CN107200714A - A kind of method for preparing orotic acid - Google Patents
A kind of method for preparing orotic acid Download PDFInfo
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- CN107200714A CN107200714A CN201610156748.XA CN201610156748A CN107200714A CN 107200714 A CN107200714 A CN 107200714A CN 201610156748 A CN201610156748 A CN 201610156748A CN 107200714 A CN107200714 A CN 107200714A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention provides a kind of method for preparing orotic acid.The method comprising the steps of：(1) at 5-20 DEG C, in atent solvent, by maleuric acid and bromine reaction, the first reactant mixture is formed；(2) the first reactant mixture for obtaining step (1) is directly poured into alkaline solution, is reacted, and the second reactant mixture containing Orotate is formed, wherein the temperature of the alkaline solution and the second reactant mixture maintains 55-85 DEG C；(3) pH of the second reactant mixture obtained with acid reagent regulating step (2) is to acidity, so as to form the 3rd reactant mixture containing orotic acid；(4) isolated or purified goes out described orotic acid from the 3rd reactant mixture.This process simplify operating procedure, health hazards of the bromine to operating personnel is reduced, and reduces the loss of the intermediate product of bromo, so as to be effectively improved the yield of final products.
Description
Technical field
The invention belongs to medicinal chemistry art, in particular it relates to a kind of method for preparing orotic acid.
Background technology
Orotic acid, i.e. 6- carboxyuracils, also referred to as orotic acid, are primarily present in rhizome vegetable, breast
The liquid part of slurry, Yoghourt or condensed milk.In the sixties, orotic acid is used to treat jaundice and general liver machine
Can obstacle, although being replaced gradually by new drug in recent years, improve liver function, promote liver cell reparation with
And other side still plays a role, such as：Orotic acid can treat goat, improve Cerebrovascular disorders, increase
Phagocyte activity, improves tissue regeneration ability, helps to heal a wound.In addition, orotic acid can be additionally used in
Immunoadjuvant, can treat chronic roentgenkater, be used as the prophylactic and therapeutic agent of chemical poisoning.
Whey acids medicine is with its good effect, Small side effects, internal residual and accumulation non-stimulated to kidney
Low feature enjoys favor and concern.Developing orotic acid in recent years is used for the synthesis of nucleic acid, and nucleic acid
It is the main matter of life, all has for the biosynthesis and human genetics for studying protein and weigh very much
The meaning wanted.The nucleic acid health food and medicine produced by raw material of orotic acid, energy are developed at present
Influence and control many vital metabolic activities, there is positive effect to delaying human body caducity.
At present, the synthetic technology that orotic acid has industrial prospect mainly has four kinds：One is by urea and careless second
Sour mono ethyl ester is condensed and obtained；Two be by 2,6- dioxo -3- methylpyrimidines potassium ferricyanide oxidative synthesis；Three
It is, using thiocarbamide as raw material, to synthesize 2- deracil -4- aldehyde, be synthesized into chromium oxide or hydrogen peroxide oxidation；
Four be using fermentation method production.Wherein, the usual product yield of fermentation method is very low, and existing chemical synthesis side
Impurity is easily included in product made from method, is difficult to prepare the whey acid product of high-purity, and industrialized production
In it is cumbersome, generally can also produce the harmful material of a large amount of environment, be unfavorable for environmental protection, be also unfavorable for
The physical and mental health of producers.
Therefore, research and develop it is a kind of in high yield, high-purity and easy to operate, environment-friendly orotic acid preparation method
It is necessary.
The content of the invention
It is an object of the invention to provide a kind of method for preparing orotic acid easily to operate, and products obtained therefrom yield
Height, purity is high.
