J. Org. Chem. 1984,49, 1959-1964
1959
Reactions of Azines. 7. Synthesis and Thermal Rearrangement of 1-0~0-3,4-diaza-2,4,6-heptatrienes and l-Oxo-3,4-diaza-2,4,6,7-octatetraenes (Allenyl Azines) Edward E. Schweizer* and Kee-Jung Lee Department of Chemistry, University of Delaware, Newark, Delaware 19716
Received October 17, 1983 The preparation and "criss-crossncycloaddition reactions of l-oxo-3,4-diaza-2,4,6-heptatrienes 5 obtained from 1-substitutedtriphenylphosphonium2- [ (2-oxo-l,2-diphenylethylidene)hydrazono]propylides 23a-e and formaldehyde, benzaldehyde, or p-nitrobenzaldehydeto give simple substituted pyrazoles 8 are examined (66-89% yield). The 1-benzoyl-substitutedphosphorane 23f fa& in the olefination reaction, giving only the corresponding acetylene 24. A similar allenylization reaction of 23a,d,e gives the corresponding pyrazolo[5,1-c][ 1,4]oxazines 27 in 65-81 % yield with ketene, phenylketene, and benzylketene via the intermediate l-oxo-3,4-diaza-2,4,6,7octatetraenes 25. The benzoyl-substitutedylide 23f only reacts with unsubstituted ketene 10a to give 27d in 21% yield.
Electrocyclic cyclizations of azines and a$-unsaturated azines are well-known in the 1 i t e r a t ~ r e . l We ~ ~ have previously shown3a simple, general synthesis of the pyrazole ring system based on the thermolysis of a'-oxo-a,P-unsaturated azines 5, which were derived from the reactions of a-diketone monohydrazones 1, with a,@-unsaturated aldehydes and ketones 2 or from the reactions of a-unsubstituted-phosphonium ylide 3, with aldehydes 4 (Scheme I). We have also shown2that cumulated azines, of structure 11, are excellent synthons for a variety of fused pyrazoles (Scheme 11). Cyclization reactions via the azomethine imine 12 have been shown to give pyrazolo[5,1-c][1,4]oxazines 13, 4,9-dihydropyrazolo[1,5-b]isoquinolines214 and 4,5-dihydropyrazolo[1,5-a]pyridines4 15, as well as 4,9-dihydropyrazolo[1,5-b]isoquinolines5 16. The cumulated azines 11 were prepared by allowing the corresponding phosphoranes 9 to react with ketenes 10. Our continued interest in cumulated azines as synthons for fused pyrazole ring systems led us to study the reaction of isocyanate 17 with the phosphorane 9a.6 As expected, the intermediate betaine 18 did not collapse to the hoped for ketimine 20 but transferred a proton to give the stabilized amide phosphorane 19 (Scheme 111). Transformations of the type 18 to 19 are well-known in the litera t ~ r e . However, ~ early in this century Staudinger and Meye9 showed that phosphoranes without a proton on the a-carbon atom underwent normal olefination reactions. Therefore, a suitable a-substituted phosphorane was made for use in the preparation of unsaturated azines. Alkylation and acylation of phosphorane 9a and formation of the corresponding phosphoranes 23 have been rep~rted.~ We now report the results of the reactions of a-substituted-phosphoranes 23 with aldehydes 4 and ketenes 10. We report the study of the reactions of 23 with isocyanates 17 in the accompanying paper. (1) Wagner-Jauregg, T. Synthesis 1976, 349. (2) Schweizer, E. E.; Evans, S. J. Org. Chem. 1978,43,4328 and ref-
erences cited therein. (3) Albright, T. A.; Evans, S.;Kim, C. S.;Labaw, C. S.; Russiello, A. B.; Schweizer, E. E. J. Org. Chem. 1977, 42, 3691 and references cited therein. (4) Schweizer. E. E.: Haves. J. E.: Hirwe. S. N. unmblished results. ( 5 ) Schweizer,'E.E.; Hsueh, W.; R&eingold,A. L.; D A e y , R. L. J. Org. Chem. 1983,48, 3889. (6) Evans, S. Ph.D. Thesis, University of Delaware, Newark, DE, June
Scheme I
R1
R'
+ /N
7
N%Rt5'
R1 H
-
R3
R 5
A
R5
R3
R4
6
N&RSN
3
\ I R4
R3
7
R' R2 "0
RR5 R4
R3
"
8
Results and Discussion Phosphoranes 23a-d were allowed to react with benzaldehyde and p-nitrobenzaldehyde under reflux in acetonitrile and gave colorless pyrazoles 8 in good yields (Table I). Attempted reactions of the benzyl-substituted phosphorane 23e with benzaldehyde or p-nitrobenzaldehyde were unsuccessful even when higher boiling solvent (toluene) was employed. The reduced reactivity may be due to either the steric effect of the a-benzyl group or the stabilizing effect that the benzyl group may have on the phosphorane. In all cases except one, the starting material was recovered unchanged. A reaction occurred successfully only when gaseous formaldehyde was passed over the solution of 23e in acetonitrile. An 88% yield of 8f was obtained. The benzoyl-substituted phosphorane 23f did not give a pyrazole product in either polar (CH3CN) or nonpolar (benzene) solvent under reflux conditions with any aldehyde, even formaldehyde. Only ylide 23f was recovered. The benzoyl group diminishes the nucleophilicity of the a-carbon enough to prevent reaction. But at the higher temperature (toluene solvent) phosphorane 23f gave the acetylenic azine 24 (Scheme IV). The formation of acetylenes from unsaturated betaines is a well-documented rea~tion.~~JO Attempted thermal rearrangement of the
1977..
