1440 J. Org. Chem., Vol. 40, No. 10, 1975
Kascheres and Rodrigues
Reaction of Diphenylcyclopropenone with 2-Aminopyridines. Synthetic and Mechanistic Implications Albert Kascheres* and J. August0 R. Rodrigues Instituto de Quimica, Universidade Estadual de Campinas, Campinas,SP, Brasil13.100 Received November 5,1974 Diphenylcyclopropenone (1) reacts with 2-aminopyridines (2) in ether to produce cis-2,3-diphenylacrylamides (3) and insoluble cis-3,4-dihydro-3,4-diphenyl-2H-pyridd 1,2-alpyrimidin-2-ones(4), which in chloroform solution readily rearrange to 3. In methanol, a slow reaction occurs, eventually forming 3 and 5 , the stable trans isomers of 4. During shorter reaction times, mixtures of 3,4, and 5 were observed. A lack of reactivity shown by aniline and 2-amino-6-methylpyridine suggests initial nucleophilic attack by the aminopyridine ring nitrogen on C-2 of the cyclopropenone. The mechanistic pathway of the reaction is discussed. The reactions of nucleophilic reagents with the electrophilic cyclopropenone ring have been described in terms of “carbonyl addition” or “conjugate addition” pr0cesses.l Thus, diphenylcyclopropenone (1) reacted with diethylamine to give a carbonyl addition product (eq 1),2while reaction with phenyllithium afforded a conjugate addition product, albeit in low yield (eq 2).3 The proposed ketene
+ Et,” Ph hP‘
-
Ph )C=C(C,NEt, H
5
n
iO N H , 2
PhAPh 1
-+
R
R
Ph
(1)
II
1
Rz = Phi R3 = R, = H 5, R, = R4 = Ph; R2 = R3 = H
4, R1 =
0
0
II c
1
+
PhLi
% Oo, N2 KHPP04
II
Ph‘CH-C-Ph Ph’
+
/Cod Ph,CHCH ‘Ph
(2)
intermediate (eq 2) was detected spectroscopically a t -70’. T h e reaction of 1 with ammonia at -78” formed an unusual conjugate addition product (eq 3).4 -0
1
+ NH,
Ph 1+
CHo
0 N’
Ph’
Ph
/NH2
‘C=C
-+
+
(3)
‘Ph
IPh
% &Ph
(4)
A.
‘OCOC(Ph)=CHPh Recently, a carbonyl addition product (40% yield) was identified in the reaction of 1 with pyridine (eq 4).j Our interest in the chemical behavior of cyclopropenones6 made it desirable to explore the possibility of participation of a “conjugate addition” mode in the reaction of pyridine by appropriately substituting the nucleus with a second functional group capable of intercepting a reactive (ketene) intermediate. The 2-aminopyridine system was chosen as a probe for this pathway with emphasis on reaction conditions, structure of products, and mechanistic implications.
Results and Discussion Diphenylcyclopropenone (1) underwent a smooth reaction with a variety of 2-aminopyridines (2) (see Table I) a t room temperature. An ether solution of the reagents began to deposit a white solid after 10 min. After 17 hr, removal of the solvent from the ether-soluble portion a t reduced
pressure afforded 3. The structure assignment was suggested by the infrared spectra (CHClS), which exhibited prominent absorption in the 3400- and 1675-cm-l regions. In addition, the NMR spectra of 3a, 3c, and 3d showed large paramagnetic shifts for H-3 (on the order of -2 ppm) in excellent agreement with the “formylation” deshielding shifts reported for the endo forms of 2-formylaminopyridines.’ Finally, the cis relationship of the phenyl groups in 3 was indicated by the presence of a sharp, one-hydrogen singlet a t 6 8.0.8 Hydrolysis of 3 (ethanolic KOH) gave 2 and cis2,3-diphenylacrylic acid, both isolated in quantitative amounts. The ether-insoluble material proved to be unstable in solution. The NMR spectra of freshly prepared samples (CDC13) showed a pair of doublets a t 6 4.3 and 5.3 (1 H each, J = 7 Hz). The spectra of the same solutions after 15 hr a t room temperature were nearly identical with those of 3. I t was possible to isolate 3 from chloroform solutions in better than 80% yield after recrystallization. These observations led to the formulation of the products as 3,4-dihydro-2H-pyridol1,2-al pyrimidin-2-ones (4). A conformational representation of 4 shows that bonds a and b are capable of an antiperiplanar arrangement, thus facilitating a concerted olefin-forming elimination reaction.9 The cis nature of the bulky phenyl groups and the unfavorable H-6-phenyl interaction are other features which may contribute to
R Ph
H
A
I
0
the instability of 4. I t was not possible to generate 4 from an ether solution of 3, leading us to believe that 4 is, in fact, a primary product of the reaction. In methanol, reaction of 1 with 2 proceeded slowly a t
J. Org. Chem., Vol. 40, No. 10, 1975
Reaction of Diphenylcyclopropenone with 2-Aminopyridines
1441
Table I Formation of Amide 3 and 3.4-Dihydro-2H-pyrido[1,2-a]pyrimidin-2-one (4 or 5) in Ether and Methanol Reaction Isomerization
2-Aminopyridine
In ether a
In methanol a
(% yield t 2%)
(% yield f 2%p
2a (R = H)
3a 4a 3b 4b 3c
(75) (16) (58) (22) (62) 4c (28) 36 (70) 4d (17)
2b (R = 3-Me) 2c (R = 4-Me)
2d (R = 5-Me)
3a 5a 3b 5b 3c 5c
of 4 in methanol Time, days
(75) (11) (41) (44) (60)
(% yield
3a (71) 5a (22) 3b (38) 5b (55) 8c (58) 5c (37) 36 (75) 5d (16)
10 24 5
(30) 36 (80)
* 2%)
10
5d (10)
Solution contained 2-mmol quantities of reagents in 15 ml of solvent. Yield based upon unrecovered minopyridine. The re ctions of all 2-aminopyridines gave small quantities of the methyl ester of cis-2,3-diphenylacrylic acid (
