

* Enolate ions are -C-CH- @ -C=CH-. The carbanion form is used throughout this paper

merely for convenience of representation.

0168-1176/87/$03.50 0 1987 Elsevier Science Publishers B.V.

0

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Cyclohexanone enolate anion fragments by loss of H, and ethene [4,5,14] and it has been suggested that ethene loss occurs as shown in Eq. (3) [4,5]. In this paper, we describe the basic fragmentations of cyclohexanone and alkylcyclohexanone enolate ions. The study was aided by examination of the spectra of a variety of deuterium-labelled derivatives. The aims of this study were: (i) to confirm that the characteristic retro process of cyclohexanones occurs by the simple mechanism shown in Eq. (3); (ii) to determine the fragmentations of differently substituted alkylcyclohexanone enolate ions; and (iii) to investigate whether fragmentations analogous to those shown in Eqs. (1) and (2) occur for 2-substituted cyclohexanones stituent is >, ethyl.

where the sub-

EXPERIMENTAL

Collisional activation (CA) mass spectra were recorded with a vacuum generators ZAB-2HF mass spectrometer [19] operating in the negative chemical ionization mode [20]. All slits were fully open to obtain maximum sensitivity and to minimise energy-resolution effects [21]. The chemical ionization slit was used in the ion source, the ionizing energy was 70 eV (tungsten filament), the ion source temperature 150 O C, and the accelerating voltage 7 kV. Enolate anions were generated from -C(O)CH(R,R,) by HO- (or H- or O-*) and from compounds -C(O)CD(R,R,) by DO- (or D- or O-‘). Reactant negative ions were generated from H,O or D,O using 70 eV electrons [22]. The indicated source pressure of H,O (or DzO) was 5 x 10e4 Torr. The cyclohexanone (or substituted cyclohexanone) pressure was typically 5 X 10F7 Torr. The cyclohexanone derivative under study was

269

introduced through the septum inlet which was maintained at 150” C. The estimated total pressure within the source was 10-l Torr. The pressure of He in the second collision cell is 2 X 10m7 Torr, measured by an ion gauge situated between the electric sector and the second collision cell. This produced a decrease in the main beam signal of ca. 10% and thus corre- sponds to essentially single-collision conditions.

Cyclohexanone, Cmethyl- and 4-ethylcyclohexanone were commercial samples. All the unlabelled 2-substituted (including 2-ethyl-4-methylcyclohexanone) [23] and 3-substituted cyclohexanones [24] are known and were prepared by reported methods. All (labelled and unlabelled) cyclohexanones were purified by vacuum distillation and their purity confirmed by ‘H NMR, 13C NMR, IR and MS. Deuterium incorporation was determined by either positive or negative ion mass spectrometry as appropriate.

The labelled compounds

Cyclohexanone 2,2,6,6-2H,, 2-methylcyclohexanone 2,6,6-2H3, 3-methylcyclohexanone 2,2,6,6- ’ H, , cyclohexanone-2,6,6- ‘H3,

4-methylcyclohexanone 2,2,6,6- ‘Hq, 2-ethyl- 3-ethylcyclohexanone 2,2,6,6-‘H,, 4-ethylcyclo-

hexanone 2,2,6,6- 2Hq, 2-n-propylcyclohexanone 2,6,6-2H3, and 3-n-propylcyclohexanone 2,2,6,6-‘H,, were all prepared in quantitative yield (‘H, or 2H, > 95%) by heating the appropriate cyclohexanone (0.1 g) with deuterium oxide (0.8 g) in a sealed glass ampoule for 16 h at 12OOC. Extraction into anhydrous diethylether (3 X 2.5 ml) followed by removal of the solvent gave the required deuterium-labelled cyclohexanone.

Cyclohexanone 3,3,5,5- *H4 This was made by a synthetic sequence based on that of Green et al. [25].

1,4-Cyclohexanedione mono-ethylene ketal [26] (1.0 g) and sodium deuter- oxide/deuterium oxide (2.0 mol dmm3, 5.1 ml) were heated in a sealed ampoule at 120°C for 16 h. Extraction of the ‘H, ketone into anhydrous diethylether (10 ml) followed by reduction with lithium aluminium hydride (0.2 g) gave the alcohol (0.96 g, 95% 2H, = 98%), which was converted to the tosylate by a standard method [27]. Yield: 0.81 g (53%); 2H, = 98%.

