CN102115453B

CN102115453B - Synthesis of adamantane sulfonyl chloride

Info

Publication number: CN102115453B
Application number: CN 201010584353
Authority: CN
Inventors: 傅志伟; 贺宝元; 张以文
Original assignee: Shanghai B & C Pharmaceutical R & D Co Ltd
Current assignee: B&C (Xuzhou) Chemical Co., Ltd.
Priority date: 2010-12-10
Filing date: 2010-12-10
Publication date: 2013-06-05
Anticipated expiration: 2030-12-10
Also published as: CN102115453A

Abstract

The invention discloses synthesis of adamantane sulfonyl chloride. The synthesis is characterized by being realized by the following steps of: (1) mixing chloroadamantane with sodium hydrosulfide in the molar ratio of (1-1.5):1 and preparing adamantane-based thiol through reaction by taking methanol as a solvent; and (2) mixing the adamantane-based thiol with water in the molar ratio of 1:(2-2.5), dripping an oxidant in an ice-water bath under a light shading condition, stirring for separating a greyish-white solid out along with reaction, removing the ice-water bath, continually dripping the oxidant, stopping introduction of the oxidant till the pH value is between 1 and 2, continually reacting for 20-30 minutes to obtain a greyish-white solid after the reaction, washing and drying the grayish-white solid to obtain the adamantine sulfony chloride. The method has the advantages that the synthesis of adamantane sulfony chloride with a stable structure and high yield is realized, small amount of acid and no byproducts are generated after the reaction, the operation is simple, the cost is low, and the method is suitable for mass production.

Description

Synthesizing of adamantane sulfonyl chloride

Technical field

The present invention relates to a kind of adamantane derivative, particularly a kind of adamantane sulfonyl chloride is synthetic.

Background technology

Although its reactive behavior of diamantane is not as benzene, due to highly symmetry and Stability Analysis of Structures, and can not damage health of human body, very easily synthesis of derivatives, become a kind of extraordinary organic synthesis raw material gradually.

SULPHURYL CHLORIDE is a kind of organic synthesis raw material and intermediate, is a kind of oxygenant, is widely used in medicine, agricultural and dyestuffs industries, so various SULPHURYL CHLORIDE is synthetic, and the improvement of synthetic method, be the emphasis of SULPHURYL CHLORIDE production field.

In the report of existing patent documentation, SULPHURYL CHLORIDE synthetic has alkyl sulfonyl chloride, and alkyl sulfonyl chloride is mainly the straight chained alkyl SULPHURYL CHLORIDE of 1-12 carbon; The benzene and its derivative SULPHURYL CHLORIDE mainly comprises benzene and a benzene derivative SULPHURYL CHLORIDE; The specific functional groups SULPHURYL CHLORIDE is mainly that preparation contains the various SULPHURYL CHLORIDE such as nitro, acid amides, ethers, quinoline take straight-chain paraffin and phenyl ring as the basis.Above various SULPHURYL CHLORIDE all has different physico-chemical properties, but most widely used is the SULPHURYL CHLORIDE of derivative one class of benzene class and benzene, but because material toxicity is larger, in the laboratory, the rate of utilization of benzene reduces gradually, and it is raw material that toluene is all adopted in various organic syntheses, and this just need to add corresponding step in synthetic route, making reaction generate the by product rate improves, sometimes also need to change temperature of reaction, make reaction complicated, productive rate also decreases.

In existing patent literature, the synthetic route of SULPHURYL CHLORIDE is, needing the hydrolysis dilution, number is 200610038437.x as Chinese patent application, and title is " benzene sulfonyl chloride production method ", key step is sulfonation reaction, hydrolysis dilution, static layering and underpressure distillation, wherein in passing into the chlorine process, chlorine and water react, and reaction also needs deacidification, for guaranteeing the reaction of chlorine and organic phase, need to add complicated operation steps; Chinese patent application number is 01818650.5, title is in " method of making alkanesulphonyl chlorides ", with the sulphur alcohol and water, adopts the dispersion form of water in mercaptan to introduce in reaction mixture, invention needs the strict control water yield and temperature, and range of application has certain limitation.Sum up above-mentioned Patents and synthetic technology, method for hydrolysis removal of impurities process is complicated, and directly synthetic yield is not high.

Summary of the invention

For solving the problems of the technologies described above, the invention provides the synthetic of a kind of adamantane sulfonyl chloride, adopting the chloro diamantane is raw material, and the raw material lipophilicity is good, and removal step is simplified, and productive rate is high, Stability Analysis of Structures, advantages of nontoxic raw materials.

The present invention realizes by following technical scheme:

Synthesizing of a kind of adamantane sulfonyl chloride is to realize by following step:

(1) be the chloro diamantane with mol ratio: Sodium sulfhydrate=(1-1.5): 1 mixes, and prepares adamantyl mercaptan take methyl alcohol as solvent reaction;

(2) be adamantyl mercaptan with mol ratio: water=1: (2-2.5) mix, drip oxygenant under lucifuge condition and ice-water bath, stir, carrying out along with reaction has pale solid to separate out, and removes ice-water bath, continue to drip oxygenant, when being 1-2 to pH, stop passing into oxygenant, continue reaction 20-30min, reaction finishes, get pale solid, through washing, oven dry, get adamantane sulfonyl chloride.

Temperature of reaction in described step (1) is between 75-95 ℃, is preferably 75-85 ℃.

The temperature of ice-water bath is controlled at-5-0 ℃ in described step (2), and removing ice-water bath afterreaction temperature is 15-35 ℃.

In described step (2), stirring is 25-35 rev/min, and the reaction times is 4-5h.

