Synthesis of Novel Symmetrical and Unsymmetrical o-Phthalic Acid Diamides

Table 1

Effect of coupling reagent, tertiary base, and temperature on condensation of 3a with 2b in DMF yielding 5a.

Entry	Coupling reagent	Tertiary base	Temp./°C	Time/min	5a (%)
1	HATU	𝐄𝐭𝟑𝐍	0–5	40–45	80
2	HATU	Et3N	RT	40–45	78
3	HATU	DBU	0–5	55–65	70
4	HATU	DBU	RT	50–55	70
5	HATU	Et3N	50–60	35–40	73
6	DCC	—	0–5	120–130	45
7	DCC	—	RT	100–110	48
8	DCC/HOBt	—	0–5	110–120	50
9	DCC/HOBt	—	RT	100–110	50
10	DCC/HOBt	—	50–60	55–60	72
11	EDC·HCl/HOBt	Et3N	0–5	80–85	70
12	EDC·HCl/HOBt	Et3N	RT	70–80	70
13	EDC·HCl/HOBt	DBU	0–5	70–80	60
14	EDC·HCl/HOBt	DBU	RT	70–75	65
15	EDC·HCl/HOBt	Et3N	50–60	65–70	72
16	HBTU	Et3N	0–5	70–75	70
17	HBTU	Et3N	RT	65–70	70
18	HBTU	DBU	0–5	70–80	65
19	HBTU	DBU	RT	65–75	65
20	HBTU	Et3N	50–60	50–55	70
21	PTSA	—	0–5	120–125	—
22	PTSA	—	RT	120–125	—
23	PPA	—	100	60–65	40