Hydrogen Bonding of Ionic Liquid Synergized with tert-Butyl Hydroperoxide Oxidation for the Synthesis of 2-Phenylquinazolinone

doi:10.6023/cjoc202510030

Abstract

Quinazolinones are nitrogen-containing heterocyclic scaffolds widely prevalent in pharmaceutical and agrochemical active molecules, thus making their green synthesis methods particularly important. A hydrogen bond-assisted oxidation strategy, employing 1-ethyl-3-methylimidazolium acetate as catalyst and tert-butyl hydroperoxide as oxidant, was developed for the green synthesis of 2-phenylquinazolin-4(3H)-one. The analysis results from density functional theory calculations and control experiments indicated a cascade process: oxidation, cyclization and dehydrogenation. The protocol provided 26 structurally diverse quinazolinone derivatives, achieved gram-scale preparation of 2-phenylquinazolin-4(3H)-one, and established an efficient new approach for synthesizing these compounds.

Key words: hydrogen bond, ionic liquid, tert-butyl hydroperoxide, oxidization, 2-phenylquinazolin-4(3H)-one

Cite this article

Yuwei Zhou, Menghan Cao, Zhanggao Le, Ran Chen, Fengtian Wu, Haibo Zhu, Zongbo Xie. Hydrogen Bonding of Ionic Liquid Synergized with tert-Butyl Hydroperoxide Oxidation for the Synthesis of 2-Phenylquinazolinone[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2369-2378.

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Fig. & Tab. 9

Figure 1. Common with quinazolinone skeleton

Figure 2. Methods for synthesing quinazolinone compounds

Figure 3. The structural formula of 1-ethyl-3-methylimidazolium

Entry	IL	Oxidant	T/℃	Solvent	Yield^b/%
1	[HSO₃PMIm][OTf]	TBHP	110	EIB	Trace
2	[EMIm][ClO₄]	TBHP	110	EIB	Trace
3	[EMIm][NO₃]	TBHP	110	EIB	Trace
4	[EMIM][OAc]	TBHP	110	EIB	91
5	[EMIM][OAc]	MnO₂	110	EIB	15
6	[EMIM][OAc]	BPO	110	EIB	65
7	[EMIM][OAc]	DTBP	110	EIB	30
8	[EMIM][OAc]	TBPB	110	EIB	15
9	[EMIM][OAc]	BPO	110	EIB	68
10	[EMIM][OAc]	TBHP	110	MB	89
11	[EMIM][OAc]	TBHP	110	1,4-dioxane	0
12	[EMIM][OAc]	TBHP	110	H₂O	0
13	[EMIM][OAc]	TBHP	110	TFE	82
14^c	[EMIM][OAc]	TBHP	110	EIB	17
15^d	[EMIM][OAc]	TBHP	110	EIB	18
16^e	[EMIM][OAc]	TBHP	110	EIB	20
17^f	[EMIM][OAc]	TBHP	110	EIB	34
18^g	[EMIM][OAc]	TBHP	110	EIB	51
19^h	[EMIM][OAc]	TBHP	90	EIB	82
20	[EMIM][OAc]	TBHP	100	EIB	13
21	[EMIM][OAc]	TBHP	120	EIB	48
22	[EMIM][OAc]	TBHP	130	EIB	57
23ⁱ	[EMIM][OAc]	TBHP	110	EIB	77
24^j	[EMIM][OAc]	TBHP	110	EIB	88
25^k	[EMIM][OAc]	TBHP	110	EIB	92

Table 1. Optimization of the reaction conditionsa

Scheme 1. Scope of the monosubstituted developed catalytic protocol for the synthesis of various 2-phenylquinazolin-4(3H)-ones

Scheme 2. Scope of the bisubstituted substrates developed catalytic protocol for the synthesis of various 2-phenylquinazolin-4(3H)-ones

Scheme 3. Control experiments

Figure 4. Mechanistic investigation. (a) Variations of hydrogen shifts of amino groups on aniline before and after addition of ILs; (b) Variations of carbon shifts of amino groups on aniline before and after addition of ILs; (c) NBO potential for hydrogen bonding between NH2 of substrate 1a and [EMIm][OAc]; (d) NBO potential for hydrogen bonding between CONH2 of substrate 1a and [EMIm][OAc]

Scheme 4. Plausible reaction mechanism

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