Fat trifluoro ethyl ester compound and preparation method thereof

Abstract

The invention relates to a fat trifluoro ethyl ester compound and a preparation method thereof. The definition of the fat acid trifluoro ethyl ester compound is same with the definition in the claim.The preparation method comprises the following steps that under the low temperature condition, 2, 2, 2-trifluoroethylamine and tert-butyl nitrite are added into an organic solution with fatty acid dissolved in, and after uniformly stirring, the mixture reacts continuously at the indoor temperature, and a fatty acid trifluoro ethyl ester product can be obtained. The molar ratio among fat acid, 2, 2, 2-trifluoroethylamine and tert-butyl nitrite is 1:(1-2.5):(1-2.5). According to the preparation method, it is not necessary to add catalyst and other additives, and a target product can be obtained,the operation is simple, reaction conditions are mild, the cost is low, the yield is high, the method is environmentally friendly, the trifluoro ethyl ester compound of fat and drug molecule carboxylic acid can be obtained, and the application is wide.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to fatty trifluoroethyl ester compounds and a preparation method thereof. The present invention also relates to the use of the fatty trifluoroethyl ester compound in pharmaceutical, food, material and other industries. Background technique

[0002] With the development of organic fluorine chemistry, fatty acid trifluoroethyl esters (RCO 2 CH 2 CF 3 ) compounds have attracted much attention. Due to its characteristics such as biodegradability, weak toxicity or even non-toxicity, some non-irritating and antibacterial and anti-oxidant properties, it is often used in pharmaceutical, food, beauty, processing and other industries. The currently known fatty acid trifluoroethyl esters used in the fields of medicine and materials are mainly unsaturated fatty acid trifluoroethyl esters, which are mainly used to synthesize ion exchange membranes, drug delivery media, ...

Examples

Embodiment 1～16

[0027] The following implementations 1-16 are prepared according to the following synthetic route, and compounds 1-16 can be prepared:

[0028]

[0029] The specific operation is: dissolve the fatty acid (0.5mmol, 1equiv) substrate in 1,1,1,3,3,3-hexafluoro-2-propanol, and add tert-butyl nitrite ( 150 μL, 1.25mmol, 2.5equiv) and 2,2,2-trifluoroethylamine (100 μL, 1.25mmol, 2.5equiv), stirred for 5min and raised to room temperature to continue the reaction for 0.5~10h, and depressurized the solution in the reaction system After spinning to dryness, the residue was purified by column chromatography to obtain fatty trifluoroethyl ester compounds.

Embodiment 1

[0031] Substrate: nonanoic acid

[0032] product:

[0033] Compound 1: colorless oil (107mg, 93% yield); IR(KBr)ν max / cm -1 :2959,2930,2859,1762, 1457,1412,1283,1170,1111,1067,979,842,807; 1 H NMR (400MHz, CDCl 3 )δ4.39(q, J=8.5 Hz, 2H, C H 2 CF 3 ), 2.34(t, J=7.5Hz, 2H, COC H 2 ),1.72–1.48(m,2H,COCH 2 C H 2 ), 1.22 (dd, J=12.8, 6.6Hz, 10H, C H 2 ),0.81(t,J=6.8Hz,3H,CH 2 C H 3 );13 C NMR (100MHz, CDCl 3 )δ 171.2(CO), 122.0(q, J=277.1Hz, C f 3 ),59.1(q,J=36.5Hz, C CF 3 ), 32.6 (CO C h 2 ), 30.8 (COCH 2 C h 2 ), 28.13, 28.08, 28.0, 23.7, 21.6, 13.0 (CH 2 C h 3 ); 19 F NMR (376MHz, CDCl 3 )δ -73.97(t, J=8.3Hz, C F 3 ); 19 F { 1 H}NMR (376MHz, CDCl 3 )δ-73.97(s,C F 3 ); HRMS(ESI): m / zcalcd for C 11 h 29 f 3 o 2 Na + [M+Na] + 263.1229, found 263.1242.

Embodiment 2

[0035] Substrate: Heptanoic acid

[0036] product:

[0037] Compound 2: colorless oil (89mg, 84% yield); IR(KBr)ν max / cm -1 :2961,2931,2858,1756,1419, 1285,1172,1107,909,807,735; 1 H NMR (400MHz, CDCl 3 )δ4.47(q, J=8.5Hz, 2H, C H 2 CF 3 ), 2.42(t,J=7.5Hz,2H,COC H 2 ), 1.66 (p, J=7.5Hz, 2H, C H 2 CH 3 ),1.48–1.22(m,6H),0.88(t,J=6.9Hz,3H,C H 3 ); 13 C NMR (100MHz, CDCl 3 )δ172.2(CO), 123.0(q, J=277.1Hz, C h 2 CF 3 ), 60.1(q, J=36.4Hz, C f 3 ), 33.7 (CO C h 2 ),31.4( C h 2 ),28.7( C h 2 ),24.7( C h 2 ),22.5( C h 2 ),14.0 ( C h 3 ); 19 F NMR (376MHz, CDCl 3 )δ-73.85(t, J=8.5Hz, C F 3 ); 19 F { 1 H}NMR (376MHz, CDCl 3 ) δ-73.85(s,C F 3 ); HRMS(ESI):m / z calcd for C 9 h 15 f 3 o 2 Na + [M+Na] + 235.0916,found235.0916.

