CN101298419A - Preparation of 3-ethoxy-4-decyloxy nitrobenzene - Google Patents
Preparation of 3-ethoxy-4-decyloxy nitrobenzene Download PDFInfo
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- CN101298419A CN101298419A CNA2008100616126A CN200810061612A CN101298419A CN 101298419 A CN101298419 A CN 101298419A CN A2008100616126 A CNA2008100616126 A CN A2008100616126A CN 200810061612 A CN200810061612 A CN 200810061612A CN 101298419 A CN101298419 A CN 101298419A
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Abstract
The invention relates to a preparation method of 3-oxyethyl group-4-decyloxy nitrobenzene; the method includes the following steps in sequence: obtaining 2, 2-dimethyl piperonyl from pyrocatechol after being protected by acetone; then obtaining 5-nitryl-2, 2-2, 2-dimethyl piperonyl by nitration and obtaining 3, 4-dihydroxy nitrobenzene by deprotection; then obtaining 3-oxyethyl group-4-decyloxy nitrobenzene by being reacted with bromodecane and an ethylation reagent (ethyl bromide or diethyl sulfate) in sequence; the preparation method of the invention provides a completely novel synthetic line; the used materials are all sold in the market; furthermore, the sources are broad and sufficient; the cost is cheap; the reaction conditions are mild; the technique is simple; the reactions in each step are normal operations; the larger defects of fussy operation steps and large toxicity of the used materials are avoided.
Description
Technical field
The present invention relates to the intermediates preparation of a kind of anticoccidial drug 4-hydroxyl-6-oxygen in last of the ten Heavenly stems base-7-oxyethyl group-3-quinoline carboxylic acid ethyl ester (decoquinate premix), relate in particular to the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene.
Background technology
In the process of feeding stock animals and poultry, livestock and poultry is easy to be subjected to coccidium infection and causes a series of coccidiosis, thereby have influence on the output and the quality of aquaculture, the coccidiosis that the livestock industry of this year whole world causes coccidium infection and the input of treatment thereof improve than before in a large number, the veterinary drug of anticoccidial also is widely used in livestock industry, anticoccidial drug 4-hydroxyl-6-oxygen in last of the ten Heavenly stems base-7-oxyethyl group-3-quinoline carboxylic acid ethyl ester (decoquinate premix) is because its consumption is big, substantially have no side effect, and the drug withdrawal metabolism is fast, it is complete that one week got final product metabolism, be difficult for developing immunity to drugs, make it extensive in the anticoccidial drug market outlook, therefore, preparation 4-hydroxyl-6-oxygen in last of the ten Heavenly stems base-7-oxyethyl group-3-quinoline carboxylic acid ethyl ester all has great significance for the research and development application of anticoccidial drug and veterinary drug.
Complete synthesis rarely seen bibliographical information about 4-hydroxyl-6-oxygen in last of the ten Heavenly stems base-7-oxyethyl group-3-quinoline carboxylic acid ethyl ester, only at English Patent (publication number 1469416, the preparation process of quinoline) