CN117304209A - Vitamin B 6 Preparation method and application of intermediate adduct - Google Patents
Vitamin B 6 Preparation method and application of intermediate adduct Download PDFInfo
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- CN117304209A CN117304209A CN202311177232.XA CN202311177232A CN117304209A CN 117304209 A CN117304209 A CN 117304209A CN 202311177232 A CN202311177232 A CN 202311177232A CN 117304209 A CN117304209 A CN 117304209A
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- RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 29
- 239000002994 raw material Substances 0.000 claims abstract description 28
- FWPDSAJKWKRRJD-UHFFFAOYSA-N 5-ethoxy-4-methyl-1,3-oxazole Chemical compound CCOC=1OC=NC=1C FWPDSAJKWKRRJD-UHFFFAOYSA-N 0.000 claims abstract description 23
- -1 n-propyl dioxygen Chemical compound 0.000 claims abstract description 17
- 229910001882 dioxygen Inorganic materials 0.000 claims abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 13
- 229930003270 Vitamin B Natural products 0.000 claims abstract description 12
- 235000019156 vitamin B Nutrition 0.000 claims abstract description 12
- 239000011720 vitamin B Substances 0.000 claims abstract description 12
- 238000002156 mixing Methods 0.000 claims description 8
- 239000006229 carbon black Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 3
- 238000004064 recycling Methods 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 31
- 230000035484 reaction time Effects 0.000 abstract description 9
- 230000006378 damage Effects 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- 238000007259 addition reaction Methods 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 7
- 238000011084 recovery Methods 0.000 description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005899 aromatization reaction Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
- 235000011837 pasties Nutrition 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
- C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
- C07D213/67—2-Methyl-3-hydroxy-4,5-bis(hydroxy-methyl)pyridine, i.e. pyridoxine
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to vitamin B 6 The synthesis field of intermediates, discloses a vitamin B 6 A process for the preparation of an intermediate adduct and its use, the process comprising: the n-propyl dioxygen heptaring, 4-methyl-5-ethoxyoxazole and a microwave sensitizer are subjected to contact reaction under the microwave condition to obtain vitamin B 6 Intermediate adducts. The method is used for synthesizing vitamin B 6 The intermediate has short reaction time and low temperature, and the materials are removed in time after continuous flow reaction, so that the damage of unreacted raw materials and products at high temperature is reduced, and the vitamin B is improved 6 Yield of intermediate.
Description
Technical Field
The present invention relates to vitamin B 6 The synthesis field of intermediates, in particular to vitamin B 6 A preparation method and application of an intermediate adduct.
Background
Vitamin B 6 Has wide physiological function, and is one of vitamins essential for human body. Industrially, vitamin B 6 The synthesis method of (1) mainly comprises the steps ofThe pyridone method and the oxazol method. The pyridone method is adopted in the early industry, and is gradually replaced by the later developed oxazol method due to the defects of long steps, low yield, serious equipment corrosion and the like.
The method uses n-propyl dioxygen heptaring and 4-methyl-5-ethoxyl oxazole to obtain vitamin B through three steps of addition, aromatic structure and hydrolysis 6 The traditional method adopts a high-temperature one-pot method for addition reaction, which has long time and high temperature, has high requirements on public systems, and can cause the damage of raw materials and auxiliary materials in the reaction system and the generated intermediate addition product.
Disclosure of Invention
The invention aims to solve the problems of high addition reaction temperature, long time, large damage of reaction raw materials and intermediates in the prior art and provide vitamin B 6 Process for the preparation of intermediate adducts for the synthesis of vitamin B 6 The intermediate addition product has short reaction time, low temperature and timely removal of materials after continuous flow reaction, reduces the damage of unreacted raw materials and products at high temperature, and improves vitamin B 6 Yield of intermediate adduct.