The tosylate (0.81 g) was heated under reflux for 48 h with anhydrous tetrahydrofuran (10 ml) and lithium triethylborohydride [28] (1.76 mol dmm3, 2.9 ml). The mixture was cooled to 0 O C, water (0.5 ml) then aqueous sodium hydroxide (15%, 5 ml), then aqueous hydrogen peroxide (30% 10 ml) were added, and the solution stirred at 20 O C for 24 h. Separation of the layers followed by removal of the solvent gave crude cyclohexanone ethylene ketal 3,3,5,5-2H, (0.25 g, 65%, 2H, = 98%), which was hgdrolysed in chloro- form/aqueous oxalic acid [29] to yield cyclohexanone 3,3,5,5-2H, (0.13 g, 75%, ‘H, = 98%).

270

Cyclohexanone 4,4-2Hz The synthesis of. this compound is the same as that of cyclohexanone

3,3,5,5-2H, to the tosylate stage, except that the initial deuterium exchange step is deleted and lithium aluminium deuteride replaces lithium aluminium hydride in the reduction step. The 4-2H,-4-tosylate is treated with lithium triethylborodeuteride to give crude cyclohexanone ethylene ketal 4,4-2H2, which was hydrolysed (as above) to yield cyclohexanone 4,4- 2 H, [25] (‘H,=99%).

2-Methylcyclohexanone 3,3,5,5- 2H4 Cyclohexanone 3,3,5,5-2H, (0.35 g) and cyclohexylamine (0.36 g) were

converted into the imine by a standard method [30] in 85% yield. The imine (0.5 g) in anhydrous, tetrahydrofuran (10 ml) was added (under nitrogen) to lithium di-isopropylamine (2.7 mmol) [from n-butyl lithium (1.6 mol dme3, 1.7 ml) and di-isopropylamine (0.3 g) in anhydrous tetrahydrofuran (5 ml)] at 0°C. The mixture was allowed to stand at 0” C for 5 min, then methyliodide (0.38 g) in anhydrous tetrahydrofuran (2 ml) was added and the solution stirred. at 0” C for 45 min. Aqueous ammonium chloride (saturated, 10 ml) was added, the organic layer separated, the aqueous layer was extracted with diethylether (2 X 7 ml), and the combined organic phase washed with aqueous sodium bisulphite (saturated, 10 ml), aqueous sodium chloride (2 x 10 ml), and dried (Na,SO,). Removal of the solvent gave 2-methylcyclohexanone 3,3,5,5-2H4 (0.2 g, 59%, 2H, = 98%).

3-Methylcyclohexanone 3,5,S2H,. l+Cyclohexanedione mono-ethylene ketal [25] (1.3 g) was converted into

the cyclohexyl imine by a standard procedure [30] (Yield: 1.5 g, 80%). Alkylation with methyl iodide (as for 2-methylcyclohexanone 3,3,5,5-2H, above) gave 2-methyl-1,Ccyclohexane dione mono-ethylene ketal (0.61 g, 57%), which was deuterated with deuterium oxide to yield 2-methyl-1,4- cyclohexane dione monoethylene ketal 2,6,6-2H3 ( 2H3 = 98%). Reduction to the alcohol (85% yield), conversion to the tosylate (65% yield) followed by reduction (83% yield) and removal of the protecting group (81% yield) (as outlined for cyclohexanone 3,3,5,5-2H,, above) gave 3-methylcyclohexanone 3,5,5-‘H, (0.07 g, ‘H, = 98%).

4-Methylcyclohexanone 3,3,5,5- 2Hq The tosylate from 4-hydroxycyclohexane ethylene ketal 3,3,5,5-2H, (see

cyclohexanone 3,3,5,5- 2Hq, above) was converted [31] into 4-iodocyclohexane ethylene ketal 3,3,5,5-2H, (78% yield).

