Aromaticity of five-membered heterocycles: an experimentally convenient theoretical model for prediction of relative aromaticity

MMO-4039/92 $5.00 + 00 Pergamon Press Ltd

Tcnahcdron Letters. Vol. 33, No. 17. pp. 2303.2306, 1992 Printed in Great Britain

AMMATICITY OF FIVE-MEMSERED RETEROCYCLES: AR EXPERIMERTALLY COWVEIIEDT THRORSTICAL WODEL FOR PREDICTION OF RELATIVE AROMATICITY Ramachandra S. Hosmane and Joel F. Liebman* Laboratory for Chemical Dynamics, Department of Chemistry and Biochemistry University of Maryland Baltimore County Baltimore, Maryland 21228

An experimentally convenient theoretical model for prediction of relative aromaticity of 5-membered heterocycles is preeented. The model is an improvement of our earlier model based on the Dewar-Breslow definition of aromaticity and can accommodate a broader range of heterocycles than the previous model. In

a

recent

theoretical

paper1

model

for

we

proposed

evaluation

of

a

new,

experimentally

relative

aromaticity

realizable,

of

monocyclic

heterocycles, in which we conceptually combined the now classic Dewar-Breslow definition of aromaticity2 with the knownthermochemicalequivalence3 and vinyl groups.

of phenyl

More precisely, we considered the quantity 8AIQ, represented

by the following equation,

as a measure of relative aromaticity

of various

heterocycles' and indeed, found it to be consistent with the experimentally observed order of aromatic characteristics based on the pattern

Rel. Aromaticity

of

individual

reactivity.

characterizable

The

organic compounds

model

employs

heterocycles whose aromaticity is in question. measurements easily

of heats of formation

synthesized

compounds,

affording

and

compare

reasonable

easily

synthesizable,

(Ph-X-Ph) ae the acyclic counterparts

those

predictions

of

This allows one to make facile

of acyclic

with

and

analogues

of

the

which

can not be

corresponding

of comparative

cyclic

aromaticity

of

heterocycles. The above model, however, is incapable of predicting the aromaticity of heterocycles which can not be represented by the formula CIH,X, such as maleic anhydride, the 4a "quinone" of furan, and vinylene carbonate, the 6n "reverse" of maleic anhydride with its -0- and -C=O atom/group exchange. Therefore, we present here a new, modified

version of the old model which

2303

is broader

in

2304

scope, and can be employed to predict relative aromaticity of a wide range of heterocycles

including

groups.

We demonstrate

examples

of

the

ones

containing

carbonyl

here the feasibility

five-membered

heterocycles.

and

other

functional

of this new model with a few

We

anticipate

the

model

to

be

applicable to other larger and smaller heterocycles as well. The new model is based on the simple observation that any species of the type C,H,X can also be represented by the simpler moiety C,B,X, wherein the new "X" becomes equal to CH=CH-X to equate to the old formula.

If aromaticity and

strain both were to be absent, then the reaction C,H,X would be thermoneutral.'

+

C,Ii, *

Therefore,

(C%CX),X

making

use once again

of the thermo-

chemical equivalence of phenyl and vinyl groups, we now can consider: [A&(Ph-X-Ph) For maleic anhydride

- &(C,H,)] (VII)

and

- [AH,(C,H,X)] = 8AH, (kcal/mol)

vinylene carbonate

(V) (CEART I), X equals

-C(O)-O-C(O)- and -0-C(O)-0-, respectively, whereas for pyrrole (I), furan

CHART

I

H

ON0

Lr

IT

Ill-3

O

VII

I (II), oxazole (III), fulvene (IV), and cyclopentadiene

(VI), X equals -CH=CH-

NH-, -CH=CH-0-, -N=CB-0-, -CH=CH-$=CH,, and -CH=CE-CH2-, respectively. The calculated values of relative aromaticity for the ring systems listed in Chart I are collected in CHART II.

We find that the aromaticity decreases

in the order I-VII. This order is consistent with the experimental observations of patterns of reactivity of these molecules, e.q, substitution versus addition reactions with electrophiles and nucleophiles. It is also consistent with other relative scales of aromaticity derived from various energetic, non-energetic, and statistical criteria, as recently reviewed by Xatritzky, -* et al 4 For example, the highly aromatic pyrrole (I) undergoes

2305

CHART

II

[Cl II

z4cvclic IAl

cvclic

m,

AH, (9)

6AH, (kcalhol)

(9)

rci

=

Rd.

I;

-CH=CH-NH-

(68.0"-12.5b)

25.8h

29.7

11;

-CH=CH-O-

(28.2C-12.5b)

-8.3h

24.0

111; -N=CH-O-

(27.9d-12.5b)

-37.0h

19.0

Iv;

-CH=CH-C=CH2 I

(70.7=12.5b)

44.4f

13.8

Vi

-O-C(O)-O-

(-74.4h-12.5b)

-100.0"

13.1

VI;

-CH=CH-CH,-

(54.69-12.5')

32.1"

10.0

VII;

-C(O)-O-C(O)-

(-76.2h-12.5b)

-95.1"

