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Table 1 Optimization of the reaction conditions for the synthesis of (3a)

From: An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid derivatives using boric acid as catalyst

Entry Ratio of 1/2 Catalyst Catalyst loading (mole %) Solvent Temp (°C) Time (h) Yieldc (%)
1 2:1 H2O Reflux 24
2 2:1 100 10 35
3 2:1 K2CO3 15 100 24 Trace
4 2:1 NEt3 15 100 24
5 2:1 K2CO3 15 H2O Reflux 24 Trace
6 2:1 NEt3 15 H2O Reflux 24
7 2:1 Fe3O4 15 H2O Reflux 24
8 2:1 DABCOa 15 H2O Reflux 24 Trace
9 2:1 PTSA 15 H2O Reflux 24 65
10 2:1 H3BO3 15 H2O Reflux 24 60
11 2:1 H3BO3 15 EtOH Reflux 24 40
12 2:1 H3BO3 15 n-Hexanol Reflux 24 62
13 2:1 H3BO3 15 PEG-400b Reflux 24 30
14 2:1 H3BO3 15 DMF Reflux 24 45
15 2:1 H3BO3 15 Xylene Reflux 24 Trace
14 2:1 H3BO3 15 Toluene Reflux 24 50
17 2:1 H3BO3 15 100 10 68
18 2:1 H3BO3 30 100 10 82
19 2:1 H3BO3 48 100 10 84
20 2:1 H3BO3 30 80 12 45
21 2:1 H 3 BO 3 30 120 10 90
22 2:1 H3BO3 30 150 10 90
23 2:1 PTSA 30 120 9 90
24 1:1 H3BO3 30 120 20 60
  1. Reaction conditions: 2-methyl-3-trifluoromethylanilin (2 mmol), 2-chloronicotinic acid (1 mmol)
  2. The optimum reaction conditions are in italics
  3. a1,4-diazabicyclo[2.2.2]octane
  4. bPolyethylene glycol
  5. cThe yields refer to the isolated product