Patai S., Rappoport Z. 1996 The chemistry of functional groups. The chemistry of amino, nitroso, nitro and related groups / 0205 248

Supplement F2: The Chemistry of Amino, Nitroso, Nitro and Related Groups.

Edited by Saul Patai Copyright 1996 John Wiley & Sons, Ltd.

ISBN: 0-471-95171-4

CHAPTER 5

The	chemistry of	ionized,
protonated and		cationated
amines in the gas phase
RICHARD D. BOWEN
Chemistry and Chemical Technology, University of Bradford, Bradford,
West Yorkshire BD7 1DP, England, UK
Fax: [phone]
I. ABBREVIATIONS . . . . . . . . . . . . . . . .		. . . . . . . . . . . . . . . . . . . . .	205
II. INTRODUCTION . . . . . . . . . . . . . . . .		. . . . . . . . . . . . . . . . . . . . .	206
III. IONIZED AMINES AND ISOMERIC STRUCTURES . . . . . . . . . . . . .			207
A. Alkylamines . . . . . . . . . . . . . . . . . .		. . . . . . . . . . . . . . . . . . . . .	207
1.	Conventional ionized amine structures . . . . . . . . . . . . . . . . . . . .		207
2.	Distonic ions (DIs) . . . . . . . . . . .	. . . . . . . . . . . . . . . . . . . . .	208
B. Reactions of Ionized Alkylamines . . .		. . . . . . . . . . . . . . . . . . . . .	217
1.	Overview and comparison with ionized alcohols and ethers . . . . . .		217
2.	Fragmentation of unrearranged ionized alkylamines . . . . . . . . . . .		218
	a. ˛-Cleavage . . . . . . . . . . . . . .	. . . . . . . . . . . . . . . . . . . . .	219
	b. Alkane elimination . . . . . . . . .	. . . . . . . . . . . . . . . . . . . . .	221
3.	Fragmentation of rearranged ionized alkylamines . . . . . . . . . . . .		221
	a. Pseudo-˛-cleavage . . . . . . . . . .	. . . . . . . . . . . . . . . . . . . . .	221
	b. Alkene or alkenyl radical elimination . . . . . . . . . . . . . . . . . .		223
	c. Other reactions . . . . . . . . . . . .	. . . . . . . . . . . . . . . . . . . . .	225
4. Reactions of immonium ions derived from ionized alkylamines . . .			226
C. Reactions of Ionized Unsaturated and Cyclic Amines . . . . . . . . . . . .			231
D. Reactions of Ionized Arylamines . . . .		. . . . . . . . . . . . . . . . . . . . .	233
IV. PROTONATED AND ALKYL CATIONATED AMINES . . . . . . . . . . . .			234
A. Formation and Properties of Protonated and Alkyl
Cationated Amines . . . . . . . . . . . . .		. . . . . . . . . . . . . . . . . . . . .	234
B. Reactions of Protonated Amines . . . . .		. . . . . . . . . . . . . . . . . . . . .	236
C. Reactions of Tetraalkylammonium Ions		. . . . . . . . . . . . . . . . . . . . .	240
D. Comparison of the Reactions of Protonated Amines
and Tetraalkylammonium Ions . . . . . .		. . . . . . . . . . . . . . . . . . . . .	241

205

206	Richard D. Bowen

V. CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 VI. ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 VII. REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

	I. ABBREVIATIONS
CA	collisional activation
CI	chemical ionization
CID	collision-induced dissociation
CIDI	collision-induced dissociative ionization
CS	charge-stripping
DHT	double hydrogen transfer
DI	distonic ion
EI	electron ionization
ERMS	energy-resolved mass spectrometry
ESR	electron spin resonance
FA	flowing afterglow
FAB	fast atom bombardment
ICR	ion-cyclotron resonance
INC	ion-neutral complex
KE	kinetic energy
LELT	low-energy low-temperature
MIKE	mass-analysed ion kinetic energy
MO	molecular orbital
NR	neutralization				reionization
PA	proton affinity
PBC	proton-bridged complex
PEP	potential energy profile
RI	relative intensity
RRKM	Rice		Ramsperger				Kassel		Marcus
SHT	single hydrogen transfer
SIFT	selected ion flow tube

