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.