Ab initio studies of molecules with NCCO units. Part 2. 1-Amino-2-propanone, 2-methylaminoethanal and 2-aminopropanal

THEO CHEM

Journal of Molecular Structure (Theochem) 360 (1996) 145-156

Ab initio studies of molecules with N-C-C=0 units. Part 2. l-Amino-2-propanone, 2-methylaminoethanal and

2-aminopropanal

Luis Carballeira*, Ignacio P&rez-Juste

Departamento de Quimica Pura y Aplicada. Laboratorio de Quimica Fisica. Faculiad de Ciencias, Apdo. 874, Vigo. Spain

Received 29 November 1994; accepted in final form 24 July 1995

Abstract

A complete conformational analysis of all the monomethylated derivatives of 2_aminoethanal(2AE) was carried out using MO ab initio with the 6-31G” basis set, and it was inferred that methylation produces an increase in stability with respect to the initial compound 2AE. Geometric tendencies related to the existence of intramolecular hydrogen bonding and anomeric effects are discussed. Finally, the differences between the ab initio results and those produced by the current consistent MM3(92) force field are analysed.

Keywords: Anomeric effect; Conformational analysis; Force field; Hydrogen bonding; N-C-C=0 unit

1. Introduction

The fact that various compounds of medium to large size with biological activity contain the N-C- C=O unit encourages the development of a force field of molecular mechanics for analysing this unit. Little experimental information has been published on the structure of simple molecules containing this unit, therefore it seems convenient to obtain MO ab initio information for the parameterization of this force field [I].

The objective of this paper is to continue the MO ab initio study of molecules containing the unit mentioned, which were commenced in Part 1 with 2-aminoethanal (2AE), the simplest compound of the series [2]. In the former paper the rotational

* Corresponding author

barrier of N-C-C=0 torsion was studied, with the NH2 group in the G arrangement, and minima were optimized without any constraints with the N-C-C=0 about O”, 150” and 180”. A “plateau” of potential energy was found between 150” and 180” which is related to the flexibility of helical forms of peptide systems [3]. The geometrical trends associated with the possible existence of hydrogen bonding between the oxygen of the car- bony1 and the hydrogens bonded to the nitrogen [4] were also analysed.

The present study involves a detailed conformational analysis of all the monomethylated derivatives of 2-aminoethanal: 1 -amino-2-propanone (lA2PN), where the methylation occurs at position 5; 2-methylaminoethanal (2MAE), methylated at position 8; and 2-aminopropanal (2AP), methylated at position 6 (Fig. 1). No experimental

0166-1280/96/%15.00 0 1996 Elsevier Science B.V. All rights reserved SSDI 0166-1280(95)04370-5

146 L. Carbaleira, I. Perez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156

HS Rf3

Y N4

01

1 l

c2 _.- c3

H7 R6

R5, R6, R8 = f-1 2-aminoethanal

R5 = CH3 R6, R8 = H 1 -amino-2-propanone

R6 = CiiJ R5, R8 = H 2-amino-propanal

R8 = CII,

R5. R6 = H 2-methylamino-ethanal

R5

2AE

lA2PN

2AP

2MAE

HB

N4C3C201 I 0’

C

01

N4C3CZOl = 180’ H9N4lXC2 = 60” H9N4C3C2 = -60”

T G G’

Fig. 1. Atom numbering and notation employed for the molecules studied.

H9N4CX2 = .I 60’

T

information whatsoever has been found regarding the structure of these compounds, nor has any quan- tum or classical theoretical study been published.

2. Method

The calculations were carried out according to the ~0~~8.4 program [5] and the parameters of the 6-3 1 G basis set which it incorporates. Polarization was introduced for C, N, 0 (d exponent = 0.80) and H (p exponent = 1.10). The geometries of the stable conformers located were obtained without any constraints, the convergence criterion being that the largest component of the gradient should be < 0.0005. The geometries of conformations that are not energy minima were obtained by constrain- ing an internal coordinate (torsion) and adopting

the same convergence criterion. In order to analyse the effect of the electronic correlation, MP2 [6] energy calculations were carried out using previously optimized 6-3 1 G** geometries,

The notation which describes the conformations consists of two terms. The first specifies the N4C3C201 torsion (Fig. 1) as cis (C), trans (T), or with its numerical value. The second term refers to the approximate value of the H9N4C3C2 dihedral: 60” (G), 180” (T) and -60” (G’).

