Choline hydroxide, an efficient, green, and recyclable base catalyst, promoted the synthesis of 3-aroylflavones via Baker–Venkataraman rearrangement

Figures & data

Scheme 1. Sequential ‘one-pot’ synthesis of 3-aroylflavones via Baker–Venkataraman rearrangement.

Table 1. The nature of base catalysts influenced the product formation in ‘one-pot’ Baker–Venkataraman rearrangement.^a

Entry	Base catalyst (mmol)	Yield^b (%)
		3a	4a	6a
1	Et3N (2.5)	61	39	0
2	Pyridine (2.5)	46	20	0
3	CaO-ES (3.0)	63	21	0
4	KOH (3.0)/pyridine (11.0)	0	0	38
5	ChOH (2.5)	12	0	0
6	ChOH (3.0)	9	0	0

^a 5′-Chloro-2′-hydroxyacetophenone (1a, 1.0 mmol), benzoyl chloride (2a, 2.1 mmol), and amount of surveyed catalyst were performed under magnetic stirring and heating at 110°C for 5 h.

^b Yields were calculated based on HPLC-ELSD analyses.

Scheme 2. Sequential ‘one-pot’ synthesis of 3-benzoyl-6-chloroflavone via Baker–Venkataraman rearrangement.

Figure 1. Influence of choline hydroxide amount in the synthesis of 3-benzoyl-6-chloroflavone from the reaction of 5′-chloro-2′-hydroxyacetophenone (1.0 mmol) and benzoyl chloride (2.3 mmol). Reaction conditions: step 1: Et₃N (2.5 mmol) under r.t. stirring for 30 min., and step 2: ChOH (varied amount) in Et₃N (11.0 mmol) under reflux for 5 hours.

Table 2. Yields of 3-aroylflavones from the reactions between 2′-hydroxyacetophenones and benzoyl chlorides.^a

Entry	6	R^1	R^2	R^3	R^4	R′	Yield^b % (LC^c, time^d) of 6
1	6a	H	Cl	H	H	H	59 (80, 8)
2	6b	H	F	H	H	H	52 (85,8)
3	6c	H	Br	H	H	H	56 (91, 8)
4	6d	H	OH	H	H	H	24 (44, 15)
5	6e	H	OMe	H	H	H	55 (90, 5)
6	6f	H	NO2	H	H	H	40 (66, 9)
7	6g	H	Br	H	H	4-F	30 (68, 15)
8	6h	H	Br	H	H	3-Cl	31 (62, 4)
9	6i	H	Br	H	H	4-Br	30 (57, 36)
10	6j	H	Br	H	H	4-Me	32 (59, 48)
11	6k	H	Br	H	H	4-CF3	33 (62, 2)
12	6l	H	Br	H	H	4-NO2	23 (30, 5)
13	6m	H	F	H	H	4-F	35 (62, 8)
14	6n	H	F	H	H	3-Cl	33 (57, 7)
15	6o	H	F	H	H	4-Br	29 (51, 15)
16	6p	H	F	H	H	4-NO2	46 (65, 3)
17	6q	H	H	F	H	4-Br	41 (53, 16)
18	6r	H	H	F	H	4-F	32 (66, 12)
19	6s	H	Cl	H	H	3-Cl	40 (61, 4)
20	6t	OH	H	H	H	H	39 (59, 9)
21	6u	OH	H	H	H	3-Cl	72 (100, 3)
22	6v	OH	H	H	H	4-CF3	48 (92, 4)
23	6w	H	H	OH	H	H	11 (24, 15)
24	6x	H	Cl	H	Cl	3-Cl	32 (64, 1.5)
25	6y	H	Cl	H	Cl	4-Me	39 (70, 14)
26	6z	H	OMe	H	H	4-NO2	35 (41, 10)
27	6aa	H	H	[h]-benzo		H	46 (53, 24)

^a 2′-Hydroxyacetophenone (1.0 mmol), benzoyl chloride (2.3 mmol), and choline hydroxide (0.5 mmol) in triethylamine (11.0 mmol) were performed under reflux for an appropriate time.

^b Isolated yields.

^c LC yields were calculated based on HPLC analyses.

^d Time: reaction time in hour.

Scheme 3. A plausible mechanism for the synthesis of 3-aroylflavones via sequential ‘one-pot’ Baker – Venkataraman rearrangement catalyzed by choline hydroxide in triethylamine.

Figure 2. Reusability of choline hydroxide in sequential ‘one-pot’ synthesis of 3-benzoyl-6-chloroflavone. Yields were calculated based on HPLC-UV analyses.

Figure 3. FT–IR spectra of fresh ChOH (a), ChOH after 1st recycle (b), and ChOH after 6th recycle (c).

Figure 4. FT–IR spectra of pairs of 6,8-dichloroflavone (Fl-3,5Cl) and 6,8,3′-trichloro-3-(3″-chlorobenzoyl)flavone (BzFl-3,5Cl) (a), pairs of 5-hydroxyflavone (Fl-6OH) and 3-benzoyl-5-hydroxyflavone (BzFl-6OH) (b), six 3-benzoylflavones (c), and five 3-aroylflavones (d).

Table 3. Comparison of previous synthesis of 3-aroylflavones from 2′-hydroxyacetophenones and benzoyl chlorides.

Condition	Catalyst	Time	Catalyst runs	Overall yield (%)
Heat (80–90°C)	DBU/pyridine	6–7 h	None	47–67^19
r.t. MW (400 W, 120°C)	DCC, 4-pyrrolidinopyridine, CH2Cl2 K2CO3/pyridine	12–20 h 10 min	None	54–58^20
r.t. then reflux	K2CO3/acetone	24 h	None	35–46^21–23
Heat (120–140°C) r.t.	DBU/pyridine 10% NaOH/dioxane, MeOH, H2O	24 h 3–4 h	None	5–23^24
Heat (60–110°C)	DBU/pyridine; KOH/pyridine; K2CO3/pyridine; K2CO3/acetone or wet K2CO3/acetone	24 h	None	11–55^25
0°C to r.t. r.t.	LiHMDS in THF, toluene 20% or 37% HCl	20 min to 24 h 1–12 h	None	51–72^26
r.t. Heat (reflux)	Et3N ChOH/Et3N	30 min 2–48 h	4	11–72 (our work)