Assessment of amination reactions via nucleophilic aromatic substitution using conventional and eco-friendly energies

Figures & data

Figure 1. Selected compounds ensemble for a S_NAr reaction.

Figure 2. General reactions to obtain target molecules.

Scheme 1. Synthetic Pathway to synthesize 3a-d and 5a-d.

Table 1. Screening the S_NAr reaction conditions for the preparation of 3b and 3c.

			3b	3c
Entry*	Solvent	Base	Yield (%)
1	EtOH	–	38	53
2	–	N(Et)3	40	53
3	DMF	K2CO3	78	79
4	N(Me)3	Pyridine	47	58
5	DMSO	Aniline	88	88
6	THF	NaOH	60	17
7	MeOH	NaHCO3	39	48
8	i-PrOH	N(Et)3	42	40

Table 2. Preparation of 3a-d from 1a-d by thermal and alternative energies.

Entry	1a-d (X)	NHR^1	Thermal	IR	US^b	IR-US^c	MW^d	Product
			(150°C)	(90°C)	(100°C)	(100°C)	(100°C)
					Time (h)/yield (%)
1		2a^a	1.17/32	2.17/50	1.00/52	2.00/69	0.42/55	3a
2		2b	0.70/78	1.25/56	1.34/50	7.00/53	1.00/60	3b
3	F	2c	0.70/85	0.75/93	0.75/70	0.30/63	0.59/78	3c
4		2d	0.70/70	2.00/42	1.00/30	3.00/56	0.50/48	3d
5		2a^a	7.00/47	5.00/80	1.50/68	4.50/77	1.00/48	3a
6		2b	10.0/27	8.00/27	1.00/15	8.00/18	2.00/20	3b
7	Cl	2c	1.75/70	3.50/57	1.50/74	2.00/70	0.92/64	3c
8		2d	6.00/40	3.50/19	2.50/24	4.00/52	1.00/48	3d
9		2a^a	4.50/30	4.50/30	4.00/24	6.50/20	1.50/39	3a
10		2b	19.0/12	6.00/20	15.34/5	9.00/14	5.00/21	3b
11	Br	2c	5.12/38	5.00/49	10.0/20	7.00/19	2.00/42	3c
12		2d	4.00/12	7.00/24	9.00/18	8.00/6	2.00/32	3d
13		2a^a	6.00/16	7.00/24	5.00/13	6.50/13	4.00/26	3a
14		2b	13.5/10	10.5/12	14.0/9	10.0/NR	8.00/ 9	3b
15	I	2c	8.00/22	7.00/34	6.50/14	8.00/20	3.50/26	3c
16		2d	5.00/18	8.00/14	8.00/9	10.0/NR	6.00/20	3d

^aDMF was used as solvent.

^bKeystrokes were carry out by cycling sequences composed of 2 minutes of activation and 5 minutes of cooling.

^cKeystrokes were carry out by cycling sequences composed of 1 minute of activation and 5 minutes of cooling.

^dMicrowave protocol include keystrokes of 20 minutes, following of 10 minutes of cooling. NR (No Reaction).

Table 3. Preparation of 5a-d.

Entry	4a-d (X)	NHR^1	Thermal	IR	US^b	IR-US^c	MW^d	Product
			(150°C)	(90°C)	(100°C)	(100°C)	(100°C)
					Time (h)/yield (%)
17		2a^a	1.50/40	3.34/38	1.59/40	3.00/38	0.44/48	5a
18		2b	4.50/72	2.50/12	1.84/42	10.0/42	0.75/51	5b
19	F	2c	1.00/69	0.34/70	1.50/65	0.50/53	0.42/69	5c
20		2d	2.00/69	1.50/36	2.00/14	6.00/54	0.40/45	5d
21		2a^a	7.00/58	6.50/73	3.34/64	7.00/55	1.42/59	5a
22		2b	16.0/NR	10.0/20	4.00/19	10.0/12	2.50/15	5b
23	Cl	2c	4.67/62	4.50/47	3.00/54	3.00/63	0.75/69	5c
24		2d	7.00/20	5.00/17	3.67/10	10.0/37	2.00/48	5d
25		2a^a	8.00/20	7.00/27	6.00/19	8.00/20	2.00/27	5a
26		2b	24.0/9	11.9/17	14.0/NR	14.0/NR	8.00/16	5b
27	Br	2c	7.50/16	8.00/39	7.00/12	9.00/9	3.50/36	5c
28		2d	6.00/9	9.00/18	6.50/9	9.00/NR	3.00/17	5d
29		2a^a	10.0/12	10.0/32	8.00/16	8.00/9	6.00/23	5a
30		2b	28.0/NR	16.0/NR	18.0/NR	15.0/NR	12.0/NR	5b
31	I	2c	9.00/15	8.00/30	9.50/10	11.0/8	5.00/17	5c
32		2d	8.00/13	9.50/9	9.00/NR	12.0/NR	6.00/NR	5d

^aDMF was used as solvent.

^bKeystrokes were carry out by cycling sequences composed of 2 minutes of activation and 5 minutes of cooling.

^cKeystrokes were carry out by cycling sequences composed of 1 minute of activation and 5 minutes of cooling.

^d(762 W), Microwave protocol include keystrokes of 20 minutes, following of 10 minutes of cooling. NR (No Reaction).

Scheme 2. Proposed mechanism to the preparation of phenyldiazenyl derivatives 3d and 5d.