A semiempirical quantum mechanical approach towards understanding of cyclopropenone reactivity

THEO CHEM ELSEVIER

Journal of Molecular Structure (Theochem) 364 (1996) 45-49

A semiempirical quantum mechanical approach towards understanding of cyclopropenone reactivity Silvio Cunha, Albert Kascheres* Universidade Estadual de Campinas, Instituto de Quimica, CP 6154. 13081-970 Campinas. SP, Brazil

Received 8 September 1995; accepted 14 November 1995

Abstract The results of semiempirical molecular orbital calculations performed on several cyclopropenones employing the MNDO, AMl, and PM3 molecular models are presented. The AM1 method, which best reproduces structural properties, is used to calculate electronic parameters for a series of cyclopropenones. The use of these parameters for the evaluation of reactivity is discussed. Keywords:

Cyclopropenone;

Reactivity; Semiempirical molecular orbital calculation

1. Introduction

Although reactivity studies of cyclopropenones (1) have spanned the past three decades, no reactivity pattern has emerged from the valencebond treatment typically employed in the literature [l]. This problem gains new proportions as derivatives of biological interest begin to appear, as exemplified by the antibiotic penitricin [2] (of microbiological origin) and a recently-synthesized cyclopropenone-containing peptide [3] which is an inhibitor of papain. In this latter report, the difficulty encountered in evaluating the mode of action is attributed to the complex reactivity pattern of cyclopropenones. It is our belief that an eventual solution to this problem resides in the application of molecular orbital methods. In so much as ab initio calculations are prohibitive for * Corresponding author.

larger molecular systems, semiempirical quantum mechanical methods represent one approach to meeting this challenge. While ab initio methods can, at least in principle, be successively improved with respect to basis set and electron correlation to provide a measure of the reliability of the methods used, the performance of semiempirical methods can only be evaluated by comparisons between calculated values and experimental data. The methods developed in the group of Dewar (and offshoot) have improved the state of the art considerably in recent years. In particular, MNDO [4], AM1 [5] and PM3 [6] methods have been important landmarks in the continual improvement of methodologies for semiempirical calculations. These have been applied with considerable success to many problems of chemical interest. We undertook the present study in search of a molecular model which would best represent ground-state molecular properties of cyclopropenones.

0166-1280/96/$15.00 0 1996 Elsevier Science B.V. All rights reserved SSDZ 0166-1280(95)04453-l

S. Cunha. A. KascheresjJournal oJMolecular

46 Table 1 Comparison

of structural

parameters

of cyclopropenone

obtained

Structure (Theochem)

by ab initio, semiempirical,

364 (1996) 45-49

and experimental

method?

0 3 /A

H’ Parameter

Cl-C2

c3-0 /HCIC2

6-31G**

6-31G*

[I41

[I41

1151

1.334 -0.015

1.429

Cl-C3 Cl-H

4-3lG

-0.003 1.062 -0.017 1.209 -0.003 152.3 8.0

1.328 -0.021 1.412 -0.011 I.071 -0.008 1.188 -0.024 152.8 8.5

1.327 -0.022 1.412 -0.011 1.071 -0.008 1.190 -0.022 154.2 0.9

a For each row, the first number is the parameter distances in angstroms and angles in degrees.

*H

MP2/ 6-3lG

CISD/ 6-31G*

iI61

1151

1.352 0.003 1.436 0.013 1.084 0.005 1.213 -0.001 144. I -0.2

1.337 -0.012 1.422 -0.001 1.078 0.001 1.202 -0.010 144.8 0.5

value and the number

2. Methods

All calculations were carried out by using the MNDO [4], AM1 [5] and PM3 [6] semiempirical molecular orbital procedures as implemented in the MOPAC 6.0 program package [7]. All geometries were fully optimized without any assumption using the standard BFGS method and the option for increased precision (PRECISE).

