Electronic structure and conformational properties of the amide linkage

Journal of Molecular Structure (Theo&em), 122 (1985) 35-45 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands

ELECTRONIC STRUCTURE OF THE AMIDE LINKAGE

AND CONFORMATIONAL

PROPERTIES

Part 1. Geometric and electronic structure of lactams as determined by

MNDO calculations*

L. TRESCHANKE and P. RADEMACHER* Institute of Organic Chemistry,

*

University of Essen, D-4300 Essen (F.R.G.)

(Received 19 July 1984)

ABSTRACT MNDO calculations have been performed for monocyclic lactams with ring sizes from three to six and for two bicyclic lactams. The functional group is planar except in a-lactams and 1-azabicyclo[3.3.1]nonan-2-one. For the last substance a preferred ring conformation was determined from a choice of four possible forms. The calculated conformations agree with experimental results, when the latter are available from the literature. Besides the Walsh orbitals of small rings the two highest-occupied MOs, nN and no, are discussed in detail and systematic shifts due to ring expansion and substitution were found. Except in aziridinone, in which the sequence is reversed, nN always appears as the HOMO, followed by no. A relation between their energy difference, AE, ,*, and the torsion of the amide group has been found. INTRODUCTION

When attempting to understand the chemical behaviour of a compound, a knowledge of its structure with particular regard to conformation is indispensable. Besides the common physical methods, photoelectron spectroscopy (PES) [l] has gained increasing importance in conformational analysis [ 21. It is based on the conformational dependence of orbital interactions, which are reflected by ionization potentials (B’s). This was first shown by Maier and Turner [3] for benzene derivatives. In practice, the investigations are normally concentrated on orbitals of the n, a or Walshtype. In combination with PES, quantum chemical methods are suitable for structure analyses. As far as orbital energies and ionization potentials are concerned, the theoretical and PES results can be related to each other by Koopmans’ theorem [ 41. *Dedicated to Professor W. Liittke on the occasion of his 65th birthday. **Author to whom correspondence should be addressed. 0166-1280/85/!$03.30

o 1985 Elsevier Science Publishers B.V.

In the present paper a systematic investigation of the amide group, which is important in chemical and biochemical processes, is undertaken by use of the semiempirical MNDO procedure [5]. Besides a drastically reduced demand on computing time compared with ab initio methods it includes as another advantage a gradient programme to locate potential minima, thus simplifying the optimization of geometrical structure. The PE spectra will be published in a later paper [6]. The applicability of the MNDO method to amide compounds has been tested for formamide and its methyl derivatives. With regard to calculated structures and eigenvalues, the agreement with theoretically or experimentally determined data from the literature was satisfactory and was at the STO-3G level. The details have been reported elsewhere [ 71. According to previously reported experimental results for small amide molecules [8], only one lone pair orbital of oxygen, no, occurs in the region of low IPs besides the orbital of the free electron pair of nitrogen, which is involved in the n system and therefore is called nN. The ionization out of the xc0 MO, which even without further information may be considered, together with TN, as an indicator of torsion around the amide C-N linkage, strongly depends on carbon substituents and so proves unsuitable for conformational analysis. Apart from this, the corresponding band can be located among the intensive u-ionizations only in the PE spectra of simple compounds [ 71, so the investigation is necessarily concentrated on the first two ionizations. STRUCTURES OF LACTAMS CALCULATED BY THE MNDO PROCEDURE

MNDO calculations have been performed for the compounds l-10, and the results are summarized in Table 1. Special attention is given to the structural parameters of the functional group and the conformation of the rings. The smallest homologue in the la&am series is aziridinone 1,a molecule which until now has only been postulated as an intermediate in a multi-step reaction sequence because of its high reactivity [9]. A number of 1,3_disubstituted derivatives have been synthesized with 1,3-di-tertbutyl-aziridinone 8 as the most stable representative [lo]. They possess a nearly planar arrangement of the ring atoms with the oxygen. For aziridine derivatives a distinct pyramidality of nitrogen [ 111 with stabilization of the free electron pair [12] is found. This remains even if interaction with another n-system can occur, e.g. in N-vinyl-aziridine [13] or N-nitrosoaziridine [ 141. According to an INDO study, the amide hydrogen in 1 deviates about 55” from the ring plane [ 151. The only X-ray analysis so far of an or-lactam (1,3diadamantylaziridinone) yielded an angle of 46.3” between the Nadamantyl group and the ring plane [16]. The calculated MNDO values for 1 and 8 are 74.1” and 58.2” (Table 1). Both p-la+ms, azetidin-a-one 2 and N-methyl-azetidin-2-one 5, are

