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Synthesis of fluorine-containing symmetrical N,N-alkylidene bisamides
Journal of Fluorine Chemistry 93 (1999) 69±71
Synthesis of ¯uorine-containing symmetrical N,N-alkylidene bisamides Shizheng Zhu*, Guolin Xu, Qianli Chu, Yong Xu, Chaoyue Qui
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China Received 21 July 1998; accepted 15 September 1998
Abstract Fluorine-containing N,N-alkylidene bisamides RCH(NHCORf)2 (R: H, Aryl; Rf: CF3, CF2Cl, 2,6-C6H3F2) are conveniently prepared in good yields by the reaction of corresponding aldehydes with ¯uorine-containing amides (RfCONH2) in the presence of ¯uoroalkanesulfonic acids R0f SO3H(Rf 0 : CF3, HCF2CF2, ICF2CF2OCF2CF2). # 1999 Elsevier Science S.A. All rights reserved. Keywords: Fluorinated bisamides; Fluoroalkanesulfonic acids; Acidic catalysis
1. Introduction The amide moiety is an important constituent of many biologically signi®cant compounds. Bisamides are of considerable interest in the synthesis of peptidomimetic compounds [1]. Speci®cally, bisamides are key fragments for the introduction of gem-diaminoalkyl residues in retro-inverso pseudopeptide derivatives [2,3] by treatment of the corresponding amide with iodobenzene bistri¯uoroactate PhI(O2CCF3)2 [4,5]. Recently preparation of symmetrical N,N-alkylidene bisamides has drawn attention and many synthetic methods have been reported [6±8]. Usually they are prepared by the direct reaction of aldehydes with the corresponding carboxamide using a strong acid catalyst, e.g. sulfuric acid, a sulfonic acid or hydrochloric acid. However, attempts to use these methods with formamide and trichloroacetamide were unsuccessful [9,10]. To the best of our knowledge, the ¯uorinated analogues RCH(NHCORf)2 have not been reported to date. 2. Experimental Melting points were determined on a Mel±Temp apparatus and are uncorrected. Solvents were puri®ed and dried before use. 1 H NMR (60 MHz) and 19 F NMR (54.6 MHz) spectra were recorded on a Varian-360L instrument or Bruker AM-300 spectrometer with TMS and TFA (CFCl3 TFA 76.8 ppm, and with up®eld positive) as internal and external standards respectively, DMSO-d6 *Corresponding author. Fax: +86-21-6416-6128.
was used as solvent. IR spectra were obtained with an IR-440 Shimadzu spectrophotometer. Low resolution mass spectra were obtained on a Finnigan GC-MS 4021 instrument. Elemental analysis was performed in this Institute. 