CN102115453A

CN102115453A - Synthesis of adamantane sulfonyl chloride

Info

Publication number: CN102115453A
Application number: CN2010105843532A
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: 2011-07-06
Anticipated expiration: 2030-12-10
Also published as: CN102115453B

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 diamantane SULPHURYL CHLORIDE

Technical field

The present invention relates to a kind of adamantane derivative, particularly a kind of diamantane SULPHURYL CHLORIDE synthetic.

Background technology

Though its reactive behavior of diamantane is not as benzene, owing to highly symmetry and Stability Analysis of Structures, and can not damage health of human body, very easily synthesis of derivatives becomes 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 mainly is the straight chained alkyl SULPHURYL CHLORIDE of 1-12 carbon; Benzene and derivative SULPHURYL CHLORIDE thereof mainly comprise a benzene and a benzene derivative SULPHURYL CHLORIDE; The specific functional groups SULPHURYL CHLORIDE mainly is based on straight-chain paraffin and phenyl ring, and preparation contains various SULPHURYL CHLORIDE such as nitro, acid amides, ethers, quinoline.More than various SULPHURYL CHLORIDE different physico-chemical properties is all arranged, but most widely used is the SULPHURYL CHLORIDE of derivative one class of benzene class and benzene, but because material toxicity is bigger, the rate of utilization of benzene reduces gradually in the laboratory, and it is raw material that toluene is all adopted in various organic syntheses, and this just need 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 the existing patent documentation report, the synthetic route of SULPHURYL CHLORIDE is, needing hydrolysis dilution, number is 200610038437.x as Chinese patent application, and title is " a benzene sulfonyl chloride production method ", key step is sulfonation reaction, hydrolysis dilution, static layering and underpressure distillation, wherein in feeding 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 the reaction mixture, invention needs the strict control water yield and temperature, and range of application has certain limitation.Sum up above-mentioned relevant patent 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 diamantane SULPHURYL CHLORIDE, adopting the chloro diamantane is raw material, the raw material lipophilicity is good, makes removal step simplify productive rate height, Stability Analysis of Structures, advantages of nontoxic raw materials.

The present invention realizes by following technical scheme:

Synthesizing of a kind of diamantane SULPHURYL CHLORIDE is to realize by following step:

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

(2) be adamantyl mercaptan with mol ratio: water=1: (2-2.5) mix, dropping oxidizing agent under lucifuge condition and ice-water bath stirs, carrying out along with reaction has pale solid to separate out, and removes ice-water bath, continue dropping oxidizing agent, when pH is 1-2, stop to feed oxygenant, continue reaction 20-30min, reaction finishes, get pale solid,, get the diamantane SULPHURYL CHLORIDE through washing, oven dry.

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

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

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

Oxygenant in the described step (2) is a kind of in the hydrogen peroxide of 3-chloroperoxybenzoic acid, 30-40% and the 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 to have reduced more than 1: 2.5 water consumption than existing disclosed document, thereby reduce combining of water and chlorine, make final product content height, 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 diamantane SULPHURYL CHLORIDE: get the above-mentioned adamantyl mercaptan 200g that obtains and be dissolved in the 45ml water, with 25-35 rev/min of stirring, under lucifuge condition and ice-water bath, begin to continue to feed 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 feed chlorine, reacted 4-5 hour, begin to have a large amount of pale solids to separate out, constantly detect pH, when pH is 1-2, stop to feed chlorine, continue reaction 20min, reaction finishes, solid is with the dissolving of 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 sodium bisulfate of 500ml washing back branch vibration layer, organic layer have anhydrous sodium sulfate drying concentrate 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 diamantane SULPHURYL CHLORIDE: get the above-mentioned adamantyl mercaptan 300g that obtains and be dissolved in the 80.5ml water, with 25-35 rev/min of stirring, under lucifuge condition and ice-water bath, begin to continue to feed 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 feed the 3-chloroperoxybenzoic acid, reacted 4-5 hour, begin to have a large amount of pale solids to separate out, constantly detect pH, when pH is 1-2, stop to feed the 3-chloroperoxybenzoic acid, continue reaction 30min, reaction finishes, solid is with the dissolving of 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 sodium bisulfate of 500ml washing back branch vibration layer, organic layer have anhydrous sodium sulfate drying concentrate product 297g, yield is 99%.

Embodiment 3

The preparation of diamantane SULPHURYL CHLORIDE: get the above-mentioned adamantyl mercaptan 250g that obtains and be dissolved in the 59.1ml water, with 25-35 rev/min of stirring, under lucifuge condition and ice-water bath, begin to continue to feed 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 feed hydrogen peroxide, reacted 4-5 hour, begin to have a large amount of pale solids to separate out, constantly detect pH, when pH is 1-2, stop to feed hydrogen peroxide, continue reaction 25min, reaction finishes, solid is with the dissolving of 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 sodium bisulfate of 500ml washing back branch vibration layer, organic layer have anhydrous sodium sulfate drying concentrate product 240g, yield is 96%.

Because the high reactivity of adamantane derivative, it is combined rapidly with chlorine in hydrolytic process, chlorine combines height with organic phase, by-product hydrochloric acid is few, need not to be provided with separately the deacidification device, do not influence reaction and carry out, and yield is higher, all remain on more than 95%, can replace benzene sulfonyl chloride to be extensive use of industrial.

Claims

1. a diamantane SULPHURYL CHLORIDE is synthetic, it is characterized in that being realizing by following step:

2. synthesizing of diamantane SULPHURYL CHLORIDE as claimed in claim 1 is characterized in that the temperature of reaction in the described step (1) is between 75-95 ℃, is preferably 75-85 ℃.

3. diamantane SULPHURYL CHLORIDE as claimed in claim 1 synthetic is characterized in that the temperature of ice-water bath in the described step (2) is controlled at-5-0 ℃, and removing ice-water bath afterreaction temperature is 15-35 ℃.

4. synthesizing of diamantane SULPHURYL CHLORIDE as claimed in claim 1 is characterized in that stirring is 25-35 rev/min in the described step (2), and the reaction times is 4-5h.

5. diamantane SULPHURYL CHLORIDE as claimed in claim 1 synthetic is characterized in that oxygenant in the described step (2) is a kind of in the hydrogen peroxide of 3-chloroperoxybenzoic acid, 30-40% and the chlorine.