METHOD FOR PREPARING PRIMARY AMIDE COMPOUNDS FROM SECONDARY OR TERTIARY AMIDES

Abstract

The present invention relates to a method for preparing primary amides from tertiary or secondary amides substituted with various alkyl groups through a transamidation reaction without a metal catalyst in room-temperature conditions by adding ammonium carbonate ((NH.sub.4).sub.2CO.sub.3), wherein the method is eco-friendly since various secondary and tertiary amides that are not toxic or corrosive are used as starting materials and ammonium carbonate ((NH.sub.4).sub.2CO.sub.3) that is neither a strong acid nor a strong base is used, and the method is economical since various primary amides can be synthesized with an excellent yield at room temperature without a metal catalyst.

Claims

1. A method for preparing a primary amide, the method comprising a step of: subjecting a secondary or tertiary amide as a substrate to transamidation with an ammonia source in absence of a catalyst.

2. A method for preparing a primary benzamide, the method including a step of: subjecting N-phenyl-N-tosyl benzamide as a substrate to transamidation with an ammonia source in absence of a catalyst.

3. The method of claim 2, wherein the ammonia source is at least one selected from the group consisting of ammonium acetate, ammonium formate, and ammonium carbonate.

4. The method of claim 2, wherein the transamidation was carried out in at least one solvent selected from the group consisting of dimethyl sulfoxide and N,N-dimethylformamide.

5. The method of claim 2, wherein the transamidation is carried out in presence of at least one selected from the group consisting of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), trisodium phosphate, and sodium carbonate in a solvent.

6. The method of claim 2, wherein the N-phenyl-N-tosyl benzamide and the ammonia source are used at an equivalent ratio of 5:2 to 5:11.

7. The method of claim 2, wherein the transamidation was carried out in a temperature condition of 20 to 45° C.

8. The method of claim 2, wherein the transamidation was carried out for 4 to 18 hours.

9. A method for preparing a benzamide, the method including a step of: subjecting substituted N-phenyl-N-tosyl benzamide as a substrate to transamidation with an ammonia source in absence of a catalyst.

10. The method of claim 9, wherein the ammonia source is ammonium carbonate.

11. The method of claim 9, wherein the N-phenyl-N-tosyl benzamide and the ammonia source are used at an equivalent ratio of 5:2 to 5:11.

12. The method of claim 9, wherein the transamidation is carried out using dimethyl sulfoxide as a solvent.

13. The method of claim 9, wherein the transamidation is carried out in a temperature condition of 20 to 45° C.

14. The method of claim 9, wherein the transamidation is carried out for 4 to 140 hours.

15. The method of claim 1, wherein the substrate is selected from the group consisting of N-4-methoxphenyl N-tosyl benzamide, N-4-fluorophenyl N-tosyl benzamide, N-benzyl N-tosyl benzamide, N-methyl N-tosyl benzamide, N-trifluoromethansulfonyl N-phenyl benzamide, N-mesityl N-phenyl benzamide, N-Boc protected N-phenyl benzamide, N-benzoyl saccharin, N-benzoyl succinimide, N-benzoyl glutarimide, N-methyl N-phenyl benzamide, and N,N-diphenyl benzamide.

16. The method of claim 1, wherein the substrate is selected from the group consisting of 1-tosyl pyrrolidin-2-one, 1-tosyl piperidin-2-one, and 1-tosyl azepan-2-one.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0059] FIG. 1 is a reaction scheme of synthesizing a benzamide from N-phenyl-N-tosyl benzamide according to an embodiment of the present disclosure.

[0060] FIG. 2 is a reaction scheme of synthesizing a benzamide from N-phenyl-N-tosyl benzamide according to an embodiment of the present disclosure.

[0061] FIG. 3 is a reaction scheme of synthesizing a primary benzamide from substituted N-phenyl-N-tosyl benzamide according to an embodiment of the present disclosure.

[0062] FIG. 4 is a reaction scheme of synthesizing a primary benzamide from N-tosyl benzamide having various substituents on the nitrogen atom thereof according to an embodiment of the present disclosure.

[0063] FIG. 5a is a reaction scheme of synthesizing a primary benzamide through transamidation of N-tosyl lactam, with 1-tosylpyrrolidin-2-one serving as a substrate, according to an embodiment of the present disclosure.

[0064] FIG. 5b is a reaction scheme of synthesizing a primary benzamide through transamidation of N-tosyl lactam, with 1-tosylpiperidin-2-one serving as a substrate, according to an embodiment of the present disclosure.

[0065] FIG. 5c is a reaction scheme of synthesizing a primary benzamide through transamidation of N-tosyl lactam, with 1-tosylazepan-2-one serving as a substrate, according to an embodiment of the present disclosure.

BEST MODE FOR CARRYING OUT THE INVENTION

[0066] The present disclosure pertains to a method for preparing a primary amide, the method including a step of:

[0067] subjecting a secondary or tertiary amide as a substrate to transamidation with an ammonia source without using a catalyst.

MODE FOR CARRYING OUT THE INVENTION

[0068] Hereinafter, the present disclosure will be described in further detail with reference to the following Examples and the accompanying drawings. It will be obvious to a person skilled in the art that the Examples are for illustrative purposes only and are not to be construed to limit the scope of the present disclosure.

Example 1. Synthesis of Benzamide from N-Phenyl-N-Tosyl Benzamide

[0069] To find out optimal ammonia sources for the synthesis of a primary benzamide, a synthesis reaction was carried out using various ammonia sources in various solvents, with N-phenyl-N-tosyl benzamide serving as a reaction substrate, as illustrated in the reaction scheme of FIG. 2, to afford as a product the primary benzamide represented by the following Chemical Formula 3:

##STR00003##

[0070] Used in the synthesis reaction were 0.2 mmol of N-phenyl-N-tosyl benzamide as a reaction substrate, 0.4 mmol of ammonium chloride, ammonium tetrafluoroborate, ammonium acetate, ammonium formate, or ammonium carbonate as an ammonia source, 0.2 mmol of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), trisodium phosphate, or sodium carbonate as an additional base, 1.0 mL of dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), ethanol (EtOH), toluene, or dichloromethane (DCM) as a solvent in the combinations listed in Table 1. The synthesis reaction was carried out at 25° C. for 6 hours.

[0071] The yields of the products were measured by gas chromatography-mass spectrometry (GCMS) and are summarized as % in Table 1.

[0072] Chromatography and 1H NMR measured as follows: Mp: 127-128° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.99 (s, 1H), 7.90-7.84 (m, 2H), 7.55-7.49 (m, 1H), 7.48-7.42 (m, 2H), 7.38 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 168.3, 134.7, 131.7, 128.7, 127.9.

