Proton-bound dimers of aliphatic carboxamides: gas-phase basicity and dissociation energy

ELSEVI E R International Journal of Mass Spectrometry and Ion Processes 165/166 (1997) 49-62 and bn F’rocsusr

Proton-bound dimers of aliphatic carboxamides: gas-phase basic@ and dissociation energy’

Matthias Witt, Hans-Friedrich Griitzmacher*

Fakultiit fk Chemie der Universitiit Bielefeld, POB 100131, D-33501 Bielefeld, Germany

Received 1 April 1997; accepted 1 May 1997

Abstract

The gas phase basic@ of butyramide (2a), caproamide (3a>, isobutyramide (5a), pivalamide (6a), cyclopentanecarboxamide (7a), cyclohexanecarboxamide @a>, their N-methyl derivatives 2b-8b and their N,N-dimethyl derivatives 2c-lk have been determined by the ‘deprotonation’ method using IT-ICR spectrometry (2a-8a only) and by the ‘kinetic’ method observing the metastable decomposition of proton-bound heterodimers by tandem mass spectrometry. Both methods give identical results for the primary carboxamides studied within the limit of error of k 6 kJ/mol. The GB(2a4a) and PA(2a-8a) correlate linearly with the GB and PA of other aliphatic carbonyl compounds (aldehydes, ketones, methyl carboxylates) as expected for a protonation of the carboxamides at the carbonyl-0 atom. The GB of the N-methyl- and N,N-dimethylcarboxamides exceed the GB of the primary carboxamides by 22 + 3 kJ/mol and 46 f 4 kJ/mol, respectively. The bond dissociation energy BDE of the proton-bound homodimer of formamide, acetamide, propionamide and pivalamide and of their N,N-dimethyl derivatives have been derived from the appearance energy AE of the protonated carboxamide from the proton-bound homodimers using collision energy resolved mass spectrometry CERMS (collision energy resolved mass spectrometry) by FT-ICR spectrometry. The BDE of all proton-bound dimers of the primary carboxamides measured are virtually constant at 1.19 f 0.08 eV in spite of a considerable variation of the GB by 0.68 eV. The BDE of the proton-bound homodimers of the N,N-dimethylcarboxamides are consistently smaller than those of the primary carboxamides in spite of the increased GB of tertiary carboxamides and decreases from the proton-bound homodimer of N,iV-dimethylformamide to N,N-dimethylpivalamide. As a consequence of this effect formamide of the lowest GB exhibits the highest BDE in its proton-bound homodimer while N,N-dimethylpivalamide with the highest GB forms the weakest ionic hydrogen bond. 0 1997 Elsevier Science B.V.

Keywords: Gas phase basic@; Kinetic method; Deprotonation method; Bracketing method; Proton affinity

’ Dedicated to Professor Keith. R. Jennings on the occasion of his 65th birthday. *Corresponding author.

016%1176/97/$17.00 0 1997 Elsevier Science B.V. All rights reserved. PI1 SO168-1176(97)00152-3

50 M. Witt, H.-F. Griitzmacher /International Journal of Mass Spectrometry and Ion Processes 165/ 166 (1997) 49-62

1. Introduction

Proton-bound homodimers and heterodimers, in which a protonated organic molecule has attached an identical and a different molecule, respectively, are often observed in the gas phase under the conditions of chemical ionization (CI) mass spectrometry. This is particularly true for polar molecules and the abundant formation of proton-bound dimers of carboxamides is observed even under the very low pressure conditions of Fourier-Transform Ion-Cyclotron Resonance (FT-ICR) spectrometry [l-3]. Carboxamides are simple models for peptides and the gas phase chemistry of protonated peptides and proteins currently attracts much attention because of the application of modem mass spectrometric techniques to peptide analysis and to advanced studies of conformations and functional group interactions within protonated peptides and proteins [4-151. The uncomplicated formation of proton- bound homo- and heterodimers of carboxamides in the gas phase provides a possibility to model experimentally structural effects on internal interactions within polypeptides by interactions between the components of these proton-bound clusters. This approach appears attractive because switching of a protonated group such as a protonated amino group at the N-terminus or at a side chain of the protonated peptide between various amide bonds of the peptide backbone is mirrored in proton-bound heterodimers of carboxamide by an easily observed ligand exchange and the strength of these functional group interactions can be deduced from a determination of the dissociation energy of the proton-bound dimer using collision energy resolved mass spectrometry (CERMS) [16,17]. Further, aliphatic carboxamides of various structures are easily available and conformational effects within protonated peptides can be mimicked by the relative orienta- tions of the amide groups within linear and alicyclic dicarboxamides defined by the molecular frame.

Considering this concept we have started an investigation of the reactions of proton-bound homo- and heterodimers in the gas phase. The results obtained so far indicate indeed distinct

