CN101195578B - Synthesis method of 1- (haloalkoxy) -2-alkoxy-5-nitrobenzene compounds - Google Patents
Synthesis method of 1- (haloalkoxy) -2-alkoxy-5-nitrobenzene compounds Download PDFInfo
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- CN101195578B CN101195578B CN200610119369XA CN200610119369A CN101195578B CN 101195578 B CN101195578 B CN 101195578B CN 200610119369X A CN200610119369X A CN 200610119369XA CN 200610119369 A CN200610119369 A CN 200610119369A CN 101195578 B CN101195578 B CN 101195578B
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- 125000004438 haloalkoxy group Chemical group 0.000 title abstract 2
- 238000001308 synthesis method Methods 0.000 title abstract 2
- -1 salt compounds Chemical class 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 24
- 239000003444 phase transfer catalyst Chemical class 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 claims description 6
- QUSAZPBBDGIVFX-UHFFFAOYSA-N 2-butoxy-5-nitrophenol Chemical class C(CCC)OC1=C(C=C(C=C1)[N+](=O)[O-])O QUSAZPBBDGIVFX-UHFFFAOYSA-N 0.000 claims description 5
- DYXKUCHKZUSDEJ-UHFFFAOYSA-N 5-nitro-2-phenoxyphenol Chemical class OC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC=C1 DYXKUCHKZUSDEJ-UHFFFAOYSA-N 0.000 claims description 5
- CFCOQFMDDRKLLN-UHFFFAOYSA-N 5-nitro-2-propoxyphenol Chemical class C(CC)OC1=C(C=C(C=C1)[N+](=O)[O-])O CFCOQFMDDRKLLN-UHFFFAOYSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 4
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 claims description 3
- JXOSPTBRSOYXGC-UHFFFAOYSA-N 1-Chloro-4-iodobutane Chemical compound ClCCCCI JXOSPTBRSOYXGC-UHFFFAOYSA-N 0.000 claims description 3
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 claims description 3
- JTYUIAOHIYZBPB-UHFFFAOYSA-N 1-bromo-6-chlorohexane Chemical compound ClCCCCCCBr JTYUIAOHIYZBPB-UHFFFAOYSA-N 0.000 claims description 3
- JTWWWQGSFTWWDL-UHFFFAOYSA-N 1-chloro-2-iodoethane Chemical compound ClCCI JTWWWQGSFTWWDL-UHFFFAOYSA-N 0.000 claims description 3
- SFOYQZYQTQDRIY-UHFFFAOYSA-N 1-chloro-3-iodopropane Chemical compound ClCCCI SFOYQZYQTQDRIY-UHFFFAOYSA-N 0.000 claims description 3
- GUUHKOCYWBEGGX-UHFFFAOYSA-N 1-chloro-5-iodopentane Chemical compound ClCCCCCI GUUHKOCYWBEGGX-UHFFFAOYSA-N 0.000 claims description 3
- QTJHNJCILMMRIQ-UHFFFAOYSA-N 1-chloro-6-iodohexane Chemical compound ClCCCCCCI QTJHNJCILMMRIQ-UHFFFAOYSA-N 0.000 claims description 3
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 3
- BIXNBGOEHFWECA-UHFFFAOYSA-N [SiH4].ClCCCCCBr Chemical compound [SiH4].ClCCCCCBr BIXNBGOEHFWECA-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 239000000920 calcium hydroxide Substances 0.000 claims description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 3
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 claims description 3
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 claims description 3
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- 159000000000 sodium salts Chemical group 0.000 claims description 3
- ZVNBVZQNVNWAOS-UHFFFAOYSA-N 5-nitro-2-phenylmethoxyphenol Chemical class OC1=CC([N+]([O-])=O)=CC=C1OCC1=CC=CC=C1 ZVNBVZQNVNWAOS-UHFFFAOYSA-N 0.000 claims description 2
- 229920000151 polyglycol Polymers 0.000 claims description 2
- 239000010695 polyglycol Substances 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 19
- 238000002360 preparation method Methods 0.000 abstract description 18
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract description 2
- 239000012429 reaction media Substances 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 37
- 229910052708 sodium Inorganic materials 0.000 description 37
- 239000011734 sodium Substances 0.000 description 37
- 238000003756 stirring Methods 0.000 description 26
- 238000001035 drying Methods 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- 239000007788 liquid Substances 0.000 description 16