TABLE-US-00001 TABLE 1 No. Ammonia source Base Solvent Yield (%) 1 NH.sub.4Cl — DMSO 0 2 NH.sub.4BF.sub.4 — DMSO 0 3 NH.sub.4OAc — DMSO 66 4 NH.sub.4OAc DBU DMSO 73 5 NH.sub.4OAc Na.sub.3PO.sub.4 DMSO 90 6 NH.sub.4OAc Na.sub.2CO.sub.3 DMSO 94 7 (NH.sub.4).sub.2CO.sub.3 — DMSO 77 8 (NH.sub.4).sub.2CO.sub.3 — DMSO 99 9 (NH.sub.4).sub.2CO.sub.3 — DMF 83 10 (NH.sub.4).sub.2CO.sub.3 — THF 27 11 (NH.sub.4).sub.2CO.sub.3 — EtOH 23 12 (NH.sub.4).sub.2CO.sub.3 — Toluene 0 13 (NH.sub.4).sub.2CO.sub.3 — DCM 0 14 (NH.sub.4).sub.2CO.sub.3 — DMSO 99 (92)

[0073] As can be seen in Table 1, the reaction between ammonium chloride (NH.sub.4Cl) and ammonium tetrafluoroborate (NH.sub.4BF.sub.4) in dimethyl sulfoxide at 25° C. did not afford any product (Nos. 1 and 2).

[0074] The product was obtained at a yield of 66% when ammonium acetate (NH.sub.4OAc) was used as an ammonia source (No. 3). The employment of ammonium acetate (NH.sub.4OAc) increased the production yield to 73% in the presence of the additional base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), to 90% in the presence of trisodium phosphate (Na.sub.3PO.sub.4), and to 94% in the presence of sodium carbonate (Na.sub.2CO.sub.3) (Nos. 4 to 6). From the data, it was understood that the product could be obtained at excellent yield in the presence of carbonate bases and thus carbonate-based ammonia is one of the optimum ammonia sources.

[0075] The production yield was 77% after the reaction with ammonium formate (HCO2NH4) and peaked at 99% for ammonium carbonate [(NH.sub.4).sub.2CO.sub.3] (Nos. 7 and 8). That is, the highest yield was obtained with ammonium carbonate [(NH.sub.4).sub.2CO.sub.3].

[0076] The product was produced at yields of 83%, 27%, and 23% when the reaction was carried out in N,N-dimethylformamide (DMF), tetrahydrofuran (THF), and ethanol (EtOH), respectively (Nos. 9 to 11).

[0077] The reaction using toluene or dichloromethane (DCM) as a solvent did not afford the product (Nos. 12 and 13). Even when the amount of ammonium carbonate [(NH.sub.4).sub.2CO.sub.3] was reduced to 0.6 equivalents, the product could be obtained at a yield of 99% (No. 14). In this regard, the isolated yield was measured to be 92%.

[0078] Hence, the optimal conditions for synthesis of benzamide from N-phenyl-N-tosyl benzamide were identified as follows: 1.0 equivalent of N-phenyl-N-tosyl benzamide as a substrate; 0.6 equivalents of (NH.sub.4).sub.2CO.sub.3 as an ammonia source; DMSO as a solvent; 25° C. as reaction time; and 6 hours for reaction.

Example 2. Synthesis of Primary Amide from Substituted N-Phenyl-N-Tosyl Benzamide

[0079] Referring to the optimal conditions, the reaction was performed, as illustrated in the reaction scheme of FIG. 3, at a reaction temperature of 25 to 40° C. for 6 to 16 hours, using 1.0 mmol of substituted N-phenyl-N-tosyl benzamide as substrates, 0.6 mmol of ammonium carbonate [(NH.sub.4).sub.2CO.sub.3] as an ammonia source, and dimethyl sulfoxide (DMSO) as a solvent, to afford corresponding primary amides.

[0080] The yields of the products were measured by gas chromatography-mass spectrometry (GCMS) and are summarized as % in Table 2.

TABLE-US-00002 TABLE 2 Yield (%) Yield (%) Yield (%) No. Substrate (25° C., 6 h) (40° C., 16 h) (40° C., 5 d) 15 2-methyl-N-phenyl-N-tosylbenzamide  4 51 83 16 3-methyl-N-phenyl-N-tosylbenzamide 91 — — 17 4-methyl-N-phenyl-N-tosylbenzamide 97 — — 18 4-(tert-butyl)-N-phenyl-N-tosylbenzamide 97 — — 19 N-phenyl-N-tosyl-[1,1′-biphenyl]- 94 — — 4-carboxamide 20 N-phenyl-N-tosyl-1-naphthamide 32 78 — 21 N-phenyl-N-tosyl-2-naphthamide 97 — — 22 2-methoxy-N-phenyl-N-tosylbenzamide 64 96 — 23 3-methoxy-N-phenyl-N-tosylbenzamide 99 — — 24 4-methoxy-N-phenyl-N-tosylbenzamide 81 — — 25 3,4-Dimethoxy-N-phenyl-N-tosylbenzamide 97 — — 26 3-(Dimethylamino)-N-phenyl-N-tosylbenzamide 90 — — 27 4-(Dimethylamino)-N-phenyl-N-tosylbenzamide 38 79 — 28 2-Fluoro-N-phenyl-N-tosylbenzamide 93 — — 29 3-Fluoro-N-phenyl-N-tosylbenzamide 94 — — 30 4-Fluoro-N-phenyl-N-tosylbenzamide 99 — — 31 2-Chloro-N-phenyl-N-tosylbenzamide 45 88 — 32 Trichloro-N-phenyl-N-tosylbenzamide  0  0  0 33 2-Bromo-N-phenyl-N-tosylbenzamide 35 75 79 34 2-Iodo-N-phenyl-N-tosylbenzamide 22 62 72 35 3-Iodo-N-phenyl-N-tosylbenzamide 86 — — 36 4-Iodo-N-phenyl-N-tosylbenzamide 83 — — 37 4-Cyano-N-phenyl-N-tosylbenzamide 85 — — 38 2-Nitro-N-phenyl-N-tosylbenzamide 74 — — 39 4-Nitro-N-phenyl-N-tosylbenzamide 91 — — 40 Methyl 4-(phenyl(tosyl)carbamoyl)benzoate 86 — — 41 4-Acetyl-N-phenyl-N-tosylbenzamide 82 — — 42 4-Amino-N-phenyl-N-tosylbenzamide trace 55 — 43 tert-butyl (4- 76 — — (phenyl(tosyl)carbamoyl)phenyl)carbamate 44 4-[Bis[(1,1- 77 — — dimethylethoxy)carbonyl]amino]-N- phenyl-Ntosylbenzamide 45 tert-butyl 44 — — (4-(phenyl(tosyl)carbamoyl)phenyl) carbonate 46 tert-butyl 19 — — (4-(phenyl(tosyl)carbamoyl)phenyl) carbonate (deprotected) 47 4-((tert-butyldimethylsilyl)oxy)- trace 50 — N-phenyl-N-tosylbenzamide 48 4-((tert-butyldimethylsilyl)oxy)- trace 43 — N-phenyl-N-tosylbenzamide (deprotected) 49 3-((tert-butyldimethylsilyl)oxy)- 44 51 — N-phenyl-N-tosylbenzamide 50 3-((tert-butyldimethylsilyl)oxy)- 43 40 — N-phenyl-N-tosylbenzamide (deprotected) 51 N-phenyl-N-tosylfuran-3-carboxamide  70 (100) — — 52 N-phenyl-N-tosylfuran-2-carboxamide 73 (93) — — 53 N-phenyl-N-tosylpicolinamide 77 (99) — — 54 N-phenyl-N-tosylisonicotinamide 39 (99) — — 55 N-phenyl-N-tosylcinnamamide 78 (80) — — 56 N,2-Diphenyl-N-tosylacetamide 81 — — 57 2-(Naphthalen-1-yl)-N-phenyl-N-tosylacetamide 88 — — 58 N-phenyl-N-tosylpentanamide 67 (70) — — 59 N-phenyl-N-tosylcyclohexanecarboxamide 79 — — 60 N-phenyl-N-tosyladamantane-1-carboxamide 15 83 —

