A method for preparing 1,4-cyclohexane diisocyanate
By performing diazotization and rearrangement reaction of 1,4-cyclohexanediformylhydrazide and sodium nitrite in the acid solution, combined with the extraction step, the use of highly toxic gases and explosive products in the prior art has been successfully solved. The safety hazards of this paper realize the preparation of high-purity 1,4-cyclohexane diisocyanate, which is suitable for large-scale production and pharmaceutical excipient applications.
Patent Information
- Application Number
- CN202410137448.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-01-30
- Publication Date
- 2024-12-13
- Estimated Expiration
- 2044-01-30
AI Technical Summary
The existing 1,4-cyclohexane diisocyanate synthesis technology uses highly toxic gas triphosgene and explosive sodium azide, which poses safety risks and is rare in materials, making it difficult to achieve large-scale production.
A one-step preparation method is adopted, by reacting 1,4-cyclohexane diformylhydrazide with sodium nitrite aqueous solution in acid solution, diazotization and rearrangement reactions, combined with the extraction step, a high purity 1 is obtained. ,4-cyclohexane diisocyanate avoids the use of highly toxic gases and explosive products, and is mild in conditions and is suitable for large-scale production.
It has achieved high purity (not less than 98.5%) preparation of 1,4-cyclohexane diisocyanate, which has good safety and easy access to raw materials. It is suitable for the application of pharmaceutical excipients and is suitable for large-scale industrial promotion.
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Figure CN118005537B_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of diisocyanate synthesis, and particularly relates to a method for preparing 1,4-cyclohexane diisocyanate. Background Art
[0002] Existing synthesis usually adopts triphosgene technology, the material toxicity is relatively high, there are many environmental and safety hazards, and the material is not easy to obtain. For example, CN102827035 discloses a method for synthesizing 1,4-cyclohexane diisocyanate, comprising: dissolving solid triphosgene in chloroform, cooling the solution to -5°C-0°C, slowly adding 1,4-cyclohexanediamine, and completing the addition; heating the reaction solution to 40-70°C and reacting for 6h. After the reaction is completed, cooling the reaction solution to 10-20°C, washing with alkali until the weak alkalinity reaches neutrality, recovering the chloroform, and performing vacuum distillation to obtain a light yellow waxy solid 1,4-cyclohexane diisocyanate.
[0003] There is also a synthesis technology using sodium azide. Sodium azide is an explosive material and is not easy to be industrially mass-produced. For example, CN101735111 discloses a method for synthesizing trans-1,4-cyclohexane diisocyanate, which comprises the following steps: (1) mixing trans-1,4-cyclohexanedicarboxylic acid with thionyl chloride, heating to reflux, and recovering excess thionyl chloride under reduced pressure to obtain trans-trans-1,4-cyclohexanedicarboxylic acid chloride; (2) adding toluene, benzene or xylene to the trans-1,4-cyclohexanedicarboxylic acid chloride, heating to 45-75°C, and then adding sodium azide to obtain a mixture; (3) keeping the mixture warm at 45-75°C for 0.5-1.5 hours; filtering to remove insoluble matter, recovering toluene under reduced pressure, and distilling to obtain trans-1,4-cyclohexane diisocyanate. CN115850117 discloses a method for preparing an aliphatic diisocyanate, namely 1,4-cyclohexane diisocyanate, which mainly comprises the following steps: (1) adding oxalyl chloride and toluene into a three-necked flask respectively, heating the oil bath to 50°C, gradually adding the prepared toluene slurry of 1,4-cyclohexanedicarboxylic acid into the three-necked flask, cooling after the reaction, and removing impurities by vacuum distillation to obtain 1,4-cyclohexanedicarboxylic acid chloride; (2) adding sodium azide, a small amount of catalyst, Deionized water is added into a three-necked flask and cooled in an ice-water bath to below 5°C; the toluene solution of 1,4-cyclohexanedicarbonyl chloride is added dropwise into the three-necked flask and the bath temperature is controlled to be below 5°C. After the reaction is completed, the phases are separated and anhydrous magnesium sulfate is added to the toluene phase for drying to obtain a toluene solution of 1,4-cyclohexanedicarbonyl azide compound; (3) the toluene solution of 1,4-cyclohexanedicarbonyl azide compound is added dropwise into a toluene solution at 80°C to 110°C and the solvent is evaporated under reduced pressure to obtain the target product. Summary of the invention
[0004] The first object of the present invention is to provide a method for preparing 1,4-cyclohexane diisocyanate. The preparation method is a one-step method to complete the overall reaction. The reaction route is simple, the raw materials are easily available, the conditions are mild, the use of highly toxic gas phosgene and explosive sodium azide is avoided, the safety is good, the product purity is not less than 98.5%, and the yield is 75% based on 1,4-cyclohexane dicarboxylic acid hydrazide. The method is suitable for large-scale production and is suitable for the application of pharmaceutical excipients.