- 229910052801 chlorine Inorganic materials 0.000 description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 231100001261 hazardous Toxicity 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000002440 industrial waste Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- KBRKFTKQRMYINW-UHFFFAOYSA-M sodium;2-methoxy-5-nitrophenolate Chemical compound [Na+].COC1=CC=C([N+]([O-])=O)C=C1[O-] KBRKFTKQRMYINW-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a method for synthesizing 1- (haloalkoxy) -2-alkoxy-5-nitrobenzene compounds, which comprises the following steps: adding 2-alkoxy-5-nitrophenol or salt compounds thereof, halogenated alkane compounds and a phase transfer catalyst into an aqueous solution of an alkaline substance, and reacting at 20-95 ℃. The method of the invention adopts water as a reaction medium, avoids the use and recovery of toxic and harmful organic solvents, thereby reducing the discharge amount of industrial three wastes and the damage to the natural environment, and is an environment-friendly synthesis method. The method is simple to operate, low in production cost, and suitable for small-scale preparation in a laboratory and industrial large-scale production.
Description
Technical field
The present invention relates to the compound method of a kind of 1-(halogen alkoxyl group)-2-alkoxyl group-5-nitrobenzene compounds.
Background technology
1-(halogen alkoxyl group)-2-alkoxyl group-5-nitrobenzene compounds is a kind of important chemical midbody; Especially at medicine; Agricultural chemicals; Industries such as makeup have purposes, for example 1-(3-chlorine propoxy-)-2-methoxyl group-5-oil of mirbane, 1-(3-chlorine propoxy-)-2-oxyethyl group-5-oil of mirbane and 1-(3-chlorine butoxy)-2-methoxyl group-5-oil of mirbane very widely.
It is raw material that USP 20050043537 discloses with 5 nitroguaiacol sodium (2-methoxyl group-5-p-nitrophenol sodium) and 1-bromo-3-chloropropane; In Virahol,, prepare the method for 1-(halogen alkoxyl group)-2-alkoxyl group-5-nitrobenzene compounds through alkoxylation.This method need be used environment and the disadvantageous poisonous and hazardous organic solvent Virahol of laborer, and the waste reaction solution aftertreatment is complicated, and the labour protection condition is harsh, is difficult to be applied to large-scale industrial production.
Summary of the invention
The objective of the invention is to disclose a kind of simple to operate, environment amenable, be easy to the compound method of industrialized 1-(halogen alkoxyl group)-2-alkoxyl group-5-nitrobenzene compounds.
The step of the inventive method is: in the aqueous solution of alkaline matter; Add 2-alkoxyl group-5-nitrophenols or its esters compound, halogenated alkane compounds and phase-transfer catalyst, promptly get 1-(halogen alkoxyl group)-2-alkoxyl group-5-nitrobenzene compounds through alkoxylation under 20-95 ℃.
Among the present invention, what described 2-alkoxyl group-5-nitrophenols or its esters compound were preferable is the salt of 2-methoxyl group-5-nitrophenols, 2-oxyethyl group-5-nitrophenols, 2-propoxy--5-nitrophenols, 2-butoxy-5-nitrophenols, 2-phenoxy-5-nitrophenols, 2-benzyloxy-5-nitrophenols or above-mentioned substance.Wherein, the sodium salt of preferred 2-methoxyl group-5-nitrophenols, 2-oxyethyl group-5-nitrophenols and said two devices.
Among the present invention, what described salt was preferable is sodium salt.
Among the present invention; What described halogenated alkane compounds was preferable is 1-chloro-2-monobromethane, 1-chloro-2-iodoethane, 1; 2-ethylene dibromide, 1-chloro-3-N-PROPYLE BROMIDE, 1-chloro-3-iodopropane, 1,3-dibromopropane, 1-chloro-4-NBB, 1-chloro-4-butyl iodide, 1,4-dibromobutane, 1-chloro-5-bromo pentane silane, 1-chloro-5-iodopentane, 1; Pentamethylene bromide, 1-chloro-6-bromohexane, 1-chloro-6-iodohexane or 1, the 6-dibromo-hexane.Wherein, preferred 1-chloro-3-N-PROPYLE BROMIDE or 1-chloro-4-NBB; More preferably 1-chloro-3-N-PROPYLE BROMIDE.
