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

5. The chemistry of ionized, protonated and cationated amines in the gas phase 235

Three main techniques have been developed. First, the pressure in the source of the mass spectrometer may be increased sufficiently to permit collisions between ions and neutral species to occur. Typically, a pulsed high-pressure source is used159. Secondly, ions may be prepared and allowed to react with neutral species in a stream of gas (the flowing afterglow, FA, method); since the ion(s) may be selected in such an apparatus, this method is known as the selected ion flow tube (SIFT) technique160. Thirdly, ions may be allowed to interact with neutrals in an ICR instrument; in this case, the pressure remains relatively low, but the ions are restrained in their cycloidal trajectories for a sufficiently long period to permit collisions to occur161. The first two methods permit true thermal equilibria to be established for proton transfer reactions. Consequently, by determining the temperature variation of the equilibrium constant for a bimolecular process162, it is possible to measure the enthalpy change ( H) for the reaction. A similar procedure is in principle possible for experiments in ICR instruments, but the pressure may be too low to allow either collisional thermalization of the reactants to precede reaction or a genuine equilibrium to be reached. However, the scope of ICR has been greatly increased by the introduction of Fourier Transform (FTICR) methods163,164.

These bimolecular reactions have provided accurate proton affinities (PAs) for many amines165,166. In addition, cation affinities are accessible, usually by combining the enthalpy of formation ( Hf) of cationic species derived from PA measurements with

1092 kJ mol 1 and Hf NH3 D 46 kJ mol 1 , the methyl cation affinity of NH3 may be deduced to be 1092 46 611 D 435 kJ mol 1.

These PA data are of obvious interest in physical-organic chemistry. Not only do they define the inherent properties of the parent bases, thus permitting a more refined understanding of the correlation between molecular structure and basicity, but they also show how solvents affect the reactivity of amines.

Thus, the order of increasing basicity of the series of amines (CH3)nNH3 n (n D 0 3) was for many years considered anomalous: in solution, (CH3)2NH is slightly more basic than CH3NH2, which is more basic than (CH3)3N, which in turn is more basic than NH3 (pKa D 10.77, 10.62, 9.80 and 9.27, respectively). Various explanations for this anomalous order were advanced, including variations in the degree of hybridization of the nitrogen atom with its level of substitution. However, the order in the gas phase is [ CH3 3N > CH3 2NH > CH3NH2 > NH3; PAs D 942, 923, 896 and 854 kJ mol 1, respectively], which would be expected on an intuitive basis if addition of each electron-rich methyl group enhanced the basicity of the amine by progressively stabilizing the protonated species. This true order of basicity is modified in solution because replacement of each N H bond by an N CH3 group reduces the efficiency of solvation of the (CH3)nNH3 nC cation by hydrogen bonding of the solvent (typically H2O) to the polarized C N H entity. Another view of the same effect is that solvation of the (CH3)nNH3 nC cations is least effective for (CH3)3NHC because this species causes the greatest disruption to the hydrogen bonding in solution. As a result, the apparent basicity of (CH3)nNH3 n is systematically and progressively diminished below the true value as n increases because the resultant (CH3)nNH3 nC ions are less efficiently stabilized by solvation. Therefore, conflicting trends arising from inherent properties and solvent effects are responsible for the apparently anomalous order of basicity in solution.

Another fallacy to be refuted by PA data was the widespread belief that the low basicity of arylamines compared to alkylamines simply reflects delocalization of the lone pair of electrons on the nitrogen atom within the aromatic ring. Thus, the low basicity of aniline (pKa D 4.58) compared to ammonia (pKa D 9.27) is often attributed to such a conjugative

effect. However, in the gas phase, aniline is a stronger base than ammonia (PA D 876 and 854 kJ mol 1, respectively)166. Indeed, almost all monoalkylamines are inherently more basic than ammonia. The apparent weak basicity of aniline in solution at least partly reflects the difficulty in solvating the conjugate acid, PhNH3C , caused by the bulky phenyl group. In contrast, the smaller NH4C ammonium cation is readily and effectively solvated. Nevertheless, the basicity of amines is affected by delocalization of the nitrogen lone pair: aniline is a weaker base than cyclohexylamine both in solution and in the gas

phase (PAs D 876 and 926 kJ mol 1166 , respectively).