To a suspension of copper cyanide (0.2 g) in tetrahydrofuran (10 ml) with methyl lithium (0.5 mol dmm3, 8.9 ml in tetrahydrofuran) at 0” C under

271

nitrogen, was added 4-iodocyclohexane ethylene ketal 3,3,5,5-*H, (0.2 g) in tetrahydrofuran (4 ml) and the mixture was stirred at 0” C for 6 h. The temperature was increased to 5 O C, whereupon aqueous ammonium chloride (saturated, 5 ml) and diethyl ether (15 ml) were added. The separated organic layer was washed with aqueous sodium bisulphite (2 N, 10 ml), aqueous sodium chloride (saturated, 10 ml), water (10 ml), then dried (Na,SO,). Removal of the solvent followed by T-tube vacuum distillation gave 4-methylcyclohexanone 3,3,5,5-*H, (0.065 g, 73%, *H, = 98%).

3-Methylcyclohexanone 4,4-IH, 1,4-Cyclohexane dione mono-ethylene ketal was converted to 2-methyl-

1,4-cyclohexane dione mono-ethylene ketal by the reaction sequence outlined above for 3-methylcyclohexanone 3,5,5-‘H,. This was transformed into 3-methylcyclohexanone 4,4-2H2 by the method outlined above for cyclohexanone 4,4-*Hz (*H, = 99%).

2-Propylcyclohexanone 3,3,5,5- *H, was made by the same procedure used for 2-methylcyclohexanone 3,3,5,5-*H,. 3-Ethyl- and 3-propylcyclohexanone 3,3,5,5-*H, were made by the same procedure used for 2-methylcyclohexanone 3,3,5,5- *H,. 4-Ethylcyclohexanone 3,3,5,5- *H, was made by the analogous procedure used for 4-methylcyclohexanone 3,3,5,5-2H4. 2- (Ethyl-l,l-2H2) cyclohexanone was made from MeCD,I by a standard procedure [23].

RESULTS AND DISCUSSION

Collisional activation (CA) mass spectra were measured using a VG ZAB 2HF mass spectrometer operating in the chemical ionization mode. Depro- tonation of cyclohexanones was effected using HO- or DO- reagent ions as appropriate. Collisional activation was achieved using He in the second collision cell. Full experimental details are recorded in the Experimental section, above.

Compounds used in this study are listed in Tables l-4. The CA mass spectra of 2-, 3-, and 4-methylcyclohexanone and 2-ethyl Cmethylcyclo- hexanone enolates are shown in Figs. 1-4; all other spectra are listed in Tables 1-4.

The cyclohexanone enolate anion

The CA mass spectra of the cyclohexanone enolate ion and of the three deuteriated derivatives are listed in Table 1. Competitive losses of H; H,, C,H,, and C,H, are observed from cyclohexanone. All peaks have major collision-induced components (see footnote ‘, Table 1). The loss of ethene is

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(5) HCECO- + C.,He f-- b- - b- + H’ (4)

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Scheme 1.

completely specific and presumably occurs as shown in Eq. (3). The peak corresponding to loss of C,H, has no fine structure, is steep-sided with a rounded top, and is very wide. The width at half-height is 99 V, in keeping with a reaction having a reverse energy barrier. This is a feature of all retro reactions of this type examined in this study. The elimination of H’ and the formation of HC,O- are characteristic of ketone enolates and the processes are summarized in Eqs. (4) and (5) *, respectively. There are two losses of H,; the major process involves elimination of H, from the 3 and 4 positions [Eqn. (6), Scheme 11, the minor process elimination from the 3 and 6 positions [Eq. (7)]. These reactions clearly proceed through a hydride ion complex (a, Scheme l), in accord with the simple rules for carbanion fragmentations enunciated earlier [13,15]. The product ions of Eqs. (6) and (7) undergo minor fragmentation to produce the phenoxide negative ion plus H, (see Scheme 1).

The methylcyclohexanone enolate ions

The CA mass spectra of 2-, 3-, and 4-methylcyclohexanones are shown in Figs. l-3; these different spectra demonstrate the analytical applicability of

* The spectrum (Table 1) of [(cyclohexanone 2,2,6,6-D,)-D+ ] shows both DC20- and H&O- (6 : 1). This indicates partial H/D exchange at positions 2,3(5,6), a process which does not occur for alkyl-substituted cyclohexanones (see Tables 2-4).

