2-Naphthalenecarboxamide

ChEBI: A naphthalenecarboxamide resulting from the formal condensation of the carboxy group of 2-naphthoic acid with ammonia.

Naphthalene-2-carboxamide is a naphthalenecarboxamide resulting from the formal condensation of the carboxy group of 2-naphthoic acid with ammonia.

2-Naphthoyl chloride (2.21 g, 11.6 mmol) was dissolved in a MeOH/NH3 solution (2 M, 20 mL) and was allowed to stir overnight. Volatiles were removed and the resulting white solid was triturated with EtOAc. The solid was filtered and washed with cold EtOAc to yield a white solid which was used without further purification (1.98 g, 100percent yield). m.p. 191-192° C. 1H NMR (CDCl3) delta 8.39 (s, 1H, ArH) , 7.90 (4H, ArH), 7.57 (m, 2H, ArH). 13C NMR (CDCl3) delta 169.3, 135.0, 132.6, 130.5, 129.0, 128.6, 128.1, 127.9, 127.8, 126.9, 123.7. IR (nujol) vmax cm-1: 3400, 3210, 1650, 1628, 1512, 1510.A solution of 2-naphthoyl chloride (5.70 g, 29.9 mmol) in tetrahydrofuran (60 ml) was added dropwise to a mixture of 28 percentaqueous ammonia (20 ml) and tetrahydrofuran (30 ml) with stirring under ice cooling, and the mixture was stirred at room temperature for 4 hrs. The solvent was distilled off under reduced pressure, and water was added to the residue. The precipitates were collected by filtration and dried to give 2-carbamoylnaphthalene (2.68 g, 52 percent) as a colorless solid. IR (Nujol): 3378, 3194, 1685, 1655 cm-1; APCI-MS m/z: 172 [M+H]+.(Preparation 1) [0083] 1) A solution of 2-naphthoyl chloride (5.70 g, 29.9 mmol) in tetrahydrofuran (60 ml) was added dropwise to a mixture of 28percent aqueous ammonia (20 ml) and tetrahydrofuran (30 ml) with stirring under ice cooling, and the mixture was stirred at room temperature for 4 hrs. The solvent was distilled off under reduced pressure, and water was added to the residue. The precipitates were collected by filtration and dried to give 2-carbamoylnaphthalene (2.68 g, 52percent) as a colorless solid. IR (Nujol) : 3378, 3194, 1685, 1655 cm-1; APCI-MS m/z: 172 [M+H]+.To a solution of 2-naphthoic acid (25 g, 0.145 mol) in MC (200ml), oxalyl chloride (38 ml, 0.4356 mol) and a catalytic amount of DMF wereadded and stirred at room temperature for 2hrs. After the solvent wasevaporated, the crude acyl chloride was diluted with MC (200 ml), to which asolution of ammonium hydroxide in water (160 ml) was dropwise added at anice bath temperature. After stirring for 1 hr, the precipitated product wascollected by suction filtration, triturated in hexane and dried to obtain the titlecompound, which was used next step without further purification.A solution of Naphthalene-2-carbonyl chloride obtained from Step A was dissolved in THF (30 mL) and this was cooled down to O0C. Ammonia gas was passed for approximately 1.5 hrs through the solution and the reaction was stirred at room temperature under a closed system for 4 hrs. A white solid precipitate was observed in the reaction mixture. The reaction mixture was dissolved in ethyl acetate and washed using water followed by brine solution. The organic layer was separated and dried over sodium sulphate and the volatiles were evaporated off in vacuo to afford the crude product.The crude product was purified by column chromatography using neutral silica gel of 60- 120 mesh size. A gradient of 50-60 percent ethyl acetate in hexane was used for elution of the title compound (0.8 g).Procedure for the synthesis of amides 2Amides 2 were prepared by reaction of naphtoic acids 1 (lmmol) commercially available with 2 mL of S0C12 and 0.5 mL of Et3 . The mixture was refluxed for 30 minutes and acyl chloride was dissolved in CH2C12 and was added to a solution of NH40H. The mixture was shaken at room temperature for 4-24 h. The alkaline layer was extracted with CH2C12 and organic layers were combined and dried over Na2SC>4 and concentrated. In some cases, the amide precipitated before separation of the two layers and was isolated by filtration. The amides were purified by column chromatography in the elution conditions reported in the experimental