3. Results and discussion

3.1. Conformational stabilities

In order to analyse the N-C-C==0 torsion, potential energy curves were derived by refining

Table 1

L. Carballeira, I. Pkrez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156 147

6-31G” optimized structures for stable conformers defined in the text

lA2PN

CC CG’ I SOG 1 SOG’ TG

c2-01 1.1930 1.1921 1.1930 1.1935 1.1929 C3-C2 1.5236 1.5184 1.5273 1.5227 1.5300 N4-C3 1.4399 1.4403 1.4448 1.4504 1.4434 cs-c2 1.5125 1.5119 1.5137 1.5104 1.5124 H6-C3 1.0877 1.0873 1.0879 1.0876 1.0851 H7-C3 1.0877 1.0959 1.0832 1.0872 1.0851 H8-N4 1.0006 0.9987 0.9991 0.9991 0.9985 H9-N4 1.0006 0.9992 0.9986 1.0009 0.9985 HlO-C5 1.0811 1.0810 1.0802 1.0809 1.0807 Hll-CS 1.0863 1.0859 1.0849 1.0830 1.0860 HlZ-C5 1.0863 1.0864 1.0869 1.0853 1.0860

C3-C2-01 121.33 121.46 119.75 119.87 118.92 N4-C3-C2 115.72 111.25 118.44 112.69 119.36 cs-c2-01 121.95 121.97 121.44 122.03 121.40 C5-C2-C3 116.72 116.54 118.77 118.06 119.68 H6-C3-C2 108.02 108.61 106.34 106.36 106.31 H6-C3-N4 109.50 109.89 108.59 108.05 109.14 H7-C3-C2 108.02 105.97 106.85 106.97 106.31 H7-C3-N4 109.50 114.82 109.64 115.03 109.14 H7-C3-H6 105.59 105.99 106.32 107.27 105.76 H8-N4-C3 110.15 111.73 112.52 110.94 112.98 H9-N4-C3 110.15 110.84 113.11 111.09 112.98 H9-N4-H8 105.98 109.44 108.79 107.26 108.81 HlO-C5-C2 109.64 109.57 109.23 108.98 109.01 Hl l-C5-C2 110.41 110.29 110.92 110.67 110.79 Hll-CS-HI0 109.58 109.56 109.50 110.33 109.51 H12-C5-C2 110.41 110.42 110.42 110.06 110.79 H12-C5-HlO 109.58 109.57 109.49 110.03 109.51 H12-C5-Hll 107.19 107.41 107.24 106.75 107.21

N4-C3-C2-01 0.00 14.43 154.48 144.96 180.00 H6-C3-C2-01 123.12 135.50 -83.07 -96.82 -56.15 H7-C3-C2-01 -123.12 -111.01 30.19 17.58 56.15 H8-N4-C3-C2 -58.28 -164.49 -60.31 166.78 -62.07 H9-N4-C3-C2 58.28 -42.15 63.47 -74.00 62.07 HlO-C5-C2-01 0.00 0.94 1.02 1.36 0.00 Hll-CS-C2-01 -120.82 - 119.74 -119.76 -120.14 -120.58 H12-C5-C2-01 120.82 121.72 121.49 122.11 120.58

2MAE

CG CG’ CT 150G 150G’ -150T

c2-0 1 1.1881 1.1870 1.1855 1.1875 1.1880 1.1878 C3-C2 1.5138 1.5057 1.5102 1.5179 1.5115 1.5130 N4-C3 1.4358 1.4325 1.4359 1.4415 1.4445 1.4450 H5-C2 1.0986 1.0965 1.0988 1.1002 1.0956 1.0957 H6-C3 1.0900 1.0895 1.0986 1.0883 1.0891 1.0900 H7-C3 1.0885 1.0993 1.0882 1.0841 1.0905 1.0886 C8-N4 1.4516 1.4439 1.4502 1.4487 1.4489 1.4504

148

Table 1 Continued.