steric and conformational effects caused by functional group interactions on the gas-phase basicity and on the ligand exchange reactions of proton-bound clusters containing carboxamides and dicarboxamides. However, for a vigorous analysis of these effects the gas phase basicities GB and proton affinities PA of the aliphatic carboxamides must be known. Recently, we have demonstrated by a comparison of standard proton transfer equilibrium methods for the determination of GB(propionamide) [18] with ‘non-equilibrium’ methods that the ‘deprotonation’ method of Bou- chow et al. [19,20] and the ‘kinetic’ method of Cooks et al. [21-231 can be used to determine reliably the GB or PA of carboxamides. It be- comes increasingly more difficult to observe the proton transfer equilibrium between a protonated reference base and a carboxamide in the gas phase with increasing molecular weight of the amide because of the low volatility of the larger carboxamides. However, protonated carboxamides and proton-bound heterodimers of carboxamides are generated conveniently in the ion source of a mass spectrometer by a choice of ionization methods which do not require a high volatility of the amide. Hence, determination of the GB (carboxamide) by kinetic methods which link the rate constants of proton transfer from protonated carboxamides to a series of reference bases to the difference AGB or APA between carboxamide and base are experimentally uncomplicated. In this paper we report the GB of a selection of aliphatic primary carboxamides and of their N-methyl and N,N-dimethyl derivatives measured by the methods of Bouchoux et al. [19,20] and Cooks et al. [21-231. These studies are complemented by a determination of the dissociation energies of proton-bound homodimers of eight primary and tertiary amides. It will be shown that the structure of the acyl group of a carboxamide exerts distinct effects analogous to those known from aliphatic ketones and esters. This confirms 0-protonation of the amide group in all cases as expected from theoretical calculations. However, the dissociation energies of the proton-bound homodimers vary only slightly if at all with the structure of the amide acyl group.

M. Wilt, H.-F. Gtitzmacher / InternationalJournal of Mass Spectrometty and Ion Processes 165 / 166 (1997) 49-62 51

2. Experimental

The carboxamides used in this study were pre- pared from the corresponding carboxylic acid chlorides and ammonia, methylamine and dimethylamine, respectively, using standard methods of organic synthesis. The structure and purity of the carboxamides were controlled by ‘H-NMR spectrometry. The pure reference bases are commercially available. Their purity was con- firmed by GC/MS and these compounds could be used without further purification.

A Bruker Spectrospin CMS 47X FT-ICR spectrometer equipped with a 4.7-T superconducting magnet, an external ion source [24] and an Infin- ity@ cell [25] was used for the ‘deprotonation’ method of Bouchoux et al. [19,20] and for CERMS experiments. The experiments with the ‘kinetic’ method by observing the dissociation of proton- bound heterodimers [21-231 were performed using a double focusing AutoSpec mass spectrometer [26].

In the ET-ICR experiments protonated carboxamides were generated in the external ion source by chemical ionization (CI) with isobutane as the CI gas. The primary ionization of the isobutane was accomplished by 30/eV electrons and a filament current of 3.5-4.0 A. The ions generated in the external ion source were transferred into the ICR cell and isolated by standard procedures of ejection of all unwanted ions by a broad band rf pulse and a series of rf pulses at the cyclotron frequency of ions with m/z values close to the selected ion. This procedure avoids unplanned excitation of the selected ions. Following this isolation procedure the ions were allowed to react with the neutral reference base present in the cell at a constant background pressure of 1.4 x 10-s-2.8 X lop7 mbar during a variable reaction time between 2 and 30 s. The pressure readings of the ionization gauge were calibrated by measuring the rate constant k = (2.2 f 0.4) x 10m9 cm3 molecule-’ s- ’ for the reaction NH:+ NH, + NH: + NH; [271 and by correcting for the different relative sensitivities of the compounds used [281.

The intensities of the signals [MH]+ in the mass spectra were determined after Gauss multi-

plication of the time domain signal and followed by Fourier transformation in the frequency domain. The bimolecular rate constants k,i were derived from the Marquard algorithm of the simple decay exponential function (Eq. (1)) on the plot of the experimental intensities vs. the reaction time t, where kexp is the pseudo-first order rate constant and [N] the number density of the neutral molecules within the IT-ICR cell.

NH+ It M-I+ lo =exp(-k,,,t)=exp(-k,;[Nlt) (1)

For the ‘kinetic’ method of Cooks et al. [21-231 proton-bound clusters of carboxamide and an appropriate base were produced in the CI ion source of the AutoSpec mass spectrometer using methane as the CI gas at a partial pressure of approximately 5 x 10F5 mbar in the ion source housing and adjusting the partial pressures of the other components for optimal formation of the proton-bound heterodimer of the carboxamide. A filament current of 4.0-4.5 A and an accelerating voltage of 8 kV were used. The proton-bound heterodimer was focused magnetically into the 3rd field free region (FFR) following the magnetic analyzer and preceding the 2nd electrostatic analyzer (ESA) of the instrument. The decomposi- tions of the proton-bound heterodimer in the 3rd FFR were observed by varying the electric potential of the ESA (MIKE-spectrometry [29]).

The CERMS studies were performed with the Bruker Spectrospin CMS47X FT-ICR spectrometer using the protocol published before 116,171. Briefly, the proton-bound homodimers were generated in the external CI ions source under the condition described above, were transferred into the Infinity @ ICR cell and were purified by standard ion ejection techniques. After a delay of at least 4 s to ensure thermalization the ions were accelerated by a i-f-pulse of the appropriate cyclotron frequency of the proton-bound heterodimer and of a constant peak-to peak voltage V,, of approximately 7 V. The kinetic energy of the proton-bound homodimer was accurately determined by the length of the if-pulse, which was varied in small steps. The background pressure of argon, p(Ar), in the IT-ICR cell of typically 3-5

52 M. Witt, H.-F. Gnkwzacher /InternationalJournal of Mass Spectrometty and Ion Processes 16S/ 166 (1997) 49-62

X 10e8 mbar and the delay time, tdiss, for collision-induced decomposition were set to satisfy the single collision criterion p(Ar)t,,,, < 7 x lo-’ mbar * ms of McMahon et al. [30]. From the set of CID mass spectra thus obtained, a plot of fragment ion yield vs. the center-of-mass energy E,, of the collision was constructed. To extract the appearance energy AE of the protonated monomer, which was the single dissociation product, from this plot a linear increase of the dissociation cross-section above AE was assumed and the Doppler broadening of the threshold curve near threshold was accounted for according to Chantry [31].