(7) Ohshiro, Y. Mori, Y.; Komatsu, K.; Agawa, T. J. Org. Chem. 1971, 36, 2029. Froyen, Acta. Chem. Scand., Ser. B 1974, %E, 586. (8) Staudinger, H.; Meyer, J. Chem. Ber. 1920,53, 72. (9) (a) Schweizer, E. E. Lee, K. J. J . Org. Chem. 1982,47, 2768. (b) Lee, K. J. Ph.D. Thesis, University of Delaware, Newark, DE, 1983.
(10)Trippett, S.; Walker D. M. J . Chem. SOC.1959, 3874. Gough, S. T. D.; Trippett, S.Proc. Chem. SOC. 1961, 302. Gough, S. T. D.; Trippett, S. J. Chem. SOC.1962, 2333. Markl, G. Chem. Ber. 1961, 94, 3005. Bestmann, H. J.; Geismann, C. Liebigs Annl. Chem. 1977, 282.
0022-3263/84/1949-1959$01.50/00 1984 American Chemical Society
1960
Schweizer and Lee
J. Org. Chem., Vol. 49, No. 11, 1984 Scheme I1
-
RYK"'
PPh3
9a, R = Ph; R' = PhCO b, R = H; R' = ArCH=CH c, R = Ph; R' = Ph or CH,
N\
I
13
12a
r
phAP -
\
R2R3C=C=0
10
I
R2
L
r
H
R3 = Ph
R'
Ph
N'
14
12a
F *,:
NFR3
L
lla-c
+
15
12b
r
1
L
J
16
12c
Scheme IV
Scheme 111 Ph + o p -h
o + Ph l
W
23f
24 no reaction
23a, R = CH, b. R = C,H. c; R = n-k,k, d, R = H,C=CHCH, e. R = PhCH, f , R = PhCO-
acetylenic azine 24 was unsuccessful (up to 200 OC,17 h). The methyl- (23a), allyl- (23d), and benzyl-substituted (2313)azinephosphonium ylides reacted completely at room temperature in benzene with ketene (loa) and phenylketene (lob). Heating of the initial Wittig reaction mixture without isolation of 25 gave the corresponding pyrazolo[5,1-c][1,4]oxazines 27 in 65-73% yield (Scheme V). The ylides 23a, 23d, and 23e did not react a t room temperature with benzylketene (1Oc); however, under re-
fluxing conditions (benzene) the corresponding pyrazolo species 27 were obtained in 72-81% yield. The attempted reaction of the benzoyl ylide 23f with a variety of substituted ketenes failed. Only the parent ketene 1Oa gave a reaction under the conditions employed. The pyrazolo[5,1-c][1,4]oxazine 27d was obtained in only 21% yield. Thus the utility of a-substituted keto azine phosphoranes 23a-f for the preparation of allenyl keto azines 25 which undergo "criss-cross" cycloaddition' reactions under thermolysis to give pyrazolo[5,1-c][1,4] oxazines 27 has been demonstrated. The inhibiting effect of electrophilic groups on the reaction has also been demonstrated. Further utility of cumulated azines as synthons for the fused pyrazolo moiety will be demonstrated in forthcoming papers. Experimental Section Melting points were obtained on a Thomas-Hoover Unimelt capillary apparatus and were uncorrected. IR spectra were recorded on a Unicap SP 1100 infrared spectrophotometer and calibrated by comparison with a standard polystyrene film sample.
Reactions of Azines
W
J . Org. Chem., Vol. 49, No. 11, 1984 1961
-m.
h
I .
0;;
i
z-
m
h
h
m
h
m
i
w
cr
0
ni
8
8
8 3 c-
* c-
3 m
3 W
BI m
B
2 8
a nN u" CD
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B
ci 0)
a
F
tCD
8
9
m 3
A
a
v S
u P
Q,
3:
1962 J. Org. Chem., Vol. 49, No. 11, 1984 Table 11. Selected
lSC NMR
Schweizer and Lee
Parameters" for 4H-Pyrazolo[B,l-c][1,410xazines 27 Ph
no. R 27a CH, b CH;=CHCH2
R2
c d e f
PhCHz PhCO CH3 CHz=CHCHz
H
g
H PhCHz CH3 H CH2=CHCH2 H
h i j
PhCH2
27 C2 C3 C3a C4 C6 C7 miscellaneous H 148.9 109.3 139.4 62.4 133.9 120.8 12.0 (C2 CH3), 7.5 (C3 CH3) H 148.7 111.4 139.6 62.4 133.7 120.8 12.1 (C2 CH3), 27.3 (CHZCH=CHz), 136.0 (CHZCH=CHZ), 115.4 (CHZCH=CHJ H 148.6 113.0 139.9 62.4 133.6 120.8 12.3 (C2 CH3), 29.3 (CHzPh) H 150.9 116.1 142.4 63.1 133.4 120.1 14.3 (C2 CH3), 213.6 (COPh) Ph 148.8 110.2 137.9 74.7 133.7 120.3 11.9 (C2 CH3), 7.2 (C3CHJ 149.0 112.4 138.2 74.7 133.8 120.5 12.3 (C2 CH3), 27.2 (CHZCH=CHZ), 135.6 Ph (CHZCH=CHz), 115.2 (CHZCH=CHZ) Ph 149.1 113.7 138.1 74.6 133.7 120.4 12.5 (C2 CH3), 28.9 (CHZPh) PhCHz 148.5 110.0 136.9 73.7 134.1 119.7 12.0 (C2 CH3), 6.9 (C3 CH3), 40.2 (C4 CHZPh) PhCHz 148.6 111.5 137.0 73.4 133.9 119.7 12.2 (C2 CH3), 27.0 (CHZCH=CHz), 135.7 (CH&H=CH2), 115.3 (CH&H=CHz), 40.1