2.1. General procedure for the preparation of RCH(NHCORf)2 3 2.1.1. Preparation of N,N-phenylidine bis (trifluoroacetyl) amide 3aa Tri¯uoroacetyl amide (1.13 g, 10 mmol) was added into a 25 ml ¯ask containing a solution of benzaldehyde (0.53 g, 5 mmol) CF3SO3H (10 ml) and CH2Cl2 (10 ml). This reaction mixture was stirred and re¯uxed for 24 h. After cooling to room temperature, the crude product 3aa was ®ltered (1.3g, 86%). Recrystallation of the crude bisamide from CH3CN:H2O 4 : 1 gave ®ne colourless crystals. Other ¯uorinated bisamides 3 were similiary prepared. C6H5CH(NHCOCF3)2 3aa: 1 H NMR(DMSO-d6) (ppm): 7.45 (m, 5H, C6H5), 6.60 (s, 1H, CH), 10.0 (broad, 2H, NH). 19 F NMR(CDCl3): ÿ74.3 (s, CF3). IR (nmax, cmÿ1): 3240 (s, NH), 1725 (s, C=O), 1190 (s, C±F). MS (m/e, %): 315 (MH, 1.15), 314 (M, 9.62), 296 (MH±F, 1.12), 237 (MC6H5, 1.68), 217 (M-CF3CO, 100.00), 202 (MCF3CONH, 33.75), 104 (PhCHN, 73.86), 77 (C6H5, 36.70), 69 (CF3, 41.13). Elemental analyses for C11H8F6N2O2: Anal Calc. C 42.04, H2.55, N 8.92, F 36.37; Found: C 41.94, H 2.17, N 8.69, F 36.70%. C6H5CH(NHCOCF2Cl)2 3ab: 1 H NMR(DMSO-d6) (ppm): 7.35(m, 5H, C6H5), 6.73 (s, 1H, CH), 9.8 (broad, 2H, NH). 19 F NMR(CDCl3): ÿ67.5 (s, ClCF3). IR (nmax, cmÿ1): 3225 (s, NH), 1730 (s, C=O), 1140 (s, C±F). MS
0022-1139/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved. PII: S0022-1139(98)00286-3
70
S. Zhu et al. / Journal of Fluorine Chemistry 93 (1999) 69±71
(m/e, %): 346/348 (M, 2.97/2.02), 216/263 (M-CF2Cl, ), 233/235 (M-ClCF2CO, 100.00/38.23), 218/220 (MClCF2CONH, 58.03/20.72), 104 (PhCHN, 70.28), 85/87 (ClCF2, 38.00/13.14), 77 (C6H5, 36.85). Elemental analyses for C11H8Cl2F4N2O2: Anal Calc. C 38.04, H 2.31, N 8.07, F 21.93; Found: C 37.84, H 2.23, N 7.79, F 22.27%.
NH), 1620 (s, C=O), 1230 (s, C±F). MS (m/e, %): 326 (M, 1.24), 298 (M-CO, 0.60), 185 (M-C6H3F2CO, 66.19), 141 (C6H3F2CO, 100.00), 113 (C6H3F, 8.07). Elemental analyses for C15H10F4N2O2: Anal Calc. C 55.21, H 3.07, N 8.59; Found: C 55.24, H 3.21, N 8.74%.
1
H NMR(DMSO-d6) (ppm): 8.53 (d, 2H, NH, JHH 7.5 Hz), 7.05 (d, 4H, 3 JHH 8.6 Hz), 5.30 (t, 1H, JHH 7.5 Hz), 3.05 (s, 2H, CH2), 2.13 (s, 3H, CH3). IR (nmax, cmÿ1): 3250 (s, NH), 1667 (s, C=O). MS (m/e, %): 204 (M, 10.81), 203 (M-H, 21.96), 189 (M-CH3, 10.06), 160 (M-H±CONH, 33.58), 91 (CH3C6H4, 68.43), 59 (CH3CO2, 100.00). Elemental analyses for C11H12N2O2: Anal Calc.: C 64.71, H 5.88, N 13.73; Found: C 64.80, H 5.63, N 13.75%. 3
1
H NMR(DMSO-d6) (ppm): 9.50 (broad, 2H, NH), 7.50 (m, 2H), 7.20 (m, 3H), 7.20±6.75 (m, 6H), 5.75(s, CH). 19 F NMR(CDCl3): ÿ115.8 (d, 4F, JH±F 18 Hz). IR (nmax, cmÿ1): 3320 (s, NH), 1640 (s, C=O), 1230 (s, C±F). MS (m/e, %): 420 (M, 2.95), 261 (M-C6H3F2CO, 100.00), 246 (M-C6H3F2CONH, 46.01), 141 (C6H3F2CO, 90.18), 104 (C6H5CHN, 13.38). Elemental analyses for C21H14F4N2O2: Anal Calcd. C 62.69, H 3.48, N 6.97; Found: C 62.54, H 3.47, N 6.79%.
