3060
J. Am. Chem. SOC.1990, 112, 3060-3063
Gas-Phase Heteroaromatic Substitution. 7. Methylation of Five-Membered Heteroaromatic Rings by Free Methyl Cations Giancarlo Angelhi,+ Cinzia Sparapani,? and Maurizio Speranza*** Contribution from the Istituto di Chimica Nucleare del C.N.R., Area della Ricerca di Roma, C.P. 10, Rome, Italy, and the Dipartimento di Agrobiologia ed Agrochimica, Universitd della Tuscia, Viterbo, Italy. Received June 26, 1989
Abstract: The results of a study of the reactions of a powerful alkylating electrophile, the CT3+ion from the 8-decay of CT4, with gaseous pyrrole, N-methylpyrrole, furan, and thiophene are reported. In all the systems investigated, two major categories of labeled products are recovered: the methylated and the tritiated substrates. The nature and the yields of the methylated products, as well as their isomeric composition, suggest that the gas-phase alkylation reaction of simple heteroaromatics by the CT3+ cation is regulated by factors related to electron mixing between the HOMO of the substrate and the LUMO of the electrophile in the transition state, a behavior that ranks CT3+ as a “soft” Lewis acid. For “harder” alkylating species, such as CH3FCH3+,the orienting properties of the heteroaromatic substrates are mainly determined by electrostatic interactions established within the encounter pair. Furan and thiophene give, although for different reasons, similar product distributions with both “hard” and ”soft” alkylating cations.
Simple five-membered heteroaromatics such as pyrrole and furan are prominent members of that very special category of aromatic compounds with a HOMO electron density distribution opposite to the total n-electron and charge-density ones.2 The HOMO orbital of such compounds is characterized by a high n-electron density at the a-carbons, while the total net negative charge is located predominantly on the &carbons and the heteroatom. Thus, in principle, these compounds may be conveniently used for assaying the electronic properties and the reactivity of virtually all electrophilic reactants. In the framework of the frontier molecular orbital theory for chemical reactivity,’ a distinct preference for the &carbons and the heteroatom of the above heteroaromatics is expected for “hard” electrophiles, whose reactivity is essentially controlled by electrostatic interaction^.^ “Soft“ electrophiles are, instead, characterized by their tendency to accept partial electron transfer from the HOMO orbital of the substrate in the transition state, thus interacting preferentially with the a-carbons of the heteroaromatic molecule. It follows that an experimental probe for the orbital configuration of a variety of electrophiles may be provided by the determination of their site selectivity toward simple heteroarenes in the dilute gaseous state. Under such conditions the intrinsic orienting properties of the substrate2 and the actual reactivity features of the electrophilic reactant4 are not affected by extraneous and variable phenomena, such as solvation, ion pairing, and catalystsubstrate interactions, which are invariably superimposed upon the intrinsic factors determining the activation energy barrier in electrophilic heteroaromatic substitutions in solution. In recent years the first experimental insight into the behavior of five-membered heteroaromatics toward charged alkylating electrophiles (e.g., CH3FCH3+,5t-C4H9+>and i-C3H7+ions’) in the gas phase was given by the application of the radiolytic technique,’ which, unlike most conventional mass spectrometric approaches, provides direct information about the site of attack of the ionic reactant on the heteroaromatic ring and the structural features of the resulting ionic intermediate(s). The relevant results are consistent with a reactivity pattern dominated by attractive electrostatic interactions between the negatively charged sites of the heteroaromatic molecule (i.e., the 8-carbons and the heteroatom of pyrroles) and the gaseous alkylating ions, which therefore behave as typical “hard” electrophiles. From these limited data it could not be decided whether the electrostatic control of the electrophilic attack of alkylating ions on heteroaromatics is a general feature of gas-phase heteroaromatic substitutions, or whether other factors related to the frontier-orbital perturbation of the reaction partners may intervene. ‘Istituto di Chimica Nucleare CNR, Rome, Italy. *University of Tuscia, Viterbo, Italy.