[0081] As shown in Table 2, the product 2-methyl benzamide, represented by the following Chemical Formula 4, was produced at a yield of 4% when 2-methyl-N-phenyl-N-tosylbenzamide was reacted at 25° C. for 6 hours (No. 15). The production yield increased to 51% when the temperature condition was raised to 40° C. and to 83% when the reaction was conducted for 5 days.

##STR00004##

[0082] Chromatography and 1H NMR measured as follows: Mp: 139-140° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.69 (s, 1H), 7.38-7.27 (m, 3H), 7.24-7.17 (m, 2H), 2.36 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 171.5, 137.5, 135.5, 130.9, 129.6, 127.4, 125.8, 20.0.

[0083] From 3-methyl-N-phenyl-N-tosylbenzamide, the product 3-methyl benzamide, represented by the following Chemical Formula 5, was obtained at a yield of 91% in the temperature condition of 25° C. (No. 16).

##STR00005##

[0084] Chromatography and 1H NMR measured as follows: Mp: 90-91° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.69 (s, 1H), 7.67-7.63 (m, 1H), 7.36-7.26 (m, 3H), 2.34 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 168.4, 137.9, 134.7, 132.2, 128.52, 128.51, 125.0, 21.4.

[0085] From 4-methyl-N-phenyl-N-tosylbenzamide, the product 4-methyl benzamide, represented by the following Chemical Formula 6, was obtained at a yield of 97% in the temperature condition of 25° C. (No. 17).

##STR00006##

[0086] Chromatography and 1H NMR measured as follows: Mp: 158-159° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.77 (d, J=8.1 Hz, 2H), 7.27 (s, 1H), 7.24 (d, J=7.9 Hz, 2H), 2.33 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 168.2, 141.5, 131.9, 129.2, 127.9, 21.4.

[0087] From 4-(tert-butyl)-N-phenyl-N-tosylbenzamide, the product 4-(tert-butyl)benzamide, represented by the following Chemical Formula 7, was obtained at a yield of 97% in the temperature condition of 25° C. (No. 18).

##STR00007##

[0088] Chromatography and 1H NMR measured as follows: Mp: 164-165° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.90 (s, 1H), 7.80 (d, J=8.6 Hz, 2H), 7.44 (d, J=8.6 Hz, 2H), 7.28 (s, 1H), 1.28 (s, 9H); 13C NMR (126 MHz, DMSO-d6) δ 168.3, 154.4, 132.0, 127.8, 125.4, 35.0, 31.4.

[0089] From N-phenyl-N-tosyl-[1,1-biphenyl]-4-carboxamide, the product 1,1-biphenyl]-4-carboxamide, represented by the following Chemical Formula 8, was obtained at a yield of 94% in the temperature condition of 25° C. (No. 19).

##STR00008##

[0090] Chromatography and 1H NMR measured as follows: Mp: 219-220° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.98 (d, J=8.4 Hz, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.72 (d, J=7.2 Hz, 2H), 7.51-7.45 (m, 2H), 7.42 (s, 1H), 7.39 (t, J=7.4 Hz, 1H); 13C NMR (126 MHz, DMSO-d6) δ 168.0, 143.21, 139.7, 133.5, 129.5, 128.6, 128.5, 127.3, 126.9.

[0091] From N-phenyl-N-tosyl-1-naphthamide, the product 1-naphthamide, represented by the following Chemical Formula 9, was obtained at a yield of 78% in the temperature condition of 25° C. (No. 20).

##STR00009##

[0092] Chromatography and 1H NMR measured as follows: Mp: 199-200° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.33 (d, J=7.5 Hz, 1H), 8.08-7.94 (m, 3H), 7.69-7.50 (m, 5H); 13C NMR (126 MHz, DMSO-d6) δ 171.0, 135.1, 133.6, 130.21, 130.17, 128.6, 127.0, 126.6, 126.0, 125.6, 125.4.

[0093] From N-phenyl-N-tosyl-2-naphthamide, the product 2-naphthamide, represented by the following Chemical Formula 10, was obtained at a yield of 97% in the temperature condition of 25° C. (No. 21).

##STR00010##

[0094] Chromatography and 1H NMR measured as follows: Mp: 192-193° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.50 (s, 1H), 8.15 (s, 1H), 8.04-7.92 (m, 4H), 7.63-7.54 (m, 2H), 7.49 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 168.4, 134.6, 132.6, 132.1, 129.31, 128.27, 128.2, 128.04, 128.01, 127.1, 124.9.

[0095] From 2-methoxy-N-phenyl-N-tosylbenzamide, the product 2-methoxybenzamide, represented by the following Chemical Formula 11, was obtained at a yield of 64% in the temperature condition of 25° C. (No. 22). The production yield was measured to be 96% in the temperature condition of 40° C.

##STR00011##

[0096] Chromatography and 1H NMR measured as follows: Mp: 120-121° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.80 (dd, J=7.7, 1.8 Hz, 1H), 7.63 (s, 1H), 7.52 (s, 1H), 7.48-7.43 (m, 1H), 7.12 (d, J=8.0 Hz, 1H), 7.04-6.99 (m, J=7.6, 0.9 Hz, 1H), 3.88 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 166.7, 157.7, 132.9, 131.2, 123.1, 120.8, 112.4, 56.2.

[0097] From 3-methoxy-N-phenyl-N-tosylbenzamide, the product 3-methoxybenzamide, represented by the following Chemical Formula 12, was obtained at a yield of 99% in the temperature condition of 25° C. (No. 23).

##STR00012##

[0098] Chromatography and 1H NMR measured as follows: Mp: 122-123° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.97 (s, 1H), 7.49-7.29 (m, 4H), 7.11-7.03 (m, 1H), 3.78 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 168.1, 159.6, 136.2, 129.8, 120.1, 117.5, 113.1, 55.7.

[0099] From 4-methoxy-N-phenyl-N-tosylbenzamide, the product 4-methoxybenzamide, represented by the following Chemical Formula 13, was obtained at a yield of 81% in the temperature condition of 25° C. (No. 24).