3. Results and discussion
1
H NMR(DMSO-d6) (ppm): 9.50 (broad, 2H, NH), 7.53 (d,3 JHH 6 Hz, 2H), 7.13 (d. 2H), 7.15±6.55 (m, 6H), 5.80 (s, CH), 3.60 (s, OCH3). 19 F NMR (CDCl3): ÿ115.5 (d, 4F) IR (nmax, cmÿ1): 3322 (s, NH), 1638 (s, C=O), 1220 (s, C±F), MS (m/e, %): 432 (M, 2.03), 291 (M-C6H3F2CO, 30.44), 141 (C6H3F2CO, 100.00), 134 (MeOC6H5CHN, 11.05). Elemental analyses for C22H16F4N2O3: Anal Calcd. C 61.11, H 3.70, N 6.48; Found: C 61.24, H 3.53, N 6.59%.
1
H NMR(DMSO-d6) (ppm): 9.33 (broad, 2H, NH), 7.30±6.80 (m, 6H), 4.84 (t, CH2), 3.60 (s, OCH3). 19 F NMR(CDCl3): ÿ115.6 (d, 4F). IR ( max, cmÿ1): 3300 (s,
This note describes a facile preparation of the title compounds by catalysis of ¯uoroalkanesulfonic acids: Cat:
2Rf CONH2 RCHO ! RCH NHCORf 2 H2 O 1
2
CH2 Cl2
3
Rf: CF3(1a), CF2Cl(1b), 2,6-C6H3F2(1c) R:C6H5(2a), 4-CH3C6H4(2b), 4-MeOC6H4(2c), H(2d) This reaction is carried out in CH2Cl2 and in the presence of a 5±10% mol ratio of RfSO3H relative to the amount of RCHO. The products are nearly insoluble in cold CH2Cl2 and are readily isolated by simple ®ltration of the reaction mixture. After washing with toluene, the crude recrystallized product from mixed hot solvent (CH3CN/H2O 4/1) gave ®ne crystals. All products are high-melting solids. Their structures are fully characterized by spectroscopic methods and microanalysis. The IR spectra of all products showed
Table 1 Preparation of the bisamides 3 and 4 Entry
Reactants 1 (or 4) 2
Catalyst
Solvents
Time (t/h)
Temperature (t/8C)
Products
Yieldsb (%)
m.p. (8C)
1 2 3 4 5 5 6 7 8 9 10
1a 2a 1b 2a 1c 2a 1a 2a 1a 2a 1c 2c 1c 2c 1c 2d 1c 2d 4a 2b 4a 2b
TfOH TfOHC TfOH RfSO3Ha TsOH TfOH TsOH TfOH TsOH RfSO3H RfSO3H
CH2Cl2 CH2Cl2 CH2Cl2 C6H6 C6H6 Me-C6H5 Me-C6H5 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2
24 24 20 10 24 8 8 24 24 24 24
50 5 50 80 80 100 100 50 50 50 50
3aa 3ba 3ca 3aa 3aa 3cc 3cc 3cd 3cd 5 6
87 84 90 86 0 92 89 82 80 78 76
234 217 283 234 234 236 236 185 185 2708 265
a. RfSO3H: Rf HCF2CF2, ICF2CF2OCF2CF2. b. Isolated yields based on 1. c. Literature reported m. p. is 2748C.