L. Carballeira, I. Pkrez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156

2MAE

CG CG’ CT 150G 150G’ -150T

H9-N4 0.9999 0.9981 0.9980 0.9992 1.0009 0.9978 HlO-C8 1.0836 1.0835 1.0836 1.0835 1.0836 1.0834 Hll-C8 1.0857 1.0858 1.0809 1.0849 1.0851 1.0855 N12-C8 1.0875 1.0936 1.0939 1.0926 1.0920 1.0917

C3-C2-01 124.43 124.45 126.11 124.03 123.69 123.90

N4-C3-C2 116.27 112.16 114.40 115.47 110.70 110.66

H5-C2-01 120.66 120.85 120.59 120.59 121.53 121.60 H5-C2-C3 114.89 114.68 113.30 115.35 114.77 114.50

H6-C3-C2 106.61 107.77 106.07 106.72 106.60 108.28

H6-C3-N4 110.20 110.19 114.27 109.01 108.38 114.72

H7-C3-C2 107.87 106.20 106.22 107.99 108.59 106.46

H7-C3-N4 109.82 114.51 109.44 110.26 115.04 108.59

H7-C3-H6 105.49 105.58 105.81 107.02 107.14 107.78

C8-N4-C3 115.03 114.41 115.16 115.25 114.16 114.16

H9-N4-C3 109.73 110.42 109.54 111.65 110.11 110.32

H9-N4-C8 110.07 112.01 110.16 111.49 109.67 110.15

HlO-C8-N4 108.92 109.43 109.03 109.33 109.39 109.40

Hl 1 -C8-N4 109.24 109.77 109.72 109.26 109.49 110.03

Hll-CS-HI0 107.42 107.60 107.89 107.72 107.75 107.47

Hl2-C8-N4 114.18 113.94 113.39 114.61 113.82 113.56

H12-C&H10 108.37 108.23 108.16 108.05 108.32 108.52

Hl2-C8-Hll 108.49 107.66 108.50 107.66 107.88 107.66

N4-C3-C2-01 -3.42 9.09 -2.71 149.58 149.56 -144.11

H6-C3-C2-01 119.88 130.54 124.18 -89.10 -92.77 -17.58

H7-C3-C2-01 -127.23 -116.70 -123.55 25.67 22.37 98.07

C8-N4-C3-C2 -73.29 -169.38 73.28 -64.74 171.18 76.82

H9-N4-C3-C2 51.45 -41.93 -161.92 63.79 -64.97 -158.52

HlO-CS-N4-C3 -179.53 178.69 176.51 178.66 178.09 177.39

Hl 1 -C8-N4-C3 -62.47 -63.44 -65.52 -61.00 -64.04 -64.76

H12-C8-N4-C3 59.19 57.38 55.96 59.89 56.78 55.99

2AP

CG CG’ CT 130G 140G’ -130G -140T

c2-01 1.1885 1.1873 1.1873 1.1879 1.1879 1.1876 1.1880

C3-C2 1.5187 1.5118 1.5125 1.5177 1.5149 1.5208 1.5177

N4-C3 1.4435 1.4426 1.4426 1.4526 1.4525 1.4566 1.4542

H5-C2 1.0981 1.0972 1.0966 1.1013 1.0962 1.1004 1.0950 C6-C3 1.5311 1.5296 1.5385 1.5279 1.5297 1.5214 1.5253

H7-C3 1.0900 1.0981 1.0894 1.0839 1.0890 1.0894 1.0902

H8-N4 1.0010 0.9986 0.9989 1.0003 1.0004 1.0006 1.0016

H9-N4 1.0019 0.9986 0.9987 1.0012 1.0009 1.0014 0.9996 HlO-C6 1.0824 1.0848 1.0849 1.0830 1.0858 1.0830 1.0861 Hll-C6 1.0855 1.0860 1.0866 1.0847 1.0839 1.0829 1.0833 Hl2-C6 1.0863 1.0839 1.0862 1.0878 1.0854 1.0852 1.0856

C3-C2-01 124.02 124.56 124.47 124.79 123.96 125.43 124.55 N4-C3-C2 113.85 110.02 109.88 112.20 108.09 111.31 107.52 H5-C2-01 120.57 120.74 120.73 120.62 121.59 120.35 121.41

L. Carballeira, I. Pt!rez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156 149

Table 1 Continued.