Correlations between the basicity of an amine and the hybridization of the nitrogen atom have been developed. Early work revealed that the basicity is diminished by increasing the s-character in the nitrogen lone pair167. Thus, the PA of piperidine (sp3 nitrogen) is 23 kJ mol 1 greater than that of pyridine (sp2 nitrogen). Similarly, the PA of aziridine is lower than that of dimethylamine by 21 kJ mol 1, because of ring strain, which tends to increase the proportion of s-character in the exocyclic bonds. However, care must be taken to allow for polarizability effects in such comparisons168.

As might have been anticipated, diamines are still more basic than amines, particularly if the added proton may occupy a site in which it is effectively bound to both amino groups. Thus, 1,4- and 1,5-diaminoalkanes have exceptionally high PAs (ca 1000 kJ mol 1)165.

B. Reactions of Protonated Amines

This section focuses on protonated alkylamines, since it is in these systems that interesting novel reactions have been uncovered.

The simplest protonated amine to be studied in detail was metastable CH3NH3C , which loses H2 with a large and relatively specific KE release (T D 78 kJ mol 1)123. This reaction has a high regioselectivity ( 99%) and it was originally classified, together with similar fragmentations of CH3CH3Cž , CH2DNH2C , CH2DOHC and CH2DSHC , as a symmetry-forbidden 1,2-elimination123,169. Subsequent detailed studies170,171 including high level molecular orbital (MO) calculations of the fragmentation of CH2DNH2C ,

CH2DOHC and, most recently, CH3NH3C172 , have led to descriptions of H2 loss in terms of molecular reaction dynamics as a 1,2-elimination in which the transition state is skewed towards the carbon atom of the system. Consequently, the initial interpretation of H2 loss from CH3NH3C as a symmetry-forbidden 1,2-elimination is an oversimplification, even though it does provide a rationalization of the regiochemistry and KE release associated with this process.

Higher homologues of CH3NH3C do not lose H2 in slow reactions. Instead, alkene elimination, which is impossible for CH3NH3C , generally dominates173. Loss of ammonia or a small alkylamine derived by C N cleavage occasionally competes with alkene elimination. Thus, metastable CnH2nC1NH3C fragments to give either CnH2nC1C and NH3 or CnH2n and NH4C depending on the nature of the alkyl substituent. The trends in the competition between ammonia (or alkylamine, in the case of the analogous protonated secondary and tertiary amines) and alkene elimination are highly significant. Contrary to a naive expectation, alkene loss is favoured in systems in which the principal alkyl substituent is secondary or tertiary. Thus, metastable CH3CH2CH2NH3C loses C3H6 and NH3 in the ratio 81:19, whereas the corresponding ratio for the isomeric species, (CH3)2CHNH3C , is 99:1. Similarly, (CH3)3CNH3C , from which facile NH3 expulsion with formation of the stable (CH3)3CC cation might have been anticipated, loses mainly (95%) C4H8, whereas CH3CH2CH2CH2NH3C and (CH3)2CHCH2NH3C eliminate predominantly NH3 (73 and 86%, respectively), even though C N cleavage in these cases would lead to unstable primary cations174.

5. The chemistry of ionized, protonated and cationated amines in the gas phase 237

This curious trend is explicable if dissociation occurs via an INC-mediated mechanism. If the cation derived by elongation of the bond joining the principal alkyl substituent to the nitrogen atom is stable, proton transfer from a ˇ-carbon atom to the developing amine occurs, thus resulting in alkene loss. This fragmentation is always favoured over amine expulsion because the PAs of amines are substantially greater than those of simple alkenes. However, if the C N bond stretching in the initial stages of the reaction leads towards an unstable cation, rearrangement occurs with the release of a substantial amount of potential energy, thus increasing the average internal energy of the system. This energizing of the species comprising an incipient stable cation and a coordinated amine allows expulsion of the amine to compete with proton transfer leading to alkene loss. An illustrative example is shown for isomeric C3H7NH3C species in Scheme 19.