In order to overcome the defect that raw materials and auxiliary materials in a reaction system and an intermediate addition product which are generated in the same time of adding by using the n-propyl dioxygen heptaring and the 4-methyl-5-ethoxyoxazole through a one-pot method are destroyed, the invention firstly provides a microwave continuous flow reaction which can reduce the reaction temperature, has shorter reaction time and fewer impurities, and obtains the vitamin B 6 The crude product content is higher, and the subsequent purification is simpler. At present, no technology for applying microwaves to the addition reaction is reported, and the invention fills the technical blank. The present invention has been made in view of the above.
To achieve the above object, an aspect of the present invention provides a vitamin B 6 A process for preparing an intermediate adduct, the process comprising: the n-propyl dioxygen heptaring, 4-methyl-5-ethoxyoxazole and a microwave sensitizer are subjected to contact reaction under the microwave condition to obtain vitamin B 6 Intermediate adducts having the structure of formula I:
（I）。
a second aspect of the invention provides vitamin B in the preparation according to the method of the invention 6 Is used in the application of (a).
Through the technical scheme, the invention has the following beneficial effects:
(1) The reaction time is shorter, the kettle type reaction needs to be kept for more than 15 hours, the microwave continuous flow reaction time is only about 30 minutes, the production period is greatly shortened, and the reaction time is further shortened by adding a microwave sensitizer into n-propyl dioxygen heptaring and 4-methyl-5-ethoxyoxazole;
(2) The reaction temperature is lower, the energy is saved, the kettle type addition reaction temperature needs 160 ℃ or higher, otherwise, the reaction speed is slow, the reaction temperature needs to be heated by about 1.0MPa in industrial production, the pressure resistance requirement on the reaction kettle is higher, and the reaction can be realized within 120 ℃ by using microwaves;
(3) Less impurity, and vitamin B obtained 6 The crude product content is higher, and the later purification is simpler; the destruction of unreacted raw materials and generated adducts at high temperature can generate a large amount of colored impurities to obtain vitamin B 6 The crude product has low content, a large amount of activated carbon is needed to be added for decolorization and impurity removal in the subsequent purification, the microwave continuous flow reaction is adopted, the residence time of raw materials and products at high temperature is greatly shortened, the damage is little, and only a small amount of activated carbon is needed to be added for decolorization in the subsequent purification.
(4) In the preferred embodiment, the continuous microwave reactor can realize continuous flow reaction, materials are removed in time after the reaction, the damage of unreacted raw materials and products at high temperature is reduced, and the yield is higher.
Detailed Description
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
The invention provides a vitamin B 6 A process for preparing an intermediate adduct, the process comprising: the n-propyl dioxygen heptaring, 4-methyl-5-ethoxyoxazole and a microwave sensitizer are subjected to contact reaction under the microwave condition to obtain vitamin B 6 Intermediate adducts having the structure of formula I:
(I)；
the reaction route is as follows:
。
vitamin B of the invention 6 The preparation method of the intermediate addition product has the advantages of short residence time, low reaction temperature and high yield, and is used for vitamin B 6 In the preparation method, good economic benefit is obtained.
According to a particularly preferred embodiment of the invention, the sensitizers are carbon black sensitizers, freguon sensitizers and Fe 3 O 4 At least one of the sensitizers, in the present invention, is exemplified by a carbon black sensitizer, but the scope of the present invention is not limited thereby. The sensitizer of the invention can greatly shorten the reaction time.
In the invention, the dosage of the microwave sensitizer is wide in optional range and can be adjusted according to actual needs, and in the embodiment, the dosage of the microwave sensitizer is exemplified by 0.5-1 wt%of the total mass of n-propyldioxyheptaring and 4-methyl-5-ethoxyoxa, but the scope of the invention is not limited by the description.
In the present invention, the conditions for the contact reaction under the microwave conditions can be selected by those skilled in the art according to actual needs.
According to a particularly preferred embodiment of the invention, the contacting reaction is carried out at a temperature of 90-120℃under microwave conditions, preferably 107-115℃107℃108℃109℃110℃111℃112℃113℃114℃115 ℃.