[0005] The second object of the present invention is to provide a method for preparing 1,4-cyclohexane diisocyanate, wherein the synthesis route aims to use conventional readily available and inexpensive chemical materials to produce cyclohexane diisocyanate under relatively mild conditions. The process has good production prospects and is easy to promote on a large scale.
[0006] The present invention is achieved through the following technical solutions:
[0007] A method for preparing 1,4-cyclohexane diisocyanate comprises the following steps:
[0008] S1. Diazotization reaction:
[0009] Add 1,4-cyclohexanedicarboxylic acid hydrazide to water and acid solution, add the organic phase and stir until dissolved, lower the reaction temperature to -5 to 20°C, add sodium nitrite aqueous solution dropwise, let stand, wash the organic phase with brine and dry;
[0010] S2, rearrangement reaction:
[0011] Rearrange the mixture at 50-60°C and release nitrogen, then recover the organic phase under reduced pressure to obtain a yellow turbid liquid.
[0012] The yellow turbid liquid is crude 1,4-cyclohexane diisocyanate;
[0013] Add an extractant to the crude 1,4-cyclohexane diisocyanate, heat and reflux for extraction at 50-60°C, recover the extractant under reduced pressure, and perform vacuum distillation to obtain a colorless to light yellow liquid;
[0014] The colorless to light yellow liquid is the finished product of 1,4-cyclohexane diisocyanate.
[0015] The following is the reaction route diagram:
[0016]
[0017] This reaction process is a continuous feeding reaction, which is carried out in the same reaction system.
[0018] Preferably, in S1, the acid solution includes any one of hydrochloric acid solution, sulfuric acid solution, phosphoric acid solution, and acetic acid solution;
[0019] The organic phase includes any one of toluene, chloroform, dichloromethane, and dichloroethane;
[0020] The mass ratios of the 1,4-cyclohexanedicarboxylic acid hydrazide, water, acid solution and organic phase are 1:1-2:1-2:10-12 respectively.
[0021] Preferably, the acid solution is a hydrochloric acid solution;
[0022] The organic phase is chloroform;
[0023] The reaction temperature was cooled to -5 to 0°C.
[0024] The water is used as a carrier to dissolve diformyl hydrazide, and the hydrochloric acid solution is used as an acidic auxiliary solvent to provide an acidic environment.
[0025] The pH value after the 1,4-cyclohexanedicarboxylic acid hydrazide is added to water and acid solution and mixed evenly is less than 1.
[0026] Preferably, in S1, the mass concentration of the sodium nitrite aqueous solution is 20wt% to 50wt%;
[0027] The mass ratio of the sodium nitrite aqueous solution to 1,4-cyclohexanedicarboxylic acid hydrazide is 1:1.
[0028] Preferably, the mass concentration of the brine is 10wt% to 20wt%;
[0029] The mass ratio of the brine to 1,4-cyclohexanedicarboxylic acid hydrazide is 5 to 6:1.
[0030] Preferably, the mass concentration of the sodium nitrite aqueous solution is 40wt%.
[0031] In the above S1, the reaction temperature is required to be controlled at -5 to 20°C because the reaction is an exothermic reaction. If the reaction temperature is not controlled, the reaction temperature will rise sharply and cause danger. The temperature control is to ensure the stability of the material.