0002-7863/90/ 15 l2-3060$02.50/0
We now report an extension of the study to the gas-phase alkylation of simple five-membered heteroaromatics by the simplest alkylating ionic electrophile, the methyl cation CT3+, which is conveniently generated in the gas phase by spontaneous fldecay in multitritiated methane (eq 1).8 The investigation has been primarily undertaken to bring into discussion the possibility of frontier-orbital control in ion-heteroaromatic molecule reactions in the gas phase, the methyl cation being considered among the softest charged ele~trophiles.~ A close comparison between the selectivities of two gaseous methylating reactants, namely the CH3+and CH3FCH3+cations, may help in elucidating the effect on the HOMO orbital energy of CH3+ when it is bonded to a CH3F moiety. CT4
B %I-.V
CTj
n ‘Y‘
lrititedprod~ds
Y = NH U), NMe, (2hO (31, S (4)
Experimental Section Materials. Multitritiated methane, used as a precursor of the labeled methyl cations, was prepared according to established procedures? The isotopic composition was measured by radio gas chromatography and mass spectrometry and corresponded to 60% CT4, 30% CHT3, 8% CH2T,, and 2% CH3T, with an uncertainty level of i l % . The heteroaromatic substrates and the gaseous additives used for the preparation of the decay mixtures were research grade chemicals from Fluka AG and Matheson Co. and were used without further purification. 2-Methylfuran and isomeric methylthiophenes, used as carriers or as standards in the radio gas chromatographic analyses, were obtained from ICN Pharmaceutical, Inc., and Fluka AG. 3-Methylfuran as well as (1) Part 6: Laguzzi, G.; Speranza, M.J . Chem. SOC.,Perkin Trans. 2 1987, 857. (2) Speranza, M. Ado. Heterocycl. Chem. 1986, 40, 25. (3) (a) Klopman, G., Ed. Chemical Reactioity and Reaction Paths; Wiley: New York, 1974. (b) Houk, K. N.; Acc. Chem. Res. 1975, 8, 361. (c)
Fleming, I. Frontier Orbitals and Organic Chemical Reactions; Wiley: New York, 1976. (d) Ho, T. L. Hard and Soft Acids and Bases Principle in Organic Chemistry; Academic Press: New York, 1977. (4) (a) Pearson, R. G. Proc. Narl. Acad. Sci. U.S.A. 1986, 83. 8440. (b) Klopman, G. J . Am. Chem. SOC.1968, 90, 223. (5) (a) Angelini, G.; Sparapani, C.; Speranza, M. J. Am. Chem. Soc. 1982, 104, 7084. (b) Angelini, G.; Lilla, G.; Speranza, M. [bid. 7091. (6) Margonelli, A.; Speranza, M. J . Chem. SOC.,Perkin Trans. 2 1983, 1491. (7) (a) Cacace, F. Acc. Chem. Res. 1988,21,215. (b) Cacace, F. Radiat. Phys. Chem. 1982, 20, 99. (c) Cacace, F. In Structure Reactiuity and Thermochemistryof Zom; Ausloos, P., Lias, S. G., Eds.; D. Reidel: Dordrecht, The Netherlands, 1987; p 467.
(8) (a) Cacace, F.;Speranza, M. In Techniques for the Study of Ion Molecules Reactions; Farrar, J. M., Saunders, W., Jr., Eds.; Wiley: New York, 1988. (b) Cacace, F. Adu. Phys. Org. Chem. 1970, 8, 79. (9) (a) Cacace, F.; Schuller, M. J . Labelled Compd. 1975, 1 1 , 313. (b) Cacace, F.; Ciranni, G.; Schuller, M. J . Am. Chem. SOC.1975, 97, 4747.
0 1990 American Chemical Society
J . Am. Chem. Soc., Vol. 112, No. 8, 1990 3061
Gas- Phase Heteroaromatic Substitution. 7
Table 1. Tritiated Products from the Attack of CT3+Decay Ions on Gaseous Heteroarenes ( T = 100 "C) relative vields of products* (5%) Me
substrate 1, 150 1. 150 150 1, 150 2, 150 2, 150 2, 150 2, 150 3, 150 3, 150 3, 150 3, 150 4, 150 4, 150 4, 150 4, 150
i:
system composition' (Torr) CH4 O2 NH, 3.7 4.1 5.1 4.6 5. I 4.8 5.1 4.5 4.0 3.7 5.1 4.9 3.7 3.7 5.1 4.3
4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5
21.3
-
21.3 -
NMe3 -
-
21.3 21.3 -
-
21.3 -
21.3 -
21.3
-
21.3 -
-
I
61.2 56.7 56.8 55.6 59.7 59.3 58.8 57.4 63.0 63.6 62.8 61.2 54.5 44.5 48.2 47.6
27.7 (72) 29.1 (67) 31.5 (73) 32.0 (72) 23.8 (59) 24.4 (60) 26.0 (63) 26.0 (61) 24.0 (65) 24.4 (67) 25.7 (69) 26.4 (68) 25.0 (55) 31.7 (57) 29.5 (57) 29.0 (55)
9.4 (24) 11.0 (25) 9.5 (22) 9.8 (22) 16.5 (41) 16.3 (40) 15.2 (37) 16.6 (39) 13.0 (35) 12.0 (33) 11.6 (31) 12.4 (32) 20.5 (45) 23.8 (43) 22.3 (43) 23.4 (45)
Me 1.7 (4) 3.2 (7) 2.2 (5) 2.6 (6) -
-
total absolute yieldC(%) 99 98 90 88 99 97 89 88 39 37 32 30
58 61 34 38
"All systems contained ca. 1.5-2.0 mCi CT,, diluted with CH, to a specific activity of 18.7 Ci mol-'. *Ratio of the activity of each product to the combined activity of all products identified. Relative composition of methylated products given in parentheses. Each value is the average of several determinations, with an uncertainty level of ca. 5%.
