CN104557712A - Preparation methods of aromatic hydroxylamine compound and N-aromatic acylated hydroxylamine compound - Google Patents

Preparation methods of aromatic hydroxylamine compound and N-aromatic acylated hydroxylamine compound Download PDF

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CN104557712A
CN104557712A CN201410835404.2A CN201410835404A CN104557712A CN 104557712 A CN104557712 A CN 104557712A CN 201410835404 A CN201410835404 A CN 201410835404A CN 104557712 A CN104557712 A CN 104557712A
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unsubstituted
phenyl
general formula
compound
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谭徐林
吴坤
王磊
罗进超
李咏静
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Nutrichem Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
    • C07C239/08—Hydroxylamino compounds or their ethers or esters
    • C07C239/10—Hydroxylamino compounds or their ethers or esters having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of unsubstituted hydrocarbon radicals or of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
    • C07C239/08—Hydroxylamino compounds or their ethers or esters
    • C07C239/12—Hydroxylamino compounds or their ethers or esters having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups

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  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a preparation method of aromatic hydroxylamine compound as shown in general formula (I). The preparation method comprises the following steps: performing reduction reaction on a compound as shown in formula (II) and hydrazine hydrate in an organic solvent in the presence of a reduction catalyst, wherein the organic solvent is at least one of aliphatic ether and cyclic ether; R1 is hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or -CH2-O-R2, wherein R2 is substituted or unsubstituted phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl or imidazolyl; in addition, the invention further discloses a preparation method of N-aromatic acylated hydroxylamine compound as shown in formula (III). According to the preparation methods of aromatic hydroxylamine compound and N-aromatic acylated hydroxylamine compound, the reduction reaction has a conversion rate of above 99% and a selectivity of above 99%; the N-acylation reaction has a conversion rate of above 99% and a selectivity of above 98%.

Description

The preparation method of aromatic hydroxyamines compound and the preparation method of N-acidylate aromatic hydroxyamines compound
Technical field
The present invention relates to the preparation method of aromatic hydroxyamines compound and the preparation method of N-acidylate aromatic hydroxyamines compound.
Background technology
At present, the preparation method of N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol of domestic and international report has a lot, the reductive agent adopted in its preparation method is mostly metallic zinc, but adopt this reductive agent also original production aromatic hydroxyamines compound can produce a large amount of three wastes, and the selectivity of reduzate is not high, is unfavorable for suitability for industrialized production.
WO 96/22967 discloses a kind of preparation method of aromatic hydroxyamines compound, the method uses carbon supported precious metal platinum or palladium as catalyzer, under heterocyclic amine is as N-methylmorpholine condition, nitrobenzene compound is carried out catalytic hydrogenation reaction, obtain the aromatic hydroxyamines compound of higher yields; But need in the method to use a large amount of N-methylmorpholines to dissolve raw material, the separation that simultaneous reactions terminates after product needs complicated post-processing operation, as needs carry out distillation removing N-methylmorpholine at relatively high temperatures, and aromatic hydroxyamines compounds at high temperature great majority be unstable, and recycle noble metal catalyst and can lose activity because of poisoning.WO 99/12911 equally openly uses carbon supported precious metal platinum or palladium as catalyzer, unlike, in reaction system, add aliphatic amide (take aromatic nitro compound as benchmark, the consumption of aliphatic amide is 1-15 mole) can higher productive rate be obtained, catalyzer described in the method can recycle and not lose activity, but same exist the problem needing Distillation recovery aliphatic amide at relatively high temperatures.
Ruthenium and the rhodium of the open working load of WO 2012/038392 and WO 2012/120029 are catalyzer, hydrazine hydrate is reductive agent, reduction nitrobenzene compound, the method can highly selective obtain phenylhydroxylamine compound, but this two classes catalyzer expensive, cost is higher.
Usually, aromatic nitro compound selectivity synthesis aromatic hydroxyamines compound can pass through borohydride reduction (CN1772728; Chem Lett.7,1069 (1986); Synthetic Communications.27,3497 (1997); Synthetic Communications.27,1547 (1997)), tin title complex reduction (Tetrahedron.46,587 (1990)), phosphite reduction (Tetrahedron.34,213 (1978)) etc. method is carried out, but aforesaid method all has, and product yield is low, the defect such as poor selectivity and narrow application range.