In the preferred embodiment of the present invention, optimum material is combined as: 2-methoxyl group-5-nitrophenols and 1-chloro-3-N-PROPYLE BROMIDE.
Among the present invention, the molar weight of described halogenated alkane compounds is preferable be described 2-alkoxyl group-5-nitrophenols or its esters compound molar weight 1.0-5.0 doubly, better be 1.0-1.5 times.
Among the present invention, described alkaline matter is preferable is selected from one or more in following: yellow soda ash, salt of wormwood, cesium carbonate, sodium hydroxide, Pottasium Hydroxide, calcium hydroxide, Lithium Hydroxide MonoHydrate, cesium hydroxide and hydrated barta.
Among the present invention, that described phase-transfer catalyst is preferable is Me
4NCl, Me
4NBr, Me
4NI, Et
4NCl, Et
4NBr, Et
4NI, n-Bu
4NCl, n-Bu
4NBr, n-Bu
4NI, n-Bu
4NF, PhCH
2NEt
3Cl, PhCH
2NEt
3Br, PhCH
2NEt
3I, PhCH
2NEt
3F, (Me (CH
2)
17)
4NCl, (Me (CH
2)
17)
4NBr, (Me (CH
2)
17)
4NF, (Me (CH
2)
17)
4NI, (Me (CH
2)
7) NMe
3Cl, (Me (CH
2)
7) NMe
3Br, (Me (CH
2)
7) NMe
3I, (Me (CH
2)
7) NMe
3F, (Me (CH
2)
7)
4NCl, (Me (CH
2)
7)
4NBr, (Me (CH
2)
7)
4NI, (Me (CH
2)
7)
4NF, PhCH
2P (Ph)
3Cl, PhCH
2P (Ph)
3Br, PhCH
2P (Ph)
3I, PhCH
2P (Et)
3Br, PhCH
2P (Et)
3Cl, PhCH
2P (Bu)
3Cl, PhCH
2P (Bu)
3Br, (Me (CH
2)
7)
4PCl, (Me (CH
2)
7)
4PBr, molecular weight are in polyglycol polymer (PEG) or the crown ether-like phase transfer catalysts of 200-800.What described crown ether-like phase transfer catalysts was preferable is dibenzo-18-crown-6 (DB18C6), 12-crown ether-4 or 15-crown ether-5.Wherein, preferred Bu
4NBr, Bu
4NCl.That the add-on of described phase-transfer catalyst is preferable is the 0.05%-10% of the weight of 2-alkoxyl group-5-nitrophenols or its esters compound, and that better is 0.1%-1%.Among the present invention, Me is writing a Chinese character in simplified form of methyl; Et is writing a Chinese character in simplified form of ethyl; N-Bu is writing a Chinese character in simplified form of normal-butyl; Ph is writing a Chinese character in simplified form of phenyl.
Among the present invention, what described temperature of reaction was preferable is 45-95 ℃.
Among the present invention, reaction can be cooled to room temperature (20-35 ℃) after finishing, and filtration drying promptly gets solid 1-(halogen alkoxyl group)-2-alkoxyl group-5-nitrobenzene compounds.
Positive progressive effect of the present invention is: method of the present invention adopts water as reaction medium; Avoided using and reclaiming of poisonous and hazardous organic solvent; Thereby can reduce the quantity discharged of three industrial wastes, alleviate the destruction to physical environment, be a kind of environmentally friendly compound method.And present method is simple to operate, and low production cost is not only applicable to the laboratory and prepares on a small scale, is applicable to large-scale industrialization production yet.
Embodiment
Further illustrate content of the present invention below in conjunction with embodiment, these embodiment are not to be the restriction to the scope of the invention or spirit.