data for each example reported.General procedure: Amides 7a'e were prepared from the corresponding commercially available carboxylic acids (1 mmol) 6a'e treated with an excess of SOCl2 (7 mmol) in presence of Et3N (0.1 mmol) under reflux for 1 h. The corresponding acylchloride was added to a mixture (45 mL) of   NH4OH (28percent),   H2O and CH2Cl2 (1:1:1). The mixture was stirred at room temperature for 4 h. Insoluble amides 7a'd were separated by filtration while the amide   7e was obtained removing the solvent under vacuo. The crude was washed with H2O (20 mL) and extracted with AcOEt (3 × 20 mL).General procedure: To a solution of an appropriate substituted carboxylic acid (10 mmol) in CHCl3 (50 mL) was added thionyl chloride (3.6 mL, 50 mmol), dropwise over 10 min. The resulting solution was refluxed for 8 h and then concentrated in vacuo. The residual light brown oil was dissolved in THF (50 mL), diluted with a solution of 30percent NH4OH (6 mL), and stirred at room temperature for an additional 2 h. At that point, saturated aqueous NaHCO3 (10 mL) was added and the reaction mixture was extracted with EtOAc (3 × 30 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The crude amide was carried directly to the next step without further purification.General procedure: Amides 2 were prepared by reaction of naphtoic acids 1 (1 mmol) commercially available with 2 mL of SOCl2 and 0.5 mL of Et3N. The mixture was refluxed for 30 minutes and acyl chloride was dissolved in CH2Cl2 and was added to a solution of NH4OH. The mixture was shaken at room temperature for 4-24 h. The alkaline layer was extracted with CH2Cl2 and organic layers were combined and dried over Na2SO4 and concentrated. In some cases, the amide precipitated before separation of the two layers and was isolated by filtration. The amides were purified by column chromatography in the elution conditions reported in the experimental data for each example reported.Procedure for the synthesis of chlorides 4A mixture of amide 2 (1 mmol) and 1, 3- dichloroacetone (1.2 mmol) was warmed at T = 200 °C in homogeneous for 4-10 h. In case of tioamides 3 the mixture was dissolved in EtOH (50 mL) with the same stoichiometric values. Aqueous layer was extracted with CH2C12 (25 mL x 3) . The organic layers were combined and dried on Na2S04. Ossazoles and thiazoles derivatives were purified by column chromatography in the experimental conditions reported for each compound.General procedure: Intermediates aryloxazoles 9a'e were prepared condensing the corresponding amides 7a'e with 1, 3-dichloroacetone (2 mmol) heating at 200 °C for 5 h. Arylthiazoles 10a'd were prepared condensing 8a'd (1 mmol) with 1, 3-dichloroacetone (2 mmol) in EtOH (25 mL). After cooling at room temperature, water (10 mL) and AcOEt (10 mL) were added. The aqueous phase was extracted with AcOEt (3 × 50 mL) and the combined solution was dried over Na2SO4 and evaporated. The residue was purified on silica gel column chromatography in specific condition below reported for each compound.General procedure: A mixture of amide 2 (1 mmol) and 1, 3-dichloroacetone (1.2 mmol) was warmed at T=200° C. in homogeneous for 4-10 h. In case of tioamides 3 the mixture was dissolved in EtOH (50 mL) with the same stoichiometric values. Aqueous layer was extracted with CH2Cl2 (25 mL×3). The organic layers were combined and dried on Na2SO4. Ossazoles and thiazoles derivatives were purified by column chromatography in the experimental conditions reported for each compound.Reference Example 43 In substantially the same manner as in Reference Example 31, 2-naphthalenecarboxamide was allowed to react with 1, 3-dichloroacetone to give 4-chloromethyl-2-(2-naphthyl)oxazole. The yield was 68percent. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 116-117° C.

Molecular Weight:171.19
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:171.068413911
Monoisotopic Mass:171.068413911
Topological Polar Surface Area:43.1
Heavy Atom Count:13
Complexity:202
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes