CN106916089B - A kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis - Google Patents
A kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis Download PDFInfo
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- CN106916089B CN106916089B CN201710150932.8A CN201710150932A CN106916089B CN 106916089 B CN106916089 B CN 106916089B CN 201710150932 A CN201710150932 A CN 201710150932A CN 106916089 B CN106916089 B CN 106916089B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
Abstract
A kind of preparation method of the cis- 4 n-pentyl cyclohexylmercaptan of selectivity synthesis, belongs to organic synthesis field.Generation reduction reaction in tetrahydrofuran water mixed solvent is added in 4 n-pentyl cyclohexanone, sodium borohydride and obtains 4 n-pentyl cyclohexanol；Mesylation further occurs in dichloroethane solvent with mesyl chloride to react, post-processing obtains the 4 n-pentyl hexamethylene methanesulfonates of content ＞ 98% by crystallization；Sulphur acetylization reaction further occurs in N, N solvent dimethylformamides with thioacetic acid potassium and obtains 4 n-pentyl cyclohexyl of sulphur acetic acid；Cis- 4 n-pentyl cyclohexylmercaptan, cis-product selectivity ＞ 99% finally is obtained by the reaction by low-temperature saponification in methanol aqueous solvent.The advantages that this method has the reaction time short, easy to operate, cis-product high selectivity.
Description
Technical field
The present invention relates to a kind of preparation methods of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis, belong in fine chemistry industry
Mesosome synthesizes field.
Background technology
4- alkyl mercaptan is a kind of important fine-chemical intermediate, and main synthetic method has：（1）Cyclohexyl halogen
It is reacted with sulphur powder for object preparation Grignard Reagent and prepares cyclohexylmercaptan（Referring to：US20030224298,2003）；（2）Cyclohexyl methylsulphur
Acid esters and thioacetic acid nak response, then obtain cyclohexylmercaptan using lithium aluminium hydride reduction deprotection base（Referring to：
J.Phys.Chem.C 2012,116,13559）.Route（1）It is middle that sulphur powder is added portionwise using Grignard Reagent, it was produced in amplification
Cheng Zhong, oxygen free condition be not easy to realize, is easy to generate byproduct cyclohexanol derivative, and the by-product is close with cyclohexylmercaptan property,
Separating-purifying difficulty is high, seriously affects subsequent reactions.Route（2）Middle to be deprotected using lithium aluminium hydride reduction, not only cost of material is high, and
And lithium aluminium hydride reduction large-scale use security risk is larger.
In addition to the inconvenience on operation, it can be used in high selectivity cis or trans configuration Isosorbide-5-Nitrae-cyclohexylmercaptan
Route also have not been reported.Usually the shown physicochemical properties of compound with single cis or trans configuration relatively mix
Object is significantly different, and generated advantageous effect increases in geometric progression.Therefore, the convenience and high-efficiency and cis- 4- of high selectivity is just
Amyl cyclohexylmercaptan can be very helpful and significant for the research and production of similar compound.
Invention content
In order to overcome problems of the prior art, it is that raw material passes through also that the present invention, which is used using 4- n-pentyls cyclohexanone,
Original, Mesylation, sulphur acetylation, saponification are highly selective obtains cis- 4- n-pentyls cyclohexylmercaptan, cis-product selection
Property ＞ 99%.This method reaction time is short, easy to operate, cis product selectivity and high income.A kind of cis- 4- of selectivity synthesis
The preparation method of n-pentyl cyclohexylmercaptan, the specific technical solution that the present invention uses for：
Generation reduction reaction in tetrahydrofuran water mixed solvent is added in 4- n-pentyls cyclohexanone, sodium borohydride and is obtaining 4- just
Amyl cyclohexanol；Mesylation further occurs in dichloroethane solvent with mesyl chloride to react, post-processing is by crystallizing
To the 4- n-pentyl hexamethylene methanesulfonates of content ＞ 98%；Further with thioacetic acid potassium in N,N-dimethylformamide solvent
Sulphur acetylization reaction occurs and obtains sulphur acetic acid 4- n-pentyl cyclohexyls；Finally reacted by low-temperature saponification in methanol aqueous solvent
To 4- n-pentyl cyclohexylmercaptans, cis-product selectivity ＞ 99%.