In addition; Synthesis.11; 938 (1984); Synthesis.24; 3907 (2007); SyntheticCommunications.38; 2437 (2008); Eur.J.Org.Chem.6; 1158 (2013) disclose aromatic hydroxyamines compound can pass through raney ni catalysis; in ethanol/ethylene dichloride (1:1) solvent, use hydrazine hydrate reduction aromatic nitro compound to be prepared, but before further N-acylation reaction is carried out to aromatic hydroxyamines compound, need the alcohol solvent that distillation removing reduction reaction process uses.
Summary of the invention
The object of the invention is to overcome the existing above-mentioned defect preparing aromatic hydroxyamines compound, provide the preparation method of aromatic hydroxyamines compound and the preparation method of N-acidylate aromatic hydroxyamines compound of easy, high conversion and highly selective.
The invention provides the preparation method of the aromatic hydroxyamines compound shown in a kind of general formula (I), the method comprises: under the existence of reducing catalyst, compound shown in general formula (II) and hydrazine hydrate are carried out reduction reaction in organic solvent, described organic solvent is at least one in aliphatic ether and cyclic ethers
Wherein, R 1for hydrogen, halogen, cyano group, C 1-C 4alkyl, C 1-C 4haloalkyl or-CH 2-O-R 2, wherein, R 2for substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted imidazolyl.
Further; present invention also offers the preparation method of the N-acidylate aromatic hydroxyamines compound shown in a kind of general formula (III); the method comprises: carry out reduction reaction according to the method described above with the mixture of preparation containing the compound shown in general formula (I); the mixture this being contained the compound shown in general formula (I) carries out solid-liquid separation, and is R by isolated liquid phase and general formula 3the compound of-CO-L carries out N-acylation reaction,
Wherein, R 1for hydrogen, halogen, cyano group, C 1-C 4alkyl, C 1-C 4haloalkyl or-CH 2-O-R 2, wherein, R 2for substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted imidazolyl, R 3for C 1-C 4alkoxyl group or C 1-C 4alkyl, L is halogen.
The method preparing aromatic hydroxyamines compound provided by the present invention simplifies reactions steps and reduces cost and drops into, organic solvent of the present invention is importantly adopted can effectively to avoid the use of solvent on the impact of reduction reaction and N-acylation reaction, and after described reduction reaction terminates, eliminate the operation steps removing reaction solvent, thus avoid the phenomenon of the reaction product loss caused because of desolventizing operation steps, therefore, in whole reaction process, the converting compounds of structure shown in general formula (II) can be made to be the converting compounds of structure shown in the reaction process of the compound of structure shown in general formula (I) and general formula (I) be the reaction process of the compound of structure shown in general formula (III) can carry out towards the direction of expection all the time, thus significantly improve transformation efficiency and the selectivity of reaction, particularly, the transformation efficiency of the reduction reaction that method according to the present invention obtains can up to more than 95% up to more than 99% and selectivity, the transformation efficiency of N-acylation reaction can up to more than 98% up to more than 99% and selectivity.In addition, can be recycled by the isolated reducing catalyst of described solid-liquid separation process.Therefore, described method of the present invention is more suitable for large-scale industrial production, is applicable to the preparation of aromatic hydroxyamines compound.
Other features and advantages of the present invention are described in detail in embodiment part subsequently.
Embodiment
Below the specific embodiment of the present invention is described in detail.Should be understood that, embodiment described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
The invention provides the preparation method of the aromatic hydroxyamines compound shown in a kind of general formula (I), the method comprises: under the existence of reducing catalyst, compound shown in general formula (II) and hydrazine hydrate are carried out reduction reaction in organic solvent, described organic solvent is at least one in aliphatic ether and cyclic ethers
Wherein, R 1for hydrogen, halogen, cyano group, C 1-C 4alkyl, C 1-C 4haloalkyl or-CH 2-O-R 2, wherein, R 2for substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted imidazolyl.
For R 1group, halogen can be fluorine, chlorine, bromine or iodine, C 1-C 4alkyl can be methyl, ethyl, propyl group or butyl, C 1-C 4haloalkyl can be chloromethyl, Chloroethyl, chloro propyl group, bromomethyl, bromoethyl or Bromopropyl.