37 TABLE1 Structuresoflactams andbicyclolactamsa R=H

n

compound

1

1

R=He

2

n

compound 5

2

2

3

6

3

3

4

7

4

4

A

N0

8

1 r( C-N) r(C? =O) r(C?-G) ;$I$; r( CW-N)b

r(N-R)C LNC?O LNCV /_CWNC= LCVCY LCww5 LRNC' LRNC~O LC~NC'C" LC'C*NC~

8

1.432 1.413 1.201 1.203 1.488 1.502 1.503 1.505 1.004 1.476 140.6 141.4 61.9 61.9 60.9 62.1 119.2 132.2 74.1 58.2 -

4 r( N--C’) r(C?=O) r(Ca-C?) r(C?+Y) r(C-W r(cs-c6) r(C6-N) r(N-R)” /-NC20 LNC’C~ LC1C3C4 LC3cxS /_C’c?c6 LCVN LC~N@

LRNC" LNC!*C%Y LC?x'C5

10

9

1.407 1.230 1.529 1.538 1.535 1.541 1.457 1.004 118.2 118.4 118.4 113.2 114.3 113.3 126.0 116.8 -22.7 42.7

-

2

5

3

6

1.405 1.213 1.544 1.560 1.466 0.989 129.8 90.3 95.7 86.6 134.0 1.2 0.3 -

1.416 1.213 1.541 1.556 1.467 1.445 129.8 90.9 94.5 86.5 134.3 1.6 0.3 -

1.404 1.223 1.532 1.545 1.550 1.456 0.996 122.4 107.8 114.7 105.7 106.9 127.7 11.8 0.8 4.7

1.415 1.223 1.531 1.539 1.546 1.467 1.460 123.0 108.5 112.9 106.1 106.5 125.1 -0.6 2.4 0.8

9

7 1.417 1.230 1.530 1.533 1.532 1.540 1.468 1.472 119.0 119.1 116.5 112.7 114.2 115.3 122.7 120.1 -26.7 41.3

r( N-P) r(Cs=O) r(N-C?) rv-w

r(c?-c? ) ifc~-c”) r(C6-c) r(C4-C?) r(C’-C*) r( N-H)

LNC?O .X?NC" LNCYY Lc?CC~ Lcvx6 LC5C6C' LC'C'N LHNC'

1.410 1.224 1.465 1.546 1.551 1.551 1.558 1.556 1.558 0.996 122.1 115.6 108.6 106.6 110.7 106.7 109.7 123.8

r(N-C') r@=O j r(CZ-C3) r&?-c?) r( C?-C? ) r(C’-C”) r(C6-C7) r( C!'-C? ) r( C?-N) r( C9-N) LNPO LNC’C? .Lc2c3c L c WC’ L cwc? L C’NC2 LC’NC~ L C’C8N

1Ocd 1.449 1.223 1.534 1.545 1.534 1.553 1.546 1.552 1.480 1.476 118:7 117.5 115.4 115.8 115.3 115.9 113.5 112.8

38 TABLE 1 (continued) 4 fcsc~csc6 /_C%?C6N LC5C6NC1 LC?NCY? L RNC?O

-48.4 38.0 -25.0 20.4 -6.8

7 -47.9 39.2 -24.5 18.7 1.9

9 LC’NC~O LHNC”CY LC’NC’C~ LHNC’O

180.0 179.7 2.0 1.7

lo& ,!_C9NC?0 LC’NC~O LNC2C3C4 LC~NC*C~ f C’C’NC2 LC6C’CaN LCVC’C’

162.6 -65.9 152.3 -16.9 -77.3 -35.1 32.1

aMNDO results: bond lengths in A, angles in degrees; numbering of atoms according to IUPAC rules. bCw is the ring atom with the highest number. CR = H in 1, 2, 3 and 4; R = C(methy1) in 56 and 7; R = C(t-but) in 8. dChair-boat conformation.

nearly planar with respect to the ring as well as to the nitrogen atom, Even large substituents are not able to cause changes in ring geometry as the X-ray analysis of 1-0,-chlorophenyl)-3-isopropyl-4-phenyl-azetidin-2-one indicates [ 171. According to X-ray analyses of 5-iodomethyl- and 5carboxamid-pyrrolidin-2-one, the amide group is approximately co-planar with its neighbouring ring atoms [18], analogous to the well-known envelope form of cyclopentane. So the atoms C?, with dihedral angles C%NC? of 8.9” and 15.1”, respectively, undergo the greatest deviation. The hybridization of the nitrogen atom remains undefined, since no adequate structure parameters are given. In the carboxamide derivative, however, sp2 hybridization seems not to be completely realized, since the deviation of Cs out of the plane of the OCN group is 0.17 a. The MNDO results in Table 1 show similar conformations for pyrrolidin2-one 3 and N-methyl-pyrrolidin-2-one 6 with dihedral angles <5”. The same is valid for the structure of 3 as calculated by Warshel et al. [19]. For the conformation of piperidin-a-one 4 and N-methyl-piperidin-2-one 7 the possibilities known from cyclohexane derivatives are under discussion. Warshel et al. obtained a distorted chair conformation for 4 with a nearly planar C6NC2C3 framework [ 191. As in dihydro-uracils and dihydrothymins the C4 and Cs methylene carbons, as the most movable ring members, are situated above and below the NC0 plane, resulting in a halfchair arrangement [20]. The X-ray analysis of 3-chloro-piperidin-2-one shows a similar molecular framework [ 211. The MNDO procedure calculates more distinct deviations from planarity in the vicinity of the nitrogen atom, so that the C6NC1C2 torsional angle differs markedly from its respective value in the chloro-compound, the others being of similar size. The resulting arrangement may be described as a half-chair or a flattened chair conformation. For 2-azabicyclo[ 2.2.21 octan9-one 9 only one conformation is possible, consisting of boat-shaped six-membered rings. Besides small distortions, the