First aspect present invention provides a kind of preparation method of orotic acid, including step：
(1) at 5-20 DEG C, in atent solvent, by maleuric acid and bromine reaction, the first reaction mixing is formed
Thing；
(2) the first reactant mixture for obtaining step (1) is directly poured into alkaline solution, is reacted, and is formed
The second reactant mixture containing Orotate, wherein the temperature of the alkaline solution and the second reactant mixture is maintained
55-85℃；
(3) pH of the second reactant mixture obtained with acid reagent regulating step (2) is to acidity, so as to be formed
The 3rd reactant mixture containing orotic acid；With
(4) isolated or purified goes out described orotic acid from the 3rd reactant mixture.
In another preference, in step (3), the 3rd described reactant mixture includes the orotic acid separated out.
In another preference, in step (1), the atent solvent includes water.
In another preference, in step (2), the alkaline solution is alkaline aqueous solution.
In another preference, the alkaline solution is alkali metal hydroxide (such as NaOH, KOH or its combination)
The aqueous solution, preferably sodium hydrate aqueous solution.
In another preference, the concentration of alkali metal hydroxide is 8-15% in the alkaline solution, preferably
It is more preferably 10% for 8-12%.
In another preference, in step (1), the time of the reaction is 10-25 hours.
In another preference, in step (1), the reaction is carried out in closed container.
In another preference, in step (1), the mass ratio of maleuric acid and bromine is 1：1.5~3.0.
In another preference, in step (1), the mass ratio of maleuric acid and atent solvent is 1：4~8；Compared with
Goodly, it is 1：5~7；It is preferred that being 1：5.5~6.5.
In another preference, in step (2), the mass/volume (g/mL) of maleuric acid and alkaline solution is than being 1：
1~0.5~4；It is preferred that being 1：1~3；It is preferred that being 1：1.5~2.5；It is preferred that being 1：2.
In another preference, between step (2) and (3), in addition to second reactant mixture is stirred
Mix, until clarification.
In another preference, in step (3), the acid reagent includes hydrochloric acid；It is preferred that for concentrated hydrochloric acid (such as
25-35wt%), watery hydrochloric acid (such as 3-20%).
In another preference, in step (3), with acid reagent adjust the pH of second reactant mixture to
After acidity, there is solid (orotic acid) precipitation.
In another preference, in step (4), the orotic acid solid of precipitation is filtered, washed and dried
Processing.
In another preference, in step (3), the pH to 1~2 of the second reactant mixture is adjusted.
In another preference, separation or purifying the orotic acid that step (4) is obtained has following characteristics：It is pure
Spend for 90%-96%.
In another preference, the yield of methods described is 72%-90%.
In another preference, methods described also includes following purification step：
(a) at 55-85 DEG C, separation or purifying orotic acid and deionized water obtained by blend step (4)
First time stirring is carried out, ammoniacal liquor is then added and carries out second of stirring, so as to form the first solution system；
(b) the first solution system is filtered, by acidification of filtrate to acidity, so as to form the second solution body
System；With
(c) isolated from second solution system through refined orotic acid.
In another preference, in step (a), the first time is stirred to the white emulsus of solution system.
In another preference, in step (a), the time of second of stirring is 3-5h.
It is 1 by acidification of filtrate to pH in step (b) in another preference.
In another preference, in step (b), after acidification of filtrate to acidity, there is the precipitation of orotic acid solid.
In another preference, in step (c), the orotic acid solid of precipitation filtered, washed, being dried.
In another preference, the maleuric acid is prepared by the method comprised the following steps：
In atent solvent, using the concentrated sulfuric acid or acetic acid as catalyst, maleic anhydride and urea reaction, from
And form maleuric acid.
In another preference, the mass ratio of maleic anhydride and urea is 1：1~2；It is preferred that being
1：1.2~1.6；It is preferred that being 1：1.2~1.4.
In another preference, the mass ratio of maleic anhydride and catalyst is 1：0.05~1；It is preferred that
For 1：0.05~0.8；It is preferred that being 1：0.05~0.6.
In another preference, the catalyst is the concentrated sulfuric acid, and the quality of maleic anhydride and catalyst
Than for 1：0.05~0.2；It is preferred that being 1：0.08~0.13；It is preferred that being 1：0.09~0.11.