S. Zhu et al. / Journal of Fluorine Chemistry 93 (1999) 69±71
secondary amide absorption in the ranges 3220±3300 cmÿ1 (N±H); 1700±1730 cmÿ1 (C=O) and 1100±1220 cmÿ1 (C±F). In the MS spectra they all have the corresponding molecular ion peak (M), and the fragment peak of MRfCO or RfCO as the base peak. The chemical shift of the ± NH± of compounds 3 are very down®eld (around 9.5±10.0). The use of benzene or toluene as solvent gave faster reaction at higher reaction temperature. For example, if the reaction of 1a with was 2a carried out in toluene, after stirring for 8 h at 1008C, the reaction was complete as determined by the 1 H NMR spectrum. Other ¯uoroalkanesulfonic acids such as I(CF2)2O(CF2)2SO3H and HCF2CF2SO3H are good catalysts for these reactions. (See Table 1). RfSO3H also catalyzes the acetamide or CH2(CONH2)2 with tolualdehyde and gives excellent yields of the bisamides:
Cat.: TsOH, TfOH, RfSO3H TsOH, which can catalyze the reaction of 1c or other amide with aldehyde, is inactive for the reaction of ¯uorinated amides. For example, in the reaction of CF3CONH2 with PhCHO, TsOH was added upto 0.5 mol ratio, but no
71
reaction occurred. Results are summarized in Table 1. In conclusion, this reported synthetic approach improves the existing procedures. Acknowledgements The authors thank the National Natural Science Foundation of China (NNSFC) (No. 29632003 and No. 29672041) for ®nancial support. References [1] C. Aleman, J. Puiggali, J. Org. Chem. 60 (1995) 910. [2] P.V. Pallai, R.S. Struthers, M. Goodman, L. Moroder, E. Wunsch, W. Vale, Biochemistry 24 (1985) 1933. [3] K.I. Nunami, T. Yamazaki, M. Goodman, Biopolymers 31 (1991) 1503. [4] M. Rodriguez, P. Dubreuil, J.P. Bali, J. Martinez, J. Med. Chem. 30 (1987) 758. [5] J. Pernak, B. Mrowczynski, J. Weglewski, Synthesis, (1994) 1415. [6] E.E. Gilbert, Synthesis, (1972) 136. [7] A.R. Katritzky, W.Q. Fan, M. Black, J. Pernak, J. Org. Chem. 57 (1992) 547. [8] A.H. Fernandez, R.M. Alverez, T.M. Abajo, Synthesis (1996) 1299. [9] R.K. Mehra, K.C. Pandya, Prod. Indian. Acad. Sci. 9A (1939) 508. [10] R.K. Mehra Pandya, K.C., Prod. (1939) 508; Chem Abstr., 33, 8589.
Synthesis of ¯uorine-containing symmetrical N,N-alkylidene bisamides Shizheng Zhu*, Guolin Xu, Qianli Chu, Yong Xu, Chaoyue Qui
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China Received 21 July 1998; accepted 15 September 1998
Abstract Fluorine-containing N,N-alkylidene bisamides RCH(NHCORf)2 (R: H, Aryl; Rf: CF3, CF2Cl, 2,6-C6H3F2) are conveniently prepared in good yields by the reaction of corresponding aldehydes with ¯uorine-containing amides (RfCONH2) in the presence of ¯uoroalkanesulfonic acids R0f SO3H(Rf 0 : CF3, HCF2CF2, ICF2CF2OCF2CF2). # 1999 Elsevier Science S.A. All rights reserved. Keywords: Fluorinated bisamides; Fluoroalkanesulfonic acids; Acidic catalysis
1. Introduction The amide moiety is an important constituent of many biologically signi®cant compounds. Bisamides are of considerable interest in the synthesis of peptidomimetic compounds [1]. Speci®cally, bisamides are key fragments for the introduction of gem-diaminoalkyl residues in retro-inverso pseudopeptide derivatives [2,3] by treatment of the corresponding amide with iodobenzene bistri¯uoroactate PhI(O2CCF3)2 [4,5]. Recently preparation of symmetrical N,N-alkylidene bisamides has drawn attention and many synthetic methods have been reported [6±8]. Usually they are prepared by the direct reaction of aldehydes with the corresponding carboxamide using a strong acid catalyst, e.g. sulfuric acid, a sulfonic acid or hydrochloric acid. However, attempts to use these methods with formamide and trichloroacetamide were unsuccessful [9,10]. To the best of our knowledge, the ¯uorinated analogues RCH(NHCORf)2 have not been reported to date. 2. Experimental Melting points were determined on a Mel±Temp apparatus and are uncorrected. Solvents were puri®ed and dried before use. 1 H NMR (60 MHz) and 19 F NMR (54.6 MHz) spectra were recorded on a Varian-360L instrument or Bruker AM-300 spectrometer with TMS and TFA (CFCl3 TFA 76.8 ppm, and with up®eld positive) as internal and external standards respectively, DMSO-d6 *Corresponding author. Fax: +86-21-6416-6128.