##STR00013##

[0100] Chromatography and 1H NMR measured as follows: Mp: 163-164° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.84 (d, J=8.9 Hz, 3H), 7.18 (s, 1H), 6.97 (d, J=8.9 Hz, 2H), 3.79 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 167.8, 162.0, 129.8, 126.9, 113.8, 55.8.

[0101] From 3,4-dimethoxy-N-phenyl-N-tosylbenzamide, the product 3,4-dimethoxybenzamide, represented by the following Chemical Formula 14, was obtained at a yield of 97% in the temperature condition of 25° C. (No. 25).

##STR00014##

[0102] Chromatography and 1H NMR measured as follows: Mp: 163-164° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.50 (dd, J=8.3, 2.0 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.21 (s, 1H), 6.99 (d, J=8.4 Hz, 1H), 3.79 (s, 3H), 3.78 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 167.9, 151.7, 148.6, 127.0, 121.2, 111.3, 111.2, 55.99, 55.93.

[0103] From 3-(dimethylamino)-N-phenyl-N-tosylbenzamide the product 3-methoxybenzamide, represented by the following Chemical Formula 15, was obtained at a yield of 90% in the temperature condition of 25° C. (No. 26).

##STR00015##

[0104] Chromatography and 1H NMR measured as follows: Mp: 150-151° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.27 (s, 1H), 7.25-7.14 (m, 3H), 6.85 (dd, J=8.1, 2.4 Hz, 1H), 2.93 (s, 6H); 13C NMR (126 MHz, DMSO-d6) δ 169.0, 150.7, 135.4, 129.1, 115.6, 115.4, 111.7, 40.6.

[0105] From 4-(dimethylamino)-N-phenyl-N-tosylbenzamide, the product 4-(dimethylamino)benzamide, represented by the following Chemical Formula 16, was obtained at a yield of 38% in the temperature condition of 25° C. (No. 27).

##STR00016##

[0106] Chromatography and 1H NMR measured as follows: Mp: 207-208° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.73 (d, J=8.9 Hz, 2H), 7.63 (s, 1H), 6.93 (s, 1H), 6.67 (d, J=9.0 Hz, 2H), 2.94 (s, 6H); 13C NMR (126 MHz, DMSO-d6) δ 168.4, 152.5, 129.4, 121.4, 111.1, 40.2.

[0107] From 2-fluoro-N-phenyl-N-tosylbenzamide, the product 2-fluorobenzamide, represented by the following Chemical Formula 17, was obtained at a yield of 93% in the temperature condition of 25° C. (No. 28).

##STR00017##

[0108] Chromatography and 1H NMR measured as follows: Mp: 113-114° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.78-7.57 (m, 3H), 7.54-7.48 (m, 1H), 7.30-7.21 (m, 2H); 13C NMR (126 MHz, DMSO-d6) δ 165.7, 159.7 (d, J=249.5 Hz), 132.9 (d, J=8.5 Hz), 130.7 (d, J=3.0 Hz), 124.8 (d, J=3.4 Hz), 124.3 (d, J=14.3 Hz), 116.5 (d, J=22.7 Hz).

[0109] From 3-fluoro-N-phenyl-N-tosylbenzamide, the product 3-fluorobenzamide, represented by the following Chemical Formula 18, was obtained at a yield of 94% in the temperature condition of 25° C. (No. 29).

##STR00018##

[0110] Chromatography and 1H NMR measured as follows: Mp: 127-129° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.70-7.64 (m, 1H), 7.54 (s, 1H), 7.54-7.48 (m, 1H), 7.42-7.34 (m, 1H); 13C NMR (126 MHz, DMSO-d6) δ 166.9 (d, J=2.4 Hz), 162.4 (d, J=244.4 Hz), 137.2 (d, J=6.6 Hz), 130.8 (d, J=8.0 Hz), 124.0 (d, J=2.8 Hz), 118.5 (d, J=21.4 Hz), 114.6 (d, J=22.7 Hz).

[0111] From 4-fluoro-N-phenyl-N-tosylbenzamide, the product 4-fluorobenzamide, represented by the following Chemical Formula 19, was obtained at a yield of 99% in the temperature condition of 25° C. (No. 30).

##STR00019##

[0112] Chromatography and 1H NMR measured as follows: Mp: 139-140° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.00 (s, 1H), 7.94 (dd, J=8.8, 5.6 Hz, 2H), 7.40 (s, 1H), 7.31-7.23 (m, 2H); 13C NMR (126 MHz, DMSO-d6) δ 167.2, 164.4 (d, J=248.2 Hz), 131.2 (d, J=2.8 Hz), 130.5 (d, J=9.0 Hz), 115.5 (d, J=22.7 Hz).

[0113] From 2-chloro-N-phenyl-N-tosylbenzamide, the product 2-chlorobenzamide, represented by the following Chemical Formula 20, was obtained at a yield of 45% in the temperature condition of 25° C. (No. 31). The production yield was measured to be 88% in the temperature condition of 40° C.

##STR00020##

[0114] Chromatography and 1H NMR measured as follows: Mp: 138-139° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.58 (s, 1H), 7.49-7.45 (m, 1H), 7.45-7.39 (m, 2H), 7.39-7.34 (m, 1H); 13C NMR (126 MHz, DMSO-d6) δ 168.6, 137.6, 131.0, 130.06, 130.04, 129.1, 127.5.

[0115] From trichloro-N-phenyl-N-tosylbenzamide, the product trichlorobenzamide, represented by the following Chemical Formula 21, was obtained at a yield of 0% in the temperature condition of 25° C. (No. 32). The product was not obtained even when the reaction was conducted for 5 days in the temperature condition of 40° C.

##STR00021##

[0116] From 2-bromo-N-phenyl-N-tosylbenzamide, the product 2-bromobenzamide, represented by the following Chemical Formula 22, was obtained at a yield of 35% in the temperature condition of 25° C. (No. 33). The production yield increased to 75% in the temperature condition of 40° C. and further to 79% when the reaction was carried out for 5 days.

##STR00022##

[0117] Chromatography and 1H NMR measured as follows: Mp: 157-158° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.57 (s, 1H), 7.45-7.39 (m, 2H), 7.37-7.31 (m, 1H); 13C NMR (126 MHz, DMSO-d6) δ 169.5, 139.8, 133.1, 131.1, 129.0, 127.9, 119.0.

[0118] From 2-iodo-N-phenyl-N-tosylbenzamide, the product 2-iodobenzamide, represented by the following Chemical Formula 23, was obtained at a yield of 22% in the temperature condition of 25° C. (No. 34). The production yield increased to 62% in the temperature condition of 40° C. and further to 72% when the reaction was carried out for 5 days.

##STR00023##

[0119] Chromatography and 1H NMR measured as follows: Mp: 178-180° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.86 (d, J=7.9 Hz, 1H), 7.81 (s, 1H), 7.51 (s, 1H), 7.44-7.39 (m, 1H), 7.36-7.30 (m, 1H), 7.17-7.11 (m, 1H); 13C NMR (126 MHz, DMSO-d6) δ 171.1, 143.6, 139.6, 131.0, 128.4, 128.2, 93.6.