Further, in the above-mentioned technical solutions, in the reduction reaction, 4- n-pentyls cyclohexanone and sodium borohydride mole
Than being 1:0.30-0.35, reaction temperature are controlled at -5 DEG C~5 DEG C.
Further, in the above-mentioned technical solutions, in the sulfonylation, gained crude product needs to tie again by ethyl alcohol
Crystalline substance, the 4- n-pentyl hexamethylene methanesulfonates for obtaining content ＞ 98% are used for sulphur acetylization reaction.
Further, in the above-mentioned technical solutions, in the sulphur acetylization reaction, 4- pentyl cyclohexyls methanesulfonates with
Sulphur potassium acetate molar ratio is 1:1.4-1.6, reaction temperature are controlled at 120 DEG C~126 DEG C.
Further, in the above-mentioned technical solutions, in the saponification, sulphur acetic acid 4- n-pentyls cyclohexyl and hydroxide
Sodium molar ratio is 1:1.0, reaction temperature is controlled at -15 DEG C~-10 DEG C.
Beneficial effects of the present invention：
1, the reaction time is short：The 1-3 step reaction time is 1~2 hour, and the reaction of the 4th step is 5 hours.
2, easy to operate：It reacts each step and is not necessarily to stringent water removal deoxygenation operation.
3, cis-product high selectivity：Cis-product selectivity ＞ 99%.
Specific implementation mode
With reference to embodiment, the invention will be further described.
Embodiment 1
The first step：
Sodium borohydride 22.2g is added in 2L four-hole bottles（586.8mmol, 0.3eq）, tetrahydrofuran 351.0g, mechanical agitation shape
Water 78.0g is added dropwise under state（4329.0mmol 2.2eq）, 20min drips off, and kettle temperature maintains essentially in 21 DEG C, no significant change.With
Four-hole bottle is placed in ice maker afterwards, is cooled to -5 DEG C for use.
N-pentyl cyclohexanone 330.0g is added dropwise（1961.0mmol 1.0eq）The solution prepared with tetrahydrofuran 171.0g, kettle
At -5~5 DEG C, 1.5h is added dropwise temperature control system, continues insulated and stirred 1.0h.
Hydrochloric acid 308.4g is added dropwise（592.0mmol, 0.3eq, 7.0Wt.%）Reaction is quenched, kettle temperature controls at 5~20 DEG C, adds
Enter dichloroethanes to be extracted twice, separates oil phase merging twice.Water washing is added to neutrality, oil reservoir is spin-dried for obtaining 329.0g colorless oils
Shape object, yield 99%, wherein cis-trans-isomer ratio 55/45.
Second step：
First step product 200.8g is added in 2L four-hole bottles（1179.0mmol 1.0eq）, dichloroethanes 800.0g, three second
Amine 131.2g（1279.0mmol 1.1eq）, 4-dimethylaminopyridine 14.4g（117.8mmol, 0.1eq）, it is put into ice maker cooling
It is for use to -5~0 DEG C.
Mesyl chloride 148.6g is added dropwise（1297.0mmol 1.1eq）The solution prepared with dichloroethanes 200.8g, 1.5h drops
It is complete, process temperature is added dropwise and controls at -5~5 DEG C, subsequent 0~5 DEG C of insulated and stirred 1.0h.
Water 600g is added, reaction is quenched, then stop cooling, kettle temperature is restored to room temperature, stirs 0.5h, stands 0.5h, separate
Oil reservoir 1268.0g, water layer return kettle and dichloroethanes 200.0g reextractions are added, and stir 0.5h, stand 0.5h, separate secondary
Oil reservoir 188.7g.Merge one or two oil reservoirs, water 400.0g washings are added, stirs 0.5h, stands 0.5h, separate oil reservoir, precipitation makes
260.0g secondary products, content ＞ 98%, yield 88%, wherein cis-trans-isomer ratio 56/44 are obtained with ethyl alcohol recrystallization.