was used as solvent. IR spectra were obtained with an IR-440 Shimadzu spectrophotometer. Low resolution mass spectra were obtained on a Finnigan GC-MS 4021 instrument. Elemental analysis was performed in this Institute. 2.1. General procedure for the preparation of RCH(NHCORf)2 3 2.1.1. Preparation of N,N-phenylidine bis (trifluoroacetyl) amide 3aa Tri¯uoroacetyl amide (1.13 g, 10 mmol) was added into a 25 ml ¯ask containing a solution of benzaldehyde (0.53 g, 5 mmol) CF3SO3H (10 ml) and CH2Cl2 (10 ml). This reaction mixture was stirred and re¯uxed for 24 h. After cooling to room temperature, the crude product 3aa was ®ltered (1.3g, 86%). Recrystallation of the crude bisamide from CH3CN:H2O 4 : 1 gave ®ne colourless crystals. Other ¯uorinated bisamides 3 were similiary prepared. C6H5CH(NHCOCF3)2 3aa: 1 H NMR(DMSO-d6) (ppm): 7.45 (m, 5H, C6H5), 6.60 (s, 1H, CH), 10.0 (broad, 2H, NH). 19 F NMR(CDCl3): ÿ74.3 (s, CF3). IR (nmax, cmÿ1): 3240 (s, NH), 1725 (s, C=O), 1190 (s, C±F). MS (m/e, %): 315 (MH, 1.15), 314 (M, 9.62), 296 (MH±F, 1.12), 237 (MC6H5, 1.68), 217 (M-CF3CO, 100.00), 202 (MCF3CONH, 33.75), 104 (PhCHN, 73.86), 77 (C6H5, 36.70), 69 (CF3, 41.13). Elemental analyses for C11H8F6N2O2: Anal Calc. C 42.04, H2.55, N 8.92, F 36.37; Found: C 41.94, H 2.17, N 8.69, F 36.70%. C6H5CH(NHCOCF2Cl)2 3ab: 1 H NMR(DMSO-d6) (ppm): 7.35(m, 5H, C6H5), 6.73 (s, 1H, CH), 9.8 (broad, 2H, NH). 19 F NMR(CDCl3): ÿ67.5 (s, ClCF3). IR (nmax, cmÿ1): 3225 (s, NH), 1730 (s, C=O), 1140 (s, C±F). MS
0022-1139/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved. PII: S0022-1139(98)00286-3
70
S. Zhu et al. / Journal of Fluorine Chemistry 93 (1999) 69±71
(m/e, %): 346/348 (M, 2.97/2.02), 216/263 (M-CF2Cl, ), 233/235 (M-ClCF2CO, 100.00/38.23), 218/220 (MClCF2CONH, 58.03/20.72), 104 (PhCHN, 70.28), 85/87 (ClCF2, 38.00/13.14), 77 (C6H5, 36.85). Elemental analyses for C11H8Cl2F4N2O2: Anal Calc. C 38.04, H 2.31, N 8.07, F 21.93; Found: C 37.84, H 2.23, N 7.79, F 22.27%.
NH), 1620 (s, C=O), 1230 (s, C±F). MS (m/e, %): 326 (M, 1.24), 298 (M-CO, 0.60), 185 (M-C6H3F2CO, 66.19), 141 (C6H3F2CO, 100.00), 113 (C6H3F, 8.07). Elemental analyses for C15H10F4N2O2: Anal Calc. C 55.21, H 3.07, N 8.59; Found: C 55.24, H 3.21, N 8.74%.
