RSS-Feed abonnieren
DOI: 10.1055/s-2005-921918
Efficient Syntheses of β-Amino-N-acylbenzotriazoles and Cinnamides through Regioselective 1,4- or 1,2-Addition of Amines to N-Cinnamoylbenzotriazoles
Publikationsverlauf
Publikationsdatum:
28. November 2005 (online)
![](https://www.thieme-connect.de/media/synlett/200520/lookinside/thumbnails/10.1055-s-2005-921918-1.jpg)
Abstract
Amines react with N-cinnamoylbenzotriazoles to afford either β-amino-N-acylbenzotriazoles or cinnamides depending on the structure of the amines. Aromatic amines react with N-cinnamoylbenzotriazoles via 1,4-addition to give β-amino-N-acylbenzotriazoles in good yields. For o-phenylenediamine, the 1,4-addition products were further acylated to provide a facile route to substituted 1,3,4,5-tetrahydro-1,5-benzodiazepine-2-ones. Aliphatic amines, however, react exclusively through the 1,2-addition pathway to produce cinnamides in good yields.
Key words
1,4-addition - 1,2-addition - amines - cinnamides - 1,5-benzodiazepine-2-ones
- For reviews, see:
-
1a
Xu LW.Xia CG.Wu H.Yang L.Zhou W.Zhang Y. Chin. J. Org. Chem. 2005, 25: 167 -
1b
Romanova NN.Gravis AG.Bundel YG. Usp. Khim. 1996, 65: 1170 ; Chem. Abstr. 1998, 128, 179940 -
2a
Bartoli G.Bosco M.Eurico M.Petrini M.Sambri L.Torregiani E. J. Org. Chem. 2001, 66: 9052 -
2b
Shaikh NS.Deshpande VH.Bedekar AV. Tetrahedron 2001, 57: 9045 -
2c
Varala R.Alam MM.Adapa SR. Synlett 2003, 720 -
2d
Yadav JS.Reddy BVS.Asak AK.Narsaiah AV. Chem. Lett. 2003, 32: 988 -
2e
Kawatsura M.Hartwig JF. Organometallics 2001, 20: 1960 -
2f
Azizi N.Saidi MR. Tetrahedron 2004, 60: 383 -
3a
Inaba T,Okada H, andSuzuki R. inventors; Eur. Pat. 775688. ; Chem. Abstr. 1997, 127, 81161 -
3b
Moghaddam FM.Mohammadi M.Hosseinnia A. Synth. Commun. 2000, 30: 643 -
3c
Um I.-H.Lee J.-S.Yuk S.-M. J. Org. Chem. 1998, 63: 9152 -
3d
Makara GM.Ma Y. Tetrahedron Lett. 2001, 42: 4123 -
3e
Tye H. Tetrahedron Lett. 2002, 43: 9421 -
3f
D’Angelo J.Maddaluno J. J. Am. Chem. Soc. 1986, 10: 8112 -
3g
Enders D.Müller SF.Raabe G. Angew. Chem. Int. Ed. 1999, 38: 195 -
3h
Gandelman M.Jacobsen EN. Angew. Chem. Int. Ed. 2005, 44: 2393 -
3i
Fadini L.Togni A. Chem. Commun. 2003, 30 -
3j
Li K.Hii KK. Chem. Commun. 2003, 1132 -
3k
Ahn KH.Lee SJ. Tetrahedron Lett. 1994, 35: 1875 -
4a
Pfau M. Bull. Soc. Chim. Fr. 1967, 1117 -
4b
Kinas R.Pankiewicz K.Stec WJ.Farmer PB.Forster AB.Jarman M. J. Org. Chem. 1977, 42: 1650 - 5
Jenner G. Tetrahedron Lett. 1995, 36: 233 -
6a
Katritzky AR.Lan X.Yang JZ.Denisko OV. Chem. Rev. 1998, 98: 409 -
6b
Katritzky AR.Manju K.Singh SK.Meher NK. Tetrahedron 2005, 61: 2555 -
6c
Katritzky AR.Suzuki K.Wang Z. Synlett 2005, 1656 -
6d
Katritzky AR.Yang Z.Cundy DJ. Aldrichimica Acta 1994, 27: 31 -
6e
Katritzky AR.Lan X. Chem. Soc. Rev. 1994, 23: 363 -
6f
Katritzky AR.Lan X.Fan WQ. Synthesis 1994, 445 -
6g
Katritzky AR.Rachwal S.Hitchings GJ. Tetrahedron 1991, 47: 2683 -
7a
Katritzky AR.Wang M.Zhang S. ARKIVOC 2001, (ix): 19 -
7b
Wang XX.Yu HP.Xu PF.Zheng RW. J. Chem. Res., Synop. 2005, 595 - 8
Katritzky AR.He HY.Suzuki K. J. Org. Chem. 2000, 65: 8210 -
9a
Heininger SA. J. Org. Chem. 1957, 22: 1213 -
9b
Zhong WH.Zhang YM. Chin. J. Org. Chem. 2000, 20: 747 -
9c
Toh TP.Wei LL. Synlett 1998, 975 -
9d
Basu B.Das P.Hossain I. Synlett 2004, 2630 -
9e
Zhuang W.Hazell RG.Jorgensen KA. Chem. Commun. 2001, 1240 -
9f
Matsubara S.Yoshioka M.Utimoto K. Chem. Lett. 1994, 827 - 10
Herpin TF.Kirk KGV.Salvino JM.Yu ST.Labaudinière RF. J. Comb. Chem. 2000, 2: 513 - 11
Nallini A.Saraboji K.Ponnuswamy MN.Venkatraj M.Jeyaraman R. Cryst. Res. Technol. 2005, 40: 622 - 12
Dubey PK.Kumar R.Kumar CR.Grossert JS.Hooper DL. Synth. Commun. 2001, 31: 3439 -
14a
Papa D.Schwenk E.Villani F.Klingsberg E. J. Am. Chem. Soc. 1950, 72: 3885 -
14b
Delaney AD.Currie DJ.Holmes HL. Can. J. Chem. 1969, 47: 3273 -
14c
Alberghina G.Arcoria A.Fisichella S. J. Org. Chem. 1978, 43: 1122
References
Typical Experimental Procedure.
