INTRODUCTION:

Synthesis of thiadiazoles is of interest as the compounds possess marked pharmacological effects. Further, the chemistry of 1,3,4- thiadiazoles constitute one of the most active class of compounds possessing diverse pharmacological and microbiological activity. Literature survey reveals that various 1,8-naphthyridines have attracted considerable attention as they are also endowed with a wide range of biological activity. [1-6]

Nalidixic acid (1-ethyl-3-carboxy-7-methyl-1,8-naphthyridin-4-one) has been found to be effective particularly against Gram-negative bacteria found in chronic urinary tract infections.[7] Studies on the synthesis of 1,8-naphthyridines have served as a fertile field of research in the perusal for antibacterial agents. [8-13]

Scheme

EXPERIMENTAL:

Unless stated otherwise, solvents and chemicals were obtained from commercial sources and were used without further purification. Reactions were monitored by thin layer chromatography (TLC) on silica gel plates (60 F254), visualizing with ultraviolet light or iodine spray. Flash chromatography was performed on silica gel (230-400 mesh) using hexane and ethyl acetate. ¹H NMR spectra were determined in DMSO-d₆ solution by using 400 MHz spectrometers, respectively. Proton chemical shifts (δ) are relative to tetramethylsilane (TMS, δ = 0.00) as internal standard and expressed in ppm. Spin multiplicities are given as s (singlet), d (doublet), t (triplet) and m (multiplet) as well as b (broad). Coupling constants (J) are given in hertz. Infrared spectra were recorded on a FT-IR spectrometer. Melting points were determined using melting point B-540 apparatus and are uncorrected. HRMS was determined using waters LCT premier XETOF ARE-047 apparatus.

N-(2-Cyclopropyl-[1,8]naphthyridine-3-carbonyl)-guanidine (2):

A solution of 2-cyclopropyl-[1,8]naphthyridine-3-carboxylic acid ethyl ester (1) (0.5g, 2.06 mmol) in ethanol (5mL), guanidine hydrochloride (0.29g, 3.09 mmol) was added. The resulting solution was irradiated under microwave for 2-3min, reaction completion was monitored by TLC, the reaction mass was cooled to room temperature. The compound (2) wasrecrystalised from ethanol to offer as a light red colour solid (0.28g, 0.96 mmol), yield : 73%.

The IR (KBr) spectra of N-(2-cyclopropyl-[1,8]naphthyridine-3-carbonyl)-guanidine (2)exhibited absorptions around 2220 (aliph. CH₂), 1735 (CO, amide), 3120 (NH), 3235(NH₂) cm^-1.

The ¹H NMR (500 MHz) Spectrum of N-(2-cyclopropyl-[1,8]naphthyridine-3-carbonyl)-guanidine (51)in DMSOd₆ displayed signals at δ 1.21-1.32(m, 4H, 2CH₂), 1.68,(m, 1H, CH ), 2.92 (m, 1H, CH), 3.62 (bs, 2H, NH₂), 7.46 (t, 1H, J = 7.5 Hz, CH), 8.14 (s, 1H, NH), 8.29 (d, 1H, J = 8.5 Hz, CH), 8.46 (d, 1H, J = 9.5 Hz, CH), 9.21 (d, 1H, J = 12 Hz,CH).

The mass spectrum ofN-(2-cyclopropyl-[1,8]naphthyridine-3-carbonyl)-guanidine (2) showed the molecular ion [M+1] peak at m/z 292 (100%).

4-(2-Cyclopropyl-[1,8]naphthyridin-3-yl)-6-phenyl-[1,3,5]triazin-2-ylamine (3a):

A solution of N-(2-cyclopropyl-[1,8]naphthyridine-3-carbonyl)-guanidine (2) (0.5g, 1.71 mmol) in ethanol (10 mL), benzonitrile (0.26g, 2.56 mmol) was added. The resulting solution was heated at 145 ^oC for about 16h, reaction completion was monitored by TLC. The reaction mass was cooled to room temperature, evaporated ethanol completely and the compound (3a) was recrystalised in acetone, to offer as a reddish colour solid (0.21g, 24%).

Other compounds in the series were prepared similarly and their characterization data are recorded below.

The IR (KBr) spectra of 4-(2-cyclopropyl-[1,8]naphthyridin-3-yl)-6-phenyl-[1,3,5]triazin-2-ylamine (3a) exhibited absorptions around 2225 (aliph. CH₂), 3231 (NH₂) cm ^-1).