3. Results and discussion

3.1. Proton affinity of aliphutic carboxamides

Gas-phase basicity (GB) and proton affinity (PA; Eq. (2)) relate to very fundamental ther- mochemical data which control inter-alia the equilibrium of proton transfer reactions between basic molecules B and M and the capability of molecules to participate in proton- or hydrogen- bridged bonds.

B + H+ --) BH+ - AG,” = GB(B)

= PA(B) - TAS MH++B*M+BH+-AG,“=AGB

(2)

= -AH,” + TAS,” (3)

Only the GB of primary, secondary and tertiary formamides and acetamides, of N-methyl propionamide and of NJ-dimethylbutyramide are found in the recent compilation of GB values by Hunter and Lias [321. Since it is well known that the first members of a series of homologues of organic compounds may exhibit unique properties it is important to extend the series GB values to higher carboxamides as well as to carboxamides with branched and alicyclic acyl groups.

The reaction efficiency efi defined as the ratio kexp/kcoll of the experimental rate constant kexp of the chemical reaction and the rate constant k,,,, of ion/molecule collisions [33], of a proton transfer depends strongly on the free reaction

enthalpy of this process, i.e. on the AGB of the two bases involved [34,35]. Usually a ‘single-well’ potential energy hypersurface is a good model for a proton transfer reaction between MH+ and B assuming proton migration in the collision complex [MHBl+ without any additional activation barrier. This model is described by Scheme 1 and results in Eq. (4) for a determination of the proton transfer efficiency effH +, where k, and k_, are the rate constants of the unimolecular dissociation of the collision complex [MHB]+ in the forward and back direction, respectively.

k eflH+ [%] = p x 100 = k, f’k_ x 100

cell I

1 = 1 +k_,/k, x 100

For an exergonic proton transfer, k, x=-k_ ,, which results in a large efficiency close to lOO%, whereas k, zs- k_ , holds for endergonic transfer reactions leading to a small efficiency below 10%. Usually the change between endergonic and exergonic proton transfer from MH+ to a series of reference bases Bi is associated with a sharp increase of the reaction efficiency and this can be used to ‘bracket’ GB(M) by the slightly different GB(B,) of a pair of bases with large and small proton transfer efficiencies. For an improved ‘deprotonation’ Bouchoux et al. [19,20] have derived the theoretical relationship shown in Eq. (5) between the rate constant kH+ or reaction efficiency eflH + of the proton transfer from MH+ to a base B, with GB(B,), where a, b and c are fitting parameters. From the parameters of Eq. (5) the GB(M1 is calculated according to Eq. (6).

k effH+ = kc,,,, H+XlOO

= l+exp(bx[rGB(B,)+c]) x 100 (5)

k cdl MH’ + B, = [M-H+...B,] 5

k-1 M + BiH+

Scheme 1.

M. Witt, H.-F. Griitzmacher /InternationalJournal of Mass Spectrometty and Ion Processes 165/ 166 (1997) 49-62 53

with a = limit at large values of GB(Bi); b = l/RTefl (see [19,20]); c = GB(M) + RTefi; and

GB(M) = c - l/b = c - RTerr (6)

The sudden change of the proton transfer efficiency used to bracket GB(M) may be drastically reduced by steric effects [36-391 or by other effects. In these cases it is difficult to predict a priori the reaction efficiency of an only slightly exergonic proton transfer from MHf and to determine clearly that pair of reference bases which brackets GB(M). Therefore, modeling the reaction efficiency by Eq. (5) by using a whole series of reference bases Bi is superior to using only one pair of bracketing bases and an error limit of + 5 kJ/mol has been estimated for this ‘deprotonation’ method by FT-ICR spectrometry [19,20].

A related approach for the determination of GB (and PA) has been developed by Cooks et al. [21-231 by observing the dissociation of a proton- bound heterodimer [M a** H+ .-* Bi] by tandem mass spectrometry. Basically this kinetic method relies on the observation that during the dissociation of an ionized cluster into its components (Scheme 2) the charge or the charged particle binding the components stays with the component of highest affinity. This is particularly true for the dissociations of metastable cluster ions because the quasi-equilibrium theory predicts for ions of low internal energy that the critical energy of the dissociations is dominated by the thermochem- istry in the absence of extra barriers [40]. Again this effect of the direction of the preferred dissociation of [M *a* H+ *.a Bi] can be used to bracket the GB(M) using GB(B,). In the more advanced modification of the kinetic method the rate constants k, and k, of the competing dissociation of the proton-bound heterodimer (or any other kind

[M...H+...Bi] 9 MH’ + Bi GB(M) > GB(Bi)

‘k\- 2 M + B,H+ GB(M) < GB(Bi)

Scheme 2.

of ionized cluster) are considered explicitly. This results in the linear correlation between the logarithm of the relative rate constants ln(k,/k,) and of the relative intensities of the protonated components hr([MH]+/[BiH]+) and the difference AGB or APA depicted in Eq. (7).

