CN105693524A - A preparing method of nitro compounds - Google Patents
A preparing method of nitro compounds Download PDFInfo
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- CN105693524A CN105693524A CN201410707925.XA CN201410707925A CN105693524A CN 105693524 A CN105693524 A CN 105693524A CN 201410707925 A CN201410707925 A CN 201410707925A CN 105693524 A CN105693524 A CN 105693524A
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Abstract
A preparing method of 4-nitro-3-hydroxy-2-substituted benzoic acid or ester (the general structure formula of which is shown in the description) is disclosed. Water is adopted as a reaction solvent. An acid or an acidic salt is adopted as a catalyst. The 4-nitro-3-hydroxy-2-substituted benzoic acid or ester is prepared by reacting a compound shown as a formula (II) (shown in the description) and a nitration agent. The method is advantaged by being high in selectivity, high in yield, few in 'there wastes', suitable for industrial production, and the like.
Description
Technical field
The preparation method that the present invention relates to a kind of nitro compound, the preparation method particularly relating to a kind of 4-nitro-3-hydroxyl-2-substituted benzoic acid or ester。
Background technology
Nitro compound, for instance 4-nitro-3-hydroxyl-2-substituted benzoic acid or ester, be a kind of important intermediate, it is possible to be used for synthesizing Multiple Pesticides, pharmaceutical compound。
Known conventional containing nitro compound preparation method, all using strong acid as reaction dissolvent, at low temperatures, carry out nitrated with nitric acid, concentrated nitric acid or fuming nitric aicd as nitrating agent, reaction is violent, difficult to be controlled, so that there is very big security risk in industrialized production, simultaneously because make reaction dissolvent with strong acid, the three wastes are very many。Especially hydroxyl aryl compound, when being prepared by conventional nitration method, owing to hydroxyl is very easy to oxidized, thus very easily producing by-product, so must react under ultralow temperature, the such as preparation 4-nitro-3-hydroxy-2-methyl-benzoic method of PCT Patent application WO2013079505 and WO2003091236 report, owing to must react under ultralow temperature so that during industrialized production energy consumption be greatly improved。In addition, when 3-hydroxyl-2-substituent group-benzoic acid and acid compound being carried out nitrated with rule nitration method, except generating 4-nitro-3-hydroxyl-2-substituted benzoic acid, also a large amount of by-product 6-nitro-3-hydroxyl-2-replacement-benzoic acid can be produced, due to the physical property between two products closely, it is difficult to separate, is not suitable for industrialized production。
It is thus desirable to develop a kind of method preparing 4-nitro-3-hydroxyl-2-substituted benzoic acid or ester of applicable industrialized production。
Summary of the invention
It is an object of the invention to provide a kind of method preparing 4-nitro-3-hydroxyl-2-substituted benzoic acid or ester, there is the features such as selectivity height, yield height, few, the applicable industrialized production of the three wastes。
For reaching goal of the invention the technical solution used in the present invention it is:
One prepares the method for compound shown in structural formula (I),
With water be reaction dissolvent, acid or acid salt for catalyst, compound and nitrating agent shown in structural formula (II) react and prepare compound shown in structural formula (I),
Wherein:
R1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C1-C6 alkyl, C2-C6 thiazolinyl, C2-C6 alkynyl, C1-C6 alkoxyl, C1-C6 alkylthio group, C1-C6 alkane sulfoxide group, C1-C6 alkane sulfuryl, C1-C6 haloalkyl, C1-C6 halogenated alkoxy, nitro or benzyloxy；
R2 is selected from hydrogen or C1-C6 alkyl。
As preferred mode, compound shown in structure above (I) and in compound shown in structural formula (II), described substituent R 1 preferably is selected from hydrogen, fluorine, chlorine, bromine, iodine, C1-C4 alkyl, C2-C4 thiazolinyl, C2-C4 alkynyl, C1-C4 alkoxyl, C1-C4 alkylthio group, C1-C4 alkane sulfoxide group, C1-C4 alkane sulfuryl, C1-C4 haloalkyl, C1-C4 halogenated alkoxy, nitro or benzyloxy；R2 preferably is selected from hydrogen or C1-C4 alkyl。