6.4

Aroaaticitv

The heat of formation of IA was estimated by assuming that the reaction Ph-CE=CE, + Ph-NEcH=CH2 --cPh-CE=CE-NH-Ph + C,E, is thennoneutral. (The ancillary data for Ph-NE-CE=CH2 was estimated by employing the 947.3kcal/mol difference of PhX and CH,=CHX from ref. 3 with the archival value for the heat of formation of diphenylamine. b The heat of formation of ethylene = +12.5 kcal/mol. 0 The heat of formation of IIAwas estimated by assuming that the reaction Ph-CH=ClQ t Ph-0-CWCH, + Ph-CH=CS-0-Ph + C,H, is thermneutral. * The heat of formation of IIIA was estimated by assuming that the reaction Me-0-CE=N-Ue t Ph-D-Me t Ph-NMe, +Ph-O-CH=N-Pht l+.O + Me,N is thermoneutral. (The ancillary data for HC(OMe)=NHe was derived by assuming the same heat of amide +imidate isomerization (16.3 kcal/mol) for Dl4Pas for DM, measured by P. Beak, J. -K. Lee, and n. Zieger, J. Org. Chem., 43, 1536 (1978)). l The heat of formation of IVA was derived by assuming that the reaction 2 (Ph-CB=C&)-+Ph-CE=CE-C(=CH2)Ph t E, is nearly thermoneutral by analogy to other olefin-diene interconveraions (J. F. Liebman, Struct. Chem., in press.). f The heat of formation of IvC was estimated by assuming that the reaction C,H,=C(CH,),t (CE,),C=CH, + (CH,),C=C(CH,), + C,Ii,=CHz is thermoneutral. s The heat of formation of VIA was estimated by assuming that the reaction Ph-CE=CH, + Ph-CH,CE=CH, 4 Ph-CIi=CH-CH2-Pht C,H, is thermoneutral. The necessary A& (Ph-CE,-CH=CH,)= 10.8 kcal/mol was derived using the 2 term equation of J. S. Chickos, A. S. Hyman, L. 8. Ladon, and J. F. Liebman, J. Org. Chem., 46, 4284 (1981). ' Any undiscussed heat of formation is from experiment and taken from J. B. Pedley, R. D. Naylor, and S. P. Kirby, "Thermochemical Data of Organic Compounds," 2nd Ed., Chapman C Hall, New York, 1980. l

2306

facile electrophilic substitution reactions,6 whereas the anti-aromatic maleic anhydride

(VII) is an excellent dienophile in Diels-Alder

(II) and oxazole

reactions.

Furan

(III) have less aromatic character than pyrrole, and often

react by overall addition as well as substitution modes,' the latter mode being more

rare with

oxazole.6'7

Fulvene

(IV), although often characterized as non-

aromatic, does show some aromatic properties.* While it shows no evidence of meaningfully ring currents, its exocyclic double bond is nevertheless polarized in the direction of the ring (cc= 0.42 D).* The molecular structure, dipole moment (CL= 4.5 D), and NMR spectral parameters of vinylene carbonate (V) show considerable delocalization of the oxygen lone pairs into the carbonyl

group;

its

however,

well-documented

homo-

reactions are highly suggestive that the delocalization The relative aromaticity

of cyclopentadiene

a non-aromatic

which

compound fulvene

Acknowledgment.

(IV)

copolymerization

is hardly complete.g

(VI) is consistent with that of

It is to be noted

it is.

predicts that the "pseudo aromatic" vinylene carbonate non-aromatic"

and

(V)

that and

our model

the

"pseudo

possess nearly the same aromatic character.

This research was supported by a grant to R.S.H. from

the National Institutes of Health (#CA 36154).

REFERENCES

AND

NOTES

[11

Hosmana,R. 8.; Liebman, J.

r21

(a) Breslow, R.; Mohacsi, E. J. Am. Chem. Sot. 1963, 85, 431. Dewar, M. J. S. J. Chem. Phyrr. 1965, 42, 756.

(31

(a) Liebman, J. F., in "Molecular Structure and Energetic%: studies of Organic Wclecules," Vol. 3, Liebman, J. F. and Greenberg, A., Ed., VCE Publishers, Deerfield Beach, 1986; Chapter 6. (b) George, P.; Bock, C. W.; Tractman, M., in "Molecular Structure and Energetica: Biophyeical Aspects," Vol. 4, Liebman, J. F. and Greenberg, A., Ed., VCH Publishers, New York, 1987; Chapter 6.

(41

For a recent comprehensive review on *HeterocyclicAromaticity," see Eatriteky, A. R.; Karelson, M.; Walhotra, N. Beterocycle8 1991, 32, 127-161.

(51

This is a generalization of the conclusions of Bachrach, S. M. J. Org. Chem. 1990, 55,

161

xatritzky,A. R. "Bandbook of Eeterocyclic Chemistry," Pergamon Press, New York, 1985;

F.

Tetrahedron

Lett.

1991, 32, 3949. (b) chung, A. L. 8.;

4961. Chapters 3.3 and 3.4.

r71

Newkome, G. R., Paudler, W. W. "ContemporaryBeterocyclic Chemistry,* John Wiley h Sons, New York, 1982; Chapters 7-10.

(81

(a) Garratt, P. J. "Arortiaticity," John Wiley C Sons, New York, 1986; Chapter I. (b) March, J. "Advanced Organic Chemrstry," 2nd Ed., McGraw-Hill, New York, 1977; pp. 46-47.

(91

"Dioxoles and Oxathiolee," in "Comprehensive Eeterocyclic Elliott, A. J. Chemistry," Vol. 6, Katritzky, A. R. and Rees, C. W., Ed., Pergamon Press, New York, 1984; Chapter 4.30.

(ReceivedinUSA27January 1992)