_1- ln [MHlf k

Ink, - 1

[B,Hl’ = AGB ’ RTcrr

1 = A PA ’ RTerr (7)

Using a series of reference bases to delineate this correlation function in the special case investi- gated the effective temperature Tefl and the GB or PA of the compound studied is obtained. In the ideal case this method furnishes reliable GB or PA values but several conditions have to be met [41,42]. In particular the dependence of k, and k, on the internal energy of the proton-bound heterodimer has to be identical (identical frequency factors), the potential energy surface of the proton-bound heterodimer should be approxi- mated by a single well and the difference of the critical energies for both dissociation pathways should correspond to the differences of the GB or

R= H,H CH,, H CH,.CH,

H,C H2C- CONR, la lb Ic

H,CH,CH&-CONR, Pa 2b 2c

H3C (H2C)., -CONR, 3a 3b 3c

H,C (H,C),,- CONR, 4a 4b 4c

(HQHC- CONR, 5a 5b 5c

(H&C- CONR, 6a 6b 6c

CONR, 7a

CONR, 8a

Scheme 3.

7b

8b

7c

8c

54 M. Witt, H.-F. Giitzmacher /IntemationalJoumal of Mass Spectrometry and Ion Processes 165/166 (1997) 49-62

PA of the components (no reverse activation energies). Likewise the molecular geometry and conformation of the components should not change very much during the dissociation because this will introduce special entropic effects [43].

The structures of the carboxamide 2-8 used in this study are depicted in Scheme 3. For a determination of the GB of the primary carboxamides 2a-8a by the ‘deprotonation’ method [19,20] the reference bases Bi listed in Table 1 were used spanning a range of GB from 829 kJ/mol to 884 kJ/mol and of PA from 856 kJ/mol to 918 kJ/mol. Table 1 contains also the reaction efficiencies measured for the deprotonation of the protonated carboxamides 2a-8a by these bases. The reaction efficiencies e&,+ of Table 1 were plotted vs. the GB of the reference bases B and four typical examples of these plots are shown in Fig. 1. The plots were fitted by Eq. (5) and the fitting parameters a, 6, and c were used to calculate the GB (carboxamide) of 2a-8a by Eq. (6).

loo-....,....,....,....,....,..,.,....

90 - GB(bulyramide) = 647 f 6 k.J/md a) -

60 - 0 -

70 -

60 -

$ 50-

s= 40-

30 -

20 -

10 -

o:...“.....,....,....,,...,,.,,,,.,,~

620 630 640 650 660 670 660 690

GB (B,)[kJ/mol]

100 . . . . . . . . . . . . . . . . . . . . . . . . . . . ...*...

!a- GB(isobutyramMe) = 650 f 6 kJ/md

An analogous plot can be obtained for the PA of the reference bases resulting in values of the PA (carboxamide) of 2a-8a. However, it has been shown that the PA calculated in this way from an GB(B) [kJ/mol]

Table 1 Deprotonation efficiency, eflH +, of primary carboxamides by reference basea

Reference base Deprotonation efficiency (%)

Butyramide Caproamide lsobutyramide Pivalamide Cyclopentane- Cyclohexane- carboxamide carboxamide

2a 3a 5a 6a 7a 8a

Di-iso-propylether (GB = 829, PA = 856) Di-set-butylether (GB = 839, PA = 866) Pyrrole (GB = 844, PA = 875) Aniline (GB = 851, PA = 883) N,N-dimethylformamide (GB = 855, PA = 886) ortho Toluidine (GB = 860, PA = 891) 2-bromopyridine (GB = 867, PA = 899) n-Propylamine (GB = 884, PA = 918)

1.3 2.3 1.2 0.4 0.5 0.8

2.4 2.3 2.3 1 .o 2.2 1.0

6.0 0.9 1.7 0.1 0.1 0.1

42.1 17.9 23.2 3.6 3.3 0.8

58.8 49.4 53.1 22.2 23.5 13.3

71.2 65.4 59.9 31.4 32.5 12.6

63.7 64.4 66.8 62.8 59.6 53.8

80.7 81.5 72.2 68.7 63.7 61.1

‘Values of GB and PA from reference 1321.

M. Witt, H.-F. Griitmacher / International Journal of Mass Spectiometry and Ion Processes 165/166 (1997) 49-62 55

lW-....,....,....,....,....,....,....

Qo-

80 -

GB(plvalamide) = 855 t 6 kJ/mol c) :

,....,,...,...,,

820 830 840 850 860 870 880 890

GB(B,) (kJ/mol]

820 830 840 850 860 870 880 990

GB (B,)[kJ/mol]

Fig. 1. Dependence of deprotonation efficiency, eflH +, on the GB of reference bases (Table 1) (al of protonated butyramide; (bl of protonated isobutyramide; (cl of protonated pivalamide; (d) of protonated cyclohexanecarboxamide.

equation analogous to Eq. (6) are less reliable than the GB values [19,20]. The GB and PA

values obtained are recorded in Table 2 which includes also the GB and PA of formamide [32], acetamide [32] and propionamide [18] la previ- ously determined.