II. INTRODUCTION

As was pointed out in Supplement F some fifteen years ago1, the principal dissociation routes of radical-cations derived from simple amines have been extensively studied and documented for several decades2. It is no accident that many basic texts on organic mass spectrometry treat the fragmentation of ionized alkylamines at an early stage. The electron ionization (EI) spectra tend to be clean, typically being dominated by abundant primary fragment ions formed by ˛-cleavage, together with secondary (and sometimes higher order) fragment ions derived by well-defined routes. Such spectra are readily interpreted and of obvious analytical value; consequently, they form an excellent illustration of structure elucidation by mass spectrometry3.

As might have been expected in a relatively established subdiscipline of chemistry of this kind, there has been a gradual but remorseless accumulation of further information in new systems of increasing complexity. However, most of this additional analytical knowledge in essence amounts to an extension and development of established ideas to cover larger or more functionalized molecules and ions. Under these circumstances, the

5. The chemistry of ionized, protonated and cationated amines in the gas phase 207

exhaustive cataloguing of the fragmentation patterns of ionized amines and related species would be of relatively little didactic value. Consequently, it has not been attempted in this chapter.

In contrast, the discovery of novel ion structures and the characterization of their reactivity by experimental and theoretical means has revolutionized what might be described as the physical organic chemistry of ionic species in the gas phase. These advances are relevant in many fields, including the mechanism of dissociation of gaseous ions and the influence of solvation on the stability of ions in solution. Therefore, the main objective of this chapter is to summarize recent progress in understanding the chemistry of ionic species derived from amines by mass spectrometry and the implications of this insight in classical solution chemistry. Even a restricted account of this nature must necessarily be selective, but it is hoped it will convey an idea of the versatility of mass spectrometry and related techniques for investigating old and new problems in chemistry. This chapter is primarily intended to give the non-specialist reader an overview of the insight which has been obtained from recent mass spectrometric studies of amines, but ample references are made to relevant comprehensive reviews aimed at a more specialized audience. Attention is focussed on alkylamines, CnH2nC3N, partly on account of their simplicity, but also because many of the most interesting developments have occurred in this field.

III.IONIZED AMINES AND ISOMERIC STRUCTURES

A.Alkylamines

1. Conventional ionized amine structures

Despite the invention during the past decade or two of numerous alternative ionization methods designed to permit formation of gaseous ions from all manner of substrates, EI remains a particularly suitable means of obtaining the mass spectra of simple alkylamines. There are two reasons: first, the low ionization energy of amines and, secondly, the powerful fragmentation directing properties of the ionized amino function2,3. Consequently, ionized amines are readily formed by EI of the parent compound and the derived molecular ions dissociate readily, especially in fast reactions occurring in the source of the instrument. The main fragmentation route is almost always ˛-cleavage, particularly at high internal energies2,3.

Traditionally, this dissociation has often been considered to be ‘triggered’ by the lone electron situated in the singly occupied non-bonding orbital on nitrogen (Scheme 1). In other words, ionization is regarded as occurring by removal of one of the lone pair electrons on the nitrogen atom, thus rendering the derived radical-cation vulnerable to

