Method for carrying out reaction on methylenecyclopropane derivative and ether compound C(sp<3>)-H bond

A technology of methylene cyclopropane and ether compounds, which is applied in the field of C-H bond reaction between methylene cyclopropane derivatives and ether compounds, achieving the effect of high atom economy, high yield, high efficiency and environmental protection of the reaction system

Inactive Publication Date: 2017-07-14
HUNAN INSTITUTE OF SCIENCE AND TECHNOLOGY
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AI-Extracted Technical Summary

Problems solved by technology

Though also have many reaction ether compounds as reactant, because ether C (sp3)-H bond is a stable inert bond, therefore, participate in the report of reaction wit...
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Abstract

The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for carrying out a reaction on a methylenecyclopropane derivative and an ether compound C(sp<3>)-H bond. According to the present invention, a methylenecyclopropane derivative represented by a formula II and an ether compound represented by a formula III are subjected to a reaction in the presence of a free radical initiator to obtain a 1,2-dihydronaphthalene derivative represented by a formula I, wherein the free radical initiator is the mixture comprising one or a plurality of materials selected from TBHP (tert-butyl hydroperoxide), CHP (Cumyl hydroperoxide), and THAP (tert-amyl hydroperoxide). The formulas I, II and III are defined in the specification.

Application Domain

Organic chemistryOrganic compound preparation

Technology Topic

Chemical compoundOrganic synthesis +6

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  • Method for carrying out reaction on methylenecyclopropane derivative and ether compound C(sp&lt;3&gt;)-H bond

Examples

  • Experimental program(4)

Example Embodiment

[0034] Example 1-16 Optimization of reaction conditions
[0035] Using the compound represented by formula II-1 and tetrahydrofuran as raw materials for the reaction, the effects of various conditions on the reaction were explored (formula 2), and representative examples 1-17 were selected. The results are shown in Table 1. Show:
[0036] (Formula 2)
[0037] The operation of embodiment 1 is as follows:
[0038] Add a magnetic stir bar to a 25 mL SCHELNK sealed tube reaction tube, and add 0.3 mmol (about 70.8 mg) of substrate II-1, and then replace the air in the reaction tube with nitrogen. After 3-5 replacements, Add 2.0 equiv TBHP (tert-butanol peroxy, 5.0 M in decane) (approximately 0.15 mL) and 2.0 mL of tetrahydrofuran under a nitrogen atmosphere, cover the reaction tube, and place it in an oil bath at 110°C for 24 hours. After the reaction is complete, use a rotary evaporator to evaporate the solvent, and use a chromatographic column to separate and purify the product. The mobile phase is petroleum ether and ethyl acetate in a ratio of 30:1. You can get product I-1, 68.8mg, the yield is about 75% ( 1 H NMR (400 MHz, CDCl 3 ): 7.44-7.37 (m, 2H), 7.35-7.32 (m, 2H), 7.31-7.24 (m, 1H), 7.03 (t, J = 8.0 Hz, 1H), 6.91 (s, 1H), 6.80-6.70 (m, 2H), 5.08 (s, 2H), 4.82 (t, J = 7.2 Hz, 1H), 4.00-3.95 (m, 1H), 3.88-3.83 (m, 1H), 2.80 (t, J = 8.0 Hz, 2H), 2.35-2.19 (m, 2H), 2.09-2.01 (m, 1H), 1.96-1.91 (m, 2H), 1.79-1.72 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ): 153.9, 140.6, 137.5, 136.9, 128.5, 127.7, 127.2, 127.1, 123.5, 120.2, 116.7, 110.4, 82.2, 70.2, 68.6, 30.6, 28.4, 26.1, 22.6.).
[0039] Table I:
[0040] Example Reaction conditions Yield (%) 1 TBHP (2 equivalents) 75 2 Without adding TBHP, other conditions are the same as in Example 1 0 3 TBHP (1.5 equivalent), other conditions are the same as in Example 1 67 4 TBHP (2.5 equivalents), other conditions are the same as in Example 1 73 5 DCP replaces TBHP, other conditions are the same as in Example 1 0 6 DTBP replaces TBHP, other conditions are the same as in Example 1 0 7 BPO replaces TBHP, other conditions are the same as in Example 1 0 8 CHP replaces TBHP, other conditions are the same as in Example 1 18 9 TAHP replaces TBHP, other conditions are the same as in Example 1 51 10 Mn(OAc) 3 Instead of TBHP, other conditions are the same as in Example 1
[0041] Among them, TBHP is tert-butanol peroxy;
[0042] DCP is dicumyl peroxide;
[0043] DTBP is di-tert-butyl peroxide;
[0044] BPO is dibenzoyl peroxide;
[0045] CHP is cumene hydrogen peroxide;
[0046] TAHP is terepentyl hydrogen peroxide;
[0047] BuOAc is n-butyl acetate;
[0048] Benzene is benzene;
[0049] AIBN is azobisisobutyronitrile.
[0050] It can be seen from the foregoing Examples 1-17 that the optimal reaction conditions of the present invention are the conditions of Example 1, that is, when the amount of TBHP added is 2 equivalents of the amount of substrate II-1, a yield of 75% can be obtained; Free radical initiators, such as CHP (cumene hydrogen peroxide), THAP (tert-amyl hydrogen peroxide) can also promote the reaction, but the effect is worse than TBHP; and when using common free radical initiators in the field such as Mn(OAc) reported by DCP, DTBP, BPO and Xian Huang research group 3 Or when AIBN replaced TBHP as the free radical initiator, the reaction did not occur through GC detection (Examples 1-11). When other solvents are added, the reaction yield decreases (see Example 12-13); and the reaction atmosphere, reaction temperature and time have a certain degree of influence on the reaction yield (see Example 14-17).