In a second series of measurements the GB and PA of the primary carboxamides 2a-8a were determined by the ‘kinetic’ method [21-231 using the reference bases B listed in Table 1 with the exception of n-propylamine and pyrrole to correlate the AGB and APA between these bases and the carboxamides to the relative abundance ratio of the protonated base and protonated amide in the MIKE spectra of the corresponding proton- bound heterodimers according to Eq. (7). In Fig. 2 four examples for this correlation are shown. The GB (carboxamide) and PA (carboxamide) obtained are shown in the middle part of Table 2. Principally the ‘kinetic’ method yields also values of GB and the corresponding PA can be obtained by measuring the relative abundance ratios of the protonated base and protonated sample molecule at different Tefi by CID of the proton-bound heterodimers 1431. However, in the case of propionamide la it has been shown [18] that Tea has no effect on the apparent GB values obtained by Eq. (6). This indicates that entropic effects on the decomposition of the proton-bound heterodimer of propionamide and the reference bases are neg- ligible in spite of using bases with different accep- tor atoms for the proton bridge. It is assumed that the dissociation of the proton-bound heterodimers of the carboxamides 2a-Sa are also not

Table 2 Gas-phase basicity and proton affinity of primary carboxamides obtained by the ‘deprotonation’ method [19,20] and ‘kinetic’ method [21-231

Carboxamide Deprotonation method Kinetic method Mean value

GB (kJ/moIl PA (kJ/mol) GB (kJ/mol) PA (kJ/mol) GB (kJ/mol) PA (kJ/mol)

Formamidea Acetamidea Propionamide lab Butyramide 2a Caproamide 3a Stearic carboxamide 4a Isobutyramide 5a Pivalamide 6a Cyclopentanecarboxamide 7a Cyclohexanecarboxamide Sa

791.2 833.0 844.9 847f6 851 f6 -

822.2 864.0 873.0 879 5 7 883 + 5

850f6 882 + 5 856 f 6 887 k 6 855 f 6 886 * 6 860 f 6 891 * 5

-

- 849f5 854 f 5

(864 f 81 851 f3 858 f 7 860*4 861 f 7

- - - 879 f 6 848 879 885 f 9 852 884

(895 *8) - - 882 f 5 850 882 889 f 8 857 888 889 f 8 857 888 892 f 5 860 891

aFrom reference [32]. ‘From reference [18].

56 M. Witt, H.-F. Griitzmacher / International Journal of Mass Spectrometty and Ion Processes 165 /I66 (1997) 49-62

influenced by a variation of TCA’. Therefore, the values of PA obtained by this ‘kinetic’ method are expected to be quite reliable. Further, it can be seen from the data of Table 2 that the agreement between the values of GB and of PA obtained by both methods is very acceptable. The fitting of the experimental parameter (eflH+ or ln[BH+]/[MH+]) by both methods is highly re- producible and results in variations of the values of GB or PA of only approximately f 2 kJ/mol. However, a mean error of + 4 kJ/mol is assumed for the values of GB or PA of the reference bases [32] which results in a much larger error of the values of GB and PA. For the ‘deprotonation’ method of Bouchoux et al. [19,201, a mean value of + 6 kJ/mol is obtained in agreement with the error limit off 5 kJ/mol given in the literature

I’.‘.I,‘,‘I”.‘I.“.I”“I’

GB(butyramlde) = 849 c 5 kJlmol

850 855 860 865 870

GB(B,) [kJ/mol]

GEI(wobulyramlde) = 851 t 3 kJ/mol W -

-6 ,-

850 055 860 065 870

GB(B,) [kJ/mol]

[19,201. A similar error of + 3- + 7 kJ/mol is estimated for the ‘kinetic’ method of Cooks et al. 121-231 as indicated in Table 2.

The GB and PA of the N-methyl derivatives 2b-8b and NJ-dimethyl derivatives 2c-8c of the carboxamides were determined by the ‘kinetic’ method only using bracketing by a pair B, and B, of bases which give a more and a less intense signal of the fragment ions BHf in the MIKE spectrum of the respective proton-bound heterodimer [B ... + H+ ... amide]. The resulting GB (carboxamide) and PA (carboxamide) are shown in Table 3 and Table 4. The accuracy of the GB and PA values obtained in this way depends on the spacing between the GB or PA values of the bracketing bases B, and B, and the accuracy of these values. Since AGB and APA of B, and B,

6

6 GE(plvalamlde) = 658 t 7 kJ/mol

a35 840 845 850 855 660 665 670

GB(B) [kJ/mol]

I “, * I I ’ ” I

GB(cyclohexaneca~xamide) = 861 t 7 kJ/mol d) .

4-

-6 - I ..,,I.... I ., , , I 650 655 860 665 870

GB(B) [kJ/mol]

Fig. 2. Dependence of the relative abundances of protonated amide and protonated reference base in the MIKE spectra of the proton-bound heterodimers on the GB of reference bases (see Table 1) (a) of butyramide; (b) of isobutyramide; (c) of pivalamide; Cd) of cyclohexanecarboxamide.

M. Witt, H.-F. Griitzmacher /International Journal of Mass Spectrometty and Ion Processes 165 /166 (1997) 49-62 57

is approximately 10 kJ/mol and an uncertainty of + 4 kJ/mol for GB(B,) has to be taken into account the error limit of + 10 kJ/mol of the

values of the GB and PA of the N-methyl- and N,N-methylcarboxamides obtained by this simple method is rather large. Further, this method does

Table 3 Gas-phase basicity and proton affinity of N-methylcarboxamides obtained by bracketing with the ‘kinetic’ method 121-231

N-methylcarboxamide GB (kJ/mol) Aa (kJ/mol) PA (kJ/mol) Reference base B, Reference base a_’