39

N atom appears in an sp2 hybrid with unrestricted amide resonance according to both MNDO and an X-ray analysis [22]. The C1NC30C4 framework is planar. The restriction to a boat conformation is no more valid for l-azabicyclo[3.3.1] nonan-a-one 10. Both six-membered rings can adopt the chair (C) or boat (B) form and so the four conformers BB lOa, BC lob, CB 10~ and CC 10d must be considered*. The hydrocarbon bicyclo[ 3.3.11 nonane is known to exist in the CC form [23]. Introduction of the amide group causes bond shortenings which enhance repulsion between the C? and C’ methylene groups and favour one of the conformers lOa-1Oc. Based on ‘H NMR spectra - the equatorial hydrogen at C8 suffers a low-field shift due to anisotropic shielding by the csrbonyl oxygen - Hall et al. [24] proposed structure 10~ for the lactam in analogy to the olefin bicyclo[3.3.1] non-1-ene [25]. The MNDO calculations also indicate 10~ to be the most stable conformer (Table 2). A possible coexistence with the CC form 10d which according to MNDO is less stable by 0.7 kcal moI’ than 1Oc should be recognized in the PE spectrum of 10 [6] due to different bonding states at the amide group (Fig. 1). EIGENFUNCTIONS

AND EIGENVALUES

The interpretation of quantum chemical calculations will be restricted to high-lying occupied orbitals. These represent the most important indicators of electronic modifications induced by changes in the molecular framework, e.g. a shift of MO energies in a series of homologues, and they are of paramount importance for the analysis of the PE spectra [6]. The construction of orbitals in ar-lactams may be traced to the Walsh procedure [26]. Starting with cyclopropane (symmetry group D& the orbit& and the correlation diagram shown in Figs. 2 and 3 [12, 271 are obtained. The substitution of a methylene group by N-H leads to aziridine (C,), in which all degenerations are removed. The replacement of an additional methylene group by C=O yields 1 with complete loss of symmetry (pyramidal N). Its n-orbitals TN, xc!, and vCO are derived from the le” and la” MOs of cyclopropane. The remaining three u MOs may be attributed to the Walsh orbital ws and to the bonding and antibonding combination of the Walsh TABLE 2 MNDO-calculated

energies of conformations 10a

AHf AAH,

-41.0 2.5

of lO/kcaI mol-* lob

1oc

-39.7 3.8

-43.5 0.0

*The second letter refers to the ring with the amide group.

10d -42.8 0.7

40 E”UW

[eVl

8ci

-lO-

“0

.'-

-15-

N

Fig. 1. Newman projection of 1Oc and 1Od.

A

A

10d

along the amide C-N

Fig. 2. Correlation diagram for high-lying [lo] and aziridinone (MNDO).

Fig. 3. The six highest-occupied and aziridine orbitals.

4

bond of MNDO-calculated

orbitals of cyclopropane,

MOs of aziridinone

aziridine

and their relation

0

structures

(ab initio)

to cyclopropane

41

orbital WA with the no orbital. This description of ring MOs also remains valid for 8, in spite of substituent effects. The Walsh method is also applicable to four-membered rings [28, 291. The construction of s MOs and the no orbital in 2 and their derivation from orbitals of cyclobutane and azetidine is shown in Fig. 4. In the fiveand six-membered ring compounds only the two highest occupied MOs are still of interest (Fig. 5). Owing to the size and sign of the coefficients at individual atoms shown in Figs. 3-5 the behaviour of nN and no can be interpreted with respect to ring expansion and substitution. The changes of the eigenvalues due to ring extension by a methylene group are small for xN and no. From 2 to 3 and 4 nN is destabilized by about 0.04 eV, from 5 to 6 and 7 by about 0.01 eV. As is evident from the orbital structure, TN contains only small contributions from a low-lying group orbital and therefore suffers only small destabilization from the rest of the ring. An additional interaction with a methyl group leads to further conjugation. The ring size affects no twice as much as nN, independently of the

