CN108704668A - A kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates - Google Patents

Abstract

The invention discloses a kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates, for the immobilized ionic catalysts of PSIM-MgBr, the catalyst can be catalyzed the reaction of diethy-aceto oxalate and the bromo- 5- chloropentanes of 1- with optimal conditions, have higher 7- chloro-2-oxoheptanoates product yield.

Description

A kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates

Technical field

The present invention relates to a kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates, belong to chemical industry synthesis field.

Background technology

7- chloro-2-oxoheptanoates are important chemical and medicine industry intermediate, synthesize 7- chloro-2-oxoheptanoates at present Method present in major defect be that synthesis condition is more harsh, production cost is high, suitable catalyst is chloro- for synthesis 7- 2- oxoheptanoates are extremely important, and present invention research improves the catalysis for the synthesis yield for promoting 7- chloro-2-oxoheptanoates Agent.

Invention content

The purpose of the present invention is to provide a kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates, the catalyst It can be catalyzed the reaction of diethy-aceto oxalate and the bromo- 5- chloropentanes of 1- with optimal conditions, there is higher product yield.

A kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates, the catalyst are that the immobilized ions of PSIM-MgBr are urged Agent.

The immobilized ionic catalyst preparation methods of the PSIM-MgBr are as follows：

Chloropolystyrene resin is dried in vacuo 12 h by step 1 at 80 DEG C, the Chloropolystyrene tree after taking l0g to dry Fat, 3.6g imidazoles react 8h with 70ml acetonitriles at 80 DEG C；

Step 2, reaction are filtered after completing, and are rinsed using ethyl acetate, water, methanol, then are carried out very at 80 DEG C Sky is dry, and obtained solid particle is named as PSIM；

Step 3, dry N₂Under protection, in the 100m1 equipped with thermometer, condenser pipe, blender and 50ml constant pressure funnels

10gPSIM, 1.44gMg and 15m1 tetrahydrofuran are added in four-hole boiling flask；

Under step 4, magnetic agitation plus 2 iodine are as initiator, reaction to be triggered；

Step 5, the mixed solution that 9.3g1- bromo- 5- chloropentanes and 25m1 tetrahydrofurans is slowly added dropwise, use ice water in reaction process Bath control temperature is no more than 30 DEG C, after magnesium has reacted, obtains immobilized ionic catalyst PSIM-MgBr.

Advantageous effect：The present invention provides a kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates, the catalyst For the immobilized ionic catalysts of PSIM-MgBr, diethy-aceto oxalate and the bromo- 5- chloropentanes of 1- are in immobilized ionic catalyst PSIM-MgBr Under the action of by addition and hydrolysis obtain 7- chloro-2-oxoheptanoates, alkyl halide is first in the preparation process of catalyst It is first reacted with magnesium chips and generates Grignard Reagent, since the electronegativity of metal is generally smaller than carbon atom；Therefore, carbon-halogen bond is usually polarity Covalent bond, and be high degree of polarization, metallic atom carries part positive charge, and the carbon atom being attached thereto carries part negative electricity Lotus, carbon-halogen bond is easier to be broken, and shows activity.During the reaction, the alkyl in Grignard Reagent is with a pair of keys It closes electronics to move on on carbonylic carbon atom from magnesium, nucleophilic atom is carbon atom, is stronger nucleopilic reagent, obtained addition production Object can be obtained target product through hydrolysis；When at a lower temperature with sour water solution, the activity that hydrogen migrates can weaken significantly, Cause enol form product to reduce, therefore when lower temperature reacts, is conducive to the generation of keto-acid product.