The ¹H NMR (500 MHz) Spectrum of 4-(2-cyclopropyl-[1,8]naphthyridin-3-yl)-6-phenyl-[1,3,5]triazin-2-ylamine (3a) in DMSOd₆ displayed signals at δ 1.25 (m, 4H, 2CH₂), 3.04,(m, 1H, CH ), 4.96 (bs, 2H, NH₂), 7.13 (m, 4H, 4CH), 7.39 (d, 2H, J = 7.5 Hz, 2CH), 7.72 (d, 1H, J = 8.5 Hz, CH), 8.32 (d, 2H,2CH), 8.71 (d, 1H, J = 12 Hz, CH), 9.41 (s, 1H, CH).

The mass spectrum of4-(2-cyclopropyl-[1,8]naphthyridin-3-yl)-6-phenyl-[1,3,5]triazin-2-ylamine (3a) showed the molecular ion [M+1] peak at m/z 341.1 (100%). Other important peaks appeared at m/z, 327.2, 223.1, 189.1 and 145.9.

4-(4-Chloro-phenyl)-6-(2-cyclopropyl-[1,8]naphthyridin-3-yl)-[1,3,5]triazin-2-ylamine (3b)

Recrystalised in acetone, filtered the solid compound and dried to offer reddish colour solid (0.21g, 24%). IR (KBr pellet): 2215 (aliph. CH₂), 3235 (NH₂) cm ^-1; ¹H NMR (500 MHz, DMSOd₆) : δ 1.25 (m, 4H, 2CH₂), 1.44,(m, 1H, CH ), 4.46 (bs, 2H, NH₂), 7.63 (m, 4H, 4CH), 8.29 (d, 1H, CH), 8.62 (d, 1H, CH), 9.34 (d, 1H,CH), Mass (m/z): 375 [M+].

4-(2-Cyclopropyl-[1,8]naphthyridin-3-yl)-6-(4-nitro-phenyl)-[1,3,5]triazin-2-ylamine (3c)

Recrystalised in acetone, filtered the solid compound and dried to offer reddish colour solid (0.13g, 21%). IR (KBr pellet): 2235 (aliph. CH₂), 3245 (NH₂) cm ^-1; ¹H NMR (500 MHz, DMSOd₆) : δ 1.35 (m, 4H, CH₂), 1.46,(m, 1H, CH ), 4.36 (bs, 2H, NH₂), 7.58 (m, 4H, 4CH), 8.29 (d, 1H, J = 7.5 Hz, CH), 8.62 (d, 1H, J = 14 Hz, CH), 9.34 (d, 1H, J = 12 Hz,CH), Mass (m/z): 386[M+].

4-(4-Bromo-phenyl)-6-(2-cyclopropyl-[1,8]naphthyridin-3-yl)-[1,3,5]triazin-2-ylamine (3d)

Recrystalised in acetone, filtered the solid compound and dried to offer reddish colour solid (0.24g, 28%). IR (KBr pellet): 2215 (aliph. CH₂), 3235 (NH₂) cm ^-1; ¹H NMR (500 MHz, DMSOd₆) : δ 1.25 (m, 4H, 2CH₂), 1.44,(m, 1H, CH ), 4.46 (bs, 2H, NH₂), 7.63 (m, 4H, 4CH), 8.29 (d, 1H, J = 7.5 Hz, CH), 8.62 (d, 1H, J = 9.5 Hz, CH), 9.34 (d, 1H, J = 12 Hz, CH), Mass (m/z): 420 [M+].

4-(3-Chloro-phenyl)-6-(2-cyclopropyl-[1,8]naphthyridin-3-yl)-[1,3,5]triazin-2-ylamine (3e)

Recrystalised in acetone, filtered the solid compound and dried to offer reddish colour solid (0.21g, 24%). IR (KBr pellet): 2215 (aliph. CH₂), 3235 (NH₂) cm ^-1; ¹H NMR (500 MHz, DMSOd₆) : δ 1.25 (m, 4H, CH₂), 1.44,(m, 1H, CH ), 4.46 (bs, 2H, NH₂), 7.56-7.63 (m, 4H, 4CH), 8.29 (d, 1H, J = 7.5 Hz, CH), 8.62 (d, 1H, J = 9.5 Hz, CH), 9.34 (d, 1H, J = 11.5 Hz, CH), Mass (m/z): 375 [M+].

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Received on 28.10.2017 Modified on 05.11.2017

Asian J. Research Chem. 2018; 11(1):109-110.

DOI:10.5958/0974-4150.2018.00022.6