generally undergoes proton transfer to [CH3CHDCH2 NH4C ], with eventual elimination of C3H6. Relatively few ions (ca 1%) generated as (CH3)2CHNH3C dissociate directly to (CH3)2CHC and NH3 because these products have a higher total enthalpy of formation ( Hf D 824 kJ mol 1) than CH3CHDCH2 and NH4C ( Hf D 653 kJ mol 1). In contrast, the analogous process leading to [CH3CH2CH2C NH3] from CH3CH2CH2NH3C is preempted by isomerization of the developing CH3CH2CH2C cation to give an energized form of [(CH3)2CHC NH3]174. The rearrangement of an incipient primary (CH3CH2CH2C) to a secondary cation [(CH3)2CHC ] releases approximately 7018,175 kJ mol 1 energy, which profoundly affects the reactivity of the resultant [(CH3)2CHC NH3] ions. These more energized ions show an enhanced tendency (ca 19%) to expel NH3, since this process does not entail the additional proton transfer required for C3H6 elimination. In cases where primary structures can rearrange to tertiary isomers, an even greater quantity of potential energy (ca 14018,175 kJ mol 1) is released, which energizes the rearranged species more strongly, thereby explaining why NH3 loss is so strongly favoured for (CH3)2CHCH2NH3C . This explanation is consistent with the increased KE release which accompanies fragmentation of protonated amines in which rearrangement of the alkyl cation is postulated174. Thus, the T1/2 values for C4H8 loss from (CH3)2CHCH2NH3C and (CH3)3CNH3C are 2.4 and 1.0 kJ mol 1, respectively.

In addition to this trend in which NH3 elimination competes more effectively with alkene loss from protonated amines containing primary alkyl substituents, a second weaker effect is observed progressively favouring alkene expulsion as the nitrogen atom is methylated. Thus, the percentage (86, 47 and 28, respectively) of C4H8 loss from

238 Richard D. Bowen

(CH3)2CHCH2NH3C , (CH3)2CHCH2NH2CH3C and (CH3)2CHCH2NH(CH3)2C declines steadily174. This subsidiary trend chiefly reflects the effects of N-methylation on the energetics of the products (the higher PAs of methylamine and dimethylamine, relative to ammonia, enhance the preference for the proton transfer leading to alkene elimination).

Early MO calculations on the mechanism of C3H6 elimination from (CH3)2CHNH3C suggested that this reaction proceeds via an intermediate proton-bridged complex (PBC), in which propene and ammonia are coordinated to a common proton173. Later research featuring MO calculations and 2H-labelling led to a refinement of the mechanism for C3H6

elimination from CH3CH2CH2NH3C130 . The labelling experiments showed that the hydrogen transfer to nitrogen was unidirectional and that the ratio of hydrogen transfer from the original ˛-, ˇ- and -carbon atoms was 2:1:3. This ratio is what would be anticipated on the basis of irreversible isomerization of CH3CH2CH2NH3C to [(CH3)2CHC NH3], followed by ˇ-H transfer in this rearranged species to give CH3CHDCH2 and NH4C . The MO calculations indicated that the transition state for dissociation of CH3CH2CH2NH3C was a species in which the C N bond was stretched and a 1,2-H shift from the ˛- to the ˇ-carbon atom was beginning to occur. Strong evidence was presented that the reactions of CH3CH2CH2NH3C were INC-mediated, but it was concluded that the INC may correspond to an ‘entropic bottleneck’, rather than to a species in a true potential energy well130.

Thus, the chemistry of protonated alkylamines, RNH3C , shows many parallels to that of the related immonium ions, RNHC DCH2 and RNC (CH3)DCH2118. Loss of an alkene derived by hydrogen abstraction from R appears to be INC-mediated; unidirectional rearrangement of the primary alkyl group occurs in cases where RC would be an unstable cation, thus resulting in a discrimination against the expected ˇ-H transfer for n-propyl and related primary alkyl substituents; this isomerization releases internal energy, which activates the ion to undergo an increased proportion of fragmentations with higher critical energies (ammonia or imine expulsion) and leads to an increase in the KE release for dissociation; and the transition state is a structure in which the C N is being broken and a concomitant 1,2-H shift is occurring. These common features reflect the underlying generic nature of the reaction.

CID experiments show that isomeric (Cm H2mC1)nNH4 nC ions (n D 1, 2 or 3) generally have distinct CID spectra; thus, CH3CH2CH2CH2NH3C , CH3CH2(CH3)CHNH3C , (CH3)2CHCH2NH3C and (CH3)3CNH3C are distinguishable on this basis, but the spectra of CH3CH2CH2CH2NH3C and (CH3)2CHCH2NH3C are similar176 178. These results confirm that these (Cm H2mC1)nNH4 nC ions occupy discrete potential energy wells, as would be expected intuitively.

Whereas metastable CnH2nC1NH3C ions do not undergo loss of molecular hydrogen and only rarely lose an alkane in comparatively low abundance for n 3158, these fragmentations are observed to a greater extent at higher internal energies (CID spectra)176 178. Therefore, the low abundance or absence of alkane and hydrogen loss from metastable ions must reflect the nature of the reactions, because both processes give rise to exceptionally favourable combinations of products in which the cationic component is an immonium ion. Early MO calculations176 indicated that 1,2-elimination of CH4 from (CH3)2CHNH3C entails a critical energy of ca 340 kJ mol 1. Consequently, this apparently favourable dissociation route competes relatively poorly with alkene and ammonia (or alkylamine) loss even when the ions have been strongly energized by high-energy (8 keV) collision.

Nevertheless, alkane losses are analytically useful in distinguishing between isomeric

5. The chemistry of ionized, protonated and cationated amines in the gas phase 239

(CH3)3CNH3C expels CH4 (11% of the base peak for NH3 loss) and no C2H6, as would be expected if the reaction predominantly involves simple 1,2-elimination across the C N bond (equation 15). In more substituted systems, three distinct channels for the 1,2-elimination may operate. Thus, protonated dimethylamine loses CH4 (equation 16), C2H6 (equation 17) and C3H8 (equation 18) to give signals 22, 49 and 55% of the intensity of the base peak for loss of C2H4178.

The CID spectra of (Cm H2mC1)nNH4 nC species have been studied over a range of collision energies. Thus, breakdown graphs, in which the relative abundances of the various fragment ions formed in these energy-resolved mass spectrometry (ERMS)179 181 experiments are plotted as a function of the (relatively low) collision energy, reveal that Cm H2m loss usually dominates the fragmentation at low energies. However, as the collision energy is increased, Cm H2m elimination declines in importance from ca 70% at 0 1 eV to ca 10% at 9 12 eV. In contrast, the ion, Cm H2mC1C , formally arising by amine expulsion, increases in significance until it accounts for 30 50% of the product ions at 9 12 eV178.

Although this behaviour is logical and correlates well with the interpretation of the fragmentation of metastable (Cm H2mC1)nNH4 nC species via a mechanism involving INCs (the product arising by C N bond cleavage is favoured at higher internal energies), the Cm H2mC1C ion is not necessarily formed from the parent in one step. Moreover, isomerization of the alkyl substituent will almost certainly occur to give a secondary or tertiary isomer of Cm H2mC1C . This caveat is underlined by the observation at high collision energies of fragment ions which correspond to elimination of two Cm H2m molecules from both (Cm H2mC1)2NH2C and (Cm H2mC1)3NHC ions; furthermore, other carbocations become noticeable at relatively high collision energies. Thus, the breakdown graphs of (C3H7)3NHC and (C4H9)3NHC show ions corresponding to loss of two molecules of C3H6 and C4H8, respectively, which reach a maximum relative abundance of 20 and 15% at about 4 and 7 eV, respectively. Moreover, the high energy regions of these graphs also show appreciable signals for C3H5C , which is known to be the principal fragment ion formed by dissociation of C3H7C and C4H9C182,183 .

240 Richard D. Bowen

C. Reactions of Tetraalkylammonium Ions

The reactions of RnNH4 nC species show many common features, including significant trends as n is increased from 1 to 4. However, the behaviour of tetraalkyl ammonium ions (n D 4) possesses some characteristics which set them aside from the homologous protonated amines.

The principal difference is the greatly increased competition of alkane loss, which sometimes occurs by more than one channel, even from metastable R4NC ions158,184 189. Thus, (Cm H2mC1)4NC species eliminate Cm H2mC2 to a far greater extent than their (Cm H2mC1)nNH4 nC homologues do when n D 1, 2 or 3. Moreover, expulsion of an alkane, C2m 1H4m , derived from one intact N-alkyl substituent and part of another (compare equation 18), generally dominates the fragmentation of (Cm H2mC1)4NC species. In contrast, the homologous metastable (Cm H2mC1)nNH4 nC ions never react in this fashion. Thus, metastable (n-C4H9)2NH2C ions lose mainly C4H8, C4H9NH2 and C4H10 in the ratio 100:32:2; (n-C4H9)3NHC reacts similarly, with a strong preference for alkene loss, a moderate side reaction involving (n-C4H9)2NH expulsion and only a slightly increased contribution from alkane elimination. However, metastable (n-C4H9)4NC loses C4H8, C4H9NH2 and C4H10 in the ratio 100:8:37; consequently, alkane loss is enhanced at the expense of amine expulsion for the tetraalkylammonium species. Moreover, (n-