2AP

CC CC’ CT 130G 140G’ -130G -140T

H5-C2-C3 115.41 114.68 114.76 114.58 114.44 114.21 114.04

C6-C3-C2 109.60 110.30 108.16 109.72 108.64 112.14 112.18

C6-C3-N4 110.74 110.68 115.42 109.77 109.84 110.68 115 86

H7-C3-C2 106.25 104.34 106.42 107.04 106.91 106.32 104.94

H7-C3-N4 108.24 113.64 108.71 108.46 114.08 106.85 106.41

H7-C3-C6 107.90 107.66 107.88 109.59 109.10 109.29 109.23

H8-N4-C3 110.21 111.47 111.25 112.05 111.34 112.20 111.08

H9-N4-C3 110.00 111.42 111.70 112.17 111.47 111.20 111.12

H9-N4-H8 106.00 109.32 109.36 108.41 107.33 108.04 107.36

HlO-C6-C3 109.48 110.07 110.00 109.49 110.32 109.57 110.16

Hll-C6-C3 111.44 111.44 111.75 111.09 110.45 110.94 Ill.16

HI l-C6-HlO 108.67 107.74 107.64 109.06 108.12 109.30 108.61

H12-C6-C3 110.87 110.28 110.69 111.04 110.79 110.77 110.70

H12-C6-HlO 108.22 108.03 108.24 108.03 108.02 108.66 108.44

H 12-C6-H 11 108.07 109.19 108.40 108.07 109.06 107.56 107.68

N4-C3-C2-01 -1.83 ii.11 -13.83 128.57 139.01 - 129.44 -139.10

C6-C3-C2-01 122.80 133.49 112.96 -109.14 -101.84 -4.83 -10.59

H7-C3-C2-01 - 120.87 -111.14 -131.35 9.70 15.78 114.56 107.89

H8-N4-C3-C2 -57.18 -163.71 44.34 -60.84 170.38 -58.70 74.83

H9-N4-C3-C2 59.34 -41.28 166.86 61.37 -69.80 62.44 -165.72

HIO-C6-C3-C2 179.37 177.27 177.08 -178.77 - 178.99 179.88 178.04

Hl l-C6-C3-C2 59.13 57.79 57.57 60.73 61.53 59.11 57.59

H 12-C6-C3-C2 -61.30 -63.64 -63.36 -59.57 -59.42 -60.26 -62.04

conformations in which this dihedral was constrained to values between - 180” and 180” at different intervals. The points of these curves were calculated for the three different arrangements of the NH2 group (G, G’ and T) and were then adjusted to five term Fourier series. Later the geometries corresponding to the areas estimated as minima in the curves were freely optimized (Table 1) [7].

In the case of lA2PN, the methyl introduced in position 5 always maintains one of its hydrogens in the cis conformation with respect to the C=O bond, independently of the arrangement of the NH2 group. This cis form is stabilized owing to a hyperconjugative effect [8] between the methyl and the C=O, which is observed in the lengthening of the C-H bonds in alternate positions with the C=O (Hll-C5 and H12-C5) with respect to the C-H bond in cis (HlO-C5) which is shorter (Table 1).

Because of this arrangement, the conformations

of lA2PN with the NH2 group in G have the same symmetry as the parent compound 2AE, and the G curve is similar to that of the latter (Fig. 2). It is worth noting that the energy “plateau” between 150” and 180” characteristic of 2AE [2] is maintained, but its relative energy changes from 2.31 kcal mol-’ (2AE) to 3.34 kcal mol-’ (lA2PN). Nevertheless, when the methylation breaks molecular symmetry, as in 2MAE and 2AP, the energy “plateau” between 150” and 180” disappears (Fig. 2).

From the curves it can be deduced that the minima have similar N-C-C=0 torsion values (Fig. 2 and Table 1). Thus, there are minima with N-C-C=0 torsions close to 0” (C conformers) for all the arrangements of the NH2 group. Among these minima, CG conformers are always the most stable of each molecule owing to the presence of hydrogen bonding between the oxygen of the carbonyl and the hydrogens of N. In fact, in lA2PN(CG) the torsion is maintained at 0”

150 L. Carballeira, I. Ptkez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156

Fog. 20 2-ominoethonol (W)

8T

0 -180 -120 -SO 0 60 120 160

N-C-C-0 torsion

6 fig. 2c 2-mdhylomino-ethanal (ZMAE)

7 WR P”o

-c 6

5

4

3

2

1

0 0

N-C-C=0 torsion

a Fig. 2b I-amino-2-proponone (1AWN)

7 y VP

-0 6 ___ 0

5

4

3

2

1

0 -160 -120 -60 0 60 120 160

N-C-C-O torsion

6 Fig. 2d P-amino-prapanal (2AP)

7 T

N-C-C-O tonIOn

Fig. 2. 6-31G” conformational energy plots of the N-C-C=0 torsion for the three arrangements of the amino group. Note: The G curve for 2AE is taken from ref. [2] and the G’ curve was calculated for this study.

because, in this way, a symmetrical hydrogen bond is produced, with the closure of two cycles of five members as occurred for 2AE [2]. Nonbonded H8,9 e . . 01 distances are 2.72 A. For 2MAE(CG) the dihedral reaches -3.42”, so that 01 goes towards H9 and the hydrogen bond is maintained (H9. . ~01 = 2.68 A), and moreover the repulsion with the methyl at 8 is minimized. A similar ten- dency is observed in ZAP(CG), although the devia- tion is less (- 1.83”) and it occurs on the side of the molecule where the methyl is in position 6 (H8...01 = 2.71 and H9...01 = 2.72 A). Some geometrical trends confirm the presence of hydrogen bonding (see below).