[0032] The sodium nitrite aqueous solution is added dropwise because the dropwise addition can ensure that the entire reaction temperature is controllable and promote a more uniform reaction.
[0033] Preferably, in S2, the rearrangement reaction temperature is 50-60° C., and the reaction time is 0.5-3 h.
[0034] Preferably, in S2, the extractant includes any one of toluene, n-hexane, cyclohexane, petroleum ether, and n-heptane;
[0035] The mass ratio of the crude 1,4-cyclohexane diisocyanate to the extractant is 1:4-5.
[0036] Preferably, in S2, the heating reflux extraction time is 2 to 2.5 hours.
[0037] Compared with the prior art, the present invention has at least the following technical effects:
[0038] The invention provides a method for preparing 1,4-cyclohexane diisocyanate. The preparation method is a one-step method to complete the overall reaction. The reaction route is simple, the raw materials are easily available, the conditions are mild, the use of highly toxic gas phosgene and explosive sodium azide is avoided, the safety is good, the product purity is not less than 98.5%, the yield is 75% based on 1,4-cyclohexane dicarboxylic acid hydrazide, the method is suitable for large-scale production, and is suitable for the application of pharmaceutical excipients.
[0039] The synthesis route aims to use conventional, readily available and inexpensive chemical materials to produce cyclohexane diisocyanate under relatively mild conditions. The process has good production prospects and is easy to promote on a large scale. BRIEF DESCRIPTION OF THE DRAWINGS
[0040] Figure 1 The NMR of 1,4-cyclohexane diisocyanate product ( 1 H NMR) detection spectrum. DETAILED DESCRIPTION
[0041] The embodiments of the present invention will be described in detail below in conjunction with examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. The specific conditions not specified in the examples are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.
[0042] A technical solution of a specific implementation of the present invention is:
[0043] A method for preparing 1,4-cyclohexane diisocyanate comprises the following steps:
[0044] S1. Diazotization reaction:
[0045] Add 1,4-cyclohexanedicarboxylic acid hydrazide to water and acid solution, add the organic phase and stir until dissolved, lower the reaction temperature to -5 to 20°C, add sodium nitrite aqueous solution dropwise, let stand, wash the organic phase with brine and dry;
[0046] S2, rearrangement reaction:
[0047] Rearrange the mixture at 50-60°C and release nitrogen, then recover the organic phase under reduced pressure to obtain a yellow turbid liquid.
[0048] The yellow turbid liquid is crude 1,4-cyclohexane diisocyanate;
[0049] Add an extractant to the crude 1,4-cyclohexane diisocyanate, heat and reflux for extraction at 50-60°C, recover the extractant under reduced pressure, and perform vacuum distillation to obtain a colorless to light yellow liquid;
[0050] The colorless to light yellow liquid is the finished product of 1,4-cyclohexane diisocyanate.
[0051] The following is the reaction route diagram:
[0052]
[0053] In S1, the acid solution includes any one of hydrochloric acid solution, sulfuric acid solution, phosphoric acid solution, and acetic acid solution;
[0054] The organic phase includes any one of toluene, chloroform, dichloromethane, and dichloroethane;
[0055] The mass ratios of the 1,4-cyclohexanedicarboxylic acid hydrazide, water, acid solution and organic phase are 1:1-2:1-2:10-12 respectively.
[0056] The acid solution is a hydrochloric acid solution;
[0057] The organic phase is chloroform;
[0058] The reaction temperature was cooled to -5 to 0°C.
[0059] In S1, the mass concentration of the sodium nitrite aqueous solution is 20wt% to 50wt%;
[0060] The mass ratio of the sodium nitrite aqueous solution to 1,4-cyclohexanedicarboxylic acid hydrazide is 1:1.
[0061] The mass concentration of the brine is 10wt% to 20wt%;
[0062] The mass ratio of the brine to 1,4-cyclohexanedicarboxylic acid hydrazide is 5 to 6:1.
[0063] The mass concentration of the sodium nitrite aqueous solution is 40 wt %.
[0064] In S2, the rearrangement reaction temperature is 50-60° C., and the reaction time is 0.5-3 h.