3. Discussion On of the tests widely used to determine the validity of a semiempirical method involves calculation of heats of formation [8]. Experimental data regarding heats of formation is available only for diphenylcyclopropenone (la), with values ranging from 75.54 to 97.2 kcal mol-’ [9]. The calculated values of 80.57 (MNDO), 80.64 (PM3), and 91.84 (AMl) kcal mol-‘, all within this range, show that this criterion cannot be employed in the case of cyclopropenones. Another criterion frequently adopted in the selection of a method is the reproduction of structural parameters [8]. Table 1 presents a comparison

MNDO

PM3

AMI

Exp.

[161 1.359 0.010 1.465 0.042 1.064 -0.015 1.206 -0.006 149.0 4.7

1.344 -0.005 1.435 0.012 1.076 -0.003 1.200 -0.012 147.7 3.4

directly below is the error in relation

1.349 0.000 1.437 0.014 1.073 -0.006 I.214 0.002 148.9 4.6

1.349 f0.003 1.423 f0.005 1.079 f0.002 1.212 f0.006 144.3 fO.l

to the experimental

value;

of calculated structural parameters for cyclopropenone (lb), as obtained by various ab initio methods at various precision levels and by semiempirical methods, with those obtained experimentally. It may be seen that of the semiempirical calculations the AM1 method is clearly superior to MNDO and somewhat better than PM3 at reproducing the experimental values, and is in fact, superior to some of the ab initio methods. This comparison may be extended to more complex systems (where ab initio methods are not viable), as illustrated in Table 2, wherein calculated structural parameters for diarylcyclopropenones (la and lc) are compared with those available from X-ray data. Again, it is the AM 1 method which best reproduces structural properties and, as a result, best represents the model sought by us. The only previously reported semiempirical calculation involving cyclopropenones is a CNDOj2 treatment of methylphenylcyclopropenone(ld), wherein only values of net charge are furnished as follows: methyl-C (O.OOO),phenyl-C (-0.014), and oxy-C (0.276) [lo]. These values have been used to support a mechanism postulated for the reaction of imines with Id involving initial nucleophilic attack at methyl-C [l l]. The fact that one is dealing with a

S. Cunha. A. KaxhereslJournal

of Molecular Structure (Theochem)

41

364 (1996) 45-49

Table 2 Comparison of calculated and experimental structural parameters of diarylcyclopropenonesa

0

Parameter

Diphenylcyclopropenone X-ray [17]

Cl-C2

1.349

Cl-C3

1.417

c3-0 Cl-Ar

1.225 1.447

iClC2C3

61.6

fClC3C2

56.9

iOC3C2

151.5

/ArC2C 1

150.6

db

2.2

AM1 1.369 0.011 1.468 0.021 1.214 -0.011 1.417 -0.030 61.8 0.2 56.4 -0.5 151.8 0.3 150.6 0.0 0.1 -2. I

(la)

Bis(p-ClPh)cyclopropenone PM3 1.355 0.006 1.437 0.020

1.200 -0.025 1.426 -0.021 61.9 0.3 56.2 -0.7 151.9 0.4 147.7 -2.9 0.6 -1.6

MNDO

X-ray [18]

1.374 0.025 1.466 0.049 1.207 -0.018 1.436 -0.011 62.1 0.5 55.9 -1.0 152.1 0.6 150.2 -0.5 22.3 20.1

1.368 1.418 1.217 1.447 61.2 57.7

149.1

(lc)

AMI

PM3

1.360 -0.008 1.438 0.020 1.214 -0.003 1.417 -0.030 61.8 0.6 56.4 -1.3

1.354 -0.014 1.438 0.020 -0.017 1.425 -0.022 61.9 0.7 56.2 -1.5

0.049 1.206 -0.01 I 1.436 -0.011 62.1 0.9 55.8 --1.9

150.5 1.4

142.8 -1.3

150.2 1.1

1.200

MNDO 1.374 0.006

1.467

a For each row, the first number is the parameter value and the number directly below is the error in relation to the experimental value; distances in angstroms and angles in degrees. b Average angle Cl-Ar, C2-Ar.