For R 2group, " replacement " refers to and adopts following substituted radical to replace: halogen, C 1-C 4alkyl or C 1-C 4alkoxyl group, wherein, described halogen can be fluorine, chlorine, bromine or iodine, C 1-C 4alkyl can be methyl, ethyl, propyl group or butyl, C 1-C 4haloalkyl can be chloromethyl, Chloroethyl, chloro propyl group, bromomethyl, bromoethyl or Bromopropyl.
Under preferable case, R 1for hydrogen, fluorine, chlorine, bromine, cyano group, methyl, ethyl, propyl group, chloromethyl, Chloroethyl, chloro propyl group or-CH 2-O-R 2, wherein, R 2for 1-(4-chloro-phenyl-) pyrazole-3-yl, phenyl, naphthyl or pyrazolyl.
Further in preferred situation, the aromatic hydroxyamines compound shown in described general formula (I) is N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol, o-methyl-phenyl-azanol or N-(2-Phenoxymethyl)-azanol.
According to the present invention, the consumption of described organic solvent is not particularly limited, can select according to the consumption of this area routine, under preferable case, relative to the consumption of the compound shown in 1mmol general formula (II), the consumption of described organic solvent is 0.1-10mL, under further selection condition, relative to the consumption of the compound shown in 1mmol general formula (II), the consumption of described organic solvent is 0.6-2.4mL.
In the present invention, described organic solvent is at least one in aliphatic ether and cyclic ethers.Described aliphatic ether can be the aliphatic ether product that this area routine uses, as at least one in methyl tertiary butyl ether, glycol dimethyl ether, ether, positive propyl ether and ethylene glycol diethyl ether.Described cyclic ethers can be the aliphatic ether product that this area routine uses, as at least one in tetrahydrofuran (THF), dioxan, propylene oxide and 1,2-butylene oxide ring.For improving transformation efficiency and the selectivity of reaction further, under preferable case, described organic solvent is selected from least one in methyl tertiary butyl ether, glycol dimethyl ether, tetrahydrofuran (THF) and dioxan.
In the present invention, do not limit particularly the consumption of described hydrazine hydrate, under preferable case, relative to the consumption of the compound shown in 1mol general formula (II), the consumption of described hydrazine hydrate can be 1-7mol, is preferably 1-3mol.
In the present invention, the consumption of described reducing catalyst is not particularly limited, under preferable case, relative to the consumption of the compound shown in 1g general formula (II), the consumption of described reducing catalyst is 0.01-0.3g, under further preferable case, relative to the consumption of the compound shown in 1g general formula (II), the consumption of described reducing catalyst is 0.01-0.1g.
The kind of described reducing catalyst is the reducing catalyst that this area routine uses, and such as, can be selected from least one in Raney's nickel and Lei Ni cobalt.
In the present invention, be not particularly limited the condition of described reduction reaction, under preferable case, the condition of described reduction reaction comprises: temperature is-20 DEG C to 100 DEG C, and the time is 1-24h; Under further preferable case, the condition of described reduction reaction comprises: temperature is-10 DEG C to 30 DEG C, and the time is 2-10h.
According to a second aspect of the invention; present invention also offers the preparation method of the N-acidylate aromatic hydroxyamines compound shown in a kind of general formula (III); the method comprises: carry out reduction reaction according to the method described above with the mixture of preparation containing the compound shown in general formula (I); the mixture this being contained the compound shown in general formula (I) carries out solid-liquid separation, and is R by isolated liquid phase and general formula 3the compound of-CO-L carries out N-acylation reaction,
Wherein, R 1for hydrogen, halogen, cyano group, C 1-C 4alkyl, C 1-C 4haloalkyl or-CH 2-O-R 2, wherein, R 2for substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted imidazolyl; R 3for C 1-C 4alkoxyl group or C 1-C 4alkyl, L is halogen.
For R 3group, C 1-C 4alkyl can be methoxyl group, methyl, oxyethyl group, ethyl, propoxy-, propyl group or butyl, L can be fluorine, chlorine, bromine or iodine.
Under preferable case, R 3for methoxyl group, methyl, oxyethyl group, ethyl, propoxy-or propyl group, L is fluorine, chlorine or bromine.
Further in preferred situation, the N-acidylate aromatic hydroxyamines compound shown in described general formula (III) is N-hydroxy-n-(2-(N '-(4-chloro-phenyl-) pyrazoles-3 '-Ji oxygen ylmethyl) phenyl) Urethylane, N-hydroxy-n-2-methYlphenvlcarbamate or N-hydroxy-n-(2-(Phenoxymethyl) phenyl) urethanum.