The preparation of embodiment 1 1-(3-chlorine propoxy-)-2-methoxyl group-5-oil of mirbane
(16.8g, 0.1mol), water (100mL), sodium hydroxide (1.12mol), 1-chloro-3-N-PROPYLE BROMIDE (0.20mol), the back that stirs adds n-Bu in reaction flask, to add 2-methoxyl group-5-nitrophenols under the room temperature (25-30 ℃) successively
4NBr (8.4mg, for 2-methoxyl group-5-nitrophenols weight 0.05%), be heated with stirring to 20 ℃ of reactions afterwards and directly react completely to TLC tracking 2-methoxyl group-5-nitrophenols.Reaction finishes afterreaction liquid and is cooled to room temperature, leaves standstill filtration, drying obtains light yellow solid, and yield is 90%.
Embodiment 2 1-(4-chlorine butoxy)-2-methoxyl group-5-oil of mirbane preparation
(19.1g, 0.1mol), water (100mL), Pottasium Hydroxide (0.05mol), 1-chloro-4-NBB (0.12mol), the back one that stirs adds (CH in reaction flask, to add 2-methoxyl group-5-p-nitrophenol sodium under the room temperature (30-35 ℃) successively
3)
4NCl (19.1mg, for 2-methoxyl group-5-p-nitrophenol sodium weight 0.1%), stir afterwards and be heated to 45 ℃ and reaction down and react completely up to TLC tracking 2-methoxyl group-5-p-nitrophenol sodium.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 77%.
Embodiment 3 1-(2-chloroethoxy)-2-oxyethyl group-5-oil of mirbane preparation
(20.5g, 0.1mol), water (100 milliliters), yellow soda ash (0.05mol), 1-chloro-2-monobromethane (0.15mol), the back that stirs adds Et in reaction flask, to add 2-oxyethyl group-5-p-nitrophenol sodium under the room temperature (20-25 ℃) successively
4NI (205mg, for 2-oxyethyl group-5-p-nitrophenol sodium weight 1%), stir afterwards and be heated to 90 ℃ of reactions down and follow the tracks of 2-oxyethyl group-5-p-nitrophenol sodium up to TLC and react.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 71%.
Embodiment 4 1-(2-bromine oxethyl)-2-propoxy--5-oil of mirbane preparation
(19.6g, 0.1mol), water (150mL), calcium hydroxide (1.15mol), glycol dibromide (0.1mol), the back that stirs adds (CH in reaction flask, to add 2-propoxy--5-nitrophenols under the room temperature (20-25 ℃) successively
3(CH
2)
7)
4NI (48mg, for 2-propoxy--5-nitrophenols weight 0.24%), stir afterwards and be heated to 95 ℃ of reactions down and follow the tracks of 2-propoxy--5-nitrophenols up to TLC and react.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 73%.
Embodiment 5 1-(3-chlorine propoxy-)-2-butoxy-5-oil of mirbane preparation
(21g, 0.1mol), water (100mL), Lithium Hydroxide MonoHydrate (1.12mol), 1-chloro-3-iodopropane (0.13mol), the back that stirs adds (CH in reaction flask, to add 2-butoxy-5-nitrophenols under the room temperature (20-25 ℃) successively
3(CH
2)
7) N (CH
3)
3F (96mg, for 2-butoxy-5-nitrophenols weight 4.6%), stir afterwards and be heated to 35 ℃ of reactions down and follow the tracks of 2-butoxy-5-nitrophenols up to TLC and react.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 87%.
Embodiment 6 1-(4-chlorine butoxy)-2-benzyloxy-5-oil of mirbane preparation
(26.7g, 0.1mol), water (100mL), cesium hydroxide (0.03mol), 1-chloro-4-butyl iodide (0.5mol), the back that stirs adds (Me (CH in reaction flask, to add 2-benzyloxy-5-p-nitrophenol sodium under the room temperature (20-25 ℃) successively
2)
7)
4PBr (2.67g, for 2-benzyloxy-5-p-nitrophenol sodium weight 10%), stir afterwards and be heated to 60 ℃ and reaction down and follow the tracks of 2-benzyloxy-5-p-nitrophenol sodium up to TLC and react.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 83%.