Example Embodiment

[0051] Example 18
[0052] (Formula 3)
[0053] Add a magnetic stir bar to a 25 mL SCHELNK sealed tube reaction tube, and add 0.3 mmol substrate II-2, and then replace the air in the reaction tube with nitrogen. After replacing it for 3-5 times, add it under nitrogen flow 2.0 equiv TBHP (tert-butanol peroxy, 5.0 M in decane) (approximately 0.15 mL) and 2.0 mL tetrahydrofuran, cover the reaction tube lid, and place it in an oil bath at 110 degrees Celsius for 24 hours. After the reaction is complete, use a rotary evaporator to evaporate the solvent, and use a chromatographic column to separate and purify the product. The mobile phase is petroleum ether and ethyl acetate in a ratio of 30:1. The product I-2 can be obtained with a yield of about 70% ( 1 HNMR (400 MHz, CDCl 3 ): 7.42-7.33 (m, 3H), 7.23-7.07 (m, 4H), 7.01 (t, J = 7.2Hz, 1H), 6.57 (d, J = 7.6 Hz, 1H), 4.34 (t, J = 8.0 Hz, 1H), 3.94-3.89 (m,1H), 3.75-3.70 (m, 1H), 2.99-2.81 (m, 2H), 2.61-2.54 (m, 1H), 2.37-2.29 (m,1H) ), 1.94-1.64 (m, 4H); 13 C NMR (100 MHz, CDCl 3 ): 138.8, 137.5, 136.5, 135.9, 129.9, 128.0, 127.0, 126.8, 126.6, 126.1, (2C), 78.7, 68.8, 30.8, 28.5, 21.5.).

Example Embodiment

[0054] Example 19
[0055] (Formula 4)
[0056] Add a magnetic stir bar to a 25 mL SCHELNK sealed tube reaction tube, and add 0.3 mmol substrate II-3, and then replace the air in the reaction tube with nitrogen. After replacing it for 3-5 times, add it under nitrogen flow 2.0 equiv TBHP (tert-butanol peroxy, 5.0 M in decane) (approximately 0.15 mL) and 2.0 mL tetrahydrofuran, cover the reaction tube lid, and place it in an oil bath at 110 degrees Celsius for 24 hours. After the reaction is complete, use a rotary evaporator to evaporate the solvent, and use a chromatographic column to separate and purify the product. The mobile phase is petroleum ether and ethyl acetate in a ratio of 30:1. The product I-3 can be obtained with a yield of about 68% ( 1 HNMR (400 MHz, CDCl 3 ): 6.84 (s, 1H), 6.72 (s, 1H), 5.94 (s, 2H), 4.46 (t, J =7.2 Hz, 1H), 4.02-3.96 (m, 1H), 3.90-3.84 (m, 1H), 2.77-2.71 (m, 2H), 2.28-2.16 (m, 2H), 2.12-2.05 (m, 1H) ), 1.99-1.94 (m, 2H), 1.76-1.70 (m, 1H); 13 C NMR(100 MHz, CDCl 3 ): 146.6, 143.9, 141.4, 127.3, 120.9, 117.8, 112.7, 110.2, 101.4, 81.8, 68.6, 30.7, 26.0, 21.8, 21.6.).

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