As most preferred mode, compound shown in structure above (I) is selected from the one in compound described in following II-a to II-h:
As preferred mode, the acid of above-mentioned use preferably is selected from sulphuric acid, acetic acid, propanoic acid, benzenesulfonic acid or p-methyl benzenesulfonic acid；Described acid salt is preferably disulfate, and more preferably sodium bisulfate or potassium acid sulfate；Described nitrating agent is preferably nitric acid or nitrate, the more preferably sodium nitrate of described nitrate or potassium nitrate。
As preferred mode, the mol ratio of above-mentioned nitrating agent and compound shown in structural formula (II) is preferably 0.7～3.0:1, and more preferably 0.9～2.0:1；Acid and the mol ratio of compound shown in structural formula (II) are preferably 0.1～5.0:1, and more preferably 0.1～3.0:1；Reaction temperature is preferably 0～100 DEG C, and more preferably 30～90 DEG C。
Structural formula (I) compound prepared by the present invention, it is also possible to further be used for preparing compound shown in structural formula (III) as intermediate,
Detailed description of the invention
The following examples are the several detailed description of the invention for the present invention is described, but do not limit the invention to these detailed description of the invention。One skilled in the art would recognize that and present invention encompasses all alternatives, improvement project and the equivalents potentially included in Claims scope。
Embodiment 1,4-nitro-3-hydroxy-2-methyl-benzoic acid synthesis
60ml water, 0.20mol sodium bisulfate and 0.2mol sodium nitrate is added to being furnished with in tri-mouthfuls of reaction bulbs of churned mechanically 250ml, then 0.1mol3-hydroxy-2-methyl-benzoic acid is under agitation added, system is slowly warmed up between 60～85 DEG C, react 3 hours, reaction is followed the tracks of by liquid chromatograph, raw material is totally converted, and cooling system is to room temperature, and filtration drying obtains light yellow solid 13.7 grams。By analysis, the light yellow solid obtained is 4-nitro-3-hydroxy-2-methyl-benzoic acid, and content is 95.0%, and test data are as follows:
1HNMR(DMSO,δppm):2.37(s,3H),7.27(d,1H),7.85(d,1H),10.63(br,1H)
Embodiment 2,4-nitro-3-hydroxy-2-methyl-benzoic acid synthesis
50ml water, 0.20mol sodium bisulfate and 0.1mol sodium nitrate is added to being furnished with in tri-mouthfuls of reaction bulbs of churned mechanically 250ml, then 0.1mol3-hydroxy-2-methyl-benzoic acid is under agitation added, system is slowly warmed up between 60～85 DEG C, react 3 hours, reaction is followed the tracks of by liquid chromatograph, raw material is totally converted, and cooling system is to room temperature, and filtration drying obtains light yellow solid 17.7 grams。By analysis, the light yellow solid obtained is 4-nitro-3-hydroxy-2-methyl-benzoic acid, and content is 97.0%。
Embodiment 3,4-nitro-3-hydroxy-2-methyl-benzoic acid synthesis
50ml water, 0.10mol sulphuric acid and 0.1mol sodium nitrate is added to being furnished with in tri-mouthfuls of reaction bulbs of churned mechanically 250ml, then 0.1mol3-hydroxy-2-methyl-benzoic acid is under agitation added, system is slowly warmed up between 60～85 DEG C, react 3 hours, reaction is followed the tracks of by liquid chromatograph, raw material is totally converted, and cooling system is to room temperature, and filtration drying obtains light yellow solid 17.0 grams。By analysis, the light yellow solid obtained is 4-nitro-3-hydroxy-2-methyl-benzoic acid, and content is 97.1%。
Embodiment 4,4-nitro-3-hydroxy-2-methyl-benzoic acid synthesis