According to a particularly preferred embodiment of the invention, the residence time for the contact reaction is 20-33.33min under microwave conditions, whereas the reaction time for the conventional one-pot process is more than 15 h.
By adopting the preferred embodiment, the reaction temperature can be greatly reduced, and the yield of the target product can be further improved.
In the invention, the mass ratio of the n-propyl dioxy heptaring and the 4-methyl-5-ethoxy oxazole can be selected in a wider range, and according to a particularly preferred embodiment of the invention, the mass ratio of the n-propyl dioxy heptaring and the 4-methyl-5-ethoxy oxazole is 5-10:1. By adopting the preferred embodiment, the conversion rate of the key raw material 4-methyl-5-ethoxyoxazole can be further improved, and meanwhile, the damage of the key raw material 4-methyl-5-ethoxyoxazole can be reduced because of the protection of a large amount of n-propyl dioxygen heptaring.
In the present invention, the microwave conditions are not particularly required, and those skilled in the art can select according to actual needs, and the following exemplary descriptions are not intended to limit the scope of the present invention.
According to a particularly preferred embodiment of the invention, the microwave power is 100-800W.
According to a particularly preferred embodiment of the invention, the microwave frequency 2450.+ -.50 MHz.
By adopting the foregoing preferred embodiment, the raw materials can be further rapidly brought to a predetermined reaction temperature.
The object of the invention is achieved by the invention being carried out under microwave conditions, without particular requirements being imposed on the reactor in which it is used, according to a particularly preferred embodiment of the invention the contact reaction is carried out in a microwave reactor comprising: a feeding pipeline and a microwave reaction zone for continuously conveying raw materials of n-propyl dioxygen heptaring, 4-methyl-5-ethoxyoxazole and a microwave sensitizer.
According to a particularly preferred embodiment of the invention, the microwave reactor is of the type MKG-H1C1B, the liquid holdup of the microwave reactor is 20L, the microwave power is linearly adjustable between 100 and 800W, the microwave frequency is 2450+/-50 MHz, the flow rate is in the range of 100 to 1000ml/min, and the microwave power is 500W and the microwave frequency is 2400MHz in the examples, but the scope of the invention is not limited thereby.
Vitamin B according to the invention 6 In the preparation method of the intermediate addition product, the step of pre-mixing and stirring the n-propyl dioxygen heptaring, the 4-methyl-5-ethoxyoxazole and the microwave sensitizer at room temperature to obtain a mixed material is also needed before the contact reaction of the n-propyl dioxygen heptaring, the 4-methyl-5-ethoxyoxazole and the microwave sensitizer under the microwave condition, the mixing condition in the step has no special requirement, the mixing speed can be exemplified by referring to the prior art, the stirring time can be selected according to the actual requirement, and the purpose of uniform mixing is only needed, but the scope of the invention is not limited.
In the present invention, the flow rate of the mixture is selected within a wide range, and according to a particularly preferred embodiment of the present invention, the flow rate of the mixture is 100 to 1000mL/min, preferably 500 to 1000mL/min. By adopting the foregoing preferred embodiment, the raw materials can be further rapidly brought to a predetermined reaction temperature.
In the present invention, the vitamin B 6 In the preparation method of the intermediate addition product, n-propyl dioxygen heptaring, 4-methyl-5-ethoxyoxazole and a microwave sensitizer are subjected to contact reaction under the microwave condition to obtain vitamin B 6 After the intermediate addition, the operation step of rectifying and recycling the unreacted excessive raw materials in the microwave reactor is also needed. This step is not particularly limited and can be carried out with reference to the prior art, by way of example, recovery by distillation under reduced pressure, but is not thereby limiting the scope of the invention.
According to a particularly preferred embodiment of the invention, the vacuum recovered is 1500-3000Pa, which is exemplified by 2000Pa in the examples, but is not thereby limiting the scope of the invention.