“soft” nucleophile in this case suggests that frontier orbital control, and not charge control, should govern the process. Also, a charge-control route would necessarily involve reaction at oxy-C. With the objective of shedding new light on the question of cyclopropenone reactivity, electronic parameters for a series of phenylcyclopropenones were calculated using the AMI method (see Table 3). It may be seen that in all cases HOMO and LUMO coefficients are smallest at oxy-C. Also, for all alkyl-substituted derivatives HOMO and LUMO coefficients are largest at alkyl-C. Thus, reactions involving “soft” reagents should be kinetically favored at this position. Also, the direction of the values of net charge at alkyl-C and phenyl-C is reversed in relation to the values obtained from the CND0/2 treatment, while oxy-C remains the most positive center. This would suggest that reactions involving “hard” nucleophiles should be

kinetically favored at the carbonyl position, as is actually observed [l]. Another aspect worthy of mention here involves LUMO energies. It is known that diphenylcyclopropenone (la) is more reactive towards nucleophiles than are alkylphenylcyclopropenones [12]. This observation may now be attributed to the lower-lying LUMO of la. The above observations show that the frontier orbital treatment in combination with the “hardness-softness” concept serves as an important probe for the understanding of the complex reactivity pattern of cyclopropenones. Some of the ideas presented here have recently been used by us in the examination of specific cases [13].

Acknowledgements

The authors thank the Conselho National

de

H Me (Id) ‘Pr ‘BLl Ph

LUMO

R

-0.494 -0.501 0.498 -0.497 -0.455

Cl

parameters

Table 3 Electronic

0.445 0.439 -0.436 -0.433 0.455

c2

coefficients

calculated

-0.088 -0.079 0.083 0.083 0.000

c3 0.074 0.066 -0.069 -0.070 -0.000

0

by the AM 1 method

-0.444 -0.436 0.439 0.438 -0.348

Cl

HOMO c3 -0.058 0.071 -0.068 0.069 -0.084

c2 -0.240 -0.298 0.289 0.291 -0.348

coefficients

for phenylcyclopropenones 0

0.275 0.290 -0.289 0.289 0.270

0 -0.19 -0.14 -0.13 -0.12 -0.10

Cl -0.11 -0.11 -0.11 -0.11 -0.11

c2

Net charge

0.28 0.28 0.28 0.28 0.28

c3

LUMO -0.82 -0.76 -0.74 -0.71 -1.14

0 -0.27 -0.27 -0.27 -0.27 -0.27

Energy

-9.54 -9.29 -9.32 -9.29 -8.90

HOMO

(kcal mol-‘)

70.71 59.86 49.82 47.27 91.84

(kcal mol-‘)

AH,

S. Cunha, A. Kascheres/Journal

of Molecular Structure [ Theochem) 364 (1996) 45-49

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49

(b) J.J.P. Stewart, Semiempirical Molecular Orbital Methods, in K.B. Lipkowitz and D.B. Boyd (Eds.), Reviews in Computational Chemistry, VCH, New York, 1990, p. 46. [91 H.E. Davis, N.L. Allinger and D.W. Rogers, J. Org. Chem., 50 (1985) 3601. PO1 H.L. Ammon, J. Am. Chem. Sot., 95 (1973) 7093. [ill T. Either, J.L. Weber and G. Chatila, Justus Liebigs Ann. Chem. (1978) 1203. [121 A. Kascheres, C. Kascheres and J.A.R. Rodrigues, J. Org. Chem., 41 (1976) 3546. [I31 (a) A. Kascheres, J. Correa Filho and S. Cunha, Tetrahedron, 49 (1993) 381. (b) A. Kascheres, C. Kascheres and A.C.H. Braga, J. Org. Chem., 58 (1993) 1702. 1141A. Komornicki, C.E. Dykstra, M.A. Vincent and L. Radom, J. Am. Chem. Sot., 103 (1981) 1652. P51 CA. Jacobs, J.C. Brahns, W.P. Daley, K. Bern and M.D. Harmony, J. Am. Chem. Sot., 114 (1992) 115. 1161SW. Staley, T.D. Norden, W.H. Taylor and M.D. Harmony, J. Am. Chem. Sot., 109 (1987) 7641. P71 H. Tsukada, H. Shimanouch and Y. Sasada, Chem. Lett., (1974) 639. [If31K. Peter and H.G.v. Schnering, Chem. Ber., 118 (1985) 2147.