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to fatty trifluoroethyl ester compounds and a preparation method thereof. The present invention also relates to the use of the fatty trifluoroethyl ester compound in pharmaceutical, food, material and other industries. Background technique

[0002] With the development of organic fluorine chemistry, fatty acid trifluoroethyl esters (RCO 2 CH 2 CF 3 ) compounds have attracted much attention. Due to its characteristics such as biodegradability, weak toxicity or even non-toxicity, some non-irritating and antibacterial and anti-oxidant properties, it is often used in pharmaceutical, food, beauty, processing and other industries. The currently known fatty acid trifluoroethyl esters used in the fields of medicine and materials are mainly unsaturated fatty acid trifluoroethyl esters, which are mainly used to synthesize ion exchange membranes, drug delivery media, ...

Examples

Embodiment 1～16

[0027] The following implementations 1-16 are prepared according to the following synthetic route, and compounds 1-16 can be prepared:

[0028]

[0029] The specific operation is: dissolve the fatty acid (0.5mmol, 1equiv) substrate in 1,1,1,3,3,3-hexafluoro-2-propanol, and add tert-butyl nitrite ( 150 μL, 1.25mmol, 2.5equiv) and 2,2,2-trifluoroethylamine (100 μL, 1.25mmol, 2.5equiv), stirred for 5min and raised to room temperature to continue the reaction for 0.5~10h, and depressurized the solution in the reaction system After spinning to dryness, the residue was purified by column chromatography to obtain fatty trifluoroethyl ester compounds.

Embodiment 1

[0031] Substrate: nonanoic acid

[0032] product:

[0033] Compound 1: colorless oil (107mg, 93% yield); IR(KBr)ν max / cm -1 :2959,2930,2859,1762, 1457,1412,1283,1170,1111,1067,979,842,807; 1 H NMR (400MHz, CDCl 3 )δ4.39(q, J=8.5 Hz, 2H, C H 2 CF 3 ), 2.34(t, J=7.5Hz, 2H, COC H 2 ),1.72–1.48(m,2H,COCH 2 C H 2 ), 1.22 (dd, J=12.8, 6.6Hz, 10H, C H 2 ),0.81(t,J=6.8Hz,3H,CH 2 C H 3 );13 C NMR (100MHz, CDCl 3 )δ 171.2(CO), 122.0(q, J=277.1Hz, C f 3 ),59.1(q,J=36.5Hz, C CF 3 ), 32.6 (CO C h 2 ), 30.8 (COCH 2 C h 2 ), 28.13, 28.08, 28.0, 23.7, 21.6, 13.0 (CH 2 C h 3 ); 19 F NMR (376MHz, CDCl 3 )δ -73.97(t, J=8.3Hz, C F 3 ); 19 F { 1 H}NMR (376MHz, CDCl 3 )δ-73.97(s,C F 3 ); HRMS(ESI): m / zcalcd for C 11 h 29 f 3 o 2 Na + [M+Na] + 263.1229, found 263.1242.

Embodiment 2

[0035] Substrate: Heptanoic acid

[0036] product:

[0037] Compound 2: colorless oil (89mg, 84% yield); IR(KBr)ν max / cm -1 :2961,2931,2858,1756,1419, 1285,1172,1107,909,807,735; 1 H NMR (400MHz, CDCl 3 )δ4.47(q, J=8.5Hz, 2H, C H 2 CF 3 ), 2.42(t,J=7.5Hz,2H,COC H 2 ), 1.66 (p, J=7.5Hz, 2H, C H 2 CH 3 ),1.48–1.22(m,6H),0.88(t,J=6.9Hz,3H,C H 3 ); 13 C NMR (100MHz, CDCl 3 )δ172.2(CO), 123.0(q, J=277.1Hz, C h 2 CF 3 ), 60.1(q, J=36.4Hz, C f 3 ), 33.7 (CO C h 2 ),31.4( C h 2 ),28.7( C h 2 ),24.7( C h 2 ),22.5( C h 2 ),14.0 ( C h 3 ); 19 F NMR (376MHz, CDCl 3 )δ-73.85(t, J=8.5Hz, C F 3 ); 19 F { 1 H}NMR (376MHz, CDCl 3 ) δ-73.85(s,C F 3 ); HRMS(ESI):m / z calcd for C 9 h 15 f 3 o 2 Na + [M+Na] + 235.0916,found235.0916.

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