N-methylpropionamide lb

N-methylbutyramide 2b

N-methylcaproamide 3b

N-methylstearic- carboxamide 4b

N-methylisobutyramide Sb

N-methylpivalamide 6b

N-methylcyclopentane- carboxamide 7b

N-methylcyclohexane- carboxamide 8b

< 866 * 5

* 866 * 5

873 rt 5

> 886 5 6

> 866 * 5 16

879 * 9 22

< 886 + 6 26

- 886 + 6 25

21 < 898 + 6

20 898 f 6

22 898 + 6

22 920 + 6

> 898 * 6

912 * 10

< 920 f 6

> 920 + 6

m-Toluidine 2-Bromopyridine GB 865; PA 896 GB 867; PA 899 m-Toluidine 2-Bromopyridine GB 865; PA 896 GB 867; PA 899 Cyclopropylamine p-Phenylenediamine GB 871; PA 905 GB 874; PA 906 n-Propylamine n-Hexylamine GB 884; PA 918 GB 887; PA 921

m-Toluidine GB 865; PA 896 p-Phenylenediamine GB 874; PA 906 n-Propylamine GB 884; PA 918

2-Bromopyridine GB 867; PA 899 n-Propylamine GB 884; PA 918 n-Hexylamine GB 887; PA 921

n-Propylamine GB 884; PA 918

n-Hexylamine GB 887; PA 921

“A, Difference of GB to GB of the corresponding primary carboxamide. hB,, reference base with lower GB; B,, reference base with higher GB (values taken from (321).

Table 4 Gas-phase basicity and proton affinity of N,N-dimethylcarboxamides obtained by bracketing with the ‘kinetic’ method [21-231

N,N-dimethylcarboxamide GB (kJ/mol) ha (kJ/molJ PA (kJ/mol) Reference base B,h Reference base Bzh

N,N-dimethylpropionamide lc

N,N-dimethylbutyramide 2c

N,N-dimethylcaproamide 3c

NjV-dimethylstearic- carboxamide 4c

N,N-methylisobutyramide 5c

N,N-dimethylpivalamide 6c

N,N-dimethylcyclopentane- carboxamide 7c

N,N-dimethylcyclohexane- carboxamide 8c

< 895 * 8 51

> 895 f 8 44

< 899 * 5 47

> 905 * 9 41

> 895 * 5 45

> 899 * 5 42

< 905 f 9 48

905+9 45

< 928 + 7

> 928 k 7

< 932 f 6

938 f 8

928 + 6

> 932 + 6

938 * 8

938 k 8

set-Butylamine GB 891; PA 925 set-Butylamine GB 891; PA 925 Pyridine GB 898; PA 930 Cyclohexylamine GB 900; PA 934

set-Butylamine GB 891; PA 925 Pyridine GB 898; PA 930 Cyclohexylamine GB 900; PA 934

Cyclohexylamine GB 900; PA 934

Pyridine GB 898; PA 930 Pyridine GB 898; PA 930 Cyclohexylamine GB 900; PA 934 N,N-dimethylaniline- GB 909; PA 941

Pyridine GB 898; PA 930 Cyclohexylamine GB 900; PA 934 N,N-dimethylaniline GB 909; PA 941

N,N-dimethylaniline GB 909; PA 941

‘A = Difference of GB to GB of the corresponding primary carboxamide. hB, = Reference base with lower GB; B, = reference base with higher GB, values taken from 1321.

58 M. Witt, H.-F. Griitzmacher /IntemationalJounud of Mass Spectrometty and Ion Processes 165 /I66 (1997) 49-62

not distinguish between carboxamides which are bracketed by the same pair of bases B, and B,. This ambiguity was resolved by observing the dissociation of metastable proton-bound heterodimers of the respective carboxamides. This test results in the following order of increasing GB (and PA) for N-methylcarboxamides (see Table 3): GB(lb) < GB(2b), GB(3b) and GB(7b) < GB@b) < GB(4b) as expected from the increasing polarizability due to the increasing NJ-dimethylcarboxamides(Table 4).

Obviously, the aliphatic carboxamides are regular with respect to protonation in the gas phase and the effect of molecular structure on the GB and PA. In the case of linear carboxamides the GB and PA increase with the chain length of the acyl group, but the increase per CH, unit decreases from 42 kJ/mol for AGB and APA between formamide and acetamide to 4 kJ/mol for AGB and APA between propionamide la and butyramide 2a and the further elongation of the alkyl chain by two CH, units to caproamide 3a results only in an additional increase of 5 kJ/mol. Due to experimental difficulties the GB and PA of stearic amide 4a was not thoroughly evaluated, but the decomposition of the proton-bound heterodimer of 8a and 4a proves GB of 4a > GB(8a) and GB(4a) is bracketed by o&o-toluidine (GB 860 kJ/mol, PA 891 M/mol) and 2-bromopyridine (GB 867 kJ/mol; PA 899 kJ/mol). There- fore, the value of the GB of linear carboxamides continues to increase slightly with the length of the alkyl chain to approximately 864 kJ/mol for 4a. The effect of branching of the acyl group at the C, atom of a primary carboxamide on the GB and PA can be seen from the corresponding values of la, Sa and 6a which increase by 6 and 13 kJ/mol for one and two methyl substituents, respectively, at C,, so that each methyl group contributes approximately 6 kJ/mol to the GB. Finally, the rather large GB of the cyclopentanecarboxamide 7a and cyclohexanecarboxamide 8a can be explained by branching at the C, atom and with the increased size of the acyl group. The regular behavior of the primary carboxamides with respect to protonation is seen most clearly from a comparison with the GB (and PA) of other aliphatic carbonyl compounds. In Fig. 3 the GB of

•I aldehyde (R’= H)

