4,8,9,10-四官能化的2-氮杂金刚烷及其2-氮杂原金刚烷骨架异构体的合成

doi:10.6023/cjoc202210027

摘要/Abstract

小分子法多步合成结构刚性的、多官能化的氮杂金刚烷骨架一直是金刚烷化学领域的一大挑战. 本工作以双环[3.3.1]壬烷-2,6-二酮为原料, 经缩酮化、溴代、消除、Prilezhaev氧化得到双环氧化物中间体, 并在120 ℃下氨解关环合成9,10-二羟基-2-氮杂金刚烷-4,8-二酮双(乙二醇缩酮), 后经N,O-硝化合成了9,10-二硝酰氧基-2-硝基-2-氮杂金刚烷- 4,8-二酮双(乙二醇缩酮), 六步反应总收率10%; 而该双环氧化物中间体在135 ℃下氨解得到2-氮杂原金刚烷(2-氮杂三环[4.3.1.0^3,8]-癸烷)的骨架异构体4,10-二羟基-2-氮杂原金刚烷-5,9-二酮双(乙二醇缩酮), 后经N-乙酰化、硝化-去缩酮化得到相应的O-硝化及N,O-硝化衍生物. 为后续多官能化的2-氮杂金刚烷及其骨架异构体2-氮杂原金刚烷的衍生提供了可靠的方法, 可用作高能量密度笼型化合物的结构框架.

关键词: 氮杂金刚烷, 氮杂原金刚烷, 官能化, 氨解, 环化, 硝胺, 合成设计

The multi-step synthesis of rigid and multifunctionalized azaadamantane skeletons from small molecules has always been a challenge in the field of adamantane chemistry. In this work, the bisepoxidized intermediate was obtained via ketalization, bromination, elimination, and Prilezhaev oxidation using bicyclo[3.3.1]nonane-2,6-dione as the raw material, which was then ammonolyzed and cyclized to generate 9,10-dihydroxy-2-azaadamantane-4,8-dione bis(ethylene ketal) with ammonia at 120 ℃. After that, 9,10-dinitroyloxy-2-nitro-2-azaadamantane-4,8-dione bis(ethylene ketal) was synthesized by N,O-nitration with the overall yield of 10% over six steps. Furthermore, when the bisepoxidized intermediate was ammonolyzed at 135 ℃, a skeleton isomer 4,10-dihydroxy-2-azaprotoadamantane-5,9-dione bis(ethylene ketal) was formed, which was then transformed to the corresponding O-nitrated and N,O-dinitrated derivatives through N-acetylation, deketalization and nitration, respectively. These provide a reliable method for the subsequent derivation of multifunctional 2-azaadamantane and its skeleton isomer 2-azaprotoadamantane, which might be used as basic scaffolds for high energy density cage-like compounds.

Key words: azaadamantane, azaprotoadamantane, functionalization, ammonolysis, cyclization, nitramine, synthesis design

引用此文

蔡荣斌, 李冰, 周琪, 朱隆懿, 罗军. 4,8,9,10-四官能化的2-氮杂金刚烷及其2-氮杂原金刚烷骨架异构体的合成[J]. 有机化学, 2023, 43(6): 2217-2225.

Rongbin Cai, Bing Li, Qi Zhou, Longyi Zhu, Jun Luo. Synthesis of 4,8,9,10-Tetrafunctionalized 2-Azaadamantanes and Their 2-Azaprotoadamantane Skeleton Isomers[J]. Chinese Journal of Organic Chemistry, 2023, 43(6): 2217-2225.

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图/表 7

图1. 含有氮杂金刚烷骨架的代表化合物

Figure 1. Representative compounds bearing azaadamantane skeleton

图2. 4,8,9,10-四官能化2-氮杂金刚烷的合成策略

Figure 2. Synthetic strategy of 4,8,9,10-tetrafunctional-2-azaadamantane

图式1. 双环[3.3.1]壬-3,7-二烯-2,6-二醇/二酮的环氧化反应探索

Scheme 1. Attempts at the epoxidation of bicyclo[3.3.1]nona-3,7-diene-2,6-diol/dione

图式2. 9,10-二羟基-2-氮杂金刚烷-4,8-二酮双(乙二醇缩酮)及其骨架异构体的构建

Scheme 2. Construction of 9,10-dihydroxy-2-azaadamantane-4,8-dione bis(ethylene ketal) and its skeleton isomer

Entry	Temp./℃	Time/h	Recovery^b/% of 9	Yield^b/% of 12/14
1	100	24	86	<5/0
2	105	24	81	8/0
3	110	24	73	12/0
4	115	24	64	21/0
5	120	24	53	30/0
6	125	24	50	26/7
7	130	24	46	19/18
8	135	24	40	14/26
9	140	24	39	12/24
10	120	36	36	37/0
11	120	48	30	42/0
12	120	60	25	40/0
13	135	36	36	18/33
14	135	48	27	17/39
15	135	60	18	11/36
16^c	120	48	34	38/0
17^c	135	48	28	13/36
18^d	135	48	—	96/0

表1. 氨解环合反应条件的优化a

Table 1. Optimization of ring closing reaction conditions for ammonolysis

图式3. 9,10-二羟基-2-氮杂金刚烷-4,8-二酮双(乙二醇缩酮)及其骨架异构体的硝化反应

Scheme 3. Nitration of 9,10-dihydroxy-2-azaadamantane-4,8- dione bis(ethylene ketal) and its isomer

图3. 化合物17和19?H2O的晶体结构

Figure 3. Crystal structures of compounds 17 and 19?H2O

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