[0120] From 3-iodo-N-phenyl-N-tosylbenzamide, the product 3-iodobenzamide, represented by the following Chemical Formula 24, was obtained at a yield of 86% in the temperature condition of 25° C. (No. 35).

##STR00024##

[0121] Chromatography and 1H NMR measured as follows: Mp: 186-187° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.24-8.18 (m, 1H), 8.06 (s, 1H), 7.90-7.84 (m, 2H), 7.48 (s, 1H), 7.29-7.23 (m, 1H); 13C NMR (126 MHz, DMSO-d6) δ 166.8, 140.2, 136.7, 136.4, 130.9, 127.3, 95.1.

[0122] From 4-iodo-N-phenyl-N-tosylbenzamide, the product 4-iodobenzamide, represented by the following Chemical Formula 25, was obtained at a yield of 83% in the temperature condition of 25° C. (No. 36).

##STR00025##

[0123] Chromatography and 1H NMR measured as follows: Mp: 217-218° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.83 (d, J=8.5 Hz, 2H), 7.64 (d, J=8.5 Hz, 2H), 7.44 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 167.6, 137.6, 134.2, 129.9, 99.4.

[0124] As is understood from the data for Nos. 28 to 36, benzamides having halide substituents at the ortho-position thereof were converted into the products at low yield in the temperature condition of 25° C. due to the steric hinderance of the substituents, but the production yields increased in the temperature condition of 40° C.

[0125] From 4-cyano-N-phenyl-N-tosylbenzamide, the product 4-cyanobenzamide, represented by the following Chemical Formula 26, was obtained at a yield of 85% in the temperature condition of 25° C. (No. 37).

##STR00026##

[0126] Chromatography and 1H NMR measured as follows: Mp: 226-227° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.21 (s, 1H), 8.01 (d, J=8.3 Hz, 2H), 7.94 (d, J=8.3 Hz, 2H), 7.67 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 166.9, 138.7, 132.8, 128.7, 118.8, 114.1.

[0127] From 2-nitro-N-phenyl-N-tosylbenzamide, the product 2-nitrobenzamide, represented by the following Chemical Formula 27, was obtained at a yield of 74% in the temperature condition of 25° C. (No. 38).

##STR00027##

[0128] Chromatography and 1H NMR measured as follows: Mp: 176-177° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.99 (dd, J=8.1, 0.9 Hz, 1H), 7.80-7.73 (m, 1H), 7.72-7.59 (m, 3H); 13C NMR (126 MHz, DMSO-d6) δ 167.6, 147.7, 133.8, 133.0, 131.1, 129.3, 124.4.

[0129] From 4-nitro-N-phenyl-N-tosylbenzamide, the product 4-nitrobenzamide, represented by the following Chemical Formula 28, was obtained at a yield of 91% in the temperature condition of 25° C. (No. 39).

##STR00028##

[0130] Chromatography and 1H NMR measured as follows: Mp: 199-200° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.36-8.21 (m, 3H), 8.09 (d, J=8.9 Hz, 2H), 7.72 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 166.6, 149.5, 140.4, 129.4, 123.9.

[0131] From methyl 4-(phenyl(tosyl)carbamoyl)benzoate, the product methyl 4-carbamoylbenzoate, represented by the following Chemical Formula 29, was obtained at a yield of 86% in the temperature condition of 25° C. (No. 40).

##STR00029##

[0132] Chromatography and 1H NMR measured as follows: Mp: 202-203° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.97 (AB q, J=8.3 Hz, 4H), 7.54 (s, 1H), 3.83 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 167.5, 166.1, 138.8, 132.2, 129.5, 128.2, 52.8.

[0133] From 4-acetyl-N-phenyl-N-tosylbenzamide, the product 4-acetylbenzamide, represented by the following Chemical Formula 30, was obtained at a yield of 82% in the temperature condition of 25° C. (No. 41).

##STR00030##

[0134] Chromatography and 1H NMR measured as follows: Mp: 190-192° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.99 (AB q, J=8.4 Hz, 4H), 7.57 (s, 1H), 2.60 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 198.2, 167.5, 139.1, 138.5, 128.5, 128.2, 27.4.

[0135] From 4-amino-N-phenyl-N-tosylbenzamide, the product 4-aminobenzamide, represented by the following Chemical Formula 31, was obtained at a yield of 55% in the temperature condition of 25° C. (No. 42).

##STR00031##

[0136] Chromatography and 1H NMR measured as follows: Mp: 181-182° C.; 1H NMR (500 MHz, DMSOd6) δ 7.55 (d, J=8.5 Hz, 2H), 7.47 (s, 1H), 6.80 (s, 1H), 6.49 (d, J=8.5 Hz, 2H), 5.56 (s, 2H); 13C NMR (126 MHz, DMSO-d6) δ 168.4, 152.1, 129.5, 121.4, 112.9.

[0137] From tert-butyl (4-(phenyl(tosyl)carbamoyl)phenyl)carbamate, the product tert-butyl (4-carbamoylphenyl)carbamate, represented by the following Chemical Formula 32, was obtained at a yield of 76% in the temperature condition of 25° C. (No. 43).

##STR00032##

[0138] Chromatography and 1H NMR measured as follows: Mp: 225-226° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.60 (s, 1H), 7.81 (s, 1H), 7.77 (d, J=8.5 Hz, 2H), 7.49 (d, J=8.5 Hz, 2H), 7.19 (s, 1H), 1.46 (s, 9H); 13C NMR (126 MHz, DMSO-d6) δ 167.9, 153.0, 142.7, 128.8, 128.0, 117.4, 79.9, 28.5; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C12H16N2O3Na 259.1059; Found 259.1060.

[0139] From 4-[bis[(1,1-dimethylethoxy)carbonyl]amino]-N-phenyl-N-tosylbenzamide, the product 4-[bis[(1,1-dimethylethoxy)carbonyl]amino] benzamide, represented by the following Chemical Formula 33, was obtained at a yield of 77% in the temperature condition of 25° C. (No. 44).

##STR00033##

[0140] Chromatography and 1H NMR measured as follows: Mp: 175-176° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.43 (s, 1H), 7.26 (d, J=8.4 Hz, 2H), 1.38 (s, 18H); 13C NMR (126 MHz, DMSO-d6) δ 167.2, 151.1, 141.5, 133.0, 128.0, 127.4, 82.5, 27.5; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H24N2O5Na 359.1583; Found 359.1582.

[0141] From tert-butyl (4-(phenyl(tosyl)carbamoyl)phenyl)carbonate, the product tert-butyl (4-carbamoylphenyl) carbonate, represented by the following Chemical Formula 34, was obtained at a yield of 44% in the temperature condition of 25° C. (No. 45).

##STR00034##

[0142] Chromatography and 1H NMR measured as follows: Mp: 146-147° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.42 (s, 1H), 7.27 (d, J=8.5 Hz, 2H), 1.49 (s, 9H); 13C NMR (126 MHz, DMSO-d6) δ 167.0, 152.7, 150.9, 131.9, 129.0, 121.2, 83.6, 27.2.