R1

α1

R2

R2

+

4 5

α 1

1

+

+

4 5

+

4 5

R2

C NR R

R

C

NR R

C

NR R

R3

R3

R3

α 3

α 2

R1

+

R1

+

R3

+

R2

+

C

NR4 R5

C

NR4 R5

R2

R3

SCHEME 1

208	Richard D. Bowen

simple C C bond fission with expulsion of an alkyl radical to give a resonance stabilized ‘immonium’ (occasionally called ‘imminium’ or ‘iminium’) ion. This view is sufficiently accurate to retain clear analytical and interpretive value. However, it is an oversimplification for at least two reasons. First, ionization with high energy (70 eV) electrons permits the production of molecular ions in excited electronic states that may decompose before collapsing to the ground state. Secondly, at low internal energies (in low voltage spectra or for long-lived metastable ions), it is possible for the initial radical-cation to undergo hydrogen transfer or even skeletal rearrangement before dissociation occurs from a structure other than the ionized molecule. The first possibility was recognized many years ago, but the importance of considering isomerization of ionized amines prior to fragmentation has been critically addressed only relatively recently. It is now known that many ionized alkylamines do rearrange to other structures before fragmenting, so it is important to review the nature and significance of these isomerizations.

2. Distonic ions (DIs)

It had long been suspected by many organic mass spectroscopists that alternative ion structures would have comparable or lower energies than the parent ionized amine. Thus, žCH2NH3C , in which the formal radical site is located on carbon and the positive charge resides on the nitrogen atom, appears to possess many favourable structural features compared to ionized methylamine, CH3NH2Cž . These isomeric species may be derived from protonated methylamine, CH3NH3C , by hydrogen atom abstraction from the isoelectronic NH3C or CH3 entities, respectively. Early molecular orbital (MO) calculations4 supported this idea and also indicated that the homologous unconventional radical-cations, žCH2CH2NH3C and žCH2CH2OH2C , should be stable species5. Subsequent experimental work established that each member of pairs of isomeric radicalcations such as CH3NH2Cž and žCH2NH3C exist in energy wells with a sizeable barrier towards their interconversion6,7. In other words, these species are kinetically and thermodynamically stable. Moreover, both experimental6 11 and theoretical12,13 studies indicated that žCH2ZHC structures (Z D OH, OR, NH2, SH, Cl, etc.) not only occupy discrete potential energy wells but also have enthalpies of formation which are comparable to, or even lower than, those of the isomeric CH3ZCž radical-cations. Higher homologues of these unconventional ion structures also were generated and shown to be stable. Important examples include žCH2CH2NH3C11 , CH3CHž NH3C14 , žCH2NH2C CH315 and

žCH2CH2CH2NH3C16,17 . Selected pertinent energetics are summarized in Table 1.

TABLE 1. Energetic data for ionized amines and their distonic isomersa

Ionized amine (ACž )	Hf ACž	Distonic ion (DI)	Hf(DI) Ec ACž ! DI
CH3NH2Cž	858b	žCH2NH3C	850c	167c
CH3CH2NH2Cž	828b	žCH2CH2NH3C	795d	138d
		CH3CH NH3C	799d	142d
(CH3)2NHCž	795b	ž	820d	192d
		žCH2NH2C CH3
CH3CH2CH2NH2Cž	795b	žCH2CH2CH2NH3C	753e	63e ;38f
CH3CH2CH2CH2NH2Cž	770g	žCH2CH2CH2CH2NH3C	720e	13e ;13f

a Values in kJ mol 1.

b Reference 18 (see also References 19, 20 and 21). c Calculated (Reference 19).

d Calculated (Reference 20). e Calculated (Reference 21).

f Experimental estimate (Reference 17). g Estimated from data in Reference 21.

5. The chemistry of ionized, protonated and cationated amines in the gas phase 209

A new generic term, distonic ion (DI)22, was coined to describe these unconventional radical-cations. The word ‘distonic’ is derived from the Greek ‘υ os’ and Latin ‘distans’, meaning ‘separate’. This name stresses that the formal charge and spin sites are located on different ‘heavy’ atoms. This emphasis is chemically valuable, because many distonic ions show reactivities which are strongly influenced by the separate ionic and radical centres. Indeed, it has been suggested that distonic ions behave as charged radicals, i.e., their chemistry is dominated by the influence of the radical site23.