1
H NMR(DMSO-d6) (ppm): 8.53 (d, 2H, NH, JHH 7.5 Hz), 7.05 (d, 4H, 3 JHH 8.6 Hz), 5.30 (t, 1H, JHH 7.5 Hz), 3.05 (s, 2H, CH2), 2.13 (s, 3H, CH3). IR (nmax, cmÿ1): 3250 (s, NH), 1667 (s, C=O). MS (m/e, %): 204 (M, 10.81), 203 (M-H, 21.96), 189 (M-CH3, 10.06), 160 (M-H±CONH, 33.58), 91 (CH3C6H4, 68.43), 59 (CH3CO2, 100.00). Elemental analyses for C11H12N2O2: Anal Calc.: C 64.71, H 5.88, N 13.73; Found: C 64.80, H 5.63, N 13.75%. 3
1
H NMR(DMSO-d6) (ppm): 9.50 (broad, 2H, NH), 7.50 (m, 2H), 7.20 (m, 3H), 7.20±6.75 (m, 6H), 5.75(s, CH). 19 F NMR(CDCl3): ÿ115.8 (d, 4F, JH±F 18 Hz). IR (nmax, cmÿ1): 3320 (s, NH), 1640 (s, C=O), 1230 (s, C±F). MS (m/e, %): 420 (M, 2.95), 261 (M-C6H3F2CO, 100.00), 246 (M-C6H3F2CONH, 46.01), 141 (C6H3F2CO, 90.18), 104 (C6H5CHN, 13.38). Elemental analyses for C21H14F4N2O2: Anal Calcd. C 62.69, H 3.48, N 6.97; Found: C 62.54, H 3.47, N 6.79%.
3. Results and discussion
1
H NMR(DMSO-d6) (ppm): 9.50 (broad, 2H, NH), 7.53 (d,3 JHH 6 Hz, 2H), 7.13 (d. 2H), 7.15±6.55 (m, 6H), 5.80 (s, CH), 3.60 (s, OCH3). 19 F NMR (CDCl3): ÿ115.5 (d, 4F) IR (nmax, cmÿ1): 3322 (s, NH), 1638 (s, C=O), 1220 (s, C±F), MS (m/e, %): 432 (M, 2.03), 291 (M-C6H3F2CO, 30.44), 141 (C6H3F2CO, 100.00), 134 (MeOC6H5CHN, 11.05). Elemental analyses for C22H16F4N2O3: Anal Calcd. C 61.11, H 3.70, N 6.48; Found: C 61.24, H 3.53, N 6.59%.
1
H NMR(DMSO-d6) (ppm): 9.33 (broad, 2H, NH), 7.30±6.80 (m, 6H), 4.84 (t, CH2), 3.60 (s, OCH3). 19 F NMR(CDCl3): ÿ115.6 (d, 4F). IR ( max, cmÿ1): 3300 (s,
This note describes a facile preparation of the title compounds by catalysis of ¯uoroalkanesulfonic acids: Cat:
2Rf CONH2 RCHO ! RCH NHCORf 2 H2 O 1
2
CH2 Cl2
3
Rf: CF3(1a), CF2Cl(1b), 2,6-C6H3F2(1c) R:C6H5(2a), 4-CH3C6H4(2b), 4-MeOC6H4(2c), H(2d) This reaction is carried out in CH2Cl2 and in the presence of a 5±10% mol ratio of RfSO3H relative to the amount of RCHO. The products are nearly insoluble in cold CH2Cl2 and are readily isolated by simple ®ltration of the reaction mixture. After washing with toluene, the crude recrystallized product from mixed hot solvent (CH3CN/H2O 4/1) gave ®ne crystals. All products are high-melting solids. Their structures are fully characterized by spectroscopic methods and microanalysis. The IR spectra of all products showed
Table 1 Preparation of the bisamides 3 and 4 Entry
Reactants 1 (or 4) 2
Catalyst
Solvents
Time (t/h)
Temperature (t/8C)
Products
Yieldsb (%)
m.p. (8C)
1 2 3 4 5 5 6 7 8 9 10
1a 2a 1b 2a 1c 2a 1a 2a 1a 2a 1c 2c 1c 2c 1c 2d 1c 2d 4a 2b 4a 2b
TfOH TfOHC TfOH RfSO3Ha TsOH TfOH TsOH TfOH TsOH RfSO3H RfSO3H
CH2Cl2 CH2Cl2 CH2Cl2 C6H6 C6H6 Me-C6H5 Me-C6H5 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2
24 24 20 10 24 8 8 24 24 24 24
50 5 50 80 80 100 100 50 50 50 50
3aa 3ba 3ca 3aa 3aa 3cc 3cc 3cd 3cd 5 6
87 84 90 86 0 92 89 82 80 78 76
234 217 283 234 234 236 236 185 185 2708 265
a. RfSO3H: Rf HCF2CF2, ICF2CF2OCF2CF2. b. Isolated yields based on 1. c. Literature reported m. p. is 2748C.