Specific implementation mode

Embodiment 1

The immobilized ionic catalyst preparation methods of PSIM-MgBr are as follows：

Chloropolystyrene resin is dried in vacuo 12 h by step 1 at 80 DEG C, the Chloropolystyrene tree after taking l0g to dry Fat, 3.6g imidazoles react 8h with 70ml acetonitriles at 80 DEG C；

Step 2, reaction are filtered after completing, and are rinsed using ethyl acetate, water, methanol, then are carried out very at 80 DEG C Sky is dry, and obtained solid particle is named as PSIM；

Step 3, dry N₂Under protection, in the 100m1 equipped with thermometer, condenser pipe, blender and 50ml constant pressure funnels

10gPSIM, 1.44gMg and 15m1 tetrahydrofuran are added in four-hole boiling flask；

Under step 4, magnetic agitation plus 2 iodine are as initiator, reaction to be triggered；

Step 5, the mixed solution that 9.3g1- bromo- 5- chloropentanes and 25m1 tetrahydrofurans is slowly added dropwise, use ice water in reaction process Bath control temperature is no more than 30 DEG C, after magnesium has reacted, obtains immobilized ionic catalyst PSIM-MgBr.

A kind of synthetic method of 7- chloro-2-oxoheptanoates, includes the following steps：

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 7.3g diethy-aceto oxalates, 9.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；

Step 2, under the conditions of -25 DEG C, rapidly join 1.0g PSIM-MgBr, reaction temperature control kept during dropwise reaction At -10 DEG C or so, after being added dropwise, the reaction was continued 1h；

Step 3 is hydrolyzed with the hydrochloric acid of 15ml concentration 4M, ensures that reaction temperature is 0 DEG C or less during acid hydrolysis.It separates organic Layer, water layer are extracted with dichloromethane, are used in combination the full sodium chloride solution that closes to wash, NaHS0 is added₃It is full to close solution oscillation；

Step 4, concussion finish, organic layer and water layer saturation NaHC0₃Solution neutralizes, and organic layer rotation steams tetrahydrofuran, closes And organic layer and with saturation NaHC0₃It neutralizes, NaHS0₃Washing, then washed with NaCl until neutrality, is evaporated off solvent, rectification under vacuum obtains To 7- chloro-2-oxoheptanoates.

Embodiment 2

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 5.3g diethy-aceto oxalates, 9.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step is same Embodiment 1.

Embodiment 3

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 3.3g diethy-aceto oxalates, 9.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step is same Embodiment 1.

Embodiment 4

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 10.3g diethy-aceto oxalates, 9.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Embodiment 5

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 13.3g diethy-aceto oxalates, 9.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Embodiment 6

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 17.3g diethy-aceto oxalates, 9.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Embodiment 7

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 7.3g diethy-aceto oxalates, 14.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Embodiment 8

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 7.3g diethy-aceto oxalates, 19.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Embodiment 9

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 7.3g diethy-aceto oxalates, 24.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Embodiment 10

Step 1, dry N₂Under protection, in four mouthfuls of burnings equipped with condenser pipe, thermometer, blender and 50ml constant pressure funnels

The mixed liquor of 7.3g diethy-aceto oxalates, 29.3g1- bromo- 5- chloropentanes and 30m1 tetrahydrofurans is added in bottle；Remaining step With embodiment 1.

Reference examples 1

It is with 1 difference of embodiment：In the synthesis step 2 of intermediate, the PSIM of equivalent is added as catalyst, remaining step It is identical with embodiment 1.

Reference examples 2

It is with 1 difference of embodiment：In the synthesis step 2 of intermediate, catalyst PSIM-MgBr is not added, remaining step It is identical with embodiment 1.

Reference examples 3

It is with 1 difference of embodiment：In the synthesis step 1 of catalyst, Chloropolystyrene resin, imidazoles mass ratio are 1：1, Remaining step is identical with embodiment 1.

Reference examples 4

It is with 1 difference of embodiment：In the synthesis step 1 of catalyst, Chloropolystyrene resin, imidazoles mass ratio are 25： 9, remaining step is identical with embodiment 1.

Reference examples 5

It is with 1 difference of embodiment：In the synthesis step 1 of catalyst, replace chlorinated polyphenyl second with the styrene resin of equivalent Olefine resin, remaining step are identical with embodiment 1.

Reference examples 6

It is with 1 difference of embodiment：In the synthesis step 1 of catalyst, Chloropolystyrene resin is not added, remaining step It is identical with embodiment 1.