The term DI was initially devised to describe species in which the charge and spin sites were located on adjacent atoms (e.g. žCH2NH3C ). These radical-cations are occasionally referred to as ionized ylids, on account of their structural relationship with the ylids (e.g.CH2NH3C ). Another name used in the early 1980s was radical-ion dipole complex11,24, but this expression has fallen into disuse, not least because the presence of a normal C Z bond25 is inconsistent with the idea that such species consist of a complex of ionized carbene and ZH2 (e.g. NH3). Nowadays, almost all radical-cations with separate charge and spin sites are referred to as DIs; exceptions include cases such as ionized alkenes, in which the ionic and radical positions located on adjacent atoms may be considered to arise by ionization of a -system26. A Greek prefix is used to indicate the separation between the radical and ionic centres; thus, žCH2NH3C is an ˛-DI, žCH2CH2NH3C is a ˇ-DI and žCH2CH2CH2NH3C is a -DI.

Early research in this area often relied upon collision-induced dissociation (CID), alias collisional activation (CA), spectra to distinguish between the isomeric conventional and unconventional radical-cations. In these CID or CA experiments27 30, undissociated ions of relatively low internal energy are energized by collision with a neutral target gas (typically oxygen, helium, argon or xenon); the energized ions then fragment relatively rapidly in ways that are frequently structure-specific. In most systems, the CID spectrum consists almost entirely of singly-charged fragment ions; however, some CID spectra also contain valuable signals corresponding to the formation of doubly (and, occasionally, triply) charged ions arising by charge-stripping (CS). Both the CID/CA and CS spectra serve as valuable ‘fingerprints’ of the parent ion. In particular, the observation of distinct CID or CA spectra for isomeric species establishes that each has an independent existence and occupies its own potential energy well. CS spectra are actually extremely useful for distinguishing conventional CH3ZCž species from their unconventional žCH2ZHC isomers.

Thus the CID spectra of CH3NH2Cž and žCH2NH3C are diagnostically different (Figure 1)11. The former shows a stronger signal at m/z 15 (CH3C , as would be expected since this ion is accessible via C N cleavage of CH3NH2Cž but not žCH2NH3C . Moreover, the spectrum of žCH2NH3C is dominated by a very narrow ‘spike’ at m/z 15.5 (i.e. 31CC) which is of very minor significance in the spectrum of CH3NH2Cž . This contrast in the CS portion of the spectrum reflects the stability of the dications derived from CH3NH2Cž and žCH2NH3C : C CH2NH3C is a stable species, existing in a distinct

energy well, but CH3NH2CC dissociates spontaneously or isomerizes to C CH2NH3C31 . In contrast to the conventional isomers, which obviously correspond to ionized neutral

molecules, none of the unconventional species has a stable neutral counterpart. This fact is very useful in characterizing the unconventional species, because the application of modern neutralization reionization (NR) techniques readily differentiates them from their conventional isomers. In the NR experiment32,33, the ions are neutralized (typically by being caused to collide with a target gas consisting of alkali metal atoms or N,N-dimethylaniline, from which an electron is readily captured) and the resultant neutral species are then reionized by collision with another gas (typically oxygen). The essence of this technique involves the formation of neutral species having the same connectivity of atoms as the ions under investigation. If this neutral species is stable, the ions should survive NR and a ‘survivor’ signal, corresponding to regeneration of the original ion, should appear in the

210	Richard D. Bowen
	15 CH3+	31+ +
		+
	CH NH
	2	3

CH3NH2+

NH3+ 14

17

FIGURE 1. Partial CID and CS Spectra of (a) CH3NH2Cž and (b) žCH2NH3C . Reproduced by permission of the Canadian Chemical Society from J. L Holmes, F. P. Lossing, J. K. Terlouw and P. C. Burgers, Can. J. Chem., 61, 2305 (1983)

NR spectrum. On the other hand, if the neutral species is not stable, no survivor signal is expected. In the present context, conventional ionized amines show survivor signals, but their unconventional isomers do not because the corresponding neutrals are unstable (thus, neutralization of žCH2NH3C , žCH2CH2NH3C and žCH2CH2CH2NH3C would give either the hypervalent biradicals žCH2NH3ž , žCH2CH2NH3ž and žCH2CH2CH2NH3ž or the zwitterionic species CH2NH3C , CH2CH2NH3C and CH2CH2CH2NH3C , respectively, all of which dissociate spontaneously).

