Preparation method of 1-phenyl trifluoromethyl N-(fluorosulfonyl) carbamate compound

Abstract

The invention discloses a preparation method of a 1-phenyl trifluoromethyl N-(fluorosulfonyl) carbamate compound, and belongs to the field of chemical daily chemicals. According to the method, aryl formaldehyde serves as a substrate, TMSCF3 and FSI which are low in price and easy to obtain are adopted as a trifluoromethyl reagent and a fluorosulfonylation reagent respectively, the substrate is wide in applicability, raw materials are simple and easy to obtain, the economic cost is low, and the target product can be obtained with the good yield.

Description

Technical Field

[0001] The invention specifically relates to a method for preparing a 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound, and belongs to the field of chemical daily chemicals. Background Art

[0002] In recent years, sulfonyl fluoride compounds have attracted more and more attention from the academic community. Sulfonyl fluoride compounds have become an important scaffold in the fields of organic synthesis, pharmaceutical medicine, and materials science due to their good balance between reactivity and stability. Sulfonyl fluoride compounds are also an important part of the new generation of "fluorine-sulfur exchange" concept proposed by Nobel Prize winner Sharpless. SuFEx click chemistry utilizes the strong nucleophilicity and electrophilicity between sulfur and fluorine, and can efficiently and selectively achieve the modification and functionalization of organic molecules. Therefore, in the past decade, there has been an urgent need to study the synthesis and modification components of sulfonyl fluoride, thereby developing many complex sulfonyl fluoride synthesis methods. However, most of the existing new methods focus on the synthesis of aryl sulfonyl fluoride compounds, while the synthesis of alkane sulfonyl fluoride compounds is relatively rare, and these synthetic reactions often use expensive metal catalysis, photocatalysis and electrocatalysis, or ClSO2F, ESF, SO2F and other reagents with low boiling points and high toxicity. Summary of the invention

[0003]

Technical issues

[0004] The invention provides a preparation method which is not suitable for expensive and complicated catalytic systems and can realize trifluoromethylation and fluorosulfonylation at the same time.

[0005]

Technical solution

[0006] The present invention uses FSI to attack the carbonyl oxygen of aromatic formaldehyde to produce C + ion, and then with [CF3] - The final product is obtained by combining to synthesize 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound.

[0007] The object of the present invention is to provide a method for preparing a 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound, wherein the method comprises the following steps: in a solvent, an aromatic formaldehyde as a substrate is reacted under the action of a trifluoromethylating agent and an FSI agent (chlorosulfonyl isocyanate), and after the reaction is completed, a 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound as shown in formula (2) is obtained;

[0008]

[0009] Wherein, R is selected from H, C 1-6 Alkyl, halogen, cyano, nitro, C 1-6Alkoxy, acyl and amide groups, aryl groups.

[0010] In one embodiment of the present invention, the acyl group is -COR1, R1 is selected from C 1-6 alkyl.

[0011] In one embodiment of the present invention, the amide group is -NR2COR3, R2 is selected from H, C 1-6 Alkyl, R3 is selected from C 1-6 alkyl.

[0012] In one embodiment of the present invention, the aryl group is a benzene ring or a naphthalene ring.

[0013] In one embodiment of the present invention, the solvent is a mixed system of dichloromethane and tetrahydrofuran.

[0014] In one embodiment of the present invention, the volume ratio of dichloromethane to tetrahydrofuran is 1:(0.8-1.2); preferably 1:1.

[0015] In one embodiment of the present invention, the reaction temperature is 20-50° C., preferably 20-30° C. (room temperature).

[0016] In one embodiment of the present invention, the reaction time is 8-15 hours, and specifically 10 hours can be selected.

[0017] In one embodiment of the present invention, the trifluoromethylation reagent is Ruppert-Prakash reagent (TMSCF3).

[0018] In one embodiment of the present invention, the molar ratio of the aromatic formaldehyde to the trifluoromethylation agent is 1:(1.0-1.5), and specifically 1:1.2.

[0019] In one embodiment of the present invention, the molar ratio of the aromatic formaldehyde to the FSI reagent is 1:(1.5-3.0), and can be specifically 1:2.0.

[0020] In one embodiment of the present invention, the molar ratio of the trifluoromethylation agent to FSI is 1:(0.5-2).

[0021] In one embodiment of the present invention, the structure of the fluorosulfonyl isocyanate (FSI) is F-SO2-N=C=O.

[0022] The reaction further comprises adding tetrabutylammonium fluoride as an additive, wherein the molar ratio of tetrabutylammonium fluoride to aromatic formaldehyde is (0.1-0.5):1. Specifically, 0.2:1 can be selected.

[0023] In one embodiment of the present invention, the reaction is carried out under an inert atmosphere, which includes nitrogen and argon.

[0024] In one embodiment of the present invention, the steps of the preparation method are as follows:

[0025] At -20 to 5°C and in a nitrogen atmosphere, aromatic formaldehyde, tetrabutylammonium fluoride and TMSCF3 are used as raw materials and tetrahydrofuran is used as a solvent, which are first mixed to form a mixed solution; then a mixed solution of FSI and DCM is slowly added dropwise to the mixed solution; after the addition is completed, it is transferred to room temperature (20-30°C) and stirred for reaction.

