3,6-二烃基咔唑-1-甲醛和3,6-二烃基咔唑-1,8-二甲醛的高效合成

doi:10.6023/cjoc202101001

摘要/Abstract

已报道的咔唑-1-甲醛或咔唑-1,8-二甲醛的合成方法要么合成步骤长, 产率低, 要么试剂毒性较大或者操作具有较大危险性, 严重影响了后续衍生物合成和应用的进展. 在本研究中, 用2-(三甲硅烷基)乙氧甲基氯(SEMCl)保护溴代咔唑9-NH, 成功利用正丁基锂/N,N-二甲基甲酰胺(DMF)代替叔丁基锂/DMF完成甲酰化, 降低了操作的危险性, 获得了一种更安全高效、适合规模化制备的3,6-二烃基咔唑-1-甲醛或1,8-二甲醛的制备方法. 此外, 还对咔唑-1-甲醛或1,8-二甲醛的反应活性进行探索, 成功制备了一系列三齿氮或双齿氮型配体.

关键词: 咔唑, 甲酰化, 咔唑-1-甲醛, 咔唑-1, 8-二甲醛

The currently reported synthesis methods of carbazole-1-formaldehyde or carbazole-1,8-diformaldehyde have some drawbacks, such as long synthetic steps with low yield, high toxicity of reagents, or high risk of operation, which affected the progress of synthesis and application of subsequent derivatives. In this work, the 9-NH of bromocarbazole was protected by 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl), the subsequent formylation was successfully accomplished by n-butyllithium/N,N-dimethylformamide (DMF) instead of tert-butyllithium/DMF to reduce the risk of operation process. Finally, a safe and efficient method that is more suitable for large-scale preparation of 3,6-dialkylcarbazole-1-formaldehyde or 1,8-diformaldehyde was developed. In addition, the reactivity of carbazole-1-formaldehyde or 1,8-diformaldehyde was explored, and a series of tridentate or bidentate ligands were successfully prepared.

Key words: carbazole, formylation, carbazole-1-formaldehyde, carbazole-1, 8-diformaldehyde

引用此文

赵雨, 刘阳, 王鑫鑫, 洪莹莹, 满英秀, 王进军, 李家柱. 3,6-二烃基咔唑-1-甲醛和3,6-二烃基咔唑-1,8-二甲醛的高效合成[J]. 有机化学, 2021, 41(6): 2435-2444.

Yu Zhao, Yang Liu, Xinxin Wang, Yingying Hong, Yingxiu Man, Jinjun Wang, Jiazhu Li. Efficient Synthesis of 3,6-Dialkylcarbazole-1-formaldehyde and 3,6-Dialkylcarbazole-1,8-diformaldehyde[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2435-2444.

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Entry^a	Protection	PG	Product^a	n-BuLi/DMF (equiv.)^b	T^c/℃	Time^d/h	Deprotection	Yield^e/% of 5
1	n-BuLi/TMSCl	TMS	4a	—	—	—	—	—
2	n-BuLi/CO₂	CO₂^-	4b	—	—	—	—	—
3	DMAP/Boc₂O	Boc	4c	—	—	—	—	—
4	NaH/Boc₂O		4c	—	—	—	—	—
5	n-BuLi/Boc₂O		4c	—	—	—	—	—
6	NaH/ClCO₂Me	CO₂Me	4d	—	—	—	—	—
7	n-BuLi/ClCO₂Me	CO₂Me	4d	—	—	—	—	—
8	NaH/CbzCl	Cbz	4e	—	—	—	—	—
9	n-BuLi /CbzCl	Cbz	4e	—	—	—	—	—
10	NaH/MOMCl	MOM	4f	2.2/5	0/r.t.	0.5/1	—	—
11			4f	2.2/5	–40/r.t.	0.5/1	HCl	18
12			4f	2.2/5	–78/r.t.	0.5/1	HCl	33
13			4f	2.2/10	–78/r.t.	1/2	HCl	56
14			4f	3/20	–78/r.t.	2/12	HCl	55
15	NaH/SEMCl	SEM	4g	2.2/5	–40/r.t.	0.5/1	TBAF	32
16			4g	2.2/5	–78/r.t.	0.5/2	TBAF	67
17			4g	2.2/10	–78/r.t.	0.5/2	TBAF	79
18			4g	2.2/10	–78/r.t.	1/2	TBAF	93
19			4g	2.2/10	–78/r.t.	1/2	HCl^f	92
20			4g	3/20	–78/r.t.	2/12	HCl^f	90

Entry^a	Protection	PG	Product^a	n-BuLi/DMF (equiv.)^b	T^c/℃	Time^d/h	Deprotection	Yield^e/% of 5
1	n-BuLi/TMSCl	TMS	4a	—	—	—	—	—
2	n-BuLi/CO₂	CO₂^-	4b	—	—	—	—	—
3	DMAP/Boc₂O	Boc	4c	—	—	—	—	—
4	NaH/Boc₂O		4c	—	—	—	—	—
5	n-BuLi/Boc₂O		4c	—	—	—	—	—
6	NaH/ClCO₂Me	CO₂Me	4d	—	—	—	—	—
7	n-BuLi/ClCO₂Me	CO₂Me	4d	—	—	—	—	—
8	NaH/CbzCl	Cbz	4e	—	—	—	—	—
9	n-BuLi /CbzCl	Cbz	4e	—	—	—	—	—
10	NaH/MOMCl	MOM	4f	2.2/5	0/r.t.	0.5/1	—	—
11			4f	2.2/5	–40/r.t.	0.5/1	HCl	18
12			4f	2.2/5	–78/r.t.	0.5/1	HCl	33
13			4f	2.2/10	–78/r.t.	1/2	HCl	56
14			4f	3/20	–78/r.t.	2/12	HCl	55
15	NaH/SEMCl	SEM	4g	2.2/5	–40/r.t.	0.5/1	TBAF	32
16			4g	2.2/5	–78/r.t.	0.5/2	TBAF	67
17			4g	2.2/10	–78/r.t.	0.5/2	TBAF	79
18			4g	2.2/10	–78/r.t.	1/2	TBAF	93
19			4g	2.2/10	–78/r.t.	1/2	HCl^f	92
20			4g	3/20	–78/r.t.	2/12	HCl^f	90