Synthesis of 1-(4-methoxybenzyl)-3-cyclopropyl-1H-pyrazol-5-amine derivatives as antimicrobial agents

Figures & data

Scheme 1.  Synthesis of compounds 9(a–h). Reactions and reagent conditions: (i) EtOH/r.t, 2–3 h; (ii) 10% Pd/C/H₂EtOAc, r.t, 3 h; (iii) dichloromethane, ether in HCl, 3 h; (iv) EtOH/EtCOONa, reflux 80°C, 2–3 h; (v) triethylamine, dichloromethane, 8(a–h), r.t, 4–5 h; where R-CO-Cl are: (8a) 3,5-dinitrobenzoyl chloride; (8b) 3-methoxybenzoyl chloride; (8c) 4-tert-butylbenzoyl chloride; (8d) 2,4-dichlorobenzoyl chloride; (8e) 4-chlorobenzoyl chloride; (8f) 3-bromobenzoyl chloride; (8g) 2,4-difluorobenzoyl chloride; (8h) benzoyl chloride.

Table 1.  Chemical structures and physical data of the synthesized compounds 9(a–h).

Compound	R	Yield (%)	M.P. (°C)
9a		89	254–256
9b		91	245–246
9c		88	263–265
9d		85	254–255
9e		81	248–249
9f		84	255–258
9g		79	273–275
9h		80	267–268

Table 2.  Inhibition zone (diameter) in mm of synthesized compounds tested against bacterial strains.

Compound	Gram-positive bacteria			Gram-negative bacteria
	S. pyogenes NCIM 2608	B. subtilis NCIM 2010	S. aureus ATCC 29737	E. coli ATCC25922	P. aeruginosa ATCC 20852	K. pneumoniae MTCC 618
9a	4.1	3.6	6.2	3.5	4.7	5.9
9b	4.3	3.9	5.9	5.8	6.6	6.9
9c	3.7	3.2	—	4.2	5.4	6.1
9d	5.8	4.9	5.4	5.8	6.6	8.0
9e	5.4	3.7	5.2	5.0	6.3	6.2
9f	5.3	3.9	—	5.0	—	4.8
9g	6.2	5.1	5.9	5.8	6.4	7.3
9h	6.1	5.8	6.7	5.9	6.1	7.2
Streptomycin	5.9	4.9	5.2	5.6	6.4	5.3

Table 3.  Minimum inhibitory concentration (MIC) in μg/mL of synthesized compounds tested against bacterial strains.

Compound	Gram-positive bacteria			Gram-negative bacteria
	S. pyogenes NCIM 2608	B. subtilis NCIM 2010	S. aureus ATCC 29737	E. coli ATCC25922	P. aeruginosa ATCC 20852	K. pneumoniae MTCC 618
9a	51	61	56	72	66	58
9b	42	51	58	54	55	58
9c	65	59	73	49	63	73
9d	33	32	37	31	39	06
9e	43	51	60	43	52	53
9f	63	50	53	77	56	53
9g	27	07	21	31	42	38
9h	29	32	35	25	09	22
Streptomycin	39	34	42	39	44	47

Table 4.  Inhibition zone (diameter) in mm of synthesized compounds tested against fungal pathogens.

Compound	Microorganism used
	F. verticilloides	A. alternata	A. flavus	A. ochraceous	P. chrysogenum
9a	1.6	0.9	1.2	1.4	0.9
9b	1.4	1.1	2.0	2.2	1.1
9c	1.6	1.4	2.1	1.4	1.3
9d	4.1	3.6	3.4	4.4	2.3
9e	2.9	1.2	3.4	3.2	2.1
9f	1.9	2.4	—	0.4	—
9g	3.3	2.4	2.3	3.5	2.9
9h	3.2	2.1	2.5	3.2	2.1
Nystatin	1.7	1.4	2.1	2.1	1.9

Table 5.  Minimum inhibitory concentration (MIC) in µg/mL of synthesized compounds tested against fungal pathogens.

Compound	Microorganism used
	F. verticilloides	A. alternata	A. flavus	A. ochraceous	P. chrysogenum
9a	56	29	42	54	59
9b	54	51	50	22	41
9c	46	44	41	34	43
9d	13	14	23	09	39
9e	19	12	54	32	41
9f	49	34	—	44	—
9g	18	20	11	24	21
9h	21	12	31	32	23
Nystatin	32	24	37	39	39