Another area of the N-C-C=0 torsion where minima are found, corresponding to the G and G’ arrangements of the NH2 group, is that which exists between 130” and 150”. The dihedral

H9N4C3C2 oscillates between 128.57” (2AP) and 154.48” (lA2PN) for the G conformers, and between 139.01” (2AP) and 149.56” (2MAE) for the G’ conformers. On the other hand, for torsions close to -140”, minima can be located with the NH, group in position T, the dihedral oscillating between -139.10” (2AP) and -144.11” (2MAE). It should be noted here that for 2AP there is a minimum with NH2 in G (N4C3C20 1 = - 129.44” and H9N4C3C2 = 62.44”) that is not found in the other compounds, as the G curve of 2AP has consider- able symmetry.

The increasing order of the rotational barriers of the N-C-C=0 torsion for the different arrangements of the NH2 group is the same for the three species, although there are small differences in energy and positions of maxima (Table 2). Both parameters were interpolated by adjusting the

Tab

le

2

Rel

ativ

e en

ergy

of

max

imaa

(E

,, kc

al

mol

-‘)

and

rota

tiona

l ba

rrie

rsb

(Ebr

kc

al

mol

-‘)

2AE

C

1 A2P

N

Cur

ve

N-C

C=O

d E

I E

B

N-C

-C=0

E

r E

B

2MA

E

N-C

-C=0

E

, E

B

2AP

N-C

-C=0

E

, E

B

G

-74.

9 3.

99

3.99

-9

0.1

3.86

3.

86

-88.

0 3.

94

3.90

-7

3.3

3.05

3.

04

74.9

3.

99

3.99

90

.1

3.86

3.

86

71.5

4.

69

4.65

73

.3

3.03

3.

02

G’

-68.

4 7.

27

5.71

-6

7.1

7.14

5.

27

-69.

6 5.

87

5.49

-6

5.7

6.25

5.

21

69.2

3.

64

2.13

72

.4

2.86

1 .

oo

72.2

2.

32

1.93

68

.3

2.63

1.

59

-61.

4 3.

97

3.68

-6

0.7

2.96

2.

27

T

70.0

5.

84

5.55

64

.4

6.53

5.

85

a T

he

posi

tion

of t

he

max

ima

is o

btai

ned

by

fitti

ng

each

of

the

cu

rves

(F

igs.

2(

a)-2

(d))

to

a

five

ter

m

Four

ier

seri

es.

The

re

lativ

e en

ergy

is

giv

en

in r

espe

ct

to

the

mos

t

stab

le

conf

orm

er

CC

of

eac

h m

olec

ule.

b T

he

rota

tiona

l ba

rrie

rs

are

the

ener

gy

diff

eren

ces

betw

een

the

max

ima

and

the

mos

t st

able

m

inim

um

of

each

of

th

e cu

rves

.

’ D

ata

of

the

G

curv

e ar

e ta

ken

from

re

f.

[2].

The

G

’ cu

rve

was

ca

lcul

ated

fo

r th

is

stud

y.

d N

-C-C

=0

tors

ion

(in

degr

ees)

co

rres

pond

ing

to

each

en

ergy

m

axim

um,

,-

_ ._

-

- ;

Tab

le 3

R

elat

ive

ener

gies

(kc

al m

ol-‘)

of

th

e st

able

con

form

ers

of 2

-am

inoe

than

al

and

its

mon

omet

hyl

ated

de

riva

tive

?

2AE

b

Con

f H

E

MP

2C

1 AZ

PN

Con

f H

F

MP

2

2MA

E

Con

f H

F

MP

2

2AP

Con

f H

F

MP

2

CC

0.00

0.00

C

C

0.00

0.

00

CC

0.

00

0.00

C

C

0.00

0.

00

CC

’ 1.

72

1.73

C

C’

1.74

1.

76

CC

’ 0.

34

0.61

C

C’

1.13

1.

09

CT

2.

17

1.99

C

T

1.83

1.

60

150G

2.

35

2.63

15

0G

3.22

3.

31

150G

1.

85

2.25

13

0G

1.79

1.

79

15O

G’

1.39

2.

06

150G

’ 1.

91

2.16

15

0G’

0.56

1.

40

14O

G’

1.03

1.

50

-130

G

1.74

1.

56

-150

T

0.44

1.

00

-140

T

0.55

0.

82

TG

2.

31

2.63

T

G

3.34

3.

49

a T

he

abso

lute

en

ergi

es (

in h

artr

ee,

1 H

=

627.

5 kc

al m

ol-‘)

ar

e:

ZA

E-C

G:

E(H

F)

=

-207

.948

709

E(M

P2)

=

-2

08.5

8604

8 lA

2PN

-CC

: E

(HF

) =

-2

46.9

9838

0 E

(MP

2)

=

-247

.784

997

2MA

E-C

C:

E(H

F)

=

-246

.976

323

E(M

P2)

=

-2

47.7

6288

4 2A

P-C

C:

E(H

F)

=

-246

.989

049

E(M

P2)

=

-2

47.7

7763

1.

b R

esu

lts

from

ref

. [2

].

’ H

F

= H

F/6

-31G

**//H

F/6

-31”

~

MP

2 =

MP

2/6-

3lG

**//H

F/6

-31G

**.

L. Carballeira, I. Pirez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156 153

points obtained from constrained conformations to Fourier series. The order of the barriers for positive values of the N-C-C=0 angle is G’ <G < T, which changes to T < G < G’ for negative values.

When the NH;! group is in the G arrangement, the barriers corresponding to positive and negative N-C-C=0 torsions are due to repulsion between the C2=01 and C2-R5 bonds with each of the N-H bonds. Moreover, in these conformations one of the two interactions of the hydrogen bond (01 with N4-H8 for negative N-C-C=0 angles and 01 with N4-H9 for positive ones) has disap- peared. This could explain the close values of the positive and negative barriers of the G conformations (Z 4 kcal mall’), although for 2AP they are somewhat lower. The abnormally high value (4.61 kcal mall’) of the positive barrier of 2MAE is due to the fact that, in this conformation, the C2=01 bond interacts with the methyl bonded to the NH, group.

For the G’ conformations, the barriers corresponding to positive N-C-C=0 are due to the repulsion of C2=01 and N4-H9 and of C2-R5 and the electron pair of N. These barriers are the smallest and practically ensure the inter- conversion between the CG’ and 150G’ forms in lA2PN (1.00 kcal mol-‘). The barriers for 2AP (1.59 kcal mol-‘) and 2MAE (1.93 kcal mol-‘) are slightly higher. These same kinds of repulsion (C2=01 with N4-R8 and C2-R5 with the electron pair of N) explain the negative barriers of the T conformations, although the energy values are higher. The highest barriers for the G’ arrangements of the NH2 group (Z 5 kcal mol-i) correspond to negative N-C-C=0 torsions, since in these conformations the 01 is located on the same side of the molecule as the pair of the N. This also occurs in the T conformations when the N-C-C=0 torsion takes on positive values.

As mentioned previously, the conformers found in the areas of energy minima were optimized without constraints, and it was observed that the methylation in the different positions produces a reduction in absolute energy relative to the parent compound 2AE (Table 3). The most stable compound is lA2PN(CG), followed by 2AP(CG) and

2MAE(CG) with an energy interval of M 14 kcal mol-’ .

On the other hand, the order of relative stabilities of the stable conformers of the methylated derivatives is not the same as that of comparable conformers of 2AE. Thus, for 2AE and 2AP, the order of increasing stability is CG > 150G’ > CG’ > TG > 150G, and for lA2PN and 2MAE the CG’ and 150G’ conformers change their stabilities relative to CG.

In order to consider, in part, the effect of electron correlation, corrected MP2 energies of the stable conformers were calculated (Table 3). As in 2AE, for lA2PN and 2MAE the relative energies increase with respect to the most stable CG conformer, except for 2MAE, where the CT conformation stabilizes. For 2AP, in contrast, the relative energies decrease, except for 140G’ and - 140T. On the other hand, the order of relative stabilities compared with the HF results is maintained for lA2PN and is altered in some conformers of 2MAE and 2AP.