The condition of the present invention to described N-acylation reaction is not particularly limited, and under preferable case, the condition of described N-acylation reaction comprises: temperature is-30 DEG C to 80 DEG C, and the time is 1-10h; Under further preferable case, the condition of described N-acylation reaction comprises: temperature is-10 DEG C to 50 DEG C, and the time is 2-5h.
According to the present invention, described method also comprises: be cycled to used in described reduction reaction process by catalytic solid isolated in solid-liquid separation process.Reducing catalyst of the present invention can recycle, and reduces the input of cost.
Reduction reaction process of the present invention can make each component in mixture fully contact and improve the effect of heat transfer, mass transfer by stirring reactant to reach with in N-acylation reaction process.Described stirring can adopt the stirring means of this area routine, such as, can be anchor formula, paddle or pusher stirring etc.
In preparation method provided by the invention, reacting the situation of carrying out can be measured by liquid chromatography.
According to the present invention; be the reduction reaction process of the compound of structure shown in general formula (I) by the converting compounds of structure general formula (II) Suo Shi and be that the N-acylation reaction process of compound of the shown structure of general formula (III) is preferably carried out in aliphatic ether and cyclic ethers by the converting compounds of structure general formula (I) Suo Shi, further preferably to carry out in methyl tertiary butyl ether, glycol dimethyl ether, tetrahydrofuran (THF) or dioxan.In this case; the cost prepared needed for aromatic hydroxyamines compound can be saved on the one hand drop into; effectively avoid on the other hand the use of solvent on the impact of reduction reaction and N-acylation reaction; and after described reduction reaction terminates; eliminate the operation steps removing reaction solvent; thus the loss of the partial reaction product that can complicated desolventizing operation steps avoided while the difficulty reducing operation to cause, therefore, significantly improve transformation efficiency and the selectivity of reaction.
Below will be described the present invention by embodiment.In following examples, the amount of reactant and product is recorded by liquid chromatography (Agilent HPLC 1260).In following examples, the transformation efficiency of reaction and selectivity are by following formulae discovery:
Transformation efficiency=(raw material drops into feed molar amount residual in molar weight-product)/raw material drops into theoretical molar amount × 100% of the actual molar quantity/target product of molar weight × 100% selectivity=target product
Embodiment 1
The present embodiment is for illustration of the preparation method of compound N-hydroxy-N-shown in compound N formula (Ia) Suo Shi-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol and formula (IIIa) (2-(N '-(4-chloro-phenyl-) pyrazoles-3 '-Ji oxygen ylmethyl) phenyl) Urethylane.
In the four-hole bottle that mechanical stirring, thermometer, prolong are housed, add 16.5g (50mmol) 2-[(N-4-chloro-phenyl-)-1H-pyrazoles-3-oxygen methyl] oil of mirbane, 0.2g Raney's nickel and 30mL methyl tertiary butyl ether, stirring makes it fully mix, in mixture, the hydrazine hydrate that 50mmol concentration is 80% is dropwise added at 30 DEG C, dropwise and react 10 hours at 30 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 96%.
Then in above-mentioned reduzate, dropwise add 4.7g (50mmol) methyl-chloroformate, dropwise and react 5 hours at 50 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 98%.
Embodiment 2
The present embodiment is for illustration of the preparation method of compound N-hydroxy-N-(2-aminomethyl phenyl) Urethylane shown in compound o-methyl-phenyl-azanol formula (Ib) Suo Shi and formula (IIIb).
In the four-hole bottle that mechanical stirring, thermometer, prolong are housed, add the 2-nitrotoluene of 6.9g (50mmol), 0.7g thunder Buddhist nun's cobalt and 120mL tetrahydrofuran (THF), stirring makes it fully mix, in mixture, the hydrazine hydrate that 150mmol concentration is 80% is dropwise added at-10 DEG C, dropwise and react 2 hours at-10 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 95%.
Then in above-mentioned reduzate, dropwise add 4.7g (50mmol) methyl-chloroformate, dropwise and react 2 hours at-10 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 96%.
Embodiment 3
The present embodiment is for illustration of the preparation method of formula (Ic) N-(2-Phenoxymethyl)-azanol and formula (IIIc) N-hydroxy-n-(2-(Phenoxymethyl) phenyl) urethanum.