[0065] In S2, the extractant includes any one of toluene, n-hexane, cyclohexane, petroleum ether, and n-heptane;
[0066] The mass ratio of the crude 1,4-cyclohexane diisocyanate to the extractant is 1:4-5.
[0067] In S2, the heating reflux extraction time is 2 to 2.5 hours.
[0068] Embodiment 1:
[0069] S1. Add 100 kg of water and 100 kg of industrial hydrochloric acid into the reaction kettle (1), and add 50 kg of 1,4-cyclohexanedicarboxylic acid hydrazide under stirring to dissolve.
[0070] After dissolution is completed, the feed liquid is transferred to the reaction kettle (2), 300 kg of chloroform is added, and the temperature begins to drop. When the internal temperature reaches -5°C, it is set aside.
[0071] Add 40 kg of sodium nitrite and 160 kg of water into the high-position tank, stir and dissolve, then add the sodium nitrite solution dropwise into the reaction kettle (2), control the reaction temperature at -5 to 0°C, and continue the reaction for half an hour after the addition is completed.
[0072] The mixture was allowed to stand for separation, and the organic phase was separated. The organic phase was washed with 300 kg of 10% sodium chloride solution, and the mixture was separated. The organic phase was dried with 50 kg of anhydrous magnesium sulfate for 2 hours.
[0073] S2. Filter and remove the desiccant, transfer the organic phase to another dry reaction kettle (3), and gradually heat to 50° C. to cause rearrangement reaction to generate 1,4-cyclohexane diisocyanate.
[0074] After reacting for 2 h, the chloroform was recovered under reduced pressure to obtain a yellow turbid liquid.
[0075] 200 kg of petroleum ether was added to the yellow turbid liquid, and the mixture was heated to reflux and extracted at 60°C for 2 h. The petroleum ether was recovered under reduced pressure to obtain crude 1,4-cyclohexane diisocyanate.
[0076] The crude product was subjected to vacuum distillation, and the 140-150°C / 30 mmHg fraction was collected to obtain 31.1 kg of colorless transparent liquid 1,4-cyclohexane diisocyanate.
[0077] The yield based on 1,4-cyclohexanedicarboxylic acid hydrazide is 74.9% and the product purity is 99.3%.
[0078] Embodiment 2:
[0079] S1. Add 200 kg of water and 200 kg of industrial hydrochloric acid into the reaction kettle (1), and add 50 kg of 1,4-cyclohexanedicarboxylic acid hydrazide under stirring to dissolve.
[0080] After dissolution is completed, the feed liquid is transferred to the reaction kettle (2), 600 kg of chloroform is added, and the temperature begins to drop. When the internal temperature reaches -5°C, it is set aside.
[0081] Add 40 kg of sodium nitrite and 40 kg of water into the high-position configuration tank, stir and dissolve, then drop the sodium nitrite solution into the reaction kettle (2), control the reaction temperature at -5 to 0°C, and continue the reaction for half an hour after the addition is completed.
[0082] The mixture was allowed to stand for separation, and the organic phase was separated. The organic phase was washed with 300 kg of 10% sodium chloride solution, and the mixture was separated. The organic phase was dried with 50 kg of anhydrous magnesium sulfate for 2 hours.
[0083] S2, filtering to remove the desiccant, transferring the organic phase to another drying reaction kettle (3), gradually heating to 60°C to cause rearrangement reaction to generate 1,4-cyclohexane diisocyanate.
[0084] After reacting for 2 h, the chloroform was recovered under reduced pressure to obtain a yellow turbid liquid.
[0085] 200 kg of petroleum ether was added to the yellow turbid liquid, and the mixture was heated to reflux and extracted at 60°C for 2 hours. The petroleum ether was recovered under reduced pressure to obtain crude 1,4-cyclohexane diisocyanate.
[0086] The crude product was subjected to vacuum distillation, and the 140-150°C / 30 mmHg fraction was collected to obtain 32.5 kg of colorless transparent liquid 1,4-cyclohexane diisocyanate.
[0087] The yield based on 1,4-cyclohexanedicarboxylic acid hydrazide is 78.3% and the product purity is 99.2%.
