Optimisation of reaction conditions for the direct reductive amination of 4-nitrobenzaldehyde and p-anisidine^a.

Entry	Catalyst loading [mol%]	Solvent	Conversionb [%]	4bb	4cb
1	10	Toluene	99	9	91
2	10	CPME	99	31	69
3	10	NBP	99	4	96
4	10	GVL	99	—	100 (90) d
5	10	2-MeTHF	99	20	80
6c	10	scCO2	NR	—	—
7	10	Neat	99	17	83
8	5	Neat	99	20	80
9	1	Neat	99	9	91
10	0	Neat	99	34	66
11	0	Toluene	99	66	34

^aReaction conditions: 4a (0.24 mmol), 4-nitrobenzaldehyde (1.2 equiv.), Hantzsch ester (1.2 equiv.), thiourea, solvent (0.4 M) stirred for 16 hours at 70 °C.

^bConversion was determined by GC-MS analysis of the reaction mixture; entries were performed in duplicate.

^cReaction conditions: stirred for 16 hours under 80 bars of CO₂ at 70 °C.

^dIsolated yield.