CN103044176A - High-efficiency method for preparing halohydrin through hydrogen involved ring opening of cyclic ether - Google Patents

Abstract

The invention discloses a high-efficiency method for preparing halohydrin through the hydrogen involved ring opening of cyclic ether, comprising the following step of preparing a halohydrin compound through the reaction of a cyclic ether compound, hydrogen, elemental halogen or a halogen containing compound under the action of a catalyst under the circumstance of having an organic solvent or no solvent. The method disclosed by the invention has the advantages of low cost, high efficiency, cleanness, environmental protection and easiness in industrial production and has a broad application prospect.

Description

A kind of hydrogen participates in the high efficiency method that the cyclic ethers open loop prepares halohydrin

Technical field

The present invention relates to a kind ofly take cyclic ethers as raw material, utilize itself and hydrogen, halogen simple substance or halogen contained compound reaction, the high efficiency method of preparation halogenated alcohols compound under catalyst action.

Background technology

The halogenated alcohols compound is being the important industrial raw material of a class and polyfunctional reactant intermediate, and it has several functions, and especially β-halohydrin and halo alcohol ether are most widely used in production and fundamental research.Halogen atom in the halogenated alcohols compound and alcoholic extract hydroxyl group all are active functional groups, are easier to obtain new compound by simple reaction.Halohydrin often is used to increase carbochain, preparation cyclo other compounds, makes up ring-type and special construction compound (Agatsuma, T.; Ogawa, H.; Akasaka, K.; Asai, A.; Yamashita, Y.; Mizukami, T.; Akinagab S.; Saitoh Y. Bioorganic ﹠amp; Medicinal Chemistry, 2002,10,3445 – 3454.).

The preparation of halohydrin mainly utilizes epoxy and double bond compound to prepare under catalyst action for substrate, and the raw materials cost of employing is higher, and difficult realization is to all open loops of different carbonatoms epoxy compoundss simultaneously, and the diversity of product also is restricted.And the preparation cost of existing halohydrin is high, and the reasons such as complex process have limited the production utilization of halohydrin.

Cyclic ether compounds extensively exists in industry, and is cheap and easy to get, all is widely used industrial chemicals such as tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane etc.Utilize the ring-opening reaction of cyclic ether compounds to prepare the effective way that the halogenated alcohols compound is the efficient preparation of realization halogenated alcohols compound.

The present invention prepares halohydrin with the inexpensive clean raw material through simple process.Utilize hydrogen under catalyst action, to prepare halohydrin with cyclic ethers cheap and easy to get and halogen simple substance or halogen contained compound generation ring-opening reaction.

Summary of the invention

The purpose of this invention is to provide a kind of hydrogen and participate in the high efficiency method that the cyclic ethers open loop prepares halohydrin.

A class halogenated alcohols compound provided by the present invention, structure suc as formula ( I) shown in

Formula ( I) in, Z is alkane, aromatic hydrocarbons, contains heteroatoms alkane, contains heteroatoms aromatic hydrocarbons; X is halogen atom.

The synthetic method of halogenated alcohols compound of the present invention is as follows:

With formula ( II)The compound of structure and formula ( III)Formula ( IV)The compound of structure is at organic solvent or solvent-free lower, behind reaction certain hour under certain temperature, the pressure, obtain described formula ( I)The halogenated alcohols compound of the molecular diversity of structure.

Utilization of the present invention be simple and easy to cyclo other compounds ( II)And hydrogen ( III)Halogen simple substance or halogen contained compound ( IV)Effect is lower carries out ring-opening reaction, by one go on foot or polystep reaction obtain target compound ( I)The synthesis material of this invention is simple and easy to, and technique is simple, and aftertreatment is easy, and productive rate is high, and product is stable.This invention has realized parallel efficient synthetic various types of halogenated alcohols compounds.The characteristics such as and it is high to have productive rate, and route is simple, quick.Preparation process and method simple practical are fit to industrial production.