[0143] From tert-butyl (4-(phenyl(tosyl)carbamoyl)phenyl)carbonate, the product 4-hydroxybenzamide, represented by the following Chemical Formula 35, was obtained at a yield of 19% in the temperature condition of 25° C. (No. 46).

##STR00035##

[0144] Chromatography and 1H NMR measured as follows: Mp: 141-142° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.89 (s, 1H), 7.73-7.63 (m, 3H), 7.03 (s, 1H), 6.74 (d, J=8.5 Hz, 2H); 13C NMR (126 MHz, DMSO-d6) δ 168.0, 160.5, 129.9, 125.4, 115.1.

[0145] It was observed that a product like deprotected 4-hydroxybenzamide was obtained at low yield from a deprotected starting material such as deprotected tert-butyl (4-carbamoylphenyl) carbonate.

[0146] From 4-((tert-butyldimethylsilyl)oxy)-N-phenyl-N-tosylbenzamide, the product 4-((tertbutyldimethylsilyl)oxy)benzamide, represented by the following Chemical Formula 36, was obtained at a yield of 50% in the temperature condition of 25° C. (No. 47).

##STR00036##

[0147] Chromatography and 1H NMR measured as follows: Mp: 135-136° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.79 (s, 1H), 7.77 (d, J=8.6 Hz, 2H), 7.16 (s, 1H), 6.85 (d, J=8.6 Hz, 2H), 0.92 (s, 9H), 0.17 (s, 6H); 13C NMR (126 MHz, DMSO-d6) δ 167.8, 158.2, 129.8, 127.9, 119.8, 25.9, 18.4, −4.1.

[0148] From 4-((tert-butyldimethylsilyl)oxy)-N-phenyl-N-tosylbenzamide, the product 4-hydroxybenzamide, represented by the following Chemical Formula 37, was obtained at a yield of 43% in the temperature condition of 25° C. (No. 48).

##STR00037##

[0149] Chromatography and 1H NMR measured as follows: Mp: 141-142° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.89 (s, 1H), 7.73-7.63 (m, 3H), 7.03 (s, 1H), 6.74 (d, J=8.5 Hz, 2H); 13C NMR (126 MHz, DMSO-d6) δ 168.0, 160.5, 129.9, 125.4, 115.1.

[0150] It was observed that a product like deprotected 4-hydroxybenzamide was obtained at low yield from a deprotected starting material such as deprotected 4-tert-(butyldimethylsilyloxy)benzamide.

[0151] From 3-methoxy-N-phenyl-N-tosylbenzamide, the product 3-((tert-butyldimethylsilyl)oxy)-N-phenyl-N-tosylbenzamide, represented by the following Chemical Formula 38, was obtained at a yield of 44% in the temperature condition of 25° C. (No. 49). The production yield increased to 51% in the temperature condition of 40° C.

##STR00038##

[0152] Chromatography and 1H NMR measured as follows: Mp: 142-143° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.45 (d, J=7.7 Hz, 1H), 7.35-7.24 (m, 3H), 6.95 (dd, J=8.0, 1.5 Hz, 1H), 0.92 (s, 9H), 0.16 (s, 6H); 13C NMR (126 MHz, DMSO-d6) δ 167.9, 155.4, 136.3, 129.8, 123.1, 121.0, 119.4, 26.0, 18.4, −4.1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C13H21 NO2SiNa 274.1239; Found 274.1239.

[0153] From 3-((tert-butyldimethylsilyl)oxy)-N-phenyl-N-tosylbenzamide, the product 3-hydroxybenzamide, represented by the following Chemical Formula 39, was obtained at a yield of 43% in the temperature condition of 25° C. (No. 50). The production yield was decreased when the reaction was carried out for 16 hours in the temperature condition of 40° C.

##STR00039##

[0154] Chromatography and 1H NMR measured as follows: Mp: 167-168° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.55 (s, 1H), 7.81 (s, 1H), 7.31-7.09 (m, 4H), 6.85 (d, J=7.2 Hz, 1H); 13C NMR (126 MHz, DMSO-d6) δ 168.4, 157.6, 136.2, 129.6, 118.5, 118.4, 114.9.

[0155] From N-phenyl-N-tosylfuran-3-carboxamide, the product furan-3-carboxamide, represented by the following Chemical Formula 40, was obtained at a yield of 70% in the temperature condition of 25° C. (No. 51). The production yield was observed to be 100% as measured by 1H NMR spectroscopy in the presence of an internal standard.

##STR00040##

[0156] Chromatography and 1H NMR measured as follows: Mp: 173-174° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.15 (dd, J=1.5, 0.8 Hz, 1H), 7.71-7.68 (m, 1H), 7.64 (s, 1H), 7.19 (s, 1H), 6.80 (dd, J=1.8, 0.8 Hz, 1H); 13C NMR (126 MHz, DMSO-d6) δ 163.8, 145.8, 144.4, 123.3, 109.7.

[0157] From N-phenyl-N-tosylfuran-2-carboxamide, the product furan-2-carboxamide, represented by the following Chemical Formula 41, was obtained at a yield of 73% in the temperature condition of 25° C. (No. 52). The production yield was observed to be 93% as measured by 1H NMR spectroscopy in the presence of an internal standard.

##STR00041##

[0158] Chromatography and 1H NMR measured as follows: Mp: 141-142° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.80 (dd, J=1.6, 0.7 Hz, 1H), 7.75 (s, 1H), 7.36 (s, 1H), 7.08 (dd, J=3.4, 0.7 Hz, 1H), 6.59 (dd, J=3.4, 1.7 Hz, 1H); 13C NMR (126 MHz, DMSO-d6) δ 159.8, 148.5, 145.4, 114.0, 112.2.

[0159] From N-phenyl-N-tosylpicolinamide, the product picolinamid, represented by the following Chemical Formula 42, was obtained at a yield of 77% in the temperature condition of 25° C. (No. 53). The production yield was observed to be 99% as measured by 1H NMR spectroscopy in the presence of an internal standard.

##STR00042##

[0160] Chromatography and 1H NMR measured as follows: Mp: 106-107° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J=4.7 Hz, 1H), 8.12 (s, 1H), 8.03 (d, J=7.8 Hz, 1H), 8.00-7.94 (m, 1H), 7.65 (s, 1H), 7.60-7.55 (m, 1H); 13C NMR (126 MHz, DMSO-d6) δ 166.5, 150.7, 148.9, 138.1, 126.9, 122.3.

[0161] From N-phenyl-N-tosylisonicotinamide, the product isonicotinamide, represented by the following Chemical Formula 43, was obtained at a yield of 39% in the temperature condition of 25° C. (No. 54). The production yield was observed to be 99% as measured by 1H NMR spectroscopy in the presence of an internal standard.

##STR00043##

[0162] Chromatography and 1H NMR measured as follows: Mp: 156-157° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.71 (d, J=5.9 Hz, 2H), 8.23 (s, 1H), 7.76 (d, J=5.9 Hz, 2H), 7.72 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 166.7, 150.7, S15 141.7, 121.8.