According to a particularly preferred embodiment of the invention, the recovery temperature is 100-130 ℃, 120 ℃ being exemplified in the examples, but not limiting the scope of the invention.
By adopting the preferred embodiment, the recovery rate of unreacted raw materials can be further improved, and the quality of the product can be improved.
The invention provides a vitamin B 6 The synthesis method of (2), the method comprises: the synthesis method of the invention synthesizes vitamin B 6 An intermediate adduct; vitamin B 6 Carrying out an aromatic reaction and a hydrolysis reaction after the intermediate addition; the reaction route is as follows:
。
vitamin B 6 The intermediate adducts are well known to those skilled in the art for carrying out the aromatization and hydrolysis reactions and are not described in detail herein.
The following exemplary description, but not limiting the scope of the invention, according to a particularly preferred embodiment of the invention, the aromatic conditions include: adding 95% ethanol with the mass 1.2 times of that of the obtained addition product, stirring for 0.5-1h, dispersing the addition product, cooling the addition product which is uniformly dispersed to about 30 ℃, controlling the temperature to 25-30 ℃, dropwise adding 0.1% hydrochloric acid solution, dropwise adding the solution into a reaction kettle, controlling the pH value to 3.5-4.5, controlling the internal temperature to 25-30 ℃, preserving heat for 15h, and then heating to 60 ℃ and preserving heat for 5h. After the heat preservation is finished, recovering ethanol under reduced pressure until the materials are pasty; the conditions of the hydrolysis reaction include: adding 10mol/L hydrochloric acid to adjust pH to below 0.5, adding hydrochloric acid, heating to 80deg.C, hydrolyzing, maintaining for 0.5-1 hr, recovering butyraldehyde as byproduct under reduced pressure, evaporating to dryness, adding 95% ethanol into the rest materials, cooling to below 20deg.C, filtering, and washing to obtain vitamin B 6 Crude product.
The present invention will be described in detail by examples.
In the following examples, temperature was measured by a thermocouple thermometer and vacuum was measured by an absolute pressure gauge;
the model of the microwave reactor is MKG-H1C1B, the liquid holdup of the microwave reactor is 20L, the microwave power is linearly adjustable at 100-800W, the microwave frequency is 2450+/-50 MHz, and the flow range is 100-1000 ml/min;
n-propyldioxyheptaring and 4-methyl-5-ethoxy-oxazole are homemade industrial grade raw materials by companies, and acids, other solvents and the like are all obtained by commercial use. Purity by gas chromatography, titration or high performance liquid chromatography, yield by actual yield/theoretical yield 100% calculation; vitamin B 6 Folding purity = vitamin B 6 Crude amount of liquid phase external standard content;
the conditions of the aromatization and hydrolysis are well known to those skilled in the art and can be carried out with reference to the prior art, the examples being illustrative but not limiting to the scope of the invention:
the aromatic conditions in the examples include: adding 95% ethanol with the mass 1.2 times of that of the obtained addition product, stirring for 1h, dispersing the addition product, cooling the addition product which is uniformly dispersed to 30 ℃, controlling the temperature to 30 ℃, dropwise adding 0.1% hydrochloric acid solution, dropwise adding the solution into a reaction kettle, controlling the internal temperature to 30 ℃ for 15h, and then heating to 60 ℃ for 5h. After the heat preservation is finished, recovering ethanol under reduced pressure until the materials are pasty; the hydrolysis conditions include: adding 10mol/L hydrochloric acid to adjust pH to below 0.5, adding hydrochloric acid, heating to 80deg.C, hydrolyzing, maintaining for 1 hr, recovering byproduct butyraldehyde under reduced pressure, evaporating to dryness, adding 95% ethanol into the rest materials, cooling to below 20deg.C, filtering, and washing to obtain vitamin B 6 Crude product.