In another preference, the mass ratio of maleic anhydride and atent solvent is 1：1~8；It is preferred that
For 1：2~6；It is preferred that being 1：3~5.
In another preference, the atent solvent is toluene.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 95%.
In another preference, when using the concentrated sulfuric acid as catalyst, the reaction is carried out 1-3 hours.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 98%.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 99%.
In another preference, the reaction is carried out at 60-80 DEG C；It is preferred that being carried out at 70 DEG C.
In another preference, after the reaction terminates, by filtering, washing, dry, obtain Malaysia acyl
Urea.
In another preference, obtained maleuric acid has following characteristics：Purity is 75%-88%.
In another preference, the yield of methods described is 80%-90%
Second aspect of the present invention provides a kind of preparation method of maleuric acid, including step：In atent solvent,
Using the concentrated sulfuric acid as catalyst, maleic anhydride and urea reaction, so as to form maleuric acid.
In another preference, the mass ratio of maleic anhydride and urea is 1：1~2；It is preferred that being
1：1.2~1.6；It is preferred that being 1：1.2~1.4.
In another preference, the mass ratio of maleic anhydride and catalyst is 1：0.05~0.2；Preferably
Ground, is 1：0.08~0.13；It is preferred that being 1：0.09~0.11.
In another preference, the mass ratio of maleic anhydride and atent solvent is 1：1~8；It is preferred that
For 1：2~6；It is preferred that being 1：3~5.
In another preference, the atent solvent is toluene.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 95%.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 98%.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 99%.
In another preference, the reaction is carried out 1-3 hours.
In another preference, the reaction is carried out at 60-80 DEG C；It is preferred that being carried out at 70 DEG C.
In another preference, after the reaction terminates, by filtering, washing, dry, obtain Malaysia acyl
Urea.
In another preference, obtained maleuric acid has following characteristics：Purity is 75%-88%.
In another preference, the yield of methods described is 80%-90%.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the invention and (such as implementation below
Example) in specifically describe each technical characteristic between can be combined with each other, so as to constitute new or preferred skill
Art scheme.As space is limited, no longer tire out one by one herein and state.
Brief description of the drawings
Fig. 1 is the IR spectrograms of orotic acid.
Fig. 2 is the HNMR spectrograms of orotic acid.
Fig. 3 is the DSC spectrograms of orotic acid.
Embodiment
The present inventor has had been surprisingly found that a kind of easy to operate, environment-friendly by in-depth study extensively
The method for preparing orotic acid.This method is using maleuric acid and bromine as raw material, after being reacted with bromine, without
Any processing is made to the Bromo-intermediates that reaction is obtained, as long as the reactant mixture of back directly is poured into one
Further reacted in the strong base solution of constant temperature degree, you can obtain high by the simple post processing such as acidifying, filtering
Purity, whey acid product in high yield.On this basis, inventor completes the present invention.
The preparation method of maleuric acid
The invention provides a kind of preparation method of maleuric acid, methods described includes step：In atent solvent (such as
Toluene) in, using the concentrated sulfuric acid as catalyst, in (such as 60-80 DEG C of certain temperature；It is preferred that 70 DEG C) under, it is suitable
Anhydride maleique and urea reaction for a period of time (such as 1-3 hours), so as to form maleuric acid.
In another preference, the concentrated sulfuric acid is the aqueous sulfuric acid that mass fraction is more than or equal to 95%；
It is preferred that being more than or equal to 98% or 99% aqueous sulfuric acid for mass fraction.
In another preference, after the reaction terminates, reactant mixture is by filtering, washing, drying etc.
Post processing, obtaining maleuric acid, (it is preferred that the purity of maleuric acid is 75%-88%, and/or yield is
80%-90%).