[0026] In one embodiment of the present invention, the reaction is monitored by TLC, and when the raw material aldehyde is consumed, stirring is immediately stopped, and the desired product is separated and purified by flash column chromatography.

[0027] In one embodiment of the present invention, the separation and purification method adopts a rapid column chromatography separation method to obtain the final product 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound.

[0028] In one embodiment of the present invention, the method is preferably carried out as follows: aromatic formaldehyde, TMSCF3, FSI, and tetrabutylammonium fluoride are added to a solvent reaction vessel containing DCM in a ratio of (1:1.2:2:0.2), and the mixture is stirred at room temperature for 10 hours for separation and purification to obtain the target product.

[0029] Beneficial effects:

[0030] The invention provides a method for preparing a 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound.

[0031] The method of the present invention can synthesize 1-phenyl trifluoromethyl N-(fluorosulfonyl) carbamate compound in one step in a nitrogen (N2) atmosphere with an aromatic formaldehyde compound as a substrate and TMSCF3 as a trifluoromethylation reagent to obtain a target compound. The reaction mechanism of the present invention is as follows: FSI attacks the carbonyl oxygen of the aromatic formaldehyde to generate a C+ ion, which then combines with [CF3]- to obtain a final product, thereby synthesizing a 1-phenyl trifluoromethyl N-(fluorosulfonyl) carbamate compound.

[0032] The method of the present invention uses cheap and easily available TMSCF3 as a trifluoromethylation reagent, has a wide substrate applicability, simple and easily available raw materials, and low economic cost; in addition, the method of the present invention only needs 8-24 hours of reaction to achieve the synthesis of the target product, and the target product can be obtained with a good yield, which is faster and more efficient.

[0033] The synthesis method of the invention uses easily available aromatic formaldehyde to synthesize 1-phenyltrifluoromethyl N-(fluorosulfonyl) carbamate compounds under relatively simple conditions, and the fluorine-containing building block compounds are widely used in the fields of medicine, pesticides and petrochemicals. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The synthetic route diagram of the method of the present invention is shown in FIG. DETAILED DESCRIPTION

[0035] The following are specific embodiments of the present invention.

[0036] The synthetic route diagram of the embodiment of the present invention is as follows: Figure 1 As shown:

[0037] Using aromatic formaldehyde, TMSCF3, tetrabutylammonium fluoride and FSI as raw materials, stirring and reacting at room temperature for a period of time to obtain 1-phenyltrifluoromethyl N-(fluorosulfonyl) carbamate compound. The reaction expression is: Figure 1 .

[0038] Example 1: Synthesis of 1-(4-nitrophenyl)trifluoromethyl N-(fluorosulfonyl)carbamate

[0039]

[0040] At 0°C, under nitrogen atmosphere, 4-nitrobenzaldehyde (1.0mmol, 1.0equiv), trifluoromethyltrimethylsilane (TMSCF3, 1.2mmol, 1.2equiv), and tetrabutylammonium fluoride (TBAF, 0.2mmol, 0.2equiv) were added to the reaction bottle, and tetrahydrofuran (5.0mL) was added via a syringe. The mixture was stirred for 10min, and then a mixture of FSI (2mmol, 2equiv) and (DCM, 5.0mL) was slowly added dropwise to the mixture via a syringe. After the addition was completed, the mixture was transferred to room temperature and stirred for 10h, during which it was monitored by TCL. When the raw material aldehyde was consumed, stirring was stopped immediately, and the desired product was separated and purified by rapid column chromatography to obtain 88.6mg of the product with a yield of 52%.

[0041] 1 H NMR (400MHz, CD3CN) δ6.15(q,J=7.1Hz,1H),7.61(t,J=8.0Hz,1H),7.85(d,J=7.7Hz,1H),8.19(d,J=8.2Hz,1H),8.26(s,1H).19F NMR (376MHz, CD3CN) δ46.97 (s, 1F), -76.64 (s, 3F).

[0042] Example 2 Investigating the Effect of Trifluoromethylation Reagents on the Synthesis of 1-Phenyltrifluoromethyl N-(Fluorosulfonyl)carbamate

[0043] Referring to Example 1, the trifluoromethylating agent was replaced by Umemoto reagent, Togni reagent and Langois reagent (CF3SO2Na), respectively, and other conditions remained unchanged to obtain the corresponding 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate. The specific yield results are shown in Table 1.

[0044] Table 1 Effect of different trifluoromethylation reagents on the synthesis of γ-oxyphenylpropanesulfonyl fluoride

[0045] Trifluoromethylation reagents Yield (%) Umemoto reagent 15 Togni reagent 21 <![CDATA[Langois reagent (CF3SO2Na)]]> 30

[0046] The results showed that when Umemoto reagent, Togni reagent and Langois reagent (CF3SO2Na) were used to replace trifluoromethyltrimethylsilane (TMSCF3) as the [CF3]-reagent in Example 1, the yield of the product obtained was worse than that in Example 1, and the yield did not exceed 30%.