Embodiment 7 1-(5-chlorine pentyloxy)-2-phenoxy-5-oil of mirbane preparation
In reaction flask, add 2-phenoxy-5-nitrophenols (25.3g under the room temperature (20-25 ℃) successively; 0.1mol), water (100mL), hydrated barta (1.1mol), 1-chloro-5-bromo pentane silane (0.25mol); Back adding dibenzo-18-crown-6 (DB18C6) (955mg stirs; For 2-phenoxy-5-nitrophenols weight 3.8%), room temperature (20-25 ℃) down reaction is followed the tracks of 2-phenoxy-5-nitrophenols reaction up to TLC.React completely postcooling to room temperature, leave standstill, filter, drying obtains light yellow solid, yield is 87%.
Embodiment 8 1-(5-chlorine pentyloxy)-2-methoxyl group-5-oil of mirbane preparation
(19.1g, 0.1mol), water (100mL), Pottasium Hydroxide (0.03mol), 1-chloro-5-iodopentane (0.25mol), the back that stirs adds (Me (CH in reaction flask, to add 2-methoxyl group-5-p-nitrophenol sodium under the room temperature (30-35 ℃) successively
2)
17)
4NBr (1.91g, for 2-methoxyl group-5-p-nitrophenol sodium weight 10%), stir afterwards and be heated to 60 ℃ and reaction down and follow the tracks of 2-methoxyl group-5-p-nitrophenol sodium up to TLC and react.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 80%.
Embodiment 9 1-(2-iodine oxyethyl group)-2-methoxyl group-5-oil of mirbane preparation
(19.1g, 0.1mol), water (100mL), sodium hydroxide (0.02mol), 1-chloro-2-iodoethane (0.25mol), the back that stirs adds PhCH in reaction flask, to add 2-methoxyl group-5-p-nitrophenol sodium under the room temperature (30-35 ℃) successively
2P (Ph)
3Br (96mg, for 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 82%.
Embodiment 10 1-(3-bromine propoxy-)-2-methoxyl group-5-oil of mirbane preparation
In reaction flask, add successively under the room temperature (30-35 ℃) 2-methoxyl group-5-p-nitrophenol sodium (19.1g, 0.1mol), water (150mL), salt of wormwood (0.05mol), 1,3-dibromopropane (0.25mol), the back that stirs adds PhCH
2NEt
3F (96mg, for 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 76%.
Embodiment 11 1-(4-bromine butoxy)-2-methoxyl group-5-oil of mirbane preparation
In reaction flask, add successively under the room temperature (30-35 ℃) 2-methoxyl group-5-p-nitrophenol sodium (19.1g, 0.1mol), water (100mL), cesium carbonate (0.03mol), 1,4-dibromobutane (0.25mol), the back that stirs adds PhCH
2P (Et)
3Br (96mg, for 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 80%.
Embodiment 12 1-(5-bromine pentyloxy)-2-methoxyl group-5-oil of mirbane preparation
(19.1g, 0.1mol), water (100mL), sodium hydroxide (0.04mol), pentamethylene bromide (0.25mol), the back that stirs adds PhCH in reaction flask, to add 2-methoxyl group-5-p-nitrophenol sodium under the room temperature (30-35 ℃) successively
2P (Bu)
3Cl (96mg, for 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 75%.Embodiment 131-(6-bromine hexyloxy)-2-methoxyl group-5-oil of mirbane preparation
In reaction flask, add 2-methoxyl group-5-p-nitrophenol sodium (19.1g under the room temperature (30-35 ℃) successively; 0.1mol), water (100mL), sodium hydroxide (0.04mol), 1-chloro-6-bromohexane (0.25mol); Back adding 15-crown ether-5 (96mg stirs; For 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 83%.
Embodiment 14 1-(6-iodine hexyloxy)-2-methoxyl group-5-oil of mirbane preparation
In reaction flask, add 2-methoxyl group-5-p-nitrophenol sodium (19.1g under the room temperature (30-35 ℃) successively; 0.1mol), water (100mL), sodium hydroxide (0.04mol), 1-chloro-6-iodohexane (0.25mol); Back adding 12-crown ether-4 (96mg stirs; For 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 74%.