In the four-hole bottle that mechanical stirring, thermometer, prolong are housed, add 11.5g (50mmol) 2-(Phenoxymethyl) oil of mirbane, 0.6g thunder Buddhist nun's cobalt and 100mL glycol dimethyl ether, stirring makes it fully mix, in said mixture, the hydrazine hydrate that 75mmol concentration is 80% is dropwise added at 0 DEG C, dropwise and react 5 hours at 0 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 96%.
Then in above-mentioned reduzate, dropwise add 5.4g (50mmol) bromine ethyl formate, dropwise and react 3 hours at 0 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 97%.
Embodiment 4
The present embodiment is for illustration of the preparation method of compound N-hydroxy-N-shown in compound N formula (Ia) Suo Shi-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol and formula (IIIa) (2-(N '-(4-chloro-phenyl-) pyrazoles-3 '-Ji oxygen ylmethyl) phenyl) Urethylane.
N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol is prepared according to the method for embodiment 1, difference is, described methyl tertiary butyl ether is replaced by ether, obtains target product, the transformation efficiency recording reaction is 90%, and selectivity is 92%.
Then in above-mentioned reduzate, dropwise add 4.7g (50mmol) methyl-chloroformate, dropwise and react 5 hours at 50 DEG C, obtain target product, the transformation efficiency recording reaction is 99%, and selectivity is 95%.
Comparative example 1
N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol of this comparative example for illustration of reference and the preparation method of N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] Urethylane.
N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol is prepared according to the method for embodiment 1, difference is, described methyl tertiary butyl ether is replaced by ethanol/ethylene dichloride (1:1), obtain target product, the transformation efficiency recording reaction is 90%, and selectivity is 80%.
Then in above-mentioned reduzate, 4.7g (50mmol) methyl-chloroformate is dropwise added, dropwise and react 5 hours at 50 DEG C, obtain target product N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] Urethylane, the transformation efficiency recording reaction is 80%, and selectivity is 80%.
As can be seen from the data of above-described embodiment and comparative example, higher reaction conversion ratio and selectivity can be obtained according to the method preparing aromatic hydroxyamines compound and N-acidylate aromatic hydroxyamines compound of the present invention.Particularly, can be found out by the result of comparative example 1-3 and comparative example 1, prepare in the process of aromatic hydroxyamines compound in employing method of the present invention, the transformation efficiency of reaction and selectivity are all better than the preparation method using ethanol/ethylene dichloride (1:1) solvent in comparative example 1.
In addition; can be found out by the result of comparative example 1-3 and embodiment 4; when the process preparing aromatic hydroxyamines compound and N-acidylate aromatic hydroxyamines compound is carried out under more preferably condition (namely reaction process uses organic solvent of the present invention), higher reaction conversion ratio and selectivity can be obtained.
More than describe the preferred embodiment of the present invention in detail; but the present invention is not limited to the detail in above-mentioned embodiment, within the scope of technical conceive of the present invention; can carry out multiple simple variant to technical scheme of the present invention, these simple variant all belong to protection scope of the present invention.

Claims (12)

1. the preparation method of the aromatic hydroxyamines compound shown in a general formula (I), the method comprises: under the existence of reducing catalyst, compound shown in general formula (II) and hydrazine hydrate are carried out reduction reaction in organic solvent, described organic solvent is at least one in aliphatic ether and cyclic ethers
Wherein, R 1for hydrogen, halogen, cyano group, C 1-C 4alkyl, C 1-C 4haloalkyl or-CH 2-O-R 2, wherein, R 2for substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted imidazolyl.
2. method according to claim 1, wherein, R 1for hydrogen, fluorine, chlorine, bromine, cyano group, methyl, ethyl, propyl group, chloromethyl, Chloroethyl, chloro propyl group or-CH 2-O-R 2, wherein, R 2for 1-(4-chloro-phenyl-) pyrazole-3-yl, phenyl, naphthyl or pyridyl.
3. method according to claim 2, wherein, the aromatic hydroxyamines compound shown in described general formula (I) is N-[2-[[1-(4-chloro-phenyl-) pyrazole-3-yl] oxygen methyl] phenyl] azanol, o-methyl-phenyl-azanol or N-(2-Phenoxymethyl)-azanol.
