摘要:

Stable ó-adducts of 6-phenyl-1,2,4-triazine 4-oxides with phenols Dmitry N. Kojevnikov,a Eugeny N. Ulomsky,a Vladimir L. Rusinov,a Oleg N. Chupakhin*a and Hans Neunhoefferb a Department of Chemistry Ural State Technical University 620002 Ekaterinburg Russian Federation. Fax +7 3432 74 0458; e-mail azine@htf.rcupi.e-burg.su b Technische Hochschule D-64287 Darmstadt Germany The formation of some very stable adducts of phenols with 1,2,4-triazine 4-oxides and their oxidation has been studied. The formation of adduct 3 (Scheme 1) is usually postulated for nucleophilic substitution reactions of hydrogen in aromatic N-oxides 1 and N-alkoxy and N-acyloxyazinium salts 2. Aromatization of the adducts 3 proceeds usually via two general pathways.1 The first (A) results in substituted N-oxides and is achieved in the presence of oxidizing agents.The reactions of quinoline and phthalazine N-oxides with cyanide ion2 or CH-active compounds,3 as well as amination of pyridazine4 or 1,2,4-triazine5 in liquid ammonia are examples of this type of reaction. The second path (B) involves auto-aromatization by elimination of an HOE fragment from the adduct 3 resulting in the formation of substituted azines 5. According to this pathway the following reactions are known to proceed interaction of quinoline N-oxides with organomagnesium compounds,6 cyanation of 1-methoxypyridinium salts,7 as well as the reaction of quinolinium or pyridazinium O-acylated salts generated in situ with alkoxides thiolates amines CH-active compounds indoles or dimethylaniline.8 Nu N + [O] – O EX NuH (A) 4 + + –HX – H Nu X (B) – N OE N OE N O –HOE N 1 2 3 Nu 5 E = R RCO H Scheme 1 We have succeeded for the first time in recording and isolating the adducts of type 3 (Nu = 2,4-dihydroxyphenyl 2,4,6-trihydroxyphenyl 2-hydroxyphenyl 3,5-dimethyl- 4-hydroxyphenyl 2-ethoxyphenyl or 4-ethoxyphenyl E = H). Resorcinol was found to react readily with 6-aryl- 1,2,4-triazine-4-oxides 6a–c in the presence of trifluoroacetic acid yielding 6-aryl-5-(2,4-dihydroxyphenyl)-4,5-dihydro- 4-hydroxy-1,2,4-triazines 7a–c (Scheme 2). The reaction of resorcinol with a two-fold excess of triazine N-oxide 6a leads to the addition of two triazine molecules yielding 2,4-bis-(6'-phenyl-4',5'-dihydro-4'-hydroxy-1',2',4'-triazin-5'-yl)- 5-hydroxyphenol 8a.Interaction of 6-aryl-1,2,4-triazine 4-oxides 6a,b with phenol affords only ortho-products 9a,b. At the same time a similar reaction with phenetole leads to a mixture of ortho- and parasubstituted phenetoles 10a 11a in the ratio 1:1. The unusual1 regioselectivity for the reaction of N-oxides 1 with phenol can obviously be explained by the formation of hydrogen bonds with the N-oxide fragment; these H-bonds determine the orientation of the reagents. Use of 2,6-dimethylphenol in the same reaction gave 6-aryl-5-(3',5'-dimethyl-4'-hydroxyphenyl)- 4,5-dihydro-4-hydroxy-1,2,4-triazines 12a,b (Scheme 2).