The value of NRMS is illustrated by the differentiation of CH3CH2CH2NH2Cž from žCH2CH2CH2NH3C . A survivor signal at m/z 59 is present only in the former case, for which it is strong17. In contrast, the CID spectra of CH3CH2CH2NH2Cž and žCH2CH2CH2NH3C are quite similar and dominated by formation of CH2DNH2Cž at m/z 3017.

Other means for distinguishing DIs from their conventional isomers include thermochemical data and bimolecular reactions. The first method relies on differences in enthalpies of formation, which may be insufficient for forming firm conclusions, especially if the isomeric species have similar enthalpies or are generated by processes which have appreciable reverse critical34 energies. Thus, CH3NH2Cž and žCH2NH3C have quite similar enthaplies and cannot be identified on this basis. Note that this similarity in enthalpy does not always occur for CH3ZHCž and žCH2ZH2C pairs: the ˛-DI

is 35 and 65 kJ mol 1 more stable than its conventional isomer when Z D OH and F, respectively18,19.

Characterization of ion structures by bimolecular reactions, in which an ion is allowed to react with a neutral gas of known structure and the ionic products are analysed by mass spectrometry, depends on isomeric species having distinctive reactivities which reflect the functional group(s) that are present. This method is conceptually analogous to the use of structure-specific test reagents in classical solution chemistry. Sometimes a group may be transferred to a particular ion from the gas (methylene transfer is commonly encountered); on other occasions, hydrogen transfer is monitored. The latter is conveniently combined with isotopic labelling.

5. The chemistry of ionized, protonated and cationated amines in the gas phase 211

It is clear that DIs of general formula CnH2nC3NCž cannot be made by direct ionization of their neutral counterparts because these species are not stable. However, these DIs have been generated by a variety of indirect means.

The first route involves a suitable bimolecular reaction. An early seminal example was the production of žCH2NH3C by reaction of NH3 with ionized cyclopropane35; this process involves ring opening to give the -DI, žCH2CH2CH2NH3C , which then eliminates ethylene (equation 1). Subsequent investigations36 confirmed the involvement of žCH2CH2CH2NH3C and also showed that this reaction is associated with ionized cyclopropane because ionized propene undergoes mainly proton transfer35,37,38. Moreover, formation of žCH2NH3C involves very little hydrogen exchange, as is shown by the production of žCH2ND3C by reaction of ionized cyclopropane with ND3 and similar labelling experiments38,39. Similarly, žCH2NH3C is formed by methylene transfer from ionized ketene to NH3 (equation 2)40.

+

+

+

+ NH3

+ CH2NH3

(1)

NH3

+

+ NH3

CO +

+

(2)

O

C

CH2

CH2 NH3

The second general route to these DIs is fragmentation of a suitable precursor, typically via a process involving hydrogen transfer to the nitrogen atom. Thus, žCH2NH3C is produced by elimination of formaldehyde from ionized ethanolamine and similar species (equation 3)13. A related route (expulsion of methylene imine from ionized 1,3-

diaminopropane, equation 4) gives access to žCH2CH2NH3C13 . This procedure suffers from the drawback that the fragmentation may entail a reverse critical energy and so produce a DI containing an appreciable internal energy, even at the threshold for its formation. Nevertheless, it is convenient in practice, especially for generating žCH2NH3C and related ˛-DIs; moreover, it has the advantage of being compatible with conventional EI methodology in ordinary instruments, provided an unambiguous fragmentation can be designed.