Example 1
(1) Uniformly mixing 42kg of n-propyl dioxyheptaring, 6.0kg of 4-methyl-5-ethoxyoxazole and 384g of carbon black sensitizer at 25 ℃ and the rotating speed of 100 rpm;
(2) Pumping the uniformly mixed raw materials into a continuous microwave reactor by a pump at a flow rate of 1000ml/min for addition reaction to obtain vitamin B 6 Intermediate addition product, reaction temperature is 110 ℃, residence time is 20min, liquid holdup of a microwave reactor is 20L, microwave power is 500W, microwave frequency is 2400MHz, and feeding amount is uniformly calculated according to 6000g of oxazole conversion;
(3) The unreacted excessive raw materials are subjected to reduced pressure rectification recovery (vacuum degree 2000Pa, temperature 120 ℃); vitamin B exiting the reactor 6 The intermediate addition product is subjected to aromatic structure and hydrolysis reaction to obtain vitamin B 6 The yield is 94.1% after 9142 g.
Example 2
(1) Mixing 30kg of n-propyldioxyheptaring, 6.0kg of 4-methyl-5-ethoxyoxazole and 180g of Freguon sensitizer uniformly at 25 ℃ and rotating speed of 100 rpm;
(2) Pumping the uniformly mixed raw materials into a continuous microwave reactor by a pump at a flow rate of 800ml/min for addition reaction to obtain vitamin B 6 Intermediate addition product, reaction temperature is 107 ℃, residence time is 25min, liquid holdup of a microwave reactor is 20L, microwave power is 500W, microwave frequency is 2400MHz, and feeding amount is uniformly calculated according to 6000g of oxazole conversion;
(3) The unreacted excessive raw materials are subjected to reduced pressure rectification recovery (vacuum degree 2000Pa, temperature 120 ℃); vitamin B exiting the reactor 6 The intermediate addition product is subjected to aromatic structure and hydrolysis reaction to obtain vitamin B 6 Pure 9035g, yield 93.0%.
Example 3
(1) 60kg of n-propyldioxyheptaring, 6.0kg of 4-methyl-5-ethoxyoxazole and 660g of Fe 3 O 4 The sensitizer is uniformly mixed at 25 ℃ and the rotating speed is 100 rpm;
(2) Pumping the uniformly mixed raw materials into a continuous microwave reactor by a pump according to the flow rate of 960ml/min for addition reaction to obtain vitamin B 6 Intermediate addition product, the reaction temperature is 113 ℃, the reaction time is 30min, the liquid holdup of a microwave reactor is 20L, the microwave power is 500W, the microwave frequency is 2400MHz, and the feeding amount is uniformly calculated according to 6000g of oxazole conversion;
(3) The unreacted excessive raw materials are subjected to reduced pressure rectification recovery (vacuum degree 2000Pa, temperature 120 ℃); vitamin B exiting the reactor 6 The intermediate addition product is subjected to aromatic structure and hydrolysis reaction to obtain vitamin B 6 The yield is 93.8% when 9113g is folded.
Example 4
The reaction temperature was changed to 105℃and the same as in example 1. Obtaining vitamin B 6 8792g of the product was recovered, and the yield was 90.5%.
Example 5
The flow rate of the raw material was changed to 450ml/min, and the same as in example 1 was repeated. Obtaining vitamin B 6 Pure 8695g was recovered in 89.5%.
Example 6
Changing the vacuum of the recovered excessive raw materials after the reaction is finished to 3000Pa, the temperature to 130 ℃, and the other steps are the same as in example 1 to obtain vitamin B 6 Pure 8899g, yield 91.6%.
Example 7
All conditions were the same as in example 1, except that: the addition amount of the carbon black sensitizer is 96g, and vitamin B is obtained 6 8773g of pure product was recovered, and the yield was 90.3%.