276

0

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I &: 107

(xi01

E volts -

Fig. 1. CA mass spectrum of enolate ions from 2-methylcyclohexanone. For experimental conditions, see Experimental section. Width of major peaks at half height, m/z (voltsf0.3) loss; 109 (44.1) H,, 83 (93.8) CzH4, 55 (40.6) C,Hs, 41 (41.8) C,H,,. When a voltage of + 2000 V is applied to the collision cell, the following collision-induced: unimolecular peak ratios are obtained, m/z (CI:u); 109 (50: 50), 83 (70: 30), 69 (90: lo), 55 (40: 60) and 41 (60 : 40).

the technique in these cases. 2-Methylcyclohexanone can form two enolate ions b and c (Scheme 2) and it is likely that these are interconvertible under the conditions of collisional activation. The losses of H,, (Hz + H,) and C,H, can occur from both b and c by processes analogous to those shown in Scheme 1 and Eq. (3). Eliminations of H; Me; C,H,, and C,H,, are represented in Eqs. (Q-(11) (Scheme 2). We suggest that the minor (and unusual) loss of C,H, is that shown in Eq. (12); no analogous process occurs from other 2-substituted cyclohexanone enolate ions (see Tables 3 and 4).

3-Methylcyclohexanone forms two enolate ions, d and e (Scheme 3) and characteristic fragmentation of each ion is apparent. There are two retro processes, loss of C,H, from e and loss of C,H, from d [Eqs. (13) and (14)]. Of the two processes, the more pronounced is that in which the Iarger olefin is lost [Eq. (I4)J. This is also true of the other 3-substituted cyclohexanones listed in Tables 3 and 4. The losses of methane [Eqs. (15) and (16)] are decompositions of e. These reactions are characteristic of 3-substitution and the major loss is that shown in Eq. (15), a situation directly comparable with

277

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Fig. 2. CA mass spectrum of enolate ions from 3-methylcyclohexanone. For experimental conditions, see Experimental section. Width of major peaks at half height, m/z (volts f 0.3) loss; 109 (47.2) H,, 95 (53.3) CH,, 83 (95.5) CzH4, 69 (87.3) CsH,, 57 (47.2) C,H,, 41 (45.5) CsH,,. When a voltage of + 2000 V is applied to the collision cell, the following collision- induced: unimolecular peak ratios are obtained, m/z (CI:u); 109 (40 : 60), 95 (60 : 40), 83 (80: 20), 69 (80: 20), 57 (45 : 55) and 41 (65 : 35).

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Fig. 3. CA mass spectrum of the enolate ion of 4methylcyclohexanone. For experimental conditions, see Experimental section. Width of major peaks at half height, m/z (volts f 0.3) loss; 109 (45.4) Ha, 95 (57.1) CH4, 83 (104.3) CO, 81 (56.2) H&O, 83 (96.4) CzH4, and 41 (41.9) C,H,,. When a voltage of +2000 V is applied to the collision cell, the following collision-induced: unimolecular peak ratios are obtained, m/z (CI:u); 109 (40: 60), 95 (80 : 20), 83 (70: 30), 81 (70 : 30), 69 (70 : 30), and 41 (50 : 50).

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Fig. 4. CA mass spectrum of enolate ions of 2-ethyl-4-methylcyclohexanone. For experimental conditions, see Experimental section. Width of major peaks at half height, M/Z (volts f 0.3) loss; 137 (45.6) H,, 123 (50.8) CH,, 111 (105.0) C,H,, 97 (91.6) C,H,. When a voltage of + 2000 V is applied to the collision cell, the following collision-induced: unimolecular peak ratios are obtained, m/z (CI:u); 137 (35 : 65), 123 (60: 40), 111 (40: 60), 97 (55 : 45), 81 (35 : 65), 69 (70 : 30) and 41 (90 : 10).

that of the H, losses illustrated in Eqs. (6) and (7) (Scheme 1). Elimination of H, can proceed from either d or e.

The most interesting fragmentation is the elimination of C,H, from the enolate ion e [Eq. (17)]. This reaction appears to be quite facile [the collision-induced and unimolecular contributions to the peak are comparable, (see legend to Fig. 2)] and it is only the second reported example of a negative ion process involving the specific transfers of two protons [15]. In this case, consideration of the spectra of the three deuteriated derivatives (Table 2) shows a methyl hydrogen and a hydrogen from position 4 to be involved. The reaction is characteristic of 3-alkyl substitution; the analogous losses from 3-ethyl-, propyl-, butyl-, and pentylcyclohexanone enolates are C,H,, CgHio, CyHiz, and CsHi4, respectively (see Tables 3 and 4). We represent this process by the sequence shown in Eq. (17). The initial proton transfer proceeds from the methyl group [see e, Eq. (17)], the second transfer involves the migration of an allylic proton of f to the carbanion centre. Subsequent cleavage forms the acetone enolate as product ion.