Embodiment 15 1-(6-bromine hexyloxy)-2-methoxyl group-5-oil of mirbane preparation
In reaction flask, add 2-methoxyl group-5-p-nitrophenol sodium (19.1g under the room temperature (30-35 ℃) successively; 0.1mol), water (100mL), sodium hydroxide (0.04mol), 1; 6-dibromo-hexane (0.25mol), the back that stirs adds polyoxyethylene glycol (molecular weight 200,96mg; For 2-methoxyl group-5-p-nitrophenol sodium weight 0.5%), room temperature (30-35 ℃) down reaction is followed the tracks of 2-methoxyl group-5-p-nitrophenol sodium reaction up to TLC.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 81%.
The preparation of embodiment 16 1-(3-chlorine propoxy-)-2-methoxyl group-5-oil of mirbane
In reaction flask, add 2-methoxyl group-5-nitrophenols (16.8g under the room temperature (25-30 ℃) successively; 0.1mol), water (100mL), sodium hydroxide (1.12mol), 1-chloro-3-N-PROPYLE BROMIDE (0.20mol); Back adding polyoxyethylene glycol (molecular weight 800 stirs; 8.4mg, for 2-methoxyl group-5-nitrophenols weight 0.05%), be heated with stirring to 20 ℃ of reactions afterwards and directly react completely to TLC tracking 2-methoxyl group-5-nitrophenols.Reaction finishes afterreaction liquid and is cooled to room temperature, leaves standstill filtration, drying obtains light yellow solid, and yield is 90%.
Embodiment 17 1-(4-chlorine butoxy)-2-methoxyl group-5-oil of mirbane preparation
In reaction flask, add 2-methoxyl group-5-p-nitrophenol sodium (19.1g under the room temperature (30-35 ℃) successively; 0.1mol), water (100mL), Pottasium Hydroxide (0.05mol), 1-chloro-4-NBB (0.12mol); Back one adding polyoxyethylene glycol (molecular weight 600 stirs; 19.1mg, for 2-methoxyl group-5-p-nitrophenol sodium weight 0.1%), stir afterwards and be heated to 45 ℃ and reaction down and react completely up to TLC tracking 2-methoxyl group-5-p-nitrophenol sodium.The afterreaction liquid that reacts completely is cooled to room temperature, leaves standstill, filters, drying obtains light yellow solid, and yield is 77%.
Among the present invention the reagent that uses and raw material is all commercially available gets.
Claims (12)
1. the compound method of a 1-(halogen alkoxyl group)-5-nitrobenzene compounds; Step is for to react 2-alkoxyl group-5-nitrophenols, 2-phenoxy-5-nitrophenols, 2-benzyloxy-5-nitrophenols or its esters compound and halogenated alkane compounds under temperature of reaction 20-95 ℃; It is characterized in that: be reflected in the aqueous solution of alkaline matter and carry out, and add phase-transfer catalyst; Described halogenated alkane compounds is 1-chloro-2-monobromethane, 1-chloro-2-iodoethane, 1; 2-ethylene dibromide, 1-chloro-3-N-PROPYLE BROMIDE, 1-chloro-3-iodopropane, 1; 3-dibromopropane, 1-chloro-4-NBB, 1-chloro-4-butyl iodide, 1; 4-dibromobutane, 1-chloro-5-bromo pentane silane, 1-chloro-5-iodopentane, pentamethylene bromide, 1-chloro-6-bromohexane, 1-chloro-6-iodohexane or 1, the 6-dibromo-hexane.
2. method according to claim 1 is characterized by: described 2-alkoxyl group-5-nitrophenols or its esters compound are the salt of 2-methoxyl group-5-nitrophenols, 2-oxyethyl group-5-nitrophenols, 2-propoxy--5-nitrophenols, 2-butoxy-5-nitrophenols or above-mentioned substance.
3. method according to claim 1 and 2 is characterized by: described salt is sodium salt.
4. method according to claim 1 is characterized by: described 2-alkoxyl group-5-nitrophenols or its esters compound are 2-methoxyl group-5-nitrophenols, and described halogenated alkane compounds is a 1-chloro-3-N-PROPYLE BROMIDE.
5. method according to claim 1 is characterized by: the molar weight of described halogenated alkane compounds is described 2-alkoxyl group-5-nitrophenols or its esters compound molar weight 1.0-5.0 a times.
