Table 1.

Optimization of Ullmann‐type C−O bond formation between halobenzene 1 and Gly of the corresponding eutectic mixture to give adducts 2  a and 3  a.^[a]

Entry	Solvent	Catalyst (mol %)	Base (equiv.)	T [°C]	2a+3a yield[b] [%]	2a/3a [c]
1	ChCl/Gly[d]	CuI (10)	K2CO3 (2)	60	–[e]	–
2	ChCl/Gly[d]	CuI (10)	K2CO3 (2)	80	98	77 : 23
3	ChCl/Gly[d]	CuI (5)	K2CO3 (1)	80	98	80 : 20
4	ChCl/Gly[f]	CuI (5)	K2CO3 (1)	80	98	80 : 20
5	ChCl/Gly[g]	CuI (5)	K2CO3 (1)	100	30[e]	80 : 20
6	ChCl/Gly[d]	CuI (5)	–	80	NR[h]	–
7	ChCl/Gly[d]	–	K2CO3 (1)	100	NR[h]	–
8	ChCl/Gly[d]	CuI (5)	Cs2CO3 (1)	80	98	78 : 22
9	ChCl/Gly[d]	CuI (5)	tBuOK (1)	80	98	77 : 23
10	ChCl/Gly[d]	CuO (5)	K2CO3 (1)	80	90	78 : 22
11	ChCl/Gly[d]	CuCl2 (5)	K2CO3 (1)	80	98	80 : 20
12	ChCl/Gly[d]	Pd(OAc)2 (5)	K2CO3 (1)	100	–[i]	–
13	Gly	CuI (5)	K2CO3 (1)	100	75	76 : 24
14	ChCl/Gly[j]	CuI (5)	K2CO3 (1)	80	96	80 : 20
15	ChCl/Gly[k]	CuI (5)	K2CO3 (1)	80	98	80 : 20
16	Pro/Gly	CuI (5)	K2CO3 (1)	100	–	–
17	betaine/Gly	CuI (5)	K2CO3 (1)	100	20[l]	78 : 22

[a] Reaction conditions: 1.0 g DES or 1 mL Gly per 1.0 mmol of 1  a–c; DES: ChCl/Gly (1 : 2, 1 : 1, or 1 : 3 mol mol⁻¹); l‐proline (Pro)/Gly (2 : 5 mol mol⁻¹); betaine/Gly (1 : 2 mol mol⁻¹). [b] The yields reported are for products isolated and purified by column chromatography. [c] Calculated by ¹H NMR spectroscopy of the crude reaction mixture using an internal standard technique (NMR internal standard: CH₂Br₂). [d] X=Br. [e] Reaction time: 24 h. [f] X=I. [g] X=Cl. [h] NR=no reaction. [i] Biphenyl was the only adduct isolated (98 % yield). [j] 1 : 1 mol mol⁻¹. [k] 1 : 3 mol mol⁻¹. [l] After 24 h: 55 % yield.