50ml water, 0.10mol sulphuric acid is added to being furnished with in tri-mouthfuls of reaction bulbs of churned mechanically 250ml, then 0.1mol3-hydroxy-2-methyl-benzoic acid is under agitation added, system is slowly warmed up between 60～85 DEG C, then taking out body dropping 0.12mol60% concentrated nitric acid, within about 30 minutes, be added dropwise to complete, architecture heat preservation reacts 3 hours, reaction is followed the tracks of by liquid chromatograph, raw material is totally converted, and cooling system is to room temperature, and filtration drying obtains light yellow solid 17.2 grams。By analysis, the light yellow solid obtained is 4-nitro-3-hydroxy-2-methyl-benzoic acid, and content is 97.0%。
The chloro-benzoic acid synthesis of embodiment 5,4-nitro-3-hydroxyl-2-
50ml water, 0.10mol sulphuric acid and 0.1mol sodium nitrate is added to being furnished with in tri-mouthfuls of reaction bulbs of churned mechanically 250ml, then the 0.1mol3-chloro-benzoic acid of hydroxyl-2-is under agitation added, system is slowly warmed up between 60～85 DEG C, react 4 hours, reaction is followed the tracks of by liquid chromatograph, raw material is totally converted, and cooling system is to room temperature, and filtration drying obtains light yellow solid 16.5 grams。By analysis, the light yellow solid obtained is the 4-nitro-3-chloro-benzoic acid of hydroxyl-2-, and content is 96.3%。
Claims (8)
1. prepare a method for compound shown in structural formula (I),
It is characterized in that with water be reaction dissolvent, acid or acid salt for catalyst, compound and nitrating agent shown in structural formula (II) react and prepare compound shown in structural formula (I),
Wherein:
R1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C1-C6 alkyl, C2-C6 thiazolinyl, C2-C6 alkynyl, C1-C6 alkoxyl, C1-C6 alkylthio group, C1-C6 alkane sulfoxide group, C1-C6 alkane sulfuryl, C1-C6 haloalkyl, C1-C6 halogenated alkoxy, nitro or benzyloxy；
R2 is selected from hydrogen or C1-C6 alkyl。
2. described in claim 1, prepare the method for compound shown in structural formula (I), it is characterised in that described in:
R1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C1-C4 alkyl, C2-C4 thiazolinyl, C2-C4 alkynyl, C1-C4 alkoxyl, C1-C4 alkylthio group, C1-C4 alkane sulfoxide group, C1-C4 alkane sulfuryl, C1-C4 haloalkyl, C1-C4 halogenated alkoxy, nitro or benzyloxy；
R2 is selected from hydrogen or C1-C4 alkyl。
3. described in claim 2, prepare the method for compound shown in structural formula (I), it is characterised in that the one in compound described in following II-a to II-h of the compound shown in described structural formula (I):
4. described in claim 1, prepare the method for compound shown in structural formula (I), it is characterized in that described acid is selected from sulphuric acid, acetic acid, propanoic acid, benzenesulfonic acid or p-methyl benzenesulfonic acid, described acid salt is disulfate, and described nitrating agent is nitric acid or nitrate。
5. described in claim 4, prepare the method for compound shown in structural formula (I), it is characterised in that described disulfate is sodium bisulfate or potassium acid sulfate, and described nitrate is sodium nitrate or potassium nitrate。
6. described in claim 1, prepare the method for compound shown in structural formula (I), it is characterized in that shown in described nitrating agent and structural formula (II), the mol ratio of compound is 0.7～3.0:1, shown in acid and structural formula (II), the mol ratio of compound is 0.1～5.0:1, and reaction temperature is 0～100 DEG C。
7. described in claim 6, prepare the method for compound shown in structural formula (I), it is characterized in that shown in described nitrating agent and structural formula (II), the mol ratio of compound is 0.9～2.0:1, shown in acid and structural formula (II), the mol ratio of compound is 0.1～3.0:1, and reaction temperature is 30～90 DEG C。
8. described in claim 1, prepare the method for compound shown in structural formula (I), it is characterised in that described structural formula (I) compound further is used for preparing compound shown in structural formula (III) as intermediate,
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| US3103476A (en) * | 1958-03-14 | 1963-09-10 | Fuel element with burnable poison within the cladding | |
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Application publication date: 20160622 |