Third walks：
Second step product 400g is added in 5L chuck kettles（1610.4mmol 1.0eq）, thioacetic acid potassium 275.9g
（2415.6mmol 1.5eq）, n,N-Dimethylformamide 2000g is heated to 120-126 DEG C of insulated and stirred 2.0h.Then stop
Water is added in heating, cooled to room temperature, is extracted 2 times using dichloroethanes, merges dichloroethanes layer, uses water washing 2 times.Oil
45 DEG C of revolving precipitation of layer obtain the residual 287.2g of kettle, yield 78%, wherein cis-trans-isomer ratio 90/10.
4th step：
Third step gained crude product 287.2g（1257.5mmol 1.0eq）It is transferred in 5L chuck kettles, is used with methanol 1436g
Ice maker is cooled to -10 DEG C for use.
4% sodium hydroxide solution 1257.5g is added dropwise（1257.5mmol 1.0eq）, 0.5h drips off, and process kettle temperature control is added dropwise
- 15~-10 DEG C of system, drips off rear insulated and stirred 5.0h.5% hydrochloric acid neutralization reaction liquid is added dropwise, dichloroethanes is added and is extracted twice, closes
And oil reservoir is extracted, water washing is added twice.Oil reservoir is spin-dried for obtaining 200g yellow oils, yield 85%, wherein cis-trans-isomer ratio
Example ＞ 99/1.
Embodiment 2
The first step：
Sodium borohydride 2.6g is added in 250mL four-hole bottles（69.2mmol 0.3eq）, tetrahydrofuran 41.2g, mechanical agitation shape
Water 9.1g is added dropwise under state（507.2mmol, 2.2eq）, 20min drips off, and kettle temperature maintains essentially in 21 DEG C, no significant change.Then
Four-hole bottle is placed in ice maker, is cooled to -5 DEG C for use.
N-pentyl cyclohexanone 38.8g is added dropwise（230.6mmol, 1.0eq）The solution prepared with tetrahydrofuran 19.4g, kettle temperature
At -5~5 DEG C, 0.5h is added dropwise for control, continues insulated and stirred 1.0h.
Hydrochloric acid 36.1g is added dropwise, reaction is quenched, kettle temperature is controlled at 5~20 DEG C, and dichloroethanes is added and is extracted twice, separates twice
Oil phase merges.Water washing is added to neutrality, oil reservoir is spin-dried for obtaining 39.3g colorless oils, yield 100%, wherein cis-trans-isomer
Ratio 57/43.
Second step：
First step product 20.5g is added in 250mL four-hole bottles（115.3mmol, 1.0eq）, dichloroethanes 80.0g, three second
Amine 13.4g（132.3mmol, 1.15eq）, 4-dimethylaminopyridine 1.5g（12.0mmol 0.1eq）, it is put into ice maker and is cooled to -5
~0 DEG C for use.
Mesyl chloride 15.2g is added dropwise（132.4mmol, 1.15eq）The solution prepared with dichloroethanes 20.2g, 0.5h drops
It is complete, process temperature is added dropwise and controls at -5~5 DEG C, subsequent 0~5 DEG C of insulated and stirred 1.0h.
Water quenching is added to go out reaction, then stops cooling, kettle temperature is restored to room temperature, and an oil reservoir is separated, and water layer returns kettle and is added
Dichloroethanes reextraction separates secondary oil reservoir.Merge one or two oil reservoirs, water washing is added, separates oil reservoir, precipitation uses second
Alcohol is recrystallized to give 27.0g secondary products, content ＞ 98%, yield 90.3%, wherein cis-trans-isomer ratio 58/42.
Third walks：
Second step product 7.0g is added in 250mL chuck kettles（29.9mmol 1.0eq）, thioacetic acid potassium 4.5g
（39.5mmol 1.4eq）, n,N-Dimethylformamide 112g is heated to 120-126 DEG C of insulated and stirred 2.0h.Then stop adding
Water is added in heat, cooled to room temperature, is extracted 2 times using dichloroethanes, merges dichloroethanes layer, uses water washing 2 times.Oil reservoir
45 DEG C of revolving precipitations obtain the residual 4.9g of kettle, yield 76.5%, wherein cis-trans-isomer ratio 91/9.
