Synthesis of 2-Substituted 4H-3,1-Benzoxazin-4-ones by Thermally Induced Cyclization of N-(2-Benzyloxycarbonyl)phenyl Ketenimines; Oxygen-to-Carbon­ Migration of a Benzyl Group

Abstract

N-(2-Benzyloxycarbonyl)phenyl ketenimines undergo a thermally induced cyclization to give 2-substituted 4H-3,1-benzoxazin-4-ones. These processes involve the formation of a new carbon-oxygen bond and the migration of the benzyl group from the oxygen atom of the benzyloxy unit at the ester function to the terminal carbon atom of the ketenimine fragment.

Key words

azides - ketenimines - cyclizations - rearrangements - benzoxazinones

References

• 1 Mayama S. Tani T. Tetrahedron Lett.  1981,  22:  2103 
• 2a Bouillant M.-L. Favre-Bonvin J. Ricci P. Tetrahedron Lett.  1983,  24:  51 
• 2b Ponchet M. Martín-Tanguy J. Marais A. Poupet A. Phytochemistry  1984,  23:  1901 
• 3 Niemann GJ. Liem J. van der Kerk-van Hoof A. Niessen WMA. Phytochemistry  1992,  31:  3761 
• 4 Teshima T. Griffin JC. Powers JC. J. Biol. Chem.  1982,  257:  5085 
• 5a Alazard R. Béchet J.-J. Dupaix A. Yon J. Biochim. Biophys. Acta  1973,  309:  379 
• 5b Hedstrom L. Moorman AR. Dobbs J. Abeles RH. Biochemistry  1984,  23:  1753 
• 6a Stein RL. Strimpler AM. Viscarello BR. Wildonger RA. Mauger RC. Trainor DA. Biochemistry  1987,  26:  4126 
• 6b Krantz A. Spencer RW. Tam TF. Liak TJ. Copp LJ. Thomas EM. J. Med. Chem.  1990,  33:  464 
• 7 Jarvest RL. Parratt MJ. Debouck CM. Gorniak JG. Jennings LJ. Serafinowska HT. Strickler JE. Bioorg. Med. Chem. Lett.  1996,  6:  2463 
• 8 Gilmore JL. Hays SJ. Caprathe BW. Lee C. Emmerling MR. Michael W. Jaén JC. Bioorg. Med. Chem. Lett.  1996,  6:  679 
• 9 Fenton G. Newton CG. Wyman BM. Bagge P. Dron DI. Riddell D. Jones GD. J. Med. Chem.  1989,  32:  265 
• 10a Clémence F. Martret OL. Collard J. J. Heterocycl. Chem.  1984,  21:  1345 
• 10b Ibrahim SS. Abdel-Halim AM. Gabr Y. El-Edfawy S. Abdel-Rahman RM. J. Chem. Res., Synop.  1997,  154 
• 11a For a review on the synthesis and reactivity of 4H-3,1-benzoxazin-4-ones bearing a carbon substituent at the 2 position see: Coppola GM. J. Heterocycl. Chem.  1999,  36:  563 
• 11b For a review on the synthesis and reactivity of 4H-3,1-benzoxazin-4-ones bearing oxy, mercapto or amino functionalities at the 2-position see: Coppola GM. J. Heterocycl. Chem.  2000,  37:  1369 
• For examples of preparations of 2-substituted 4H-3,1-benzoxazin-4-ones from anthranilic acids, see:
• 12a Bain DI. Smalley RK. J. Chem. Soc. C  1968,  1593 
• 12b Bergman J. Bergman S. J. Org. Chem.  1985,  50:  1246 
• 12c Hauteville M. Ponchet M. Ricci P. Favre-Bonvin J. J. Heterocycl. Chem  1988,  25:  715 
• 12d Parkanyi C. Yuan HL. Stromberg BHE. Evenzahav A. J. Heterocycl. Chem.  1992,  29:  749 
• 12e Atkinson RS. Coogan MP. Cornell CL. J. Chem. Soc., Perkin Trans. 1  1995,  157 
• 12f Khajavi MS. Montazari N. Hosseini SSS. J. Chem. Res., Synop.  1997,  286 
• For examples of preparations of 2-substituted 4H-3,1-benzoxazin-4-ones from N-acylanthranilic acids see:
• 13a Zentmyer DT. Wagner EC. J. Org. Chem.  1948,  13:  967 
• 13b Rabilloud G. Sillion B. J. Heterocycl. Chem.  1980,  17:  1065 
• 13c Conley RA. Barton DL. Stefanick SM. Lam MM. Lindabery GC. Kasulanis CF. Cesco-Cancian S. Currey S. Fabian AC. Levine SD. J. Heterocycl. Chem.  1995,  32:  761 
• 13d Marsham PR. Jackman AL. Barker AJ. Boyle FT. Pegg SJ. Wardleworth JM. Kimbell R. O’Connor BM. Calvert AH. Hughes LR. J. Med. Chem.  1995,  38:  994 
• 13e Mohapatra DK. Datta A. Synlett  1996,  1129 
• For examples of preparations of 2-substituted 4H-3,1-benzoxazin-4-ones from isatoic anhydride see:
• 14a Minami T. Ogata M. Hirao I. Tanaka M. Agawa T. Synthesis  1982,  231 
• 14b Tsubota M. Hamashima M. Heterocycles  1984,  21:  706 
• 15 Larock RC. Fellows CA. J. Org. Chem.  1980,  45:  363 
• 16 Cacchi S. Fabrizi G. Marinelli F. Synlett  1996,  997 
• 17 Larksarp C. Alper H. Org. Lett.  1999,  1:  1619 