3.2. Geometrical trends: hydrogen bond and anomeric effect

With regard to the CG conformers, and as occurred with 2AE, the presence of geometrical trends that would suggest the existence of hydrogen bonding is worth noting. These tendencies can be summed up in that, when this occurs, the C=O and H-N bonds lengthen and the H-N-C angles close compared with cases in which there is no interaction [9]. Thus, in the CG conformers the C2=01, H&N4 and H9-N4 bond lengths are greater and the H&N4-C3 and H9-N4-C3 angles are smaller (Table 1) than in those with N-C-C=0 around 150” and -150”, where hydrogen bonding is impossible. Certain excep- tions to these tendencies can be observed in the C2=01 lengths of lA2PN(150G’), H9-N4 of lA2PN( 150G’) and 2MAE( 150G’), and H8-N4 of 2AP(-140T), which are greater than expected. Although expect geometrical trends are generally followed, it should be noted that H. . .O distances (between 2.68 and 2.72 A) indicate nonbonded interactions weaker than typical hydrogen bonding.

Moreover, some geometric features can be related to the so called anomeric effect [lo]. This

154 L. Carballeira, I. Perez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156

8

I

Z-aminoethanal (ZAE)

7 1-amino-2-propanone (lA2PN)

7 -G

G

-180 -120 -60 0 60 120 180

N-C-C=0 torsion

a

3

2.methylamino-ethanal (ZMAE) *1

2-amine-propanal (2AP)

7

i

-G

G

T

4

6 E 6

-G -_

s -_ G

r 5 T

0 / 1, /- I I I I I I

-180 -120 -60 0 00 120 180

1

0

-180 -120 -00 0 60 120 180

N-C-C=0 towon N-C-C=0 torsion

Fig. 3. MM3(92) curves obtained driving the N-C-C=0 torsion for the three arrangements of the amino group.

-180 -120 -60 0 00 120 180

N-C-C=0 torsion

is produced in molecules which contain an X-A- B-Lp unit when the lone pair of the B atom (Lp) is in trans arrangement with respect to the X-A bond. Because of this, the electrons of the lone pair are donated to the vacant antibonding orbital X-A and, as a result, lengthening of the X-A bond occurs and the X-A-B angle opens. In accordance with Fig. 1, there could possibly be anomeric effects in the three arrangements of the amino group studied. Thus, G conformers (including 2AE [2]), where the pair of the N is trans with respect to the C3-C2 bond, have C3-C2 bond lengths and N4- C3-C2 bond angles larger than in any of the other G’ and T conformers (see Table 1).

The anomeric effect may be the cause for obser- ving a departure from standard geometries, espe- cially in G’ and T conformers, although expected geometrical trends related with bond lengths are not always followed. Thus, in G’ conformers,

where there could be an anomeric interaction between the nitrogen lone pair and the H7-C3 bond in trans (see Fig. l), this bond is always larger in CG’ conformers [lA2PN(CG’) = 1.0959, 2MAE(CG’) = 1.0993 and 2AP(CG’) = 1.0981 A]. However, this trend is not observed for some G’ conformers [ lA2PN( 150G’) and 2AP( 14OG’)], as should be expected. The same fact is observed in T conformers: CT conformers have larger R6-C3 bond lengths [2MAE(CT) = 1.0986 and 2AP(CT) = 1.5385 A], which can be due to an anomeric interaction between the R6-C3 bond trans with respect to the nitrogen lone pair. Again, the same trend is not strictly observed for the other T conformers such as 2MAE(-150T) and 2AP(-140T). However, trends related with bond angles are clear: H7-C3-N4 and R6-C3- N4 always take greater values in G’ and T conformers, respectively (see Table 1). The non-systematic

L. Carballeira, I. Ptkez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156 155

trends in some bond lengths of G’ and T conformers do not permit one to confirm the presence of an anomeric effect. This could be due to the low polarity of the H7-C3 and R6-C3 bonds, because anomeric interactions are more significant when polar bonds are involved [10(a)].

3.3. Comparison with results obtained by molecular mechanics

Fig. 3 shows the N-C-C=0 curves obtained by MM3(92) molecular mechanics [ 1 l] using the same procedure as for the ab initio calculations, that is, driving the N-C-C=0 torsion for each of the arrangements of the amino group. Large dis- crepancies are observed between the curves obtained by both methods, as the positions of the minima and maxima do not coincide, except in the case of the G curves of 2AE and lA2PN, where one minimum in common is located in a position around 0”. The discrepancy is even greater in the relative energies, since the stabilities of the minima of each molecule do not fit and maxima not obtained by ab initio calculations can be observed (at z 180” for all the curves).