%x2 - ketone(R’=CH,)

I. 780 790 800 810 820 830 940 850 860

GB(primary carboxamide; R’ = NH,) [kJ/mol]

Fig. 3. Correlation between the GB of primary carboxamides and carbonyl compounds (aldehyde, ketone, methyl carboxylate).

the primary carboxamides formamide, acetamide and la-8a are plotted against the GB of aldehydes, ketones and methyl carboxylates with corresponding acyl groups which are available from the literature [32]. The linear correlation is good with all three types of aliphatic carbonyl compounds and the slope of the correlation line is close to 1 for the ketones and methyl carboxylates indicat- ing comparable stabilization of charge in the protonated carboxamides and these protonated car- bony1 compounds (GB (carboxamide) = 0.73. GB (aldehyde) + 296, r = 0.998; GB (carboxamide) = 0.92 * GB (ketone) + 111, T = 0.997; GB (carboxamide) = 1.06 . GB (methyl carboxylate) - 6, r = 0.996. A similar linear correlation is obtained for the PA of aliphatic primary carboxamides and the PA of the other aliphatic carbonyl compounds (PA (carboxamide) = 0.71. PA (aldehyde) + 318, r = 0.999; PA (carboxamide) = 0.92 . PA (ketone) + 115, r = 0.995; PA (carboxamide) = 1.05. PA (methyl carboxylate) + 4, r = 0.997).

N-methylation and N,N-dimethylation of the carboxamides increases considerably the GB of the carboxamides. This is expected because of the direct methyl substitution at the O-protonated amide group with a distribution of the positive charge by resonance between the 0- and N-atom and this effect is known from the GB of formamide and acetamide and their N,N-dimethyl derivatives [321. Omitting the formamides which

M. Witt, H.-F. Gtiitzmacher /Internutional Journal of Mass Spectrometty and Ion Processes 165 / 166 (1997) 49-62 59

appear to be especially sensitive to the N-substitution the mean increment for the increase of the GB by N-methylation corresponds to 22 &- 3 kJ/mol and 46 + 4 kJ/mol for one and two N- methyl groups (Table 3 and Table 4). This is more than three times the effect of methyl substitution at the C,-atom of the acyl group. The compilation of GB and PA data of Hunter and Lias [32] contain the values GB (N-methylpropionamide) = 889.8 kJ/mol and GB (N,N-dimethylbutyramide) = 891.2 kJ/mol. The former value is much too large and certainly in error for some unknown reason. In fact, this value is close to the GB (N, N-dimethyl-propionamide) determined in this work (see Table 4). The latter value supports the GB (N, N-dimethylbutyramide) determined by bracketing using the ‘kinetic’ method (Table 4).

A large effect of N-methylation on the GB (carboxamide) is also expected if the protonation of the amide group occurs at the N-atom. In fact, at least for tertiary carboxamides N-protonation has been discussed in solution [44,45], but an evaluation of polar substituent effects on the GB of substituted primary and tertiary benzamides [46] indicates 0-protonation, in line with theoretical calculations [44,47]. In the case of the aliphatic carboxamides discussed here the values of the GB within the series of primary, secondary and tertiary carboxamides differ by a constant increment. Since it has been shown (see Fig. 3) that the values of the GB of primary carboxamides correlate well with those of other carbonyl compounds which unquestionably are protonated at the car- bony1 O-atom, this correlation holds also for the N-methyl and N,N-dimethyl carboxamides and supports 0-protonation in the gas phase for all carboxamides.

3.2. Binding energies of proton-bound hornodimers of carboxamides

The knowledge of the binding energy of proton-bound clusters is of particular interest. The bond energy can be derived from the bond dissociation energy (BDE) which can be determined by appearance energy AE measurement of the disso-

ciation products of the cluster by Eq. (8) and (9).

[M-.-H+ . ..B]+MH++B

AE=AH,+ez,

BDE = AH, + AnRT

(8)

= AE + AnRT (Le,ev# = 0) (9)

AE = appearance energy of MH+; AH, = enthalpy of dissociation; BDE = bond dissociation energy; e#,, = reverse activation energy.

The binding energy of some proton-bound homo- and heterodimers of N-methyl- and N,N- dimethylacetamide (DMA) has been determined by Meot-Ner (Mautner) [2] using equilibrium studies by pulsed high pressure mass spectrometry which gives the enthalpy of dissociation AH,. Recently, the BDE of the proton-bound homodimers of DMA has been determined also by using blackbody infrared radiative dissociation (BIRD) [48] in a FI-ICR instrument. However, most binding energies of clusters have been derived from BDE obtained from AE measurements by observing the energy dependence of collision induced dissociation (CID) [49,50]. This technique has been developed especially by Armentrout et al. [Sll using the guide beam technique, but collision energy resolved mass spectrometry (CERMS) has been performed also with triple-quadrupole mass spectrometers [52,53] and FT-ICR instruments [54-561. The CERMS technique has been recently adopted and tested for FI-ICR mass spectrometry using the cylindrical Infinity @ cell [16,17] and this variant has been used in this work to measure the AE of the protonated carboxamides from the proton-bound homodimers of formamide, acetamide, propionamide (la) and pivalamide (6a) and their N,N-dimethyl derivatives DMF, DMA, lc and 6c. The results of the AE measurements are shown in Table 5 and in Fig. 4.