The preparation method of orotic acid
The invention provides a kind of preparation method of orotic acid, methods described includes step：
(1) at 5-20 DEG C, in atent solvent (such as water), by maleuric acid and bromine reaction for a period of time (such as
10-25 hours), form the first reactant mixture；
(2) the first reactant mixture for obtaining step (1) is directly poured into alkaline solution, is reacted (preferably
Ground, reaction to reactant mixture is clarification), the second reactant mixture containing Orotate is formed, wherein the alkali
The temperature of property solution and the second reactant mixture maintains 55-85 DEG C；
(3) with acid reagent (including hydrochloric acid；It is preferred that for concentrated hydrochloric acid, watery hydrochloric acid) regulating step (2) obtains
The pH of second reactant mixture is to acid (such as pH to 1~2), so as to form the 3rd reaction mixing containing orotic acid
Thing；With
(4) isolated or purified goes out described orotic acid (it is preferred that purity is 90 from the 3rd reactant mixture
%-96%, and/or yield are 72%-90%).
In another preference, in step (2), the alkaline solution is alkaline aqueous solution；It is preferred that being alkali gold
Belong to the aqueous solution of hydroxide (such as NaOH, KOH or its combination)；It is preferred that alkali metal hydrogen in the alkaline solution
The concentration of oxide is 8-15%, preferably 8-12%, is more preferably 10%.
In another preference, in step (3), with acid reagent adjust the pH of second reactant mixture to
After acidity, separated out to orotic acid solid.
In another preference, in step (4), orotic acid solid is filtered, washed, drying process.
In another preference, described preparation method, in addition to following purification step：
(a) at 55-85 DEG C, separation or purifying orotic acid and deionized water obtained by blend step (4)
First time stirring (such as to the white emulsus of solution system) is carried out, ammoniacal liquor is then added and carries out second of stirring
(such as 3-5h), so as to form the first solution system；
(b) the first solution system is filtered, by acidification of filtrate to acidity (such as pH is 1), so as to be formed
Second solution system；With
(c) isolated from second solution system through refined orotic acid.
It is described to be separated into filtering, washing and dry in step (c) in another preference.
In another preference, the preparation side that the maleuric acid passes through present invention maleuric acid described above
Method is made.In addition, also the method for the concentrated sulfuric acid can be replaced to carry out by using acetic acid.With the side using the concentrated sulfuric acid as catalyst
Method is compared, during with acetic acid as catalyst, other operations and reaction result all same or essentially identical, except anti-
Extend between seasonable, need to such as carry out 6-10 hours.
Main advantages of the present invention：
(1) a kind of preparation method of maleuric acid is provided, methods described is using the concentrated sulfuric acid as catalyst, reaction
Time greatly shortens and stable reaction, and product yield and purity are high.
(2) a kind of preparation method of orotic acid is provided, in methods described, without by the intermediate product of bromo
Any post processing (such as filter, dry) is carried out, but directly by the intermediate product for containing the bromo
Reactant mixture is added in the alkaline solution (such as sodium hydrate aqueous solution) of heat.This process simplify operation
Step, reduces health hazards of the bromine to operating personnel, is additionally, since the intermediate product thing of the bromo to heat
It is very sensitive, therefore, save after middle post-processing step, reduce the loss of the intermediate product of bromo, so that
It is effectively improved the yield of final products.Therefore, this method is especially suitable for industrialized production.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are only used for
The bright present invention rather than limitation the scope of the present invention.The experiment side of unreceipted actual conditions in the following example
Method, generally according to normal condition, or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise
Percentage and number are calculated by weight.
Embodiment 1 is using the concentrated sulfuric acid as catalyst preparation maleuric acid
4000g toluene, 1000g maleic anhydrides and 1300g urea are taken, with 98% (mass percent)
The concentrated sulfuric acid (consumption is 100g) is catalyst, under the conditions of 70 DEG C, is reacted 1 hour, filter, wash,
Maleuric acid is made in drying, and product purity is 80%, and yield is 85%.
According to above-mentioned experimental method, experimenter has carried out the preparation of 4-6 maleuric acid, reaction time again
For 1-3 hours, as a result the purity of product was 75%-88%, and yield is 80%-90%.