The major fragmentations of the 4-methylcyclohexanone enolate (Fig. 3) are similar to those outlined in Scheme 1. However, there are three minor processes, viz. the losses of CH,, CO, and H&O (see Fig. 3) which merit discussion. These are summarised in Scheme 4. The loss of methane prob-

280

TABLE 3

CA - spectra of emlate negative ions of cthylcyclohexanones and labelled derivatives

Neutral precursor

I-Ethykyclohexanone M-H+ 2_(Ethyl-1,1-D,)~clohyclohuranone M-H+ 2-Ethylcyclohcxanone 2,6,6-D, M-D+ 3-Ethylcyclobexanone M-H+ 3-Etbykyclohexanone 2,2,6,6-D., M-D+ 3-Ethylcydohaanone 3.5,5-D, M-H+

4-Ethylcyclohemnone M-H+

4-Ethykyclohuanoae 2,2.6,6-D, M-D+

4Ethylcyclohuanone 3.3.5.5-D. M-H+

4-Etbylcyclohexarmne 4-D, M-H+

Las

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17 100 2

20 100 2 b loo 21 2

23 100 1

20 100 2

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b D’andH1-2u.

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TABLE 4

CA mass spectra of 2- and 3-propylcyclohexanones and higher homologues

Neutral precursor

2-n-Propylcyclohexaoone M-H+ 2-n-Propylcyclohexanone 2.6.6-4 M-D+ 2-n-Propylcyclohexanone 3,3,5,5-D, M-H+ 3-n-Propylcyclohexanone M-H+ 3-n-Propylcyclohexanone 2,2,6,6-D., M-D+ 3-n-Propylcyclohexanone 3,5,5-D, M-H+ 2-n-Butylcyclohexanone M-H+ 3-n-Butylcyclohexanone M-H+ 2-iso-Butylcyclohexanone M-H+ 3-iso-Butylcyclohexaone M-H+ 2-n-Pentylcyclohexanone M-H+ 3-n-Pentylcyclohexanone M-H+

ion(s) H’ D’ H, HD (H,+H,) (H,+HD) (HD+HD)

a 100 3 b 1OOb 2

16 100 2 P 100 3

b 100 2 22 100 3 a 100 4 a 100 2 a 100 2 D. 100 5 a 100 2 a 100 2

Neutral Precursor Initial Loss (Abundance)

2-n-Propylcyclohexanone

Ion(s)

2-n-Propylcyclohexanone 2,6,6-D3 M-D+ 2-n-Propylcyclohexanone 3,3,5,5-D, M-H+ 3-n-Propylcyclohexanone M-H+ 5 6 3-n-Propylcyclohexanone 2,2,6,6-D, M-D+ 6 6 3-n-Propylcyclohexaoone 3,5,5-D, M-H+ 7 6 2-n-Butylcyclohexanone M-H+ 3-n-Butylcyclohexanone M-H+ 29 5 2-iso-Butylcyclohexaone M-H+ 3-iso-Butylcyclohcxaone M-H+ ,8 0.5 2-n-Pentylcyclohexanone M-H+ 5 8 3-n-Pentylcyclohexanone M-H+ 31

’ Not resolved. b D-and Hz=2 u.

281

C,H, CzH,D, C,H, ‘AHJ’ CA GHG ‘=dW% C,H, ‘Y’,D, W-h GH,,” W-hoD, GH@, Ct.HsD~

20 1 1

8 9 1 1 22 1 1

5 22 8 3 2

6 25 7 3 1 37c 375 8 3 1.5

2 9 0.5 2 12 1

1.5 9 0.5 2 10 0.5

13 15

16 5 6

6 15

3 10 1

12 5

18 18 1s

2 50 1.5 53

55 6

1 4

0.5

1

1

1 2

2

15

6

1

C,% W-b, ‘GH,,D C,H,,D, ‘Vh14 CAoD, V-h6 C8W4 Cs% v-h8

2 2

2 1

1 1

1 4 1

0.5 0.5 0.1

1

2 2 0.2

282

0

Q- Me

* + CH4 (18)