Embodiment

Various types of halogenated alcohols compou nd synthesis method of the present invention is as follows:

With formula ( II)The compound of structure and formula ( III), (IV)The compound of structure is at organic solvent or solvent-free lower, behind reaction certain hour under certain temperature, the pressure, the TLC detection reaction fully after, column chromatography separate formula ( I)Target product, concrete reaction formula is as follows:

Formula ( II) in, Z is alkane, aromatic hydrocarbons, contains heteroatoms alkane, contains heteroatoms aromatic hydrocarbons; X is halogen atom.

Formula ( IV) in, R is halogen, hydrogen, aryl, heterocyclic aryl, fused ring aryl, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl.

R is hydrogen, alkyl, substituted alkyl, silylation, substituted silane base, aroyl, heterocycle aroyl, condensed ring aroyl, alkyloyl, ester group.

In the reaction, temperature of reaction is not made concrete regulation, often is-80-200 ℃; Type of heating can be heating jacket, oil bath, microwave oven; Reaction pressure is not made concrete regulation, often is normal atmosphere 1Pa-10 ⁸Pa; Pressuring method can be autoclave; Reaction times is not made concrete regulation, often is 5 minutes to 7 days.Reaction process adopts TLC to detect and follows the tracks of, the rear stopped heating that reacts completely, reaction solution is taken out concentrated, through column chromatography separate compound ( I)

In the reaction, for 1 mole formula (IV) material, formula (II) compound amount is more than or equal to 2 moles, and the consumption of formula (III) is more than or equal to 1 mole, and catalyst levels is 1% mole.The total recovery of reaction is generally at 75-95%.

The halogenated alcohols compound structure general formula (I) that is synthesized:

Its representation compound is as follows:

I-A

I-B

I-C

I-D

I-E

I-F

The present invention is from the raw material cyclic ethers that is easy to get, hydrogen, halogen simple substance or halogen contained compound, by the synthetic a series of halogenated alcohols compounds of simple and fast method.In whole building-up process, adopt catalyst hydrogen, halogen simple substance or halogen contained compound to participate in the cyclic ethers ring-opening reaction, have that raw material is easy to get, synthetic route is succinct, easy and simple to handle, aftertreatment simple, the productive rate advantages of higher.

Below in conjunction with the part specific embodiments the present invention is described in detail.

Embodiment 1

The 2-ethylene iodohydrin ( I-A) synthetic: under the normal pressure, with 76mg(0.3 mmol) I ₂, 59 μ L(1.2 mmol) to add volume be in the reactor of 15mL for oxyethane, 6.36mg palladium carbon (Pd content 5%), passes into 1 normal atmosphere hydrogen, stirring at room to reaction is finished.Epoxy compounds that unreacted is complete steams and removes, residuum through column chromatography (PE:EA=5:1) product 2-ethylene iodohydrin, colourless liquid, productive rate 90%. ¹H NMR (400 MHz, CDCl ₃) δ 3.89 – 3.79 (m, 2H), 3.34 (t, J = 5.9 Hz, 2H), 1.96 (s, 1H).

Embodiment 2

3-iodo propyl alcohol ( I-B) synthetic: under the normal pressure, with 76mg(0.3 mmol) I ₂, 78 μ L(1.2 mmol) to add volume be in the reactor of 15mL for propylene oxide, 6.36mg palladium carbon (Pd content 5%), passes into 10 normal atmosphere hydrogen, stirring at room to reaction is finished.Epoxy compounds that unreacted is complete steams and removes, residuum through column chromatography (PE:EA=5:1) product 3-iodo propyl alcohol, colourless liquid, productive rate 89%. ¹H NMR (400 MHz, CDCl ₃) δ 4.17 – 4.10 (m, 2H), 3.75 (s, 1H), 3.38 – 3.26 (m, 2H), 2.09 – 2.05 (m, 2H).

Embodiment 3

4-iodo butanols ( I-C) synthetic: under the normal pressure, with 76mg(0.3mmol) I ₂, 97 μ L(1.2mmol) to add volume be in the reactor of 15mL for tetrahydrofuran (THF), 6.36mg palladium carbon (Pd content 5%), passes into 2 normal atmosphere hydrogen, stirring at room to reaction is finished.Epoxy compounds that unreacted is complete steams and removes, residuum through column chromatography (PE:EA=5:1) product 4-iodo butanols, light yellow liquid, productive rate 91%. ¹H NMR (400 MHz, CDCl ₃) δ 3.69 (t, J = 6.4 Hz, 2H), δ 3.24 (t, J = 6.9 Hz, 2H), 2.28 (s, 1H), 2.00 – 1.87 (m, 2H), 1.75 – 1.64 (m, 2H).

