A Simple Key for Benzylic Mono- and gem-Dibromination of Primary Aromatic Amine Derivatives Using Molecular Bromine [1]

Abstract

Quantitative benzylic mono- and gem-dibromination on primary aromatic amine derivatives have been achieved using molecular bromine and by protecting the amino group as a succinimide moiety. The reactions of N-(o/m/p-tolyl)succinimides 5a-c with 1.25 equivalents of molecular bromine in CCl₄ at room temperature furnished the corresponding benzylic monobrominated products 6a-c in 92-94% yields, while with 2.5 equivalents of molecular bromine in refluxing CCl₄ gem-dibromo products 7a-c were obtained in 94-96% yields. It is also possible to carry out nuclear bromination in these N-protected primary aromatic amines at an alternate site by using suitably substituted aniline derivatives. Thus the reaction of 3 with 1.25 equivalents of molecular bromine in acetic acid gave the desired monobrominated product 4 in nearly 100% yield.

Key words

primary aromatic amines - succinimide derivatives - molecular bromine - benzylic mono-/gem-dibromination

1

NCL Communication No. 6615.

References

• 2a Kirk-Othmer Encyclopedia of Chemical Technology   4th ed., Vol.2:  Kirk RE. Othmer DF. Wiley; New York: 1991.  p.426 
• 2b Ullmann’s Encyclopedia of Industrial Chemistry   5th ed., Vol. A2:  Ullmann F. Gerhartz W. Yamamoto YS. Campbell FT. Pfefferkorn R. Rounsaville JF. VCH; Weinheim: 1985.  p.303 
• 2c Vogel AI. Vogel’s Textbook of Practical Organic Chemistry   5th ed.:  Furniss BS. Stanley B. Longman; Harlow: 1989.  Chap. 6. p.824 
• 2d March J. Advanced Organic Chemistry   4th ed.:  Wiley; New York: 1992.  Chap. 11. p.501 
• 2e Morrison RT. Boyd RN. Organic Chemistry   6th ed.:  Prentice-Hall; New Delhi: 1996.  Chap. 15. p.517 
• 2f Morrison RT. Boyd RN. Organic Chemistry   6th ed.:  Prentice Hall; New Delhi: 1996.  Chap. 22. p.821 
• 2g Morrison RT. Boyd RN. Organic Chemistry   6th ed.:  Prentice-Hall; New Delhi: 1996.  Chap. 23. p.845 
• 3 Gassman PG. Drewes HR. J. Am. Chem. Soc.  1978,  100:  7600 
• 4 Ayyangar NR. Kalkote UR. Nikrad PV. Tetrahedron Lett.  1982,  23:  1099 
• 6 Argade NP. Balasubramaniyan V. Heterocycles  2000,  53:  475 ; and references cited therein
• 7a Mhaske SB. Argade NP. J. Org. Chem.  2002,  67 
• 7b Mangaleswaran S. Argade NP. J. Chem. Soc., Perkin Trans. 1  2001,  1764 
• 7c Mangaleswaran S. Argade NP. J. Org. Chem.  2001,  66:  5259 
• 7d Deshpande AM. Natu AA. Argade NP. Synthesis  2001,  702 
• 7e Mangaleswaran S. Argade NP. J. Chem. Soc., Perkin Trans. 1  2000,  3290 
• 7f Deshpande AM. Natu AA. Argade NP. J. Org. Chem.  1998,  63:  9557 
• 7g Desai SB. Argade NP. J. Org. Chem.  1997,  62:  4862 
• 7h Argade NP. Naik RH. Bioorg. Med. Chem.  1996,  4:  881 
• 8 Balasubramaniyan V. Argade NP. Tetrahedron  1989,  45:  835 
• 9 Balasubramaniyan V. Argade NP. Tetrahedron Lett.  1986,  27:  2487 
• 11 Sheng W. Zhongguo Yiyao Gongye Zazhi  1993,  24:  276 ; Chem. Abstr. 1994, 120, 54281
• 12 Orlemans EOM. Schreuder AH. Conti PGM. Verboom W. Reinhoudt DN. Tetrahedron  1987,  43:  3817 
• 13a Kornblum N. Iffland DC. J. Am. Chem. Soc.  1949,  71:  2137 
• 13b Georgiev VS. Bennett GA. Radov LA. Kamp DK. Trusso LA. J. Heterocycl. Chem.  1986,  23:  1359 
• 14a Coleman GH. Johnson HL. Org. Synth. Coll. Vol. 3   Wiley; New York: 1955.  p.60 
• 14b Conover LH. Tarbell DS. J. Am. Chem. Soc.  1950,  72:  3586 
• 15 Abraham DJ. Kennedy PE. Mehanna AS. Patwa DC. Williams FL. J. Med. Chem.  1984,  27:  967 
• 16 Le Henaff P. Bull. Soc. Chim. Fr.  1968,  4687 
• 17 Mayer R. Hiller G. Nitzschke M. Jentzsch DCJ. Angew. Chem., Int. Ed. Engl.  1963,  2:  370 
• 18a Smith LI. Opie JW. Org. Synth. Coll. Vol. 3   Wiley; New York: 1955.  p.56 
• 18b Foy BD. Smudde RA. Wood WF. J. Chem. Educ.  1993,  70:  322 
• 18c Anderson WK. Dalvie DK. J. Heterocycl. Chem.  1993,  30:  1533 
• 18d Icke RN. Redemann CE. Wisegarver BB. Alles GA. Org. Synth.  1955,  Coll. Vol. 3:  59 
• 18e Campaigne E. Budde WM. Schaefer GF. Org. Synth.  1963,  Coll. Vol.4:  31 
• 19a Yoon NM. Choi J. Synlett  1993,  135 
• 19b Joshi MV. Narasimhan CS. J. Catal.  1989,  120:  282 
• 20a Blickenstaff RT. Brandstadter SM. Foster E. Reddy S. Witt R. Ind. Eng. Chem. Res.  1993,  32:  2455 
• 20b Tzeng YL. Yang PF. Mei NW. Yuan TM. Yu CC. Luh TY. J. Org. Chem.  1991,  56:  5289 
• 21 Danishefsky SJ. Schkeryantz JM. Synlett  1995,  475 ; and references cited therein

1

NCL Communication No. 6615.

5

Ref.,^2a see page 437.

10

Ref.,^2c see page 1265.