† The adducts yielded are fairly stable this stability being possibly determined by hydrogen bonds between the phenols and the N-oxide hydroxy groups.Thermal dehydration (pathway B Scheme 1) by refluxing in butanol DMF or trifluoroacetic acid does not take place. At the same time oxidation of the adducts (pathway A Scheme 1) proceeds very readily yielding oxidized products in practically theoretical amounts. Treatment of compounds 7a,b 12a,b with potassium permanganate leads to the 6-aryl-5-R-1,2,4-triazine 4-oxides 13a,b 14a,b (Scheme 2) thus confirming that this simple method can be used for modification of 1,2,4-triazines with retention of the N-oxide group. † General procedure for 7a,b 9a,b 10a 11a 12a,b. Equimolar amounts of the triazine 4-oxide 6a,b and corresponding phenol were dissolved in a mixture of CH2Cl2–trifluoroacetic acid 3:1 and left at room temperature for 0.5–5 h.Triethylamine was added and the resulting precipitate was filtered off and recrystallized from ethanol. General procedure for 13a,b 14a,b. The adduct 7a,b or 12a,b (3 mmol) and potassium permanganate (2 mmol) were mixed at room temperature in 100 ml of acetone for 1–2 h. After removal of magnesium oxide the solution was evaporated and the residue recrystallized from ethanol. Spectral data for the compounds obtained. For all compounds satisfactory analytical data were obtained. For 7a mp > 300 °C 1H NMR ([2H6]DMSO) d/ppm 6.05 (s 1H H5) 6.32 (dd ,1H) 6.42 (d 1H) 7.15 (d ,1H) 7.3–7.9 (m 5H Ph) 9.4 (br. s 1H OH) 12.3 (br. s 2H 2OH); MS m/z 283 (22.3 M+) 265 (38.2) 236 (12) 224 (22.7) 210 (100) 181 (20) 165 (10) 152 (33) 136 (40).For 7b mp > 250 °C; 1H NMR ([2H6]DMSO) d/ppm 6.00 (s 1H H5) 6.10–6.47 (m 3H) 7.38–7.72 (m 4H p-Cl-Ph) 8.40 (s 1H H3) 9.4 (br. s 1H OH) 11.5–13.0 (br. s 2H 2OH). For 7c mp > 250 °C; 1H NMR ([2H6]DMSO) d/ppm 2.37 (s 3H C3- Me) 6.22 (dd 1H) 6.25 (s 1H H5) 6.28 (d 1H) 7.21 (d 1H) 7.35– 7.83 (m 5H Ph) 9.6 (br. s 1H OH) 11.8 (br. s 2H 2OH). For 8a mp > 250 °C; 1H NMR ([2H6]DMSO) d/ppm 6.31 (br. s 2H) 6.40 (s 1H) 7.23–7.76 (m 11H) 9.17 (s 2H) 7.0–11.0 (br. s 4H 4OH). 6]DMSO) d/ppm 6.45 (s 1H H5) For 9a mp 184 °C; 1H NMR ([2H 6.6–8.0 (m 9H) 9.21 (s 1H H3). For 9b mp > 250 °C; 1H NMR ([2H6]DMSO) d/ppm 5.71 (s 1H H5) 6.4–7.3 (m 4H) 7.41–7.49 (dd 2H) 7.63–7.77 (dd 2H) 7.95 (s 1H H3).For 10a mp 101 °C; 1H NMR ([2H6]DMSO) d/ppm 1.3–1.5 (t 3H Me) 3.9–4.2 (q 2H CH2) 6.46 (s 1H H5) 6.9–7.9 (m 9H) 9.22 (s 1H H3). For 11a mp 105 °C; 1H NMR ([2H6]DMSO) d/ppm 1.2–1.4 (t 3H Me) 3.9–4.2 (q 2H CH2) 6.30 (s 1H H5) 6.9–7.9 (m 9H) 9.17 (s 1H H3). For 12a mp 243 °C; 1H NMR ([2H6]DMSO) d/ppm 2.13 (s 6H 2Me) 6.16 (s 1H H5) 7.00 (s 2H) 7.4–8.0 (m 5H Ph) 9.14 (s 1H H3) 8.0–10.0 (br. s 3H 3OH). For 12b mp 211–213 °C; 1H NMR ([2H6]DMSO) d/ppm 2.12 (s 6H 2Me) 5.62 (s 1H H3) 6.95 (s 2H) 7.3–8.8 (m 4H p-Cl-Ph) 7.92 (s 1H H3) 8.45 (br. s 1H OH) 10.5–11.5 (br. s 1H OH). For 13a mp > 250 °C; 1H NMR ([2H6]DMSO) d/ppm 6.24 (dd 1H) 6.28 (d 1H) 6.95 (d 1H) 7.41 (s 4H Ph) 9.60 (br. s 3H 2OH H3). For 13b mp > 250 °C; 1H NMR ([2H6]DMSO) d/ppm 6.24–7.00 (m 3H) 7.41 (s 4H p-Cl-Ph) 9.60 (br.s 3H H3 and 2OH) MS m/z 317 (24) 315 (54) 316 (24) 299 (19) 272 (29) 270 (91) 244 (48) 235 (100) 178 (17) 152 (80) 139 (18). For 14a mp 202–204 °C; 1H NMR ([2H6]DMSO) d/ppm 2.08 (s 6H 2Me) 6.98 (s 2H) 7.39 (s 5H Ph) 9.63 (s 1H H3). For 14b mp 233–235 °C; 1H NMR ([2H6]DMSO) d/ppm 2.12 (s 6H 2Me) 6.95 (s 2H) 7.4 (s 4H p-Cl-Ph) 9.63 (s 1H H3). Mendeleev Commun. Electronic Version 1997 1 R6 R5 Ar R6 N N Ar R2 R4 R3 R5 N R N N N + R CF3COOH OH – H R2 R4 O R3 6a–c 7a–c 9a,b 10a 11a 12a,b 4 6a Ar = Ph R = H 6b Ar = p-Cl-Ph R = H 6c Ar = Ph R = Me KMnO acetone CF3COOH 6a Ar Ph Ph N R6 N N N R5 N N N + R N N H H – R2 O R4 OH OH HO HO R3 13a,b 14a,b 8a R6 R4 R3 R2 R Ar R5 Ph Ph Ph 7a 13a 7b 13b 7c 9a 9b 10a Ph Ph Ph H H H H H H H Me Me OH OH OH H H H OEt H H H H H H H H H Me Me OH OH OH OH OH OEt H OH OH H p-Cl-Ph H Me H p-Cl-Ph H H H H p-Cl-Ph H 11a 12a 14a 12b 14b H H H H H H H H H Scheme 2 The research described in this publication was made possible due to grant no.1/68782 from the Volkswagen Foundation. 2 Mendeleev Commun. Electronic Version 1997 References 1 O. N. Chupakhin V. N. Charushin and H. van der Plas Nucleophilic Aromatic Substitution of Hydrogen Academic Press New York San Diego 1994.2 (a) T. Okamota and H. Takahashi Chem. Pharm. Bull. 1971 19 1809; (b) Y. Kobayashi J. Kumadaki and H. Seto J. Org. Chem. 1972 37 7588; (c) Y. Kobajashi J. Kumadaki Y. Hirose and Y. Hanzawa J. Org. Chem. 1974 39 1836. 3 (a) M. Hamana F. Sato Y. Kimura M. Nishikava and H. Noda Heterocycles 1978 11 371; (b) M. Hamana G. Iwasaki and S. Saeki Heterocycles 1982 17 177; (c) G. Iwasaki K. Wada S. Saeki and M. Hamana Heterocycles 1984 22 1811; (d) T. Kato and H. Yamanaka J. Org. Chem. 1965 30 910; (e) M. Colonna L. Greci and M. Poloni J. Heterocycl. Chem. 1980 17 293; (f) M. Hamana and Y. Fujimura Heterocycles 1987 25 229; (g) M. Hamana Y. Fujimura and Y. Nawata Heterocycles 1987 25 235; (h) A. Polak B. Stanovnik M. Tisler and J. Venetic-Fortuna Monatsch. Chem. 1975 106 473. 4 H. Tondis and H. C. van der Plas J. Heterocycl. Chem. 1986 23 621. 5 A. Rykowsky and H. C. van der Plas Synthesis 1985 884. 6 M. Colonna and A. Risaliti Ann. Chim. (Rome) 1954 44 1029. 7 E. Ochiai Aromatic Amine Oxides Elsevier Amsterdam 1967. 8 M. Hamana Croat. Chem. Acta 1986 59 89. Received Moscow 25th September 1996 Cambridge 20th January 1997; Com. 6/06615A

ISSN:0959-9436     

出版商:RSC    

年代:1997

数据来源: RSC