A mixture of aromatic or aliphatic amine (1.1 mmol),
N-cinnamoybenzotriazole (1 mmol) and Et3N (1 mL) was refluxed in dry THF (10 mL) for the indicated time (monitored by TLC). Removal of THF and Et3N under reduced pressure afforded a residue, which was separated by preparative TLC on silica gel with EtOAc and cyclohexane (1:6) as eluent to afford β-amino N-acylbenzotriazoles. Alternatively, Et2O was added to the reaction mixture, followed by washing with sat. Na2CO3 solution, drying with anhyd MgSO4 and removal of the solvent under reduced pressure. The residue solidified and was recrystallized from EtOH or other appropriate solvent to afford pure α,β-unsaturated amides.
Physical Data of Selected Compounds.
1-{(1
H
-Benzo[
d
][1,2,3]triazol-1-yl)-3-phenyl-3-phenyl-amino}propan-1-one (3a).
Mp 167-169 °C. IR: νmax = 3299 (NH), 3257, 3138, 3085, 1682 (C=O), 1602, 1548 (Ar) cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.02 (d, 1 H, J = 8.2 Hz, ArH), 7.97 (br, 1 H, NH), 7.23-7.46 (m, 12 H, ArH), 7.03-7.06 (m, 1 H, ArH), 6.45 (dd, 1 H, J = 5.2, 10.0 Hz, CH), 4.09 (dd, 1 H, J = 10.0, 15.2 Hz, CH), 3.46 (dd, 1 H, J = 5.20, 15.2 Hz, CH). 13C NMR (100 MHz, CDCl3): δ = 167.5, 146.0, 138.7, 137.7, 129.1, 129.0, 128.9, 128.6, 127.7, 126.6, 124.5, 124.4, 120.2, 119.6, 110.1, 56.0, 43.6. Anal. Calcd for C21H18N4O: C, 73.67; H, 5.30; N, 16.36. Found: C, 73.36; H, 5.36; N, 16.28.
1,3,4,5-Tetrahydro-4-aryl-1,5-benzodiazepine-2-one (4a).
Decomposed beyond 83 °C. IR: νmax = 3345 (NH), 3178, 3060, 2958, 2904, 1666 (C=O), 1596 (Ar) cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.92 (s, 2 H, ArH, NH), 7.30-7.45 (m, 5 H, ArH), 7.07-7.09 (m, 1 H, ArH), 6.94-6.96 (m, 1 H, ArH), 6.85 (d, 1 H, J = 8.0 Hz, ArH), 5.04 (dd, 1 H, J = 4.0, 12.0 Hz, CH), 3.85 (br, 1 H, NH), 2.91 (dd, 1 H, J = 12.0, 4 Hz, CH), 2.78 (dd, 1 H, J = 12.0, 4.0 Hz, CH). 13C NMR (100 MHz, CDCl3): δ = 172.8, 144.2, 138.5, 129.0, 128.2, 127.7, 126.3, 126.1, 122.6, 121.6, 121.2, 63.5, 41.8. Anal. Calcd for C15H14N2O: C, 75.61; H, 5.92; N, 11.76. Found: C, 75.38; H, 5.97; N, 11.69.
(E
)-
N
-Cyclohexyl-3-
p
-tolylacrylamide (5a).
Mp 166-167 °C. IR: νmax = 3288 (NH), 3072, 3025, 2927, 2853, 1660 (C=O), 1618, 1553 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.57 (1 H, d, J = 15.6 Hz, C=CH), 7.39 (2 H, d, J = 8.0 Hz, ArH), 7.16 (2 H, d, J = 8.0 Hz, ArH), 6.31 (1 H, d, J = 15.6 Hz, C=CH), 5.44 (1 H, br d, J = 6.1 Hz, NH), 3.90-3.92 (1 H, m, CH), 2.36 (3 H, s, CH3); the following peaks all result from cyclohexyl: 1.97-2.00 (2 H, m), 1.72-1.75 (2 H, m), 1.36-1.43 (2 H, m), 1.14-1.25 (4 H, m). 13C NMR (100 MHz, CDCl3): δ = 165.1, 140.6, 139.8, 132.2, 129.5, 127.7, 120.1, 48.3, 33.3, 25.6, 24.9, 21.4. Anal. Calcd for C16H21NO: C, 78.97; H, 8.70; N, 5.76. Found: C, 78.66; H, 8.81; N, 5.71.