O

+

+

(3)

+

CH2

O

CH2NH3

H

NH2

+

+

CH2

NH

+ CH2CH2NH3

(4)

NH2

NH2

The third method by which DIs are formed is isomerization of the corresponding ionized amines. In the present context, this route is the most important because it reflects the chemistry of ionized amines. However, it is not always viable, particularly for smaller DIs. Thus, žCH2NH3C is not accessible by isomerization of CH3NH2Cž because of the substantial energy barrier (ca 16519 kJ mol 1) towards the required 1,2-H shift. Similar remarks apply to ˇ-DIs, which cannot be readily formed from the corresponding ionized amines by a 1,3-H shift. Thus, there is a barrier of ca 14020 kJ mol 1 towards rearrangement of CH3CH2NH2Cž to žCH2CH2NH3C . On progressing to the homologous -DIs, 1,4-H shifts in the corresponding ionized amines become easier. Thus,

an early upper limit of ca 38 kJ mol 1 was inferred for the barrier to isomerization of CH3CH2CH2NH2Cž to žCH2CH2CH2NH3C17 . This rearrangement of CH3CH2CH2NH2Cž

certainly has a lower critical energy than that (ca 80 kJ mol 1) for ethyl radical loss

212	Richard D. Bowen

because exchange of the hydrogen atoms of the amino function with those attached to carbon precedes ˛-cleavage at low internal energies17. Despite the increased facility of these 1,4-H transfers, žCH2CH2CH2NH3C is more conveniently generated by fragmentation of ionized bifunctional precursors (e.g. by loss of methylene imine from ionized 1,4-diaminobutane, equation 5).

H2N	+			+
			CH2		NH + CH2CH2CH2NH3	(5)
	NH2

Even smaller barriers exist towards hydrogen transfers through larger transition states17,26. Consequently, DIs are formed from the corresponding ionized amines with increasing facility as the length of the alkyl chain increases. Similarly, rearrangement to DIs sometimes occurs readily for ionized amines containing two N-alkyl substituents because hydrogen transfers between the hydrocarbon chains becomes possible. Thus, an ˛-DI derived from an isopropyl group is formed by a route involving such reciprocal hydrogen transfer, (Scheme 2)41,42.

+			1,5-H		+
N				H	N
H					H2
	H
						1,6-H
+	+ C5H11				+
NH2					N
					H2

SCHEME 2

Three main factors influence the ease of formation of DIs from ionized amines. The hydrogen transfer(s) necessary to effect this transformation occur more readily at low energies and long lifetimes because they then compete more effectively with dissociations involving bond cleavages. Moreover, hydrogen transfers through six-, sevenand eightmembered ring transition states are especially favourable43. Finally, isomerization to DIs occurs most readily for ionized primary and secondary amines; indeed, there is little or no evidence for the formation of DIs from ionized tertiary alkylamines. This trend reflects the reduction in the hydrogen abstraction capacity of the nitrogen atom on progressing from ionized primary to tertiary amines44.

The existence of stable DIs in CnH2nC3NCž systems has significant implications. It is no longer necessarily correct to assume that the ionized amine retains this structure until it fragments. Furthermore, new dissociation pathways which are not open to unrearranged ionized amines become accessible via DIs. The most general of these novel pathways is probably pseudo-˛-cleavage, in which a radical apparently accessible only by unfavourable ˇ-cleavage of an ionized linear 1-alkylamine or similar substrate is lost43 50. This process involves isomerization of the ionized 1-alkylamine to the corresponding ionized 2-alkylamine, which then fragments to give CH3CHDNH2C , (Scheme 3). Other fragmentations intelligible in terms of reciprocal hydrogen transfers involving DIs include an unusual C N cleavage starting from ionized isopropyl-n-pentylamine (Scheme 2)41,42. In order to understand these processes, it is necessary to summarize the basic types fragmentation and isomerization of simple DIs.