Comparative example 1
All conditions were the same as in example 1 except that the raw materials n-propyldioxyheptacyclo and 4-methyl-5-ethoxyoxazole were uniformly mixed (mixing ratio was the same as in example 1), and the unreacted raw materials were recovered after the addition reaction at 160℃was kept for 15 hours. The residual materials in the kettle are subjected to aromatization and hydrolysis reaction to obtain vitamin B 6 8268g was recovered and the yield was 85.1%.
Comparative example 2
All conditions were the same as in example 1, except that: the vitamin B is obtained without adding carbon black sensitizer 6 8608g of pure product is obtained, and the yield is 88.6%.
TABLE 1
| Numbering device | Crude quantity/g | Content of external standard/% | Fold purity/g | Yield/% |
| Example 1 | 9244 | 98.9 | 9142 | 94.1 |
| Example 2 | 9191 | 98.3 | 9035 | 93.0 |
| Example 3 | 9252 | 98.5 | 9113 | 93.8 |
| Example 4 | 8872 | 99.1 | 8792 | 90.5 |
| Example 5 | 9076 | 95.8 | 8695 | 89.5 |
| Example 6 | 9193 | 96.8 | 8899 | 91.6 |
| Example 7 | 8970 | 97.8 | 8773 | 90.3 |
| Comparative example 1 | 8541 | 96.8 | 8268 | 85.1 |
| Comparative example 2 | 8801 | 97.8 | 8608 | 88.6 |
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.
Claims (10)
1. Vitamin B 6 A process for the preparation of an intermediate adduct, comprising: the n-propyl dioxygen heptaring, 4-methyl-5-ethoxyoxazole and a microwave sensitizer are subjected to contact reaction under the microwave condition to obtain vitamin B 6 Intermediate adducts having the structure of formula I:
（I）。
2. the method of claim 1, wherein,
the microwave sensitizer is selected from carbon black sensitizer, freguon sensitizer and Fe 3 O 4 At least one of the sensitizers;
and/or
The dosage of the microwave sensitizer is 0.5-1wt% of the total mass of the n-propyl dioxygen heptaring and the 4-methyl-5-ethoxyl.
3. The method of claim 1, wherein,
the temperature of the contact reaction is 90-120 ℃, preferably 107-115 ℃; and/or residence time of 20-33.33min.
4. The method of claim 1, wherein,
the mass ratio of the n-propyl dioxy heptaring to the 4-methyl-5-ethoxyoxazole is 5-10:1.
5. The method of claim 1, wherein the microwave conditions comprise:
the microwave power is 100-800W; and/or
The microwave frequency is 2450+/-50 MHz;
preferably, the method comprises the steps of,
the contact reaction is carried out in a microwave reactor comprising:
a feed pipe and a microwave reaction zone for continuously conveying raw materials n-propyl dioxyheptaring and 4-methyl-5-ethoxyoxazole;
preferably, the model of the microwave reactor is MKG-H1C1B, the microwave power is linearly adjustable at 100-800W, the microwave frequency is 2450+/-50 MHz, and the flow range is 100-1000ml/min.
6. A method according to any one of claims 1-5, wherein the method comprises: mixing n-propyl dioxygen heptaring and 4-methyl-5-ethoxyoxazole to obtain a mixed material, adding the mixed material into a sensitizer, and then carrying out the contact reaction under the microwave condition.
7. The method according to claim 4 or 5, wherein,
the flow rate of the mixture is 100-1000mL/min, preferably 500-1000mL/min.
8. The method according to any one of claims 1-7, wherein the method further comprises:
and after the contact reaction, rectifying and recycling the unreacted excessive raw materials of the microwave reactor.
9. The method of claim 8, wherein the recycling conditions include: the vacuum degree is 1500-3000Pa, preferably 1900-2000Pa; and/or a temperature of 100-130 ℃, preferably a temperature of 110-120 ℃.
10. Vitamin B in preparation by a method according to any one of claims 1-9 6 Is used in the application of (a).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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