Reference examples 7

It is with 1 difference of embodiment：In the synthesis step 3 of catalyst, PSIM, Mg mass ratio are 7:50, remaining step and reality It is identical to apply example 1.

Reference examples 8

It is with 1 difference of embodiment：In the synthesis step 3 of catalyst, PSIM, Mg mass ratio are 1:1, remaining step with implement Example 1 is identical.

Reference examples 9

It is with 1 difference of embodiment：In the synthesis step 5 of catalyst, replace the bromo- 5- chloropentanes of 1- with the vinyl chloride of equivalent, Remaining step is identical with embodiment 1.

Reference examples 10

It is with 1 difference of embodiment：In the synthesis step 5 of catalyst, replace the bromo- 5- chlorine of 1- with 1, the 2- Bromofumes of equivalent Pentane, remaining step are identical with embodiment 1.

It is as shown in the table for reaction result under embodiment and reference examples different condition

The experimental results showed that catalyst imitates the synthetic reaction of diethy-aceto oxalate and the bromo- 5- chloropentanes of 1- with good catalysis Fruit, in one timing of reaction condition, intermediate yield is higher, and catalytic performance is better, otherwise poorer；The bromo- 5- chlorine of diethyl phthalate, 1- penta Alkane mass ratio is 7：When 9, other dispensings are fixed, and synthetic effect is best, with embodiment 1 the difference lies in that embodiment 2 is to embodiment 10 change the dosage and proportioning of primary raw material diethyl phthalate, the bromo- 5- chloropentanes of 1- respectively, in spite of certain effect, but not strictly according to the facts Apply 1 high income of example；Reference examples 1 to reference examples 2 no longer use PSIM-MgBr to replace as catalyst and with PSIM, other steps are complete It is exactly the same, cause product yield to be substantially reduced, illustrates that ion is immobilized very big on the influence of the product of reaction；Reference examples 3 are to reference examples 6 Chloropolystyrene resin is not added and changes the proportioning with imidazoles, and effect is still bad, illustrates Chloropolystyrene resin And its dosage is very crucial；Reference examples 7 to reference examples 8 change PSIM, Mg mass ratio, are catalyzed the variation with obvious effects of reaction, say Bright PSIM, Mg mass ratio is 50:7 pairs of catalyst improvements are preferable；Reference examples 9 to the equivalent of reference examples 10 1,2- dibromo second Alkane and vinyl chloride replace the bromo- 5- chloropentanes of 1-, the activity of catalyst to reduce, and reaction effect is obviously deteriorated, and product yield obviously drops It is low；Therefore there is excellent catalytic effect to the synthetic reaction of intermediate senecioic acid methyl esters using the catalyst of the present invention.

Claims (2)

1. a kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates, which is characterized in that the catalyst is PSIM-MgBr Immobilized ionic catalyst.

2. a kind of catalyst for synthesizing 7- chloro-2-oxoheptanoates according to claim 1, which is characterized in that its It is characterized in that,

The immobilized ionic catalyst preparation methods of the PSIM-MgBr are as follows：

Chloropolystyrene resin is dried in vacuo 12 h by step 1 at 80 DEG C, the Chloropolystyrene tree after taking l0g to dry Fat, 3.6g imidazoles react 8h with 70ml acetonitriles at 80 DEG C；

Step 2, reaction are filtered after completing, and are rinsed using ethyl acetate, water, methanol, then are carried out very at 80 DEG C Sky is dry, and obtained solid particle is named as PSIM；

Step 3, dry N₂Under protection, in the 100m1 equipped with thermometer, condenser pipe, blender and 50ml constant pressure funnels

10gPSIM, 1.44gMg and 15m1 tetrahydrofuran are added in four-hole boiling flask；

Under step 4, magnetic agitation plus 2 iodine are as initiator, reaction to be triggered；

Step 5, the mixed solution that 9.3g1- bromo- 5- chloropentanes and 25m1 tetrahydrofurans is slowly added dropwise, use ice water in reaction process Bath control temperature is no more than 30 DEG C, after magnesium has reacted, obtains immobilized ionic catalyst PSIM-MgBr.