[0088] Embodiment 3:
[0089] S1. Add 100 kg of water and 100 kg of industrial hydrochloric acid into the reaction kettle (1), and add 50 kg of 1,4-cyclohexanedicarboxylic acid hydrazide under stirring to dissolve.
[0090] After dissolution is completed, the feed liquid is transferred to the reaction kettle (2), 400 kg of chloroform is added, and the temperature begins to drop. When the internal temperature reaches 10°C, it is set aside.
[0091] Add 40 kg of sodium nitrite and 40 kg of water into the high-position configuration tank, stir and dissolve, then add the sodium nitrite solution dropwise into the reaction kettle (2), control the reaction temperature at 10° C., and continue the reaction for half an hour after the addition is completed.
[0092] The mixture was allowed to stand for separation, and the organic phase was separated. The organic phase was washed with 300 kg of 20% sodium chloride solution, and the organic phase was separated and dried with 50 kg of anhydrous magnesium sulfate for 2 hours.
[0093] S2, filtering and removing the desiccant, transferring the organic phase to another drying reaction kettle (3), gradually heating to 50-60°C to cause rearrangement reaction, and generating 1,4-cyclohexane diisocyanate.
[0094] After reacting for 2 h, the chloroform was recovered under reduced pressure to obtain a yellow turbid liquid.
[0095] 200 kg of petroleum ether was added to the yellow turbid liquid, and the mixture was heated to reflux and extracted at 50°C for 2 hours. The petroleum ether was recovered under reduced pressure to obtain crude 1,4-cyclohexane diisocyanate.
[0096] The crude product was subjected to vacuum distillation, and the 140-150°C / 30 mmHg fraction was collected to obtain 29.3 kg of colorless transparent liquid 1,4-cyclohexane diisocyanate.
[0097] The yield based on 1,4-cyclohexanedicarboxylic acid hydrazide is 70.6% and the product purity is 99.1%.
[0098] like Figure 1 As shown, the NMR of 1,4-cyclohexane diisocyanate product ( 1 H NMR) detection spectrum (deuterated chloroform was used as the test solvent).
[0099] Product structure confirmation information:
[0100] 1 H NMR (500MHz, CDCl3) δ1.52-1.58(m,4H),2.02-2.05(m,4H),3.55(s,2H).
[0101] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the protection scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims
1. A method for preparing 1,4-cyclohexane diisocyanate, characterized in that: It is obtained by the following steps: S1. Diazotization reaction: Add 200 kg of water and 200 kg of industrial hydrochloric acid into the reaction kettle (1), and add 50 kg of 1,4-cyclohexanedicarboxylic acid hydrazide under stirring to dissolve; After dissolution is completed, transfer the feed liquid to the reaction kettle (2), add 600 kg of chloroform, and start cooling. When the internal temperature reaches -5°C, set aside; Add 40 kg of sodium nitrite and 40 kg of water into the high-position tank, stir and dissolve, then drop the sodium nitrite solution into the reaction kettle (2), control the reaction temperature at -5 to 0°C, and continue the reaction for half an hour after the addition is completed; The organic phase was separated by standing and washed with 300 kg of 10% sodium chloride solution, and the organic phase was dried with 50 kg of anhydrous magnesium sulfate for 2 hours. S2, rearrangement reaction: The desiccant was removed by filtration, and the organic phase was transferred to another dry reaction kettle (3), and gradually heated to 60°C to cause a rearrangement reaction to generate 1,4-cyclohexane diisocyanate; After reacting for 2 h, chloroform was recovered under reduced pressure to obtain a yellow turbid liquid; Add 200 kg of petroleum ether to the yellow turbid liquid, heat and reflux at 60°C for extraction for 2 hours; recover the petroleum ether under reduced pressure to obtain crude 1,4-cyclohexane diisocyanate; After the crude product was distilled under reduced pressure, the 140-150°C / 30 mmHg fraction was collected to obtain 32.5 kg of colorless transparent liquid 1,4-cyclohexane diisocyanate; The yield based on 1,4-cyclohexanedicarboxylic acid hydrazide is 78.3% and the product purity is 99.2%.