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One-pot Synthesis of 1,2,3,4-Tetrafluoroacridines frompentafluorobenzaldehyde1

 

作者: Adrian J. Adamson,  

 

期刊: Journal of Chemical Research, Synopses  (RSC Available online 1997)
卷期: Volume 0, issue 3  

页码: 76-77

 

ISSN:0308-2342

 

年代: 1997

 

DOI:10.1039/a607642d

 

出版商: RSC

 

数据来源: RSC

 

摘要:

N F F F F R N C6F5CH R N F F HN F R R N F F X F Me Me N F a R = H b R = OMe c R = Me d R = But e R = F f R = Cl g R = Br a R = H b R = OMe c R = Me d R = But e R = F f R = Cl g R = Br 4 1 a R = H b R = OMe c R = Me d R = But e R = F f R = Cl g R = Br 7 a X = F b X = 3, 5-Me2C6H3NH 11 12 OMe J. Chem. Research (S), 1997, 76–77 J. Chem. Research (M), 1997, 0530–0555 One-pot Synthesis of 1,2,3,4-Tetrafluoroacridines from Pentafluorobenzaldehyde1 Adrian J. Adamson, R. Eric Banks,* Roy Fields and Anthony E.Tipping* Chemistry Department, University of Manchester Institute of Science and Technology (UMIST), Manchester M60 1QD, UK 1,2,3,4-Tetrafluoroacridines (accompanied in certain cases by their 3-arylamino derivatives) have been prepared in onepot fashion (via formation in situ of the corresponding Schiff bases) by heating pentafluorobenzaldehyde with a 2 molar equivalence of aniline, para-substituted anilines 4-RC6H4NH2 (R=OMe, Me, But, F, Cl, Br) or 3,5-dimethylaniline in boiling o-dichlorobenzene.It seems that 1,2,3,4-tetrafluoroacridine (1a) was first synthesised in the early 1960s from bromobenzene via a low-yield, laborious, multi-step synthesis based on a modified Lehmstedt –Tanasescu rearrangement.2 Since this route involved both 1,2,3,4-tetrafluoro-9(10H)-acridone and 9-chloro- 1,2,3,4-tetrafluoroacridine as intermediates, it possessed potential as a source of several other derivatives of 1,2,3,4-tetrafluoroacridine; however, this opportunity seems not to have been pursued, although the development of other routes to 1,2,3,4-tetrafluoro-9(10H)-acridone (electrochemical oxidation of 2-amino-3,4,5,6-tetrafluorobenzophenone; KF-driven cyclization of 2p-amino-2,3,4,5,6-pentafluorobenzophenone) was undertaken, and this led to the synthesis of octafluoro-9(10H)-acridone.3,4 Of more relevance to the work described in detail1 here are reports concerning fluorinated acridones from Russian researchers in the 1970s, notably that (i) thermal treatment of methyl pentafluorophenyl ketone with aniline affords, inter alia, 3-anilino-1,2,4-tri- fluoro-9-methylacridine5 (a reaction extended later to derivatives of aniline6) and (ii) the preparation of 1,2,3,4-tetra- fluoroacridine (1a) from pentafluorobenzaldehyde and the Grignard reagent PhNHMgBr.7 The work reported here stemmed from a serenedipitous discovery, made during mass spectrometric studies on fluorinated Schiff bases,8,9 that condensation of pentafluorobenzaldehyde with p-anisidine under forcing conditions yields 4-methoxy-N-(pentafluorobenzylidene)aniline (4b) contaminated with, inter alia, a product of molecular formula C14H7F4NO.Having shown by X-ray crystallographic analysis12 that the by-product was 1,2,3,4-tetrafluoro-7-methoxyacridine (1b), the generality of the pentafluorobenzaldehyde –primary arylamine reaction as a route to 1,2,3,4-tetrafluoroacridines carrying no 9-substituent has been probed.We have established that 1,2,3,4-tetrafluoroacridine (1a) and a range of 7-substituted analogues (1b–g) can be produced by heating pre-formed Schiff bases (E)-C6F5CH� NC6H4R-p (4a–g) (from C6F5CHO+H2NC6H4R-p) with the parent aniline H2NC6H4R-p (1:1 molar ratio) or a 1: 2 molar mixture of the aldehyde C6F5CHO and the aniline H2NC6H4R-p (R=H, OMe, Me, But, F, Cl and Br) in boiling toluene or, preferably, 1,2-dichlorobenzene. Except where R=But, F, Cl or Br, substantial amounts of the corresponding 3-anilino-1,2,4-trifluoroacridines (7a–e) are also formed.Inter alia, 1,2,3,4-tetrafluoro-6,8-dimethylacridine (11a) and its 3-(3,5-dimethylanilino) derivative (11b) can be obtained by heating pentafluorobenzaldehyde with 2 molar equivalence of 3,5-dimethylaniline at 180 °C in o-C6H4Cl2, while 1-fluoro-7-methoxyacridine (12) is produced under similar conditions from 2,6-difluorobenzaldehyde and p-anisidine · a conversion which heralds numerous extensions envisioned for this new acridine ring synthesis.The formation of 1,2,3,4-tetrafluoroacridines 1a–g is best rationalized in terms of intramolecular ring closure of 2-arylamino derivatives of Schiff bases 4a–g generated in situ via ortho-SNAr attack on those Schiff bases by the arylamines involved. The 19F NMR spectra of tetrafluoroacridines 1a–g and 11a are unexpectedly simple (four equally intense 17 Hz triplets under routine operating conditions, with digital resolution of 1.6 Hz/point).Techniques used: UV, MS, NMR (1H, 19F, 13C) References: 18 Tables: 4 (yields, mps, elemental analyses and spectrsopic data for products of thermal reactions between C6F5CHO and arylamines) Schemes: 4 Received, 11th November 1996; Accepted, 18th November 1996 Paper E/6/07642D References cited in this synopsis 1 Preliminary communication: A. J. Adamson, R. E. Banks and A. E. Tipping, J. Fluorine Chem., 1993, 64, 5. 76 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.2 P.L. Coe, A. E. Jukes and J. C. Tatlow, J. Chem. Soc. C, 1966, 2020. 3 C. M. Jenkins, A. E. Pedler and J. C. Tatlow, Tetrahedron, 1971, 27, 2557. 4 D. M. Owen, A. E. Pedler and J. C. Tatlow, J. Chem. Soc., Perkin Trans. 1, 1975, 1380. 5 T. N. Vasilevskaya, I. I. Baturina, M. I. Kollegova, T. N. Gerasimova and V. A. Barkhash, J. Org. Chem. USSR, 1971, 7, 1269. 6 T. N. Gerasimova, L. L. Gelumbovskaya, I. I. Baturina and E. P. Fokin, Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk, 1973 (part 2), 88 (Chem. Abstr., 1973, 79, 53161r). 7 T. N. Gerasimova, N. V. Semikolenova and E. P. Fokin, Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk, 1977 (part 2), 142 (Chem. Abstr., 1977, 87, 134160g). 8 W. T. Flowers and P. DeFigueredo, unpublished results. 9 D. J. Bell and W. T. Flowers, unpublished results; D. J. Bell, Ph.D. Thesis, University of Manchester, 1987. 12 A. J. Adamson, Y. Archambeau, R. E. Banks, B. Beagley, M. Helliwell, R. G. Pritchard and A. E. Tipping, Acta Crystallogr., Sect. C, 1994, 50, 967. J. CHEM. RESEARCH (S), 1997

 



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