C4H9)4NC is unique among the (Cm H2mC1)4 nNHnC ions in expelling C7H16 (87% of the relative abundance of C4H8 loss). Similarly, the major reaction of metastable (n-

C3H7)4NC is elimination of C5H12; in contrast, the corresponding (n-C3H7)2NH2C and (n-C3H7)3NHC species lose mainly C3H6, together with minor amounts of C3H7NH2 or (n-C3H7)2NH and an even smaller quantity of C3H8, but no C5H12158.

Elimination of C2m 1H4m from metastable (Cm H2mC1)4NC species may be explained as a 1,2-elimination, resulting in formation of the immonium ion, (Cm H2mC1)2C NDCH2. This process is analogous to the loss of Cm H2mC2 from (Cm H2mC1)nNH4 nC ions (n D 1, 2 or 3). Loss of Cm H2mC2 entails C N cleavage and abstraction of a hydrogen atom from the ˛-carbon atom of another N-alkyl substituent; elimination of C2m 1H4m requires C N cleavage and abstraction of an alkyl group from the same position of an N-alkyl substituent. Thus, (C4H9)2NH2C and (C4H9)3NHC lose C4H10 (equations 19 and 20, respectively), but (C4H9)4NC eliminates either C4H10 or C7H16 (equations 21 and 22, respectively)158.

5. The chemistry of ionized, protonated and cationated amines in the gas phase 241

It is interesting that abstraction of a hydrogen atom, rather than an alkyl radical, from the ˛-carbon is strongly favoured as long as an N H entity is present in the ion. The loss of C2m 1H4m from (Cm H2mC1)4NC ions could be considered to correspond to sequential elimination of two neutral species, rather than expulsion of an alkane in which a new C C bond is formed. Very few other examples of such C C bond formation in the fragmentation of low energy ions have been reported.

However, there are sound thermochemical arguments for rejecting the possibility of consecutive loss of Cm H2mC1 ž radicals, which would lead to products at least 300 kJ mol 1 higher in energy than those formed by C2m 1H4m elimination158. Another possibility is successive loss of Cm H2mC2 and Cm 1H2m 2. This explanation is at first sight consistent with the known reactions of many of the immonium ions, (Cm H2mC1)2C NDCH2, which often expel Cm 1H2m 2 over a wide range of internal

energies118. However, a weakness of this suggestion is the absence of C2m H2mC2 loss from (Cm H2mC1)4NC ions. Thus, several (n-C3H7)2C NDCHR ions eliminate C2H4 and C3H6

at similar rates118,132. Therefore, if ‘C5H12’ loss from (C3H7)4NC actually occurred by elimination of C3H8 to give (C3H7)2C NDCHC2H5, which subsequently expelled C2H4, a contribution from C3H8 loss from the latter would also be expected, giving the impression that (C3H7)4NC eliminated C6H14. However, no such reaction is observed158. Consequently, the interpretation of C2m 1H4m elimination as sequential loss of Cm H2mC2 and Cm 1H2m 2, although thermochemically plausible, is unsatisfactory.

The CID spectra of the tetraalkylammonium ions are dominated by alkane elimination. Thus, breakdown graphs reveal that loss of C5H12 is the most abundant ion in the spectrum of (n-C3H7)4NC over a wide range of collision energies, reaching a maximum of ca 70% of the total at about 3 eV. Elimination of C3H6 and, to a lesser degree, C3H8 are also important at lower collision energies; however, the abundance of the corresponding fragment ions declines quite sharply as the collision energy is increased and a new signal appears for formation of C3H7C . Although this signal corresponds to elimination of (n- C3H7)3N from (n-C3H7)4NC , it need not necessarily arise in one step because both the ions formed by C3H6 and C3H8 loss from (n-C3H7)4NC are likely to give C3H7C when activated by high energy collisions. A qualitatively similar breakdown graph is found for the higher homologue, (n-C4H9)4NC158 .

