Synthesis, spectral characterization, and in vitro antibacterial and antifungal activities of novel 1,3-thiazine-2-amines comprising morpholine nucleus

Figures & data

Scheme 1.  Novel synthesized compounds having core thiazine and morpholine nuclei of therapeutic importance.

Scheme 2.  Synthesis reaction pathway for formation of 4-(4-morphlinophenyl)-6-aryl-6H-1,3-thiazin-2-amines.

Scheme 3.  Proposed reaction mechanism for formation of target molecules.

Table 1.  Physical and analytical data of (E)-1-4-morpholinophenyl)-3-aryl-prop-2-en-1-ones (11–19) and 4-(4-morpholinophenyl)-6-aryl-6H-1,3-thiazin-2-amines (20–28).

Entry	X	Y	Yield (%)	m.p. (°C)	Elemental analysis			m/z (M + 1)^+ Molecular formula
					C found (Calculated)	H found (Calculated)	N found (Calculated)
11	H	H	98	149	77.78 (77.81)	6.46 (6.48)	4.76 (4.77)	294 C19H19NO2
12	CH3	H	92	179	78.15 (78.17)	6.81 (6.84)	4.54 (4.56)	308 C20H21NO2
13	Cl	H	90	143	69.70 (69.72)	5.47 (5.50)	4.26 (4.28)	328, 330 C19H18NO2Cl
14	OCH3	H	95	111	74.29 (74.30)	6.48 (6.50)	4.31 (4.33)	324 C20H21NO3
15	F	H	95	160	73.29 (73.31)	5.76 (5.78)	4.48 (4.50)	312 C19H18NO2F
16	Br	H	95	145	61.27 (61.30)	4.83 (4.87)	3.74 (3.76)	372, 374 C19H18BrNO2
17	H	NO2	90	135	67.43 (67.45)	5.29 (5.32)	8.26 (8.28)	339 C19H18N2O4
18	H	Cl	90	138	69.69 (69.72)	5.48 (5.50)	4.25 (4.28)	328, 330 C19H18NO2Cl
19	H	F	95	154	73.28 (73.31)	5.74 (5.78)	4.47 (4.50)	312 C19H18NO2F
20	H	H	75	61	68.31 (68.35)	6.05 (6.07)	11.94 (11.96)	352 C20H21N3OS
21	CH3	H	70	185	69.00 (69.01)	6.30 (6.34)	11.46 (11.50)	366 C21H23N3OS
22	Cl	H	75	180	62.23 (62.25)	5.19 (5.22)	10.85 (10.89)	386, 388 C20H20N3OSCl
23	OCH3	H	70	124	66.08 (66.12)	6.04 (6.08)	10.98 (11.01)	382 C21H23N3O2S
24	F	H	80	182	64.97 (65.02)	5.42 (5.46)	11.33 (11.37)	370 C20H20N3OSF
25	Br	H	80	161	55.77 (55.82)	4.65 (4.68)	9.71 (9.76)	431, 433 C20H20N3OSBr
26	H	NO2	85	157	60.55 (60.59)	4.65 (4.68)	9.73 (9.76)	397 C20H20N4O3S
27	H	Cl	85	184	62.20 (62.25)	5.18 (5.22)	10.86 (10.89)	386, 388 C20H20N3OSCl
28	H	F	80	188	64.99 (65.02)	5.44 (5.46)	11.32 (11.37)	370 C20H20N3OSF

Table 2.  In vitro antibacterial activity (MIC) values for compounds 20–28.

Compound	Minimum inhibitory concentration (MIC) (μg/mL)
	S. aureus	B. subtilis	V. cholerae	E. coli	P. aeruginosa
20	100	50	200	12.5	25
21	100	100	25	25	6.25
22	50	100	25	50	25
23	100	12.5	25	25	—^a
24	100	50	12.5	25	6.25
25	50	25	50	50	50
26	6.25	12.5	—^a	200	25
27	25	6.25	25	12.5	25
28	12.5	50	12.5	6.25	6.25
Ciprofloxacin	25	25	50	25	25

^aNo inhibition even at higher concentration, i.e. at 200 μg/mL.

Table 3.  In vitro antifungal activity (MIC) values for compounds 20–28.

Compound	Minimum inhibitory concentration (MIC) (μg/mL)
	A. flavus	Mucor	Rhizopus	M. gypseum
20	12.5	100	12.5	100
21	25	100	12.5	50
22	—^a	6.25	100	50
23	6.25	100	50	50
24	12.5	6.25	100	—^a
25	25	25	12.5	6.25
26	50	100	6.25	25
27	100	12.5	50	25
28	50	—^a	6.25	6.25
Fluconazole	50	25	25	25

^aNo inhibition even at higher concentration, i.e. at 200 μg/mL.