5. The chemistry of ionized, protonated and cationated amines in the gas phase 213

H

+

1, 6-H

+

R

NH2

R

H

NH3

H

1, 4-H

1-2-NH3

+

R

+ NH3

R

NH3

1, 5-H

1, 5-H

α

RCH2 CH2 CH2

R

R

+

+NH

+NH

3

2

+ NH2

SCHEME 3

DIs usually fragment via quite different routes to those of the corresponding ionized amines. Thus, unlike ionized amines, ˛-DIs rarely, if ever, undergo ˛-cleavage. Instead, C N fission occurs, especially for ˛-DIs containing more than one N-alkyl substituent26. Thus, žCH2NH2C CH3 expels CH3ž , with production of CH2DNH2C15 . Similarly, CH3CH2CHž NH2C CH2CH3 (generated from CH3CH2CH2NH2C CH2CH2ž ) loses C2H5ž , (Scheme 4)42. This distinction between ˛-DIs and ionized amines may, however, be blurred by the possibility of interconversion of these conventional and unconventional isomers of CnH2nC3NCž , particularly at low internal energies and in systems containing long alkyl chains.

H H

	+		1, 4-H				+
	N						N
	H2						H2
	1, 6-H							C		N
	+						+			+ C2 H5
	N						NH2
	H2
	1, 4-H
	+		α		C2 H5	+	+
	N							N
	H							H

SCHEME 4

or C2H4Cž ).

214	Richard D. Bowen

Although this process appears to be a simple cleavage, which intuitively might have been expected to occur with little or no reverse critical energy, there is evidence from thermochemical measurements51 and MO calculations12,21,52 for a barrier towards the reverse reaction, particularly when small radicals are lost. The metastable peak for loss of CH3ž from žCH2NH2C CH3 is broad and dish-topped15, so confirming the presence of a sizeable reverse critical energy. This behaviour is fairly general for loss of an N-alkyl group from ˛-DIs (equation 6)41,42. One possible explanation is that N-alkyl elimination is preceded by a 1,2-shift from nitrogen to carbon, to give an energetic (or ‘hot’) form of the corresponding ionized amine (here CH3CH2NH2Cž ). Such a rationalization is not consistent with labelling experiments, which reveal that the alkyl groups in potentially symmetric systems do not become equivalent prior to fragmentation. Thus, CH3CH2CHž NH2C CD2CH3 is not able to reach CH3CH2(CH3CD2)CHNH2Cž before an ethyl radical is expelled (Scheme 5), because the metastable peaks for loss of CH3CH2ž and CH3CD2ž have different shapes41,42.

+

+

+ R

(6)

H2C

N

R

CH2 NH2

H2

D

D

D

D

+

C2H3D2

+

+

+

N

NH2

NH2

H2

+

C2H5

+

+

C2H3D2

+

NH2

NH2

D

D

SCHEME 5

ˇ-DIs also fragment by C N cleavage, usually accompanied by hydrogen transfer to nitrogen. These processes result in loss of an alkene or an alkenyl radical, respectively. Thus, žCH2CH2NH3C loses C2H3ž , with formation of NH4C , though the dominant reaction at low internal energies is actually CH3ž loss14. The hydrogen transfer associated with CnH2n 1ž elimination in these systems is favoured by the relatively high proton affinity (PA) of the ammonia (or alkylamine) molecule accessible by C N cleavage. This hydrogen transfer tends to show a strong 1,4-regioselectivity. Thus, (CH3)2CžCD2NH3C yields only NH4C in butenyl radical loss42.

Loss of CH3ž requires hydrogen transfer from nitrogen to carbon, presumably to give CH3CH2NH2Cž , which then fragments by ˛-cleavage (Scheme 6). Both these hydrogen transfer processes are subject to substantial isotope effects discriminating against D-migration14, so indicating that these steps are probably rate-limiting is each case. Fragmentations corresponding to loss of an alkenyl radical (or production of an alkenyl cation or related ionized alkene) from ˇ-DIs often persist at high internal energies (e.g. the CID spectrum11 of žCH2CH2NH3C is dominated by C2H3ž loss, which also occurs for metastable ions, and production of C2H3C