4. method according to claim 1, wherein, described organic solvent is selected from least one in methyl tertiary butyl ether, glycol dimethyl ether, ether, positive propyl ether, ethylene glycol diethyl ether, tetrahydrofuran (THF), dioxan, propylene oxide and 1,2-butylene oxide ring; Preferably, described organic solvent is selected from least one in methyl tertiary butyl ether, glycol dimethyl ether, tetrahydrofuran (THF) and dioxan.
5. method according to claim 1, wherein, relative to the consumption of the compound shown in 1mol general formula (II), the consumption of described hydrazine hydrate is 1-7mol, is preferably 1-3mol.
6. method according to claim 1, wherein, relative to the consumption of the compound shown in 1g general formula (II), the consumption of described reducing catalyst is 0.01-0.3g, is preferably 0.01-0.1g;
Preferably, described reducing catalyst is at least one in Raney's nickel and Lei Ni cobalt.
7. method according to claim 1, wherein, the condition of described reduction reaction comprises: temperature is-20 DEG C to 100 DEG C, is preferably-10 DEG C to 30 DEG C; Time is 1-24h, is preferably 2-10h.
8. the preparation method of the N-acidylate aromatic hydroxyamines compound shown in a general formula (III); the method comprises: carry out reduction reaction with the mixture of preparation containing the compound shown in general formula (I) according to the method for claim 1-7; the mixture this being contained the compound shown in general formula (I) carries out solid-liquid separation, and is L-CO-R by isolated liquid phase and general formula 3compound carry out N-acylation reaction,
Wherein, R 1for hydrogen, halogen, cyano group, C 1-C 4alkyl, C 1-C 4haloalkyl or-CH 2-O-R 2, wherein, R 2for substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted imidazolyl; R 3for C 1-C 4alkoxyl group or C 1-C 4alkyl, L is halogen.
9. method according to claim 8, wherein, R 3for methoxyl group, methyl, oxyethyl group, ethyl, propoxy-or propyl group, L is fluorine, chlorine or bromine.
10. method according to claim 9; wherein, the N-acidylate aromatic hydroxyamines compound shown in described general formula (III) is N-hydroxy-n-(2-(N '-(4-chloro-phenyl-) pyrazoles-3 '-Ji oxygen ylmethyl) phenyl) Urethylane, N-hydroxy-n-2-methYlphenvlcarbamate or N-hydroxy-n-(2-(Phenoxymethyl) phenyl) urethanum.
11. methods according to claim 8, wherein, the condition of described N-acylation reaction comprises: temperature is-30 DEG C to 80 DEG C, is preferably-10 DEG C to 50 DEG C; Time is 1-10h, is preferably 2-5h.
12. methods according to Claim 8 in-11 described in any one, wherein, described method also comprises: be cycled to used in described reduction reaction process by catalytic solid isolated in solid-liquid separation process.
CN201410835404.2A 2014-12-26 2014-12-26 Preparation methods of aromatic hydroxylamine compound and N-aromatic acylated hydroxylamine compound Pending CN104557712A (en)

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CN104910050A (en) * 2015-05-13 2015-09-16 安徽国星生物化学有限公司 Preparation method for N-hydroxyl-N-2-methyl phenyl carbamate
CN105646276A (en) * 2016-03-04 2016-06-08 安徽国星生物化学有限公司 Preparation method of o-methyl phenyl hydroxylamine
CN109232261A (en) * 2018-10-31 2019-01-18 周银平 A kind of preparation method of benzyl bromine compounds
CN110494417A (en) * 2017-02-01 2019-11-22 索尔维亚斯股份公司 The production for the aromatic hydroxyamines that N- replaces

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104910050A (en) * 2015-05-13 2015-09-16 安徽国星生物化学有限公司 Preparation method for N-hydroxyl-N-2-methyl phenyl carbamate
CN105646276A (en) * 2016-03-04 2016-06-08 安徽国星生物化学有限公司 Preparation method of o-methyl phenyl hydroxylamine
CN110494417A (en) * 2017-02-01 2019-11-22 索尔维亚斯股份公司 The production for the aromatic hydroxyamines that N- replaces
CN109232261A (en) * 2018-10-31 2019-01-18 周银平 A kind of preparation method of benzyl bromine compounds
CN109232261B (en) * 2018-10-31 2021-07-23 江苏中旗科技股份有限公司 Preparation method of benzyl bromide compound

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