[0047] Example 3 investigates the effect of solvent selection on the synthesis of 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate.

[0048] Referring to Example 1, the solvent was replaced by 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, acetonitrile, respectively, from a tetrahydrofuran / dichloromethane mixture system, and other conditions remained unchanged to obtain the corresponding 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate.

[0049] The specific yield results are shown in Table 2.

[0050] Table 2 Effect of different solvents on the synthesis of 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate

[0051] Solvents Yield (%) DMSO 0 DMF 0 Dioxane 10 MeCN 4 MeOH 26 Tetrahydrofuran 16 Dichloromethane 25

[0052] The results showed that when DMSO, DMF, Dioxane, MeCN, and MeOH were used as solvents instead of tetrahydrofuran / dichloromethane in Example 2, the yield of the product obtained was lower than that of Example 1, and the yield did not exceed 26%.

[0053] Example 4 investigates the effect of reaction temperature on the synthesis of 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate.

[0054] Referring to Example 1, the reaction temperature after the dropwise addition was changed from 25°C to -20°C, 0°C, and 50°C, respectively, while other conditions remained unchanged, to obtain the corresponding 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate.

[0055] The specific yield results are shown in Table 3.

[0056] Table 3 Effect of different reaction temperatures on the synthesis of 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate

[0057] Temperature(℃) Yield (%) -20 0 0 15 25 52 50 40

[0058] The results showed that when -20°C, 0°C, and 50°C were used to replace 25°C in Example 1, the yield of the product obtained was worse than that in Example 1, and the yield did not exceed 40%.

[0059] Application Examples

[0060] Synthesis of lithium fluorosulfonylbenzyloxycarbonylamide:

[0061]

[0062] The 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate (4.55 g) obtained in Example 1 and methanol (25 mL) as a solvent were charged into a 100 mL four-necked flask replaced with nitrogen, and then lithium carbonate (2.33 g, 31.5 mmol) was added, and the reaction was stirred for 1 hour; the reaction solution was concentrated under reduced pressure, and ethyl acetate (20 mL) was added to form a suspension; the suspension was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure; dichloromethane (20 mL) was added and the mixture was stirred at room temperature for 1 hour to precipitate a solid, and the residual solvent of the obtained solid was removed to obtain the target product, fluorosulfonyl (1-phenyltrifluoromethylmethoxy) carbonylamide lithium.

[0063] Fluorosulfonyl (1-phenyltrifluoromethylmethoxy) carbonylamide lithium was used as an electrolyte component, and the corresponding lithium battery was prepared according to the method reported in WO2022196230A1. The obtained lithium battery can be effectively charged and discharged.

Claims

1. A method for preparing a 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound, wherein the aromatic formaldehyde represented by formula (1) is used as a substrate and reacts in a solvent under the action of a trifluoromethylating agent and an FSI agent. After the reaction is completed, a 1-phenyltrifluoromethyl N-(fluorosulfonyl)carbamate compound represented by formula (2) is obtained; in, R is selected from H, C 1-6 Alkyl, halogen, cyano, nitro, C 1-6 Alkoxy, acyl and amide groups, aryl groups.

2. The method according to claim 1, characterized in that Acyl is -COR1, R1 is selected from C 1-6 Alkyl; amide is -NR2COR3, R2 is selected from H, C 1-6 Alkyl, R3 is selected from C 1-6 Alkyl; aryl is a benzene ring or a naphthalene ring.

3. The method according to claim 1, characterized in that: The solvent is a mixed system of dichloromethane and tetrahydrofuran.

4. The method according to claim 3, characterized in that The volume ratio of dichloromethane to tetrahydrofuran is 1:(0.8-1.2).

5. The method according to claim 1, characterized in that The reaction temperature is 20-50°C.

6. The method according to claim 1, characterized in that The trifluoromethylation reagent is TMSCF3.

7. The method according to claim 1, characterized in that The molar ratio of the aromatic formaldehyde to the trifluoromethylation reagent is 1:(1.0-1.5); the molar ratio of the aromatic formaldehyde to the FSI reagent is 1:(1.5-3.0).

8. The method according to claim 1, characterized in that: The reaction further comprises adding tetrabutylammonium fluoride as an additive, wherein the molar ratio of the tetrabutylammonium fluoride to the aromatic formaldehyde is (0.1-0.5):

1.

9. The method according to claim 1, characterized in that ,, the reaction is carried out under an inert atmosphere, which includes nitrogen and argon.

10. The method according to any one of claims 1 to 9, characterized in that: The steps of the preparation method are as follows: At -20 to 5°C and in a nitrogen atmosphere, aromatic formaldehyde, tetrabutylammonium fluoride and TMSCF3 are used as raw materials and tetrahydrofuran is used as a solvent, which are first mixed to form a mixed solution; then a mixed solution of FSI and DCM is slowly added dropwise to the mixed solution; after the addition is completed, it is transferred to room temperature and stirred for reaction.

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