Since dissociation of proton bound clusters occurs without a reverse activation energy eEV, the AE298 values correspond directly to the corresponding BDE298 value by adding RT (see Eq. (9)). Within this set of proton-bound homodimers the GB as well as the steric situation around the

60 M. Witt, H.-F. Griitzmacher / Intemationd Journal of Mass Spectrometry and Ion Processes 165 / 166 (1997) 49-62

Table 5 Appearance energy, AEz9s, and bond dissociation energy, BDEz9s, of proton-bound homodimers of primary and tertiary carboxamides

prim. Carboxamide AEz9s (eV)

Formamide 1.22 Acetamide 1.22 Propionamide 1.08 Pivalamide 1.14

BDE*‘s (eV)

1.25 1.25 1.11 1.17

tert. Carboxamide AEz9” (eV)

N,N-dimethylformamide 1.11 N,N-dimethylacetamide 1.12 N,N-dimethylpropionamide 0.96 N, N-dimethylpivalamide 0.86

BDE298 (eV)

1.14 1.15 0.99 0.89

amide group varies considerably and is of impor- tance for the understanding of the factors govem- ing the interactions of amide groups which effect is observed on the BDE of the proton bridge. In the case of the proton-bound homodimer of DMA the BDE298 obtained by CERMS can be com- pared with values taken from the literature [2,481. However, no correction for the different tempera-

0.5 1.0 1.5 2.0 2.5 3.0

LWI

5.0 -

3 4.5 -

40- 'I . 0) - E 3.5 . g 3.0 -

. 'ii - 2.5

1_=15ms

2 .

‘f 2.0 -

"_ =6.82"

t"=m-420~

c 1.5 -

J l.O-

t,xp(Ar,=47x10~m+mbar

2. 1 0.5 -

NO-, . , . ,

0.0 0.5 1.0 1.5 2.0 2.5

Em WI

Fig. 4. Threshold curves for collision induced dissociation of (a) proton-bound homodimer of formamide; (b) proton-bound homodimer of N,N-dimethylpivalamide 5c (the solid lines are the fitted threshold curves).

tures used in the different experiments was tried. Nevertheless, the value 1.15 eV obtained in this work at 298 K agrees well with the value of 1.25 eV of the dissociation enthalpy of the proton- bound homodimer at 0 K calculated [48] from the dissociation enthalpy at 500 K [2] and from the zero-pressure activation energy E, measured by BIRD [48]. This shows that the experimental error of the CERMS measurements is very likely < ~-0.15 eV [16,171.

It is remarkable that in particular the BDE*‘* measured for the dissociation of the proton-bound homodimers of primary amides are virtually identical within the limit of error. Although the GB of formamide and pivalamide 6a differ by 66 kJ/mol (0.68 eV> and 6a carries a bulky tert.butyl group, this is not reflected in the values of the BDE298. Rather small effects of structural parameters on the BDE of proton-bound homodimers have been observed before [2,48]. For example the dissociation enthalpies of the proton-bound homodimer of N-methylacetamide (GB 858.0 kJ/mol [321) and DMA (GB 877.4 kJ/mol[321) at 500 K differ only by approximately 6 kJ/mol [21. This insensi- tivity of the BDE 298 of the proton-bound homodimers of the primary amides may be attributed to multiple hydrogen bonding.* Indeed, the AE298 and BDE298 obtained for the four proton-bound

211 has been suggested by a referee that multiple hydrogen bonding in the proton bound homodimers of primary amides should result in a reverse activation energy ez, for the unimolecular dissociation of the proton bound homodimers. However, the kinetic energy release (KER) measured for a series of metastable proton bound homodimers yield small T of 4-14 meV (evaluted by the META program, 2. S%gi, K. Vekey, Eur. Mass Spectrom. 1 (1995) 507-518). in agreement with the absence of ez,.

M. Wilt, H.-F. Griitzmacher /International Journal of Mass Spectrometry and lon Processes 165 / 166 (1997) 49-62 61

homodimem of tertiary N,N-dimethylcarboxamides are smaller than for primary carboxamides although the GB of the tertiary carboxamides is approximately 44 kJ/mol larger. Although the effect is small and probably just outside the limit of error, the data of Table 5 demonstrate clearly a systematic trend. Further, in the series of tertiary carboxamides the BDEzg8 exhibit a decrease with the steric requirement of the acyl group of the carboxamide. As a consequence the proton bridge within the proton-bound homodimer of the most basic tertiary carboxamide 6a is signifi- cantly weaker than the bond of the proton-bound homodimer of the least basic primary formamide. This, even if the GB of the components of a proton-bound homodimer of the carboxamides play a role for the strength of the ionic hydrogen bond, these results show unambiguously that other effects are more important. Besides steric hin- drance, which weakens the proton bridge, probably by forcing a deviation from the optimal geometry of the ionic hydrogen bond, a reinforce- ment of the interaction by multiple hydrogen bridging between the amide groups is very likely a prominent factor as discussed before [2]. It will be shown in a forthcoming paper that multiple hydrogen bonding and related effects in proton- bound homo- and heterodimers of carboxamides also exert large effects on the kinetics of ligand switching reactions and that obviously proton- bound dimers and larger proton bound clusters of carboxamides may accommodate rather different structures.

Acknowledgements

The ET-ICR spectrometer used in this work is a donation from the Deutsche Forschungs- gemeinschaft. The financial support of this pro- ject by the Deutsche Forschungsgemeinschaft and additional financial assistance by the Fonds der Chemischen Industrie is gratefully acknowledged.

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Proton-bound dimers of aliphatic carboxamides: gas-phase basicity and dissociation energy

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