4th step：
Third step gained crude product 10.1g（44.2mmol 1.0eq）It is transferred in 250mL four-hole bottles with methanol 101g, uses ice
Machine is cooled to -10 DEG C for use.
4% sodium hydroxide solution 44.2g is added dropwise（44.2mmol 1.0eq）, 0.5h drips off, and process kettle temperature control -15 is added dropwise
~-10 DEG C, drip off rear insulated and stirred 5.0h.5% hydrochloric acid neutralization reaction liquid is added dropwise, dichloroethanes is added and is extracted twice, merges extraction
Water washing is added twice in oil reservoir.Oil reservoir is spin-dried for obtaining 6.6g yellow oils, yield 80.0%, wherein cis-trans-isomer ratio ＞
99/1。
Claims (6)
1. a kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis, it is characterised in that：4- n-pentyl cyclohexanone
4- n-pentyl cyclohexanol is obtained with sodium borohydride reduction, then carrying out sulfonylation with mesyl chloride obtains 4- n-pentyl hexamethylene methylsulphurs
Acetic acid 4- n-pentyl cyclohexylmercaptan esters are further obtained by the reaction in acid esters with thioacetic acid potassium, and subsequent -15 DEG C~-10 DEG C saponification are anti-
It answers and highly selective obtains cis- 4- n-pentyls cyclohexylmercaptan.
2. according to a kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis of claim 1：The reduction reaction
In, 4- n-pentyls cyclohexanone is 1 with sodium borohydride molar ratio:0.30-0.35, reaction temperature are controlled at -5~5 DEG C.
3. according to a kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis of claim 1：The sulfonylation is anti-
Ying Zhong, gained crude product need the 4- n-pentyl hexamethylene methanesulfonates for obtaining content ＞ 98% by ethyl alcohol recrystallization to be used for sulphur acetyl
Change reaction.
4. according to a kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis of claim 1：The sulphur acetylation
In reaction, 4- pentyl cyclohexyls methanesulfonates is 1 with thioacetic acid potassium molar ratio:1.4-1.6 reaction temperature is controlled 120
DEG C~126 DEG C.
5. according to a kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis of claim 1：The saponification
In, acetic acid 4- n-pentyl cyclohexylmercaptan esters are 1 with sodium hydroxide molar ratio:1.0.
6. according to a kind of preparation method of the cis- 4- n-pentyls cyclohexylmercaptan of selectivity synthesis of claim 1：It is suitable in the product
Formula selectivity of product ＞ 99%.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| TW200405128A (en) * | 2002-05-01 | 2004-04-01 | Shinetsu Chemical Co | Novel sulfonyldiazomethanes, photoacid generators, resist compositions, and patterning process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| TW200405128A (en) * | 2002-05-01 | 2004-04-01 | Shinetsu Chemical Co | Novel sulfonyldiazomethanes, photoacid generators, resist compositions, and patterning process |
Non-Patent Citations (5)
| Title |
|---|
| Resolution of Racemic 2-Aminocyclohexanol Derivatives and Their Application as Ligands in Asymmetric Catalysis.;Ingo Schiffers et al.;《J.Org.Chem.》;20060210;第71卷;第2320-2331页 * |
| Self-Assembled Monolayers of Cyclic Aliphatic Thiols and Their Reaction toward Electron Irradiation;Prashant A et al.;《The Journal of Physical Chemistry C》;20120604;第116卷;第13559-13568页 * |
| 医药中间体环己基硫醇的制备;姚文惠等;《科技资讯》;20090313(第8期);第214页 * |
| 顺反异构化过程及其机理;李锋等;《化学试剂》;20050128;第27卷(第1期);第21-23页 * |
| 顺式对叔丁基环己醇的合成及分离研究进展;高丰琴等;《应用化工》;20141020;第43卷(第10期);第1874-1878页 * |
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