The detection method of maleuric acid：
HPLC methods detect purity：
Mobile phase：0.02MKH2PO4, plus 0.005M TBABs (pH2.5)：Acetonitrile (95：5)
Sampling volume：10ul
Column temperature：25℃
Flow velocity：1.0ml/min
Chromatographic column：Kromasil Eternity-5-c18,4.6×250mm
Maleuric acid main peak appearance time is in 6.6min or so.
Embodiment 2 prepares crude product orotic acid
500g maleuric acids are taken, (mass ratio of maleuric acid and bromine is 1 to bromine:1.5) with 3000g water,
10h is reacted under the conditions of 20 DEG C bromo-derivative intermediate is made.Take 10% sodium hydroxide solution 1L, be heated to 60
DEG C, then bromo-derivative intermediate is poured into the hot alkaline solution, temperature control is at 60 DEG C, and stirring reaction 5h obtains clear
Clear solution.Then it is 1 with concentrated hydrochloric acid (commercially available) regulation reaction solution to pH, obtains solid precipitation, pass through
Filter, wash, drying and to obtain crude product orotic acid, product purity 96%, product yield 80%.
According to above-mentioned experimental method, experimenter has carried out the preparation of 4-6 orotic acid again.Wherein, Malaysia
The mass ratio of uride and bromine is 1:The reaction temperature of 1.5-3.0, maleuric acid and bromine is 5-20 DEG C, during reaction
Between be 10-25h；The usage amount 1-2L of 10% sodium hydroxide solution, temperature is maintained when bromo-derivative is poured into
55-85℃；Mixing time is 5-10h.As a result orotic acid product purity 90%-96%, product yield 72%
- 90%.
The detection method of crude product orotic acid：
HPLC methods detect purity：
Mobile phase：0.02MKH2PO4, plus 0.005M TBABs (pH2.5)：Acetonitrile (95：5)
Sampling volume：10ul
Column temperature：25℃
Flow velocity：1.0ml/min
Chromatographic column：Kromasil Eternity-5-c18,4.6×250mm
Crude product orotic acid appearance time is in 12min or so.
In the preparation method, without the intermediate product of bromo is carried out into any post processing, but directly this is contained
The reactant mixture for having the intermediate product of the bromo is added in the alkaline solution of heat, simplifies operating procedure
(especially filtration step), greatly reduces health hazards of the bromine to operating personnel, and reduce bromo
The loss of intermediate product, so as to be effectively improved the yield of final products.
The orotic acid crude product refining of embodiment 3
150g crude product orotic acids are taken, deionized water (consumption is 1000g) is stirred under the conditions of 60 DEG C,
The white emulsus of solution system；Then ammoniacal liquor 100g, stirring reaction 3h are added dropwise under the system.Filtering,
Filtrate is obtained, it is 1 that pH is acidified to hydrochloric acid, stirring is cooled to room temperature filtering, washing is collected solid, done
Dry to obtain Lactinium product, product purity 96%, yield is 70%.
According to above-mentioned experimental method, experimenter has carried out the refined of 4-6 orotic acid again.Wherein, first
Secondary ammonia volume is 100-300g, and whipping temp is 55-85 DEG C, and mixing time is 3-5h, second of ammoniacal liquor
Consumption is 100-300g, stirring reaction 3-5h.As a result Lactinium product product purity >=96% is obtained,
Yield is 65%-85%.
The detection method of orotic acid finished product：
HPLC methods detect purity：
Mobile phase：0.02MKH2PO4, plus 0.005M TBABs (pH2.5)：Acetonitrile (95：5)
Sampling volume：10ul
Column temperature：25℃
Flow velocity：1.0ml/min
Chromatographic column：Kromasil Eternity-5-c18,4.6×250mm
Orotic acid appearance time is in 12min or so.
In addition, the IR spectrograms of orotic acid, HNMR spectrograms and DSC spectrograms are successively as shown in Figure 1, Figure 2 and Fig. 3
It is shown.