-co

\

(19) H2 + -a - 7 - v- - v

/” “:, Me

(20) H2 + \ c,

+ “2 (21)

(22)

Scheme 4.

ably occurs by an SNi reaction in the ion complex as shown in Eq. (18); there is a similar loss of C,H, from the 4-ethylcyclohexanone enolate (see Table 3). However, the losses of CO and H&O appear to be unique in this series of enolates. Loss of CO is predominantly collision induced (see legend to Fig. 3); the elimination should form g (Scheme 4). The product peak is very broad with a width at half-height of 104 V, indicative of a reaction with a considerable reverse activation barrier.- The loss of H,CO could involve loss of H, from g, but the data from labelled compounds (footnotes d, e, and f of Table 2) indicate that the losses of H, must occur from both g and h *. The four losses of H&O are summarised in Scheme 4; of these, the major losses are those shown in Eqs. (19) and (21).

* Conversion of g to h involves a 1,2 hydride shift; a similar process must occur in order to explain the formation of HC,O- from [(cyclohexanone 2,2,6,6-D,)-D+]- (see earlier). It has been suggested that 1,2 hydride shifts are forbidden [16] and the barrier for the degenerate 1,2-hydrogen rearrangement in the ethyl anion is calculated to be 202 kJ mol-’ [17]. We have, however, recently observed 1,2 hydride ion shifts when a variety of carbanions are subjected to collisional activation [18]. This work will be presented for publication in due course.

283

Ethyl- and propylcyclohexanone enolates and higher homologues

Collisional activation mass spectra are recorded in Fig. 4 or Tables 3 and 4. The spectra of the 3- and 4-substituted derivatives show completely analogous fragmentations to those described in Schemes 1 and 3 and Eq. (18) and need be discussed no further. The 2-substituted derivatives show all the features described in Scheme 2, but they also exhibit additional fragmentations. In the Introduction, we raised the question of whether enolate ions of 2-substituted cyclohexanones would show the characteristic cleavages 1 and 2 observed for acyclic ketone enolates. The answer is yes and these features can be seen for all the 2-substituted cyclohexanones listed in Tables 3 and 4 (see also Fig. 4). As an illustration, deprotonated 2-MeCD, cyclohexanone loses CH, together with C,H, and C,H,D, (1: l), while (M - D+)- species from 2-ethylcyclohexanone 2,6,6-D, eliminate CH,D and C,H, (see Table 3). Thus, there are two losses of ethene, the standard retro reaction [cf. Eq. (3)] and the proton transfer/cleavage reaction shown in Eq. (23) [Scheme 5; cf. Eq. (l)]. The analogous losses from 2-propyl-, butyl-, and pentylcyclohexanones are C3H6, C,H,, and C,H,, (see Table 4). The loss of methane is represented by Eqn. (24) [cf. Eq. (2)], the corresponding reactions of 2-propyl-, butyl-, and pentylcyclohexanone are loss of C,H,, C,H,, and C,H,,, respectively (see Table 4). These three characteristic reactions are clearly seen in Fig. 4, i.e. loss of C,H, [retro process, cf. Eq. (3)], C,H, [cf. Eq. (23)] and CH, [cf. Eq. (24)] *.

0 + &HA (23)

Me 0 .* . H k.3 - H :

- .. 0 d 0 -b+ + CH., (24)

Scheme 5

* A minor loss of CH, could take place by an SNi reaction analogous to that shown in E@.

(18).

284

In conclusion, the answers to the three questions posed in the Introduc- tion are: (i) the retro mechanism first described by Hunt [4,5], and shown in Eq. (3) is specific, occurring without migration of hydrogens on the cyclohexanone ring. In the case of a 3alkylcyclohexanone (which may form two enolate ions), the retro process involving the loss of the larger olefin is the more pronounced; (ii) differently substituted alkylcyclohexanones have characteristic fragmentation patterns, thus the technique is a viable one for analytical purposes, and (iii) 2-substituted (Z Et) cyclohexanone enolates undergo the same characteristic fragmentations [Eqs. (1) and (2)] as acyclic ketone enolates.

ACKNOWLEDGEMENT

We thank the Australian Research Grants Scheme for continuing finan- cial support.

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collision-induced dissociations of enolate negative ions. deprotonated cyclohexanones

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