reaction conditions and utilizing heterocyclic-2-diazonium
species (eq 2), free radical intermediates appear to be
involved only to a minor degree.10-12 In addition to the novel
mechanistic aspects, these reactions have synthetic utility;
the ring-centered heterocyclic cations (4) formed react with
aromatic or heterocyclic compounds to produce, in one step,
interesting derivatives (eq 3) that would normally be syn-
thesizable only by multistep approaches.13
The formation of the heterocyclic carbocations in these
studies appears to involve the formation of nitrogen-separated
ion pairs (4) in which insulation of the cation from the
counterion extends the lifetime of the cation sufficient to
allow reactions with the molecules in the solvent cage1,2,7
and to depend on (1) stabilization of the carbocation via
electron delocalization from an adjacent electron donor atom
(as in 4) and (2) the use of low-temperature reaction
conditions that serve to minimize free-radical formation.10
The heterocyclic carbocations are also capable of hetero-
cyclating nucleophiles such as amines (eq 4).14
Data are presented for reactions of 2-pyridine (1a),
2-pyrazine (1b), 2-pyrimidine (1c), and 6-purine (10a)
diazotates (Table 1 and text). As in the case of alkyl
analogues,1,2,7 the carbocations formed as reaction intermedi-
ates (eq 2) have the option of reacting with the counterion
or with essentially any nucleophile in the vicinity (eq 3). In
unreactive solvents (e.g., CHCl3 in the case of diazotates
1b,c), the products consist of only the corresponding hydroxy
(5) and acetoxy (6) compounds, indicative of an ionic
pathway;10 the former compound ostensibly arose from
aqueous interception of the aryl cation whereas formation
of the latter compound is consistent with ion pair collapse
in species 4. In the presence of aromatic or heterocyclic
compounds (eq 3), however, a surprisingly competitive
reaction of the highly active deaminatively formed carbo-
cation with those π-donors occurs (Table 1).
This reaction and those listed in Table 1 are satisfactorily
accounted for by the carbocation mechanism (eq 2). A
nucleophilic displacement of nitrogen from the diazonium
ion would ostensibly lead to the same products, but the high
reactivity exhibited by the electrophilic species formed in
(10) (a) At the low-temperature conditions (25 °C) used in our study of
diazotates 1a-c, trace amounts of pyrazine (maximum yield < 1%) were
formed (by hydrogen abstraction from chloroform)11 when a mixed solvent
of chloroform-benzene (1/1, v/v) was used in the protonation of diazotate
1b. (b) In the absence of the stabilizing electron delocalization from the
R-position, free-radical reactions do take precedence (eq 5). Indeed, in many
The product distributions are a function of the reactivity
of the carbocation and the nucleophilicities of the counterion
and the trapping reagent used.1b,c The yields of the benzene-
derived products are modest, while, in accordance with the
principle just stated, the yield in the case of N-methylpyrrole
(eq 2) is considerably higher (∼56%; Table 1). In a particular
case the yield of a desired compound may be low, but that
aspect is compensated for by the one-step nature of the
reaction, the mild conditions employed, and the limited
number of byproducts formed; these characteristics recom-
mend this approach for microscale syntheses in particular,
especially where the value of the amine (precursors) is a
consideration.
cases, free-radical reactions have been deliberately courted in syntheses
analogous to the Gomberg-Bachmann reaction (usually at elevated
temperatures).12 In the reaction of 1a in CHCl3, ∼15% of 2-chloropyridine
was also formed (8% chlorine transfer was noted with 10a). Since hydrogen
transfer was not observed, the chloropyridine was probably the product of
chloride ion abstraction from the solvent by the carbocation7b (Note: radicals
normally abstract hydrogen much faster than chlorine.11) Additionally, no
solvent-derived product was observed in the reaction of 1a and acetic acid
in nitrobenzene. A free-radical mechanism would have resulted in nitroben-
zene-derived products. Generally, making the aromatic ring electron-poor
accelerates reaction with nucleophilic radicals, see: Fossey, J.; Lefort, D.;
Sorba, J. Free Radicals in Organic Chemistry; John Wiley & Sons: New
York, 1995; p 168.
(11) Bridger, R. F.; Russell, G. A. J. Am. Chem. Soc. 1963, 85, 3754-
3765. Cadogan, J. I. G.; Hey, D. H.; Hibbert, P. G. J. Chem. Soc. 1965,
3939-3949.
(12) Free-radical reactions of diazotates in which aryl derivatives such
as 7 are formed have been reported (higher temperatures used), but the
desired products are accompanied by more complex, unresolved sets of
byproducts (Vernin, G.; Metzger, J.; Pa´rka´nyi, C. J. Org. Chem. 1975, 40,
3183-3189. McKenzie, T. C.; Epstein, J. W. J. Org. Chem. 1982, 47,
4881-4884).
In the case of the purine-based diazotate (10a), analogous
sets of products are formed in chloroform at 25 °C (10b,c,e,f
in yields of 78, 12, 8, and 2%, respectively) and in benzene
(10b-d in yields of 76, 8, and 16%, respectively).
(8) Intermediates 2b,c, or tautomers,9 with half-lives at 25 °C of a few
minutes can be detected immediately after the addition of acetic acid to the
diazotate (1H NMR).
(9) Butler, R. N.; Lambe, T. M.; Tobin, J. C.; Scott, F. L. J. Chem. Soc.,
Perkin Trans. 1 1973, 1357-1361.
(13) For example, in the case of compound 8: (a) Mullen, G. B.;
Georgiev, V. S. J. Org. Chem. 1989, 54, 2476-2478. (b) Savoia, D.;
Concialini, V.; Roffia, S.; Tarsi, L. J. Org. Chem. 1991, 56, 1822-1827.
(14) A related experiment with 2-aminopyridine (10.9 M) in a water
medium yielded 12% of 2,2′-dipyridylamine.
1958
Org. Lett., Vol. 1, No. 12, 1999
Song, Fenhong