[0163] The heterogenous aromatic compounds such as furan carboxamide, picolinamide, and isonicotinamide were observed to be produced at a yield of 93 to 99% as measured by 1H NMR spectroscopy in the presence of an internal standard, but their isolated yields were measured to be as low as 70%, 73%, and 77%, respectively, because they were highly soluble to water.

[0164] From N-phenyl-N-tosylcinnamamide, the product cinnamamide, represented by the following Chemical Formula 44, was obtained at a yield of 78% in the temperature condition of 25° C. (No. 55). The production yield was observed to be 80% as measured by 1H NMR spectroscopy in the presence of an internal standard.

##STR00044##

[0165] Chromatography and 1H NMR measured as follows: Mp: 148-149° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.63-7.49 (m, 3H), 7.45-7.33 (m, 4H), 7.12 (s, 1H), 6.61 (d, J=15.9 Hz, 1H); 13C NMR (126 MHz, DMSO-d6) δ 167.1, 139.6, 135.3, 129.9, 129.4, 128.0, 122.8.

[0166] From N,2-diphenyl-N-tosylacetamide, the product 2-phenylacetamide, represented by the following Chemical Formula 56, was obtained at a yield of 81% in the temperature condition of 25° C. (No. 56).

##STR00045##

[0167] Chromatography and 1H NMR measured as follows: Mp: 158-159° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.46 (s, 1H), 7.32-7.23 (m, 4H), 7.23-7.18 (m, 1H), 6.88 (s, 1H), 3.36 (s, 2H); 13C NMR (126 MHz, DMSO-d6) δ 172.7, 136.9, 129.5, 128.6, 126.7, 42.7.

[0168] From 2-(naphthalen-1-yl)-N-phenyl-N-tosylacetamide, the product 2-(naphthalen-1-yl)acetamide, represented by the following Chemical Formula 46, was obtained at a yield of 88% in the temperature condition of 25° C. (No. 57).

##STR00046##

[0169] Chromatography and 1H NMR measured as follows: Mp: 181-182° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.09 (d, J=8.1 Hz, 1H), 7.92 (d, J=7.6 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.63-7.48 (m, 3H), 7.48-7.40 (m, 2H), 7.01 (s, 1H), 3.88 (s, 2H); 13C NMR (126 MHz, DMSO-d6) δ 172.6, 133.8, 133.4, 132.5, 128.8, 128.3, 127.4, 126.4, 126.1, 126.0, 124.8, 40.2.

[0170] Cinnamamide, phenyl acetamide, and naphthyl acetamide were all obtained at good yield.

[0171] From N-phenyl-N-tosylpentanamide, the product pentanamide, represented by the following Chemical Formula 47, was obtained at a yield of 67% in the temperature condition of 25° C. (No. 58). The production yield was observed to be 70% as measured by 1H NMR spectroscopy in the presence of an internal standard.

##STR00047##

[0172] Chromatography and 1H NMR measured as follows: Mp: 107-108° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.21 (s, 1H), 6.67 (s, 1H), 2.02 (t, J=7.5 Hz, 2H), 1.49-1.40 (m, 2H), 1.29-1.21 (m, 2H), 0.85 (t, J=7.4 Hz, 3H); 13C NMR (126 MHz, DMSO-d6) δ 174.7, 35.3, 27.7, 22.3, 14.2.

[0173] From N-phenyl-N-tosylcyclohexanecarboxamide, the product represented by the following Chemical Formula 48 was obtained at a yield of 79% in the temperature condition of 25° C. (No. 59).

##STR00048##

[0174] Chromatography and 1H NMR measured as follows: Mp: 182-183° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.13 (s, 1H), 6.62 (s, 1H), 2.11-1.96 (m, 1H), 1.78-1.49 (m, 5H), 1.34-1.05 (m, 5H); 13C NMR (126 MHz, DMSO-d6) δ 177.8, 44.1, 29.6, 26.0, 25.8.

[0175] From N-phenyl-N-tosyladamantane-1-carboxamide, the product adamantane-1-carboxamide, represented by the following Chemical Formula 49, was obtained at a yield of 15% in the temperature condition of 25° C. (No. 60). The production yield increased to 83% when the reaction was carried out for 16 hours in the temperature condition of 40° C.

##STR00049##

[0176] Chromatography and 1H NMR measured as follows: Mp: 187-188° C.; 1H NMR (500 MHz, DMSO-d6) δ 6.92 (s, 1H), 6.66 (s, 1H), 1.93 (br s, 3H), 1.78-1.57 (m, 12H); 13C NMR (126 MHz, DMSO-d6) δ 179.7, 40.1, 39.2, 36.6, 28.1.

[0177] Primary, secondary, and tertiary alkyl carboxamides exhibited good yields while N-phenyl-N-tosyladamantane-1-carboxamide allowed for a good yield only after the reaction for hours in the temperature condition of 40° C.

Example 3. Synthesis of Primary Amide from Benzamide Having Various Substituents on Nitrogen Atom Thereof

[0178] Referring to the optimal conditions, the reaction was performed, as illustrated in the reaction scheme of FIG. 4, at a reaction temperature of 25 to 40° C. for 6 to 16 hours, using 1.0 mmol of each of benzamides having various substituents on the nitrogen atom thereof as substrates, 0.6 mmol of ammonium carbonate [(NH.sub.4).sub.2CO.sub.3] as an ammonia source, and dimethyl sulfoxide (DMSO) as a solvent, to afford the benzamide represented by Chemical Formula 3, which is a primary amide.

[0179] The yields of the products were measured by gas chromatography-mass spectrometry (GCMS) and are summarized as % in Table 3.

TABLE-US-00003 TABLE 3 Yield (%) Yield (%) No. Substrate (25° C., 6 h) (40° C., 16 h) 61 N-4-methoxphenyl N-tosyl 65 — benzamide 62 N-4-fluorophenyl N-tosyl 92 — benzamide 63 N-benzyl N-tosyl benzamide 62 — 64 N-methyl N-tosyl benzamide 76 — 65 N-Trifluoromethansulfonyl 93 — N-phenyl benzamide 66 N-mesityl N-phenyl benzamide 90 — 67 N-Boc protected N-phenyl 11 — benzamide 68 N-benzoyl saccharin N-phenyl 69 — benzamide 69 N-benzoyl succinimide N-phenyl 89 — benzamide 70 N-benzoyl glutarimide N-phenyl 57 — benzamide 71 N-methyl-N-phenyl benzamide 0 0 72 N,N-diphenyl benzamides 0 0

[0180] As shown in Table 3, the primary benzamide represented by Chemical Formula 3 was produced at a yield of 65% in the temperature condition of 25° C. from N-4-methoxyphenyl N-tosylbenzamide, represented by Chemical formula 50 (No. 61).

##STR00050##

[0181] The primary benzamide represented by Chemical Formula 3 was produced at a yield of 92% in the temperature condition of 25° C. from N-4-fluorophenyl N-tosyl benzamide, represented by Chemical formula 51 (No. 62).