Oxygenant in described step (2) is a kind of in the hydrogen peroxide of 3-chloroperoxybenzoic acid, 30-40% and chlorine.

Beneficial effect of the present invention is:

Chlorine very easily with the adamantyl thiol reactant, contact few with water, the hydrochloric acid content that produces is few, aftertreatment is easy, wherein the mol ratio of hydrolytic process mercaptan and water can remain on 1: (2-2.5), need the ratio of mercaptan and water to remain on than existing disclosed document and reduced water consumption more than 1: 2.5, thus the combination of minimizing water and chlorine, make final product content high, yield can remain on 95-99%; The reaction raw materials hypotoxicity, activity improves greatly after generating adamantane derivative.

Embodiment

Below in conjunction with embodiment, the present invention will be further described.

Embodiment 1

The preparation of adamantyl mercaptan: 1.53Kg chloro diamantane is mixed with the 500g Sodium sulfhydrate, in the 2500ml methanol solution, be warming up to 75 ℃, react, it is 48h that the reaction times is set, and obtains adamantyl mercaptan.

the preparation of adamantane sulfonyl chloride: get adamantyl mercaptan 200g obtained above and be dissolved in 45ml water, with 25-35 rev/min of stirring, under lucifuge condition and ice-water bath, begin to continue to pass into chlorine, keeping the ice-water bath temperature is-5～-2, after reacting 0.5h, separate out a small amount of pale solid, remove ice-water bath, keep 15-18 ℃ of temperature of reaction, continue to continue to pass into chlorine, reacted 4-5 hour, begin to have a large amount of pale solids to separate out, constantly detect pH, when being 1-2 to pH, stop passing into chlorine, continue reaction 20min, reaction finishes, solid dissolves with the 500ml methyl tertiary butyl ether, and with 500ml water/time washed twice, water layer is used 200ml methyl tertiary butyl ether/time extracting twice again, merge with organic layer, organic layer re-uses the saturated rear branch vibration layer of sodium bisulfate washing of 500ml, organic layer has anhydrous sodium sulfate drying to concentrate to get product 195.8g, yield is 98%.

Embodiment 2

The preparation of adamantyl mercaptan: 1.53Kg chloro diamantane is mixed with the 500g Sodium sulfhydrate, in the 2500ml methanol solution, be warming up to 85 ℃, react, it is 48h that the reaction times is set, and obtains adamantyl mercaptan.

the preparation of adamantane sulfonyl chloride: get adamantyl mercaptan 300g obtained above and be dissolved in 80.5ml water, with 25-35 rev/min of stirring, under lucifuge condition and ice-water bath, begin to continue to pass into the 3-chloroperoxybenzoic acid, keeping the ice-water bath temperature is-2～-1 ℃, after reacting 0.5h, separate out a small amount of pale solid, remove ice-water bath, keep 20-25 ℃ of temperature of reaction, continue to continue to pass into the 3-chloroperoxybenzoic acid, reacted 4-5 hour, begin to have a large amount of pale solids to separate out, constantly detect pH, when being 1-2 to pH, stop passing into the 3-chloroperoxybenzoic acid, continue reaction 30min, reaction finishes, solid dissolves with the 500ml methyl tertiary butyl ether, and with 500ml water/time washed twice, water layer is used 200ml methyl tertiary butyl ether/time extracting twice again, merge with organic layer, organic layer re-uses the saturated rear branch vibration layer of sodium bisulfate washing of 500ml, organic layer has anhydrous sodium sulfate drying to concentrate to get product 297g, yield is 99%.

Embodiment 3

the preparation of adamantane sulfonyl chloride: get adamantyl mercaptan 250g obtained above and be dissolved in 59.1ml water, with 25-35 rev/min of stirring, under lucifuge condition and ice-water bath, begin to continue to pass into hydrogen peroxide, keeping the ice-water bath temperature is-1～0 ℃, after reacting 0.5h, separate out a small amount of pale solid, remove ice-water bath, keep 25-35 ℃ of temperature of reaction, continue to continue to pass into hydrogen peroxide, reacted 4-5 hour, begin to have a large amount of pale solids to separate out, constantly detect pH, when being 1-2 to pH, stop passing into hydrogen peroxide, continue reaction 25min, reaction finishes, solid dissolves with the 500ml methyl tertiary butyl ether, and with 500ml water/time washed twice, water layer is used 200ml methyl tertiary butyl ether/time extracting twice again, merge with organic layer, organic layer re-uses the saturated rear branch vibration layer of sodium bisulfate washing of 500ml, organic layer has anhydrous sodium sulfate drying to concentrate to get product 240g, yield is 96%.

High reactivity due to adamantane derivative, it is combined with chlorine rapidly in hydrolytic process, chlorine is combined high with organic phase, by-product hydrochloric acid is few, need not to arrange separately deacidification device, do not affect reaction and carry out, and yield is higher, all remain on more than 95%, can replace benzene sulfonyl chloride to be widely used industrial.

Claims

1. an adamantane sulfonyl chloride is synthetic, it is characterized in that realizing by following step:

(2) be adamantyl mercaptan with mol ratio: water=1: (2-2.5) mix, drip oxygenant under lucifuge condition and ice-water bath, stir, carrying out along with reaction has pale solid to separate out, and removes ice-water bath, continue to drip oxygenant, when being 1-2 to pH, stop passing into oxygenant, continue reaction 20-30min, reaction finishes, and gets pale solid, through washing, oven dry, get adamantane sulfonyl chloride, described oxygenant is the hydrogen peroxide of 3-chloroperoxybenzoic acid or 30-40%.