D. Comparison of the Reactions of Protonated Amines and Tetraalkylammonium Ions

The trends that are observed in the reactions of (Cm H2mC1)4 nNHnC ions have been interpreted in terms of changes in the underlying energetics of the species arising by heterolytic and homolytic cleavage of the C N bond189. Elimination of Cm H2m [and, occasionally, (Cm H2mC1)3 nNHn] occurs after heterolytic cleavage to form [Cm H2mC1C (Cm H2mC1)3 nNHn], which undergoes proton transfer to give [Cm H2m (Cm H2mC1)3 nNHnC1C ]. Rearrangement of the cation to a stable isomer accompanies heterolytic cleavage, whenever possible. Separation of the components results in alkene expulsion. The occasional occurrence of amine loss to give Cm H2mC1C is explained by dissociation of [Cm H2mC1C (Cm H2mC1)3 nNHn] without proton transfer. In contrast, homolytic cleavage yields [Cm H2mC1ž (Cm H2mC1)3 nNHnCž ]. Hydrogen atom abstraction

from the ˛-carbon atom then leads to elimination of Cm H2mC2; alternatively, alkyl radical abstraction from this position results in C2m 1H4m loss. This mechanism is illustrated for (C3H7)4 nNHnC in Scheme 20.

H

(R = H, CH2CH2CH3)

SCHEME 20

When only one or two alkyl groups are present, the energy of the species produced by heterolytic cleavage is substantially lower (by 60 100 kJ mol 1, depending on the stabilization of the species by ion dipole and related forces) than that arising from homolytic cleavage. Addition of a further alkyl group favours the homolytic cleavage somewhat more strongly than the heterolytic alternative, but the former remains significantly lower in energy. However, continuation of this process to the tetraalkylammonium ion results in a differential stabilization of the homolytic cleavage which is so great that the alternative cleavages have very similar critical energies158,189.

The changes in the relative energies of the species formed by heterolytic and homolytic cleavages chiefly reflect the strong influence of progressive N-alkylation in lowering the ionization energy of the (Cm H2mC1)3 nNHn amine which outstrips the corresponding trend in the PA of these amines. Thus, Hf(C3H7)nNH3 nCž declines markedly from 778 kJ mol 1 for C3H7NH2Cž to 552 kJ mol 1 for (C3H7)3NHCž . In contrast, the corresponding decrease in Hf(C3H7)nNH4 nC from 548 kJ mol 1 for C3H7NH3C to

5. The chemistry of ionized, protonated and cationated amines in the gas phase 243

389 kJ mol 1 for (C3H7)3NHC is less pronounced158. Therefore, alkane loss via homolytic cleavage competes much more effectively with alkene elimination via heterolytic cleavage for the tetraalkylammonium ions.

V. CONCLUSIONS

Much insight has been gained during the last 15 20 years into the structure and reactivity of ions derived from amines. Advances in instrumentation, the invention of new methods for generating ions and characterizing the structure of both the charged and neutral products of their reactions, together with the complementary information accessible by MO calculations, have permitted detailed descriptions of many of these ionic fragmentations. Novel ion structures, especially distonic species and ion-neutral complexes, play a vital role in the chemistry of many ions generated from amines. Some fragmentations reflect the influence of a radical site; for instance, the hydrogen abstractions through 5-, 6-, 7- and 8-membered ring transitions states which initiate the rearrangement of ionized n-alkylamines prior to pseudo-˛-cleavage. Others reflect features of classical cation chemistry; for example, the rearrangement of primary N-alkyl substituents which precedes alkene elimination from immonium ions and protonated alkylamines. These mechanistic studies have brought the behaviour of ionized, protonated and cationated amines in the gas phase firmly within the compass of physical-organic chemistry. The resultant knowledge of the inherent properties of ions derived from amines has further enhanced the analytical value of mass spectrometry and shed light on the influence of solvent effects on the properties of amines.

VI. ACKNOWLEDGEMENTS

This review would not have been possible without the pioneering work of numerous scientists, many of whom (including Dr S. Hammerum, Professors H. E. Audier, G. Bouchoux, P. J. Derrick, A. G. Harrison, J. L. Holmes, P. Longevialle, F. P. Lossing, A. Maccoll, T. H. Morton, N. M. M. Nibberring, H. Schwarz, J. K. Terlouw and H. -J. Veith) provided reprints and/or engaged in valuable discussions. I am grateful to all of them, particularly Steen Hammerum, with whom I have enjoyed a long and informative debate on the reactions of ionized amines and immonium ions.

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