Embodiment 4

4-bromo butanols ( I-D) synthetic: under the normal pressure, with 47mg(0.3mmol) Br ₂, 97 μ L(1.2mmol) to add volume be in the reactor of 15mL for tetrahydrofuran (THF), 6.36mg palladium carbon (Pd content 5%), passes into 10 normal atmosphere hydrogen, stirring at room to reaction is finished.Epoxy compounds that unreacted is complete steams and removes, residuum through column chromatography (PE:EA=5:1) product 4-bromo butanols, colourless liquid, productive rate 88%. ¹H NMR (400 MHz, CDCl ₃) δ 3.69 (t, J = 6.4 Hz, 2H), δ 3.46 (t, J = 6.8 Hz, 2H), 2.02 – 1.93 (m, 2H), 1.77 – 1.69 (m, 2H), 1.61 (s, 1H).

Embodiment 5

5-iodo amylalcohol ( I-E) synthetic: under the normal pressure, with 76mg(0.3mmol) I ₂, 116 μ L(1.2mmol) to add volume be in the reactor of 15mL for tetrahydropyrans, 6.36mg palladium carbon (Pd content 5%), passes into 5 normal atmosphere hydrogen, stirring at room to reaction is finished.Epoxy compounds that unreacted is complete steams and removes, residuum through column chromatography (PE:EA=5:1) product 5-iodo amylalcohol, colourless liquid, productive rate 86%. ¹H NMR (400 MHz, CDCl ₃) δ 3.67 (t, J = 6.4 Hz, 2H), 3.21 (t, J = 7.0 Hz, 2H), 1.91 – 1.83 (m, 2H), 1.64 – 1.58 (m, 2H), 1.53 – 1.46 (m, 2H).

Embodiment 6

The 2-iodocyclohexanol ( I-F) synthetic: under the normal pressure, with 76mg(0.3mmol) I ₂, 132 μ L(1.2mmol) to add volume be in the reactor of 15mL for 1,2 epoxy cyclohexane, 6.36mg palladium carbon (Pd content 5%), passes into 1 normal atmosphere hydrogen, stirring at room to reaction is finished.Epoxy compounds that unreacted is complete steams and removes, residuum through column chromatography (PE:EA=5:1) product 2-iodocyclohexanol, colourless liquid, productive rate 85%. ¹H NMR (400 MHz, CDCl ₃) δ 4.07 – 4.01 (m, 1H), 3.71 – 3.63 (m, 1H), 2.51 – 2.45 (m, 1H), 2.33 (s, 1H), 2.14 – 2.03 (m, 2H), 1.88 – 1.82 (m, 1H), 1.56 – 1.50 (m, 1H), 1.47 – 1.29 (m, 3H)。

Claims (6)

1. a hydrogen participates in the high efficiency method that the cyclic ethers open loop prepares halohydrin:

X is halogen in the formula, and Z is alkane, aromatic hydrocarbons, contains heteroatoms alkane, contains heteroatoms aromatic hydrocarbons; The method has been included under inert solvent or the solvent-free existence, and cyclo other compounds and hydrogen, halogen simple substance or halogen contained compound are reacted under catalyst action.

2. method according to claim 1, required catalyzer is metal, metallic salt, metal-containing complex, comprises metal and its esters or its title complexs such as ruthenium, rhodium, palladium, iridium.

3. method according to claim 1, wherein halogen contained compound is the inorganic or organic substance that has at least a halogen atom.

4. method according to claim 1, wherein inert solvent is aprotic solvent.

5. method according to claim 1, the method is carried out at-80 ℃ to 200 ℃.

6. method according to claim 1, the method is at 1Pa to 10 ⁸Carry out under the Pa pressure.