##STR00051##

[0182] The primary benzamide represented by Chemical Formula 3 was produced at a yield of 62% in the temperature condition of 25° C. from N-benzyl N-tosyl benzamide, represented by Chemical formula 52 (No. 63).

##STR00052##

[0183] The primary benzamide represented by Chemical Formula 3 was produced at a yield of 76% in the temperature condition of 25° C. from N-methyl N-tosyl benzamide, represented by Chemical formula 53 (No. 64).

##STR00053##

[0184] The primary benzamide represented by Chemical Formula 3 was produced at a yield of 93% in the temperature condition of 25° C. from N-trifluoromethansulfonyl N-phenyl benzamide, represented by Chemical formula 54 (No. 65).

##STR00054##

[0185] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 90% in the temperature condition of 25° C. from N-mesityl N-phenyl benzamide, represented by Chemical formula 55 (No. 66).

##STR00055##

[0186] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 11% in the temperature condition of 25° C. from N-Boc protected N-phenyl benzamide, represented by Chemical formula 56 (No. 67).

##STR00056##

[0187] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 69% in the temperature condition of 25° C. from N-benzoyl saccharin, represented by Chemical formula 57 (No. 68).

##STR00057##

[0188] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 89% in the temperature condition of 25° C. from N-benzoyl succinimide, represented by Chemical formula 58 (No. 69).

##STR00058##

[0189] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 57% in the temperature condition of 25° C. from N-benzoyl glutarimide, represented by Chemical formula 59 (No. 70).

##STR00059##

[0190] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 0% in the temperature condition of 25° C. from N-methyl N-phenyl benzamide, represented by Chemical formula 60 (No. 71). Even after the reaction was carried out for 16 hours in the temperature condition of 40° C., the yield was measured to be 0%.

##STR00060##

[0191] The primary benzamide represented by Chemical Formula 2 was produced at a yield of 0% in the temperature condition of 25° C. from N,N-diphenyl benzamide, represented by Chemical formula 61 (No. 72). Even after the reaction was carried out for 16 hours in the temperature condition of 40° C., the yield was measured to be 0%.

##STR00061##

Example 4. Transamidation of N-Tosyl Lactam

[0192] Referring to the optimal conditions, the reaction was performed at a reaction temperature of 40° C. for 16 to 36 hours, using 1.0 mmol of each of 1-tosylpyrrolidin-2-one, 1-tosylpiperidin-2-one and 1-Tosylazepan-2-one as substrates, 0.5 or 1.0 equivalent of ammonium carbonate [(NH.sub.4).sub.2CO.sub.3] as an ammonia source, and DMSO as a solvent, to afford corresponding primary benzamides (see FIGS. 5a to 5c).

[0193] The yields of the products were measured by gas chromatography-mass spectrometry (GCMS) and are summarized as % in Table 4.

TABLE-US-00004 TABLE 4 Yield (%) Yield(%) No. Substrate (40° C., 16 h) (40° C., 36 h) 73 1-Tosylpyrrolidin-2-one 48 50 74 1-Tosylpiperidin-2-one 80 90 75 1-Tosylazepan-2-one 36 50

[0194] As shown in Table 4, the product 4-(4-methylphenylsulfonamido)butanamide represented by Chemical Formula 62 was obtained at a yield of 48% from 1-tosylpyrrolidin-2-one after the reaction for 16 hours in the temperature condition of 40° C. (No. 73). The production yield increased to 50% when the reaction was carried out for 36 hours in the temperature condition of 40° C.

##STR00062##

[0195] Chromatography and 1H NMR measured as follows: Mp: 132-133° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.65 (d, J=8.2 Hz, 2H), 7.50 (s, 1H), 7.38 (d, J=8.2 Hz, 2H), 7.21 (s, 1H), 6.71 (s, 1H), 2.67 (t, J=7.2 Hz, 2H), 2.37 (s, 3H), 2.02 (t, J=7.4 Hz, 2H), 1.60-1.51 (m, 2H); 13C NMR (126 MHz, DMSO-d6) δ 174.1, 143.0, 138.0, 130.1, 126.9, 42.7, 32.5, 25.5, 21.4; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C11H16N2O3SNa 279.0779; Found 279.0779.

[0196] The product 5-(4-methylphenylsulfonamido)pentanamide represented by Chemical Formula 63 was obtained at a yield of 80% from 1-tosylpiperidin-2-one after the reaction for 16 hours in the temperature condition of 40° C. (No. 74). The production yield increased to 90% when the reaction was carried out for 36 hours in the temperature condition of 40° C.

##STR00063##

[0197] Chromatography and 1H NMR measured as follows: Mp: 130-131° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.66 (d, J=8.2 Hz, 2H), 7.47 (s, 1H), 7.38 (d, J=8.2 Hz, 2H), 7.19 (s, 1H), 6.68 (s, 1H), 2.67 (t, J=7.0 Hz, 2H), 2.37 (s, 3H), 1.96 (t, J=7.3 Hz, 2H), 1.46-1.37 (m, 2H), 1.37-1.28 (m, 2H); 13C NMR (126 MHz, DMSO-d6) δ 174.4, 142.9, 138.1, 130.0, 126.9, 42.8, 34.9, 29.1, 22.7, 21.4; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C12H18N2O3SNa 293.0936; Found 293.0936.

[0198] The product 6-(4-methylphenylsulfonamido)hexanamide represented by Chemical Formula 64 was obtained at a yield of 36% from 1-tosylazepan-2-one after the reaction for 16 hours in the temperature condition of 40° C. (No. 75). The production yield increased to 50% when the reaction was carried out for 36 hours in the temperature condition of 40° C.

##STR00064##

[0199] Chromatography and 1H NMR measured as follows: Mp: 75-77° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.65 (d, J=8.2 Hz, 2H), 7.46 (s, 1H), 7.38 (d, J=8.2 Hz, 2H), 7.19 (s, 1H), 6.66 (s, 1H), 2.66 (t, J=7.0 Hz, 2H), 2.37 (s, 3H), 1.96 (t, J=7.4 Hz, 2H), 1.42-1.29 (m, 4H), 1.21-1.12 (m, 2H). 13C NMR (126 MHz, DMSO-d6) δ 174.6, 142.9, 138.1, 130.0, 126.9, 42.9, 35.4, 29.2, 26.3, 25.1, 21.4.

[0200] As shown in Nos. 73 to 75, production yields of corresponding benzamides from 1-tosyl pyrrolidin-2-one, 1-tosyl piperidin-2-one, and 1-tosyl azepan-2-one increased with increasing of the reaction time.

INDUSTRIAL APPLICABILITY

[0201] The present disclosure is drawn a method for preparing primary amides and, specifically, to a method for preparation of primary amides from tertiary or secondary amides having various alkyl substituents through transamidation with ammonium carbonate [(NH.sub.4).sub.2CO.sub.3] in a room temperature condition without using a metal catalyst.