Embodiment 4 is using acetic acid as catalyst preparation maleuric acid
4000g toluene, 1000g maleic anhydrides and appropriate urea (consumption is 1200g) are taken, (is used with acetic acid
Measure as 600g) it is catalyst, under the conditions of 70 DEG C, react 6 hours, horse is made in filtering, washing, drying
Carry out uride, product purity is 78%, and yield is 80%.
According to above-mentioned experimental method, experimenter has carried out the preparation of 4-6 maleuric acid, reaction time again
For 6-10 hours, as a result the purity of product was 70%-78%, and yield is 70%-80%.
Method for detecting purity be the same as Example 1.
With using acetic acid compared with catalyst preparation maleuric acid, using the concentrated sulfuric acid as catalyst preparation maleuric acid
Major advantage is：In the case of rate of charge and reaction condition all identicals, the reaction time is shorter and stably.
All documents referred in the present invention are all incorporated as reference in this application, just as each document
It is individually recited as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content of the present invention has been read,
Those skilled in the art can make various changes or modifications to the present invention, and these equivalent form of values equally fall within this Shen
Please appended claims limited range.
Claims (10)
1. a kind of preparation method of orotic acid, it is characterised in that including step：
(1) at 5-20 DEG C, in atent solvent, by maleuric acid and bromine reaction, the first reaction mixing is formed
Thing；
(2) the first reactant mixture for obtaining step (1) is directly poured into alkaline solution, is reacted, and is formed
The second reactant mixture containing Orotate, wherein the temperature of the alkaline solution and the second reactant mixture is maintained
55-85℃；
(3) pH of the second reactant mixture obtained with acid reagent regulating step (2) is to acidity, so as to be formed
The 3rd reactant mixture containing orotic acid；With
(4) isolated or purified goes out described orotic acid from the 3rd reactant mixture.
2. preparation method as claimed in claim 1, it is characterised in that also including following purification step：
(a) at 55-85 DEG C, separation or purifying orotic acid and deionized water obtained by blend step (4)
First time stirring is carried out, ammoniacal liquor is then added and carries out second of stirring, so as to form the first solution system；
(b) the first solution system is filtered, by acidification of filtrate to acidity, so as to form the second solution body
System；With
(c) isolated from second solution system through refined orotic acid.
3. preparation method as claimed in claim 1, it is characterised in that the maleuric acid passes through including following
It is prepared by the method for step：
In atent solvent, using the concentrated sulfuric acid or acetic acid as catalyst, maleic anhydride and urea reaction, from
And form maleuric acid.
4. preparation method as claimed in claim 3, it is characterised in that the concentrated sulfuric acid is mass fraction
Aqueous sulfuric acid more than or equal to 95%.
5. preparation method as claimed in claim 3, it is characterised in that when using the concentrated sulfuric acid as catalyst,
The reaction is carried out 1-3 hours.
6. a kind of preparation method of maleuric acid, it is characterised in that including step：In atent solvent, with dense
Sulfuric acid is catalyst, maleic anhydride and urea reaction, so as to form maleuric acid.
7. preparation method as claimed in claim 6, it is characterised in that the concentrated sulfuric acid is mass fraction
Aqueous sulfuric acid more than or equal to 95%.
8. preparation method as claimed in claim 6, it is characterised in that the concentrated sulfuric acid is mass fraction
Aqueous sulfuric acid more than or equal to 98%.
9. preparation method as claimed in claim 6, it is characterised in that the concentrated sulfuric acid is mass fraction
Aqueous sulfuric acid more than or equal to 99%.
10. preparation method as claimed in claim 6, it is characterised in that the reaction is carried out 1-3 hours.
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| CN1332162A (en) * | 2001-07-13 | 2002-01-23 | 中国科学院上海有机化学研究所 | Technological process of producing orotic acid |
| CN105153043A (en) * | 2015-09-22 | 2015-12-16 | 蓬莱海洋（山东）股份有限公司 | VB13 production method |
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- 2016-03-18 CN CN201610156748.XA patent/CN107200714A/en not_active Withdrawn
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