S. Zhu et al. / Journal of Fluorine Chemistry 93 (1999) 69±71
secondary amide absorption in the ranges 3220±3300 cmÿ1 (N±H); 1700±1730 cmÿ1 (C=O) and 1100±1220 cmÿ1 (C±F). In the MS spectra they all have the corresponding molecular ion peak (M), and the fragment peak of MRfCO or RfCO as the base peak. The chemical shift of the ± NH± of compounds 3 are very down®eld (around 9.5±10.0). The use of benzene or toluene as solvent gave faster reaction at higher reaction temperature. For example, if the reaction of 1a with was 2a carried out in toluene, after stirring for 8 h at 1008C, the reaction was complete as determined by the 1 H NMR spectrum. Other ¯uoroalkanesulfonic acids such as I(CF2)2O(CF2)2SO3H and HCF2CF2SO3H are good catalysts for these reactions. (See Table 1). RfSO3H also catalyzes the acetamide or CH2(CONH2)2 with tolualdehyde and gives excellent yields of the bisamides:
Cat.: TsOH, TfOH, RfSO3H TsOH, which can catalyze the reaction of 1c or other amide with aldehyde, is inactive for the reaction of ¯uorinated amides. For example, in the reaction of CF3CONH2 with PhCHO, TsOH was added upto 0.5 mol ratio, but no
71
reaction occurred. Results are summarized in Table 1. In conclusion, this reported synthetic approach improves the existing procedures. Acknowledgements The authors thank the National Natural Science Foundation of China (NNSFC) (No. 29632003 and No. 29672041) for ®nancial support. References [1] C. Aleman, J. Puiggali, J. Org. Chem. 60 (1995) 910. [2] P.V. Pallai, R.S. Struthers, M. Goodman, L. Moroder, E. Wunsch, W. Vale, Biochemistry 24 (1985) 1933. [3] K.I. Nunami, T. Yamazaki, M. Goodman, Biopolymers 31 (1991) 1503. [4] M. Rodriguez, P. Dubreuil, J.P. Bali, J. Martinez, J. Med. Chem. 30 (1987) 758. [5] J. Pernak, B. Mrowczynski, J. Weglewski, Synthesis, (1994) 1415. [6] E.E. Gilbert, Synthesis, (1972) 136. [7] A.R. Katritzky, W.Q. Fan, M. Black, J. Pernak, J. Org. Chem. 57 (1992) 547. [8] A.H. Fernandez, R.M. Alverez, T.M. Abajo, Synthesis (1996) 1299. [9] R.K. Mehra, K.C. Pandya, Prod. Indian. Acad. Sci. 9A (1939) 508. [10] R.K. Mehra Pandya, K.C., Prod. (1939) 508; Chem Abstr., 33, 8589.