Fig. 4. The four w-M013 and no of azetidinone and their relation to cyclobutane azetidine orbitals.

and

42

Fig. 5. HOMO (nN) and s-HOMO (no) of pyrrolidin-a-one to MNDO.

and piperidin-a-one,

according

TABLE 3 Eigenvalues

of lactams according to MNDO/eV’ 2

1 -10.40 -12.18 -13.99 -14.21 -16.04 -16.70

no nN

;z

-10.30 -10.94

-10.28 -10.92

:“,

5

;z

-10.02 -10.95

;“o

nCH,

wS wA nco 7

6 -10.01 -10.86

-10.34 -11.01

4

3

“N no

-10.01 -10.82

“N no

-9.96 -11.05 -14.36 -15.49 -16.15 -16.48

10

9

8

:“, nCO wg WA nCH

-10.18 -10.73

:“,

-9.94 -11.16

“N

no

i

aThe two highest-occupied MOs are listed (in the case of cu-lactams, the Walsh orbitals and the remaining m-MOs as well).

substituent on nitrogen. In the MNDO results (Figs. 3-5) this orbital obtains a significant coefficient at the C atom in the u-position to the carbonyl group. Therefore, lengthening of the carbon chain must destabilize no even more. The eigenvalues of 9 also demonstrate this. Compared with 4, however, C’C4 alkyl substitution shifts no by about 0.19 eV, A~ by about 0.10 eV. N-methylation from secondary to tertiary lactam influences A~ with 0.29 eV more distinctly than no with only 0.08 eV. Within the scope of the MNDO formalism, this again may be explained by the orbital structure. The no orbital is localized mainly on oxygen and only to a small extent on

43

nitrogen. It thus “feels” the insertion of a methyl group weakly, whereas in 7rN this substituent, being situated at the position with the greatest orbital coefficient, shows a more distinct effect. The ar-lactams and compound 10 are discussed separately. As is to be seen from the structures, in these molecules the dihedral angle Cp between the electron lone pair of nitrogen and the C=O bond (a = L :NCO) obviously differs from 90”. Therefore, the n/o separation is removed and interactions between nN and no raise AETlz2to 1.22 eV in 10 and to 1.09 eV in 8. As mentioned above, azuidine possesses only a small x-donor capacity and stabilizes the free electron pair in a hybrid orbital by means of high s-contribution [13]. Compared to other tertiary amines, the nN orbital is markedly stabilized [4, 131. In 1 the low value of -12.18 eV is calculated for 7rN. The change in the orbital sequence may be explained as follows: The inductive effect of the carbonyl group causes a further stabilization of the low-lying xN, so that no becomes the HOMO. Torsion around the amide C-N linkage now enables n/a conjugation to occur at the cost of no and raises AE1,z to 1.78 eV. This result, which cannot be verified experimentally at present, does not seem unrealistic in view of another quantum chemical investigation. Formerly, the isomerization of aziridinone to imino-oxiran was thought to begin with the breaking of the N-C3 linkage [9]. Talaty and Zandler found an in-plane vibration of the oxygen atom towards C3 to be energetically much more favourable [15]. The reactive centre would then be localized at the position with the greatest coefficient of the HOMO. CONCLUSION

The aim of this investigation was to find a relation between the geometrical and electronic structure of amide compounds. The calculated geometries showed, in comparison with available literature data, that the functional group is planar or nearly planar in most of the compounds. As in other aziridine derivatives, nitrogen appears clearly pyramidal in the lactams 1 and 8, therefore the substituent at the N atom must be twisted out of the NC0 plane. In the bicyclic compound 10 it is the bridgehead position of the nitrogen which is responsible for restricted amide resonance. The chair-boat form 10~ is calculated to be the most stable conformer, in accordance with the literature. To answer the question of its possible coexistence with the boat-boat conformation lOd,analysis of the PE spectrum is necessary, which will be reported in a forthcoming paper [6]. The two highest-occupied MOs are significantly similar with regard to the orbital structure for the series of secondary and N-methyl-lactams. A systematically greater shift due to N substitution for xN eigenvalues and a greater influence of ring extension on no have been explained with respect to the electron distribution.

44

Except in compound 1, nN always appears as the HOMO, followed by no as the s-HOMO. The reversion of this orbital sequence for aziridinone derives from a stabilization of the nitrogen lone pair due to rehybridization below the level of the oxygen electron lone pair and subsequent n/a conjugation. In the compounds with restricted resonance a greater AEI,P value was ascertained, which could be attributed to interaction between the orbit& ITS and ~zo. Within the scope of the MNDO results, this represents an indicator of conformational changes. ACKNOWLEDGEMENT

We are indebted to the Deutsche Forschungsgemeinschaft support.

for financial

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