6. method according to claim 5 is characterized by: the molar weight of described halogenated alkane compounds is described 2-alkoxyl group-5-nitrophenols or its esters compound molar weight 1.0-1.5 a times.
7. method according to claim 1 is characterized by: described alkaline matter is selected from one or more in following: yellow soda ash, salt of wormwood, cesium carbonate, sodium hydroxide, Pottasium Hydroxide, calcium hydroxide, Lithium Hydroxide MonoHydrate, cesium hydroxide and hydrated barta.
8. method according to claim 1 is characterized by: described phase-transfer catalyst is Me
4NCl, Me
4NBr, Me
4NI, Et
4NCl, Et
4NBr, Et
4NI, n-Bu
4NCl, n-Bu
4NBr, n-Bu
4NI, n-Bu
4NF, PhCH
2NEt
3Cl, PhCH
2NEt
3Br, PhCH
2NEt
3I, PhCH
2NEt
3F, (Me (CH
2)
17)
4NCl, (Me (CH
2)
17)
4NBr, (Me (CH
2)
17)
4NF, (Me (CH
2)
17)
4NI, (Me (CH
2)
7) NMe
3Cl, (Me (CH
2)
7) NMe
3Br, (Me (CH
2)
7) NMe
3I, (Me (CH
2)
7) NMe
3F, (Me (CH
2)
7)
4NCl, (Me (CH
2)
7)
4NBr, (Me (CH
2)
7)
4NI, (Me (CH
2)
7)
4NF, PhCH
2P (Ph)
3Cl, PhCH
2P (Ph)
3Br, PhCH
2P (Ph)
3I, PhCH
2P (Et)
3Br, PhCH
2P (Et)
3Cl, PhCH
2P (Bu)
3Cl, PhCH
2P (Bu)
3Br, (Me (CH
2)
7)
4PCl, (Me (CH
2)
7)
4PBr, molecular weight polyglycol polymer or the crown ether-like phase transfer catalysts between 200-800.
9. method according to claim 8 is characterized by: described crown ether-like phase transfer catalysts is dibenzo-18-crown-6 (DB18C6), 12-crown ether-4 or 15-crown ether-5.
10. method according to claim 1 is characterized by: the add-on of described phase-transfer catalyst is the 0.05%-10% of the weight of 2-alkoxyl group-5-nitrophenols or its esters compound.
11. method according to claim 10 is characterized by: described add-on is the 0.1%-1% of the weight of 2-alkoxyl group-5-nitrophenols or its esters compound.
12. method according to claim 1 is characterized by: described temperature of reaction is 45-95 ℃.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1348951A (en) * | 2001-10-11 | 2002-05-15 | 巨化集团公司 | Water phase synthesis process of difluoromethoxy nitrobenzene |
| US20050043537A1 (en) * | 2003-08-19 | 2005-02-24 | Wyeth Holdings Corporation | Process for preparation of 4-amino-3-quinolinecarbonitriles |
-
2006
- 2006-12-08 CN CN200610119369XA patent/CN101195578B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1348951A (en) * | 2001-10-11 | 2002-05-15 | 巨化集团公司 | Water phase synthesis process of difluoromethoxy nitrobenzene |
| US20050043537A1 (en) * | 2003-08-19 | 2005-02-24 | Wyeth Holdings Corporation | Process for preparation of 4-amino-3-quinolinecarbonitriles |
Non-Patent Citations (2)
| Title |
|---|
| Kiyoshi Mutai et al.photoinduced intramolecular substitution-III photlcyclization of ω-anilinoalkyl m-nitrophenyl ethers.《Tetrahedron》.1984,第40卷(第10期),1755-1759. * |
| 马良晓.200610119369xSTN检索过程.《STN检索》.2011, * |
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Address after: Building 3, No. 99 Lianhe North Road, Fengxian District, Shanghai, 2014 Patentee after: Shanghai Boteng Zhituo Pharmaceutical Technology Co.,Ltd. Address before: No. 99, Lianhe North Road, Fengxian District, Shanghai 201203 Patentee before: Kaihui Pharmaceutical (Shanghai) Co.,Ltd. |