• 18a Richman RJ. Hassner A. J. Org. Chem.  1968,  33:  2548 
• 18b Bristow THC. Foster HE. Hooper M. J. Chem. Soc., Chem. Commun.  1974,  677 
• 18c Adam J.-M. Winkler T. Helv. Chim. Acta  1984,  67:  2186 
• 19a Smalley RK. Suschitzky H. Tanner EM. Tetrahedron Lett.  1966,  29:  3465 
• 19b Crabtree HE. Smalley RK. Suschitzky H. J. Chem. Soc. C  1968,  2730 
• 19c Archer JG. Barker AJ. Smalley RK. J. Chem. Soc., Perkin Trans. 1  1973,  1169 
• 20 Reddy GS. Reddy KK. Indian J. Chem., Sect. B  1978,  16:  1109 
• 21 Molina P. Conesa C. Velasco MD. Tetrahedron Lett.  1993,  34:  175 
• 22a Alajarín M. Vidal A. Tovar F. Targets Heterocycl. Syst.  2000,  4:  293 
• 22b Barker MW. McHenry WE. In The Chemistry of Ketenes, Allenes, and Related Compounds   part 2:  Patai S. Wiley Interscience; Chichester: 1980.  p.701 
• 22c Dondoni A. Heterocycles  1980,  14:  1547 
• 23a Molina P. Vidal A. Barquero I. Synthesis  1996,  1199 
• 23b Molina P. Vidal A. Tovar F. Synthesis  1997,  963 ; and references cited therein
• 24a Alajarín M. Molina P. Vidal A. Tetrahedron Lett.  1996,  37:  8945 
• 24b Alajarín M. Vidal A. Tovar F. Arrieta A. Lecea B. Cossío FP. Chem. Eur. J.  1999,  5:  1106 
• 24c Alajarín M. Vidal A. Tovar F. Ramírez de Arellano MC. Tetrahedron: Asymmetry  2004,  15:  489 ; and references cited therein
• 25 Alajarín M. Vidal A. Ortín M.-M. Tovar F. Synthesis  2002,  2393 
• 26 Alajarín M. Vidal A. Tovar F. Conesa C. Tetrahedron Lett.  1999,  40:  6127 
• 27 Alajarín M. Vidal A. Tovar F. Tetrahedron Lett.  2000,  41:  7029 
• 28a Alajarín M. Vidal A. Ortín M.-M. Org. Biomol. Chem.  2003,  1:  4282 
• 28b Alajarín M. Vidal A. Ortín M.-M. Bautista D. New J. Chem.  2004,  28:  570 
• 28c Alajarín M. Vidal A. Ortín M.-M. Bautista D. Synlett  2004,  991 
• 32a Pinhey JT. Schaffner K. Aust. J. Chem.  1968,  21:  2265 
• 32b Arnold RT. Kulenovic ST. J. Org. Chem.  1980,  45:  891 
• 32c Reinaud O. Capdevielle P. Maumy M. Tetrahedron  1987,  43:  4167 
• 32d Andreichikov YS. Gein VL. Ivanenko OI. Brigadnova EV. Maslivets AN. J. Org. Chem. USSR (Engl. Transl.)  1988,  24:  1007 
• 32e Burger K. Gaa K. Geith K. Schierlinger C. Synthesis  1989,  850 
• 32f West FG. Naidu BN. Tester RW. J. Org. Chem.  1994,  59:  6892 
• 32g Desai VN. Saha NN. Dhavale DD. J. Chem. Soc., Perkin Trans. 1  2000,  147 
• 32h Burger K. Fuchs A. Hennig L. Helmreich B. Greif D. Monatsh. Chem.  2001,  132:  929 
• 32i Karche NP. Jachak SM. Dhavale DD. J. Org. Chem.  2001,  66:  6323 
• 33 2-Azidobenzoyl chloride (1a) and 2-azido-5-chlorobenzoyl chloride (1b) were both prepared following the experimental procedure described for 1a: Porter TC. Smalley RK. Teguiche M. Purwono B. Synthesis  1997,  773 
• 34 Taylor EC. McKillop A. Hawks GH. Org. Synth.  1973,  52:  36 
• 35 Pracejus H. Wallura G. J. Prakt. Chem.  1962,  19:  33 

29

Ketenimines 5 and 7 remained unaltered when heated in boiling toluene or boiling ortho-xylene.

30

In the thermal treatment of the N-(2-benzyloxycarbo­-nyl)phenyl ketenimines 5 small amounts of the corres­-ponding 4H-3,1-benzoxazin-4-ones 9 (Figure [3] ) were always formed (8-13%).
Probably, compounds 9 resulted from the hydrolysis of the ketenimine function in the N-(2-benzyloxycarbonyl)phenyl ketenimines 5 to yield the corresponding amides, followed by intramolecular nucleophilic displacement of the benzyloxy group from the ester group by the carbonyl oxygen of the amide function. We tried very hard to exclude water from the reaction mixtures, but probably we did not succeed as the results were invariable, and small amounts of benzoxazinones 9 were always formed.
Compounds 9a (R¹ = H) and 9b (R¹ = Cl) could not be separated from the 4H-3,1-benzoxazin-4-ones 6c [R¹ = H; R² = Ph; Ar = 4-MeOC₆H₄] and 6f [R¹ = Cl; R² = Ph; Ar = 4-MeOC₆H₃], respectively.

31

CCDC 264507 contains the supplementary crystallographic data for 6g. The data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; e-mail:[e-mail]).