In addition, the stable conformers predicted by MM3(92) were located, and in this case there were also great differences with regard to ab initio data. Thus, for lA2PN four minima were detected (compared with five according to ab initio) and only the CG conformer coincides in any appreciable way. On the other hand, as can be observed in Table 1, for 2MAE and 2AP six and seven ab initio conformers respectively were determined, compared with eight located by MM3(92) for each of the species, and neither the optimized geometries nor the relative energies were comparable [12].

4. Conclusions

From the conformational analysis of the molecules studied, it can be concluded that, according to the MO ab initio 6-31G” method, methylation in different positions produces an increase in stability with respect to the compound initially consid- ered, 2-aminoethanal (2AE). The rotational barriers due to interactions between C2=01 and

C2-R5 bonds and the substituents on the N have been studied, of particular note being the barrier heights due to repulsions with the pair of the N.

Similarly to what occurred in 2AE, geometrical tendencies have been found which could indicate the existence of hydrogen bonding in the CG conformers of the three derivatives. On the other hand, some trends suggest the possibility of an anomeric effect for the three arrangements of the amino group.

However, as was expected, the results obtained with the present MM3(92) version disagree consid- erably with those obtained by HONDO~.~ owing to the lack of parameters for the N-C-C=0 torsion. This confirms the necessity to continue studying simple molecules with this unit in order to obtain a reliable set of data and to carry out the parameterization of the unit.

Acknowledgements

The authors are indebted to the Xunta de Galicia for financial support granted for carrying out this work. I.P.J. also thanks the Spanish Ministerio de Education y Ciencia for the award of a doctoral (FPI) grant.

References

[l] K.B. Lipkowitz and D.B. Boyd (Eds.), Reviews in Compu- tational Chemistry, Vol. 2, VCH, New York, 1991.

[2] L. Carballeira and I. Perez-Juste, J. Mol. Struct. (Theo- them), 309 (1994) 267.

[3] V.J. Klimkowski, J.N. Scarsdale and L. Schafer, J. Com- put. Chem., 4 (4) (1983) 494.

[4] L. Van den Enden, C. Van Alsenoy, J.N. Scarsdale, V.J. Klimkowski and L. Schafer, J. Mol. Struct., 105 (1983) 407.

[5] M. Dupuis, S. Chin and A. Marquez, CHEM-Station and HONDO, in G.L. Malli (Ed.), Relativistic and Electron Correlation Effects in Molecules and Clusters, NATO AS1 Series, Plenum Press, New York, 1992.

[6] C. Moller and M.S. Plesset, Phys. Rev., 46 (1934) 618. [7] Because of the size of the tables, only the energies and

geometries of the stable conformers of the molecules studied have been included. The energies and geometries of the conformations used to obtain the curves in which the N4C3C201 torsion has been restrained can be requested from the authors.

[8] (a) A. Pross, L. Radom and N.V. Riggs, J. Am. Chem. Sot.,

156 L. Carballeira, I. Perez-Juste/Journal of Molecular Structure (Theochem) 360 (1996) 145-156

102 (1980) 2253; (b) D. Cremer, J.S. Binkley, J.A. Pople and W.J. Hehre, J. Am. Chem. Sot., 96 (1974) 6900.

[9] (a) J.O. Williams, C. Van Alsenoy and L. Schafer, J. Mol. Struct. (Theochem), 76 (1981) 109,171; (b) C. Van Alsenoy, J.O. Williams and L. Schafer, J. Mol. Struct. (Theochem), 76 (1981) 179.

[lo] (a) L. Schafer, C. Van Alsenoy, J.O. Williams and J.N. Scarsdale, J. Mol. Struct. (Theochem), 76 (1981) 349;

(b) C. Romers, C. Altona, H.R. Buys and E. Havinga, Top. Stereochem., 4 (1969) 39.

[ll] MM3, 1992 Version, N.L. Allinger, Y.H. Yuh and J.-H. Lii, J. Am. Chem. Sot., 111 (1989) 8551.

[12] The geometrical and energy data of the conformers obtained can also be requested. Their inclusion in this paper was not thought appropriate because of their low reliability, as indicated in the text.

Documents

Ab initio studies of molecules with NCCO units. Part 2. 1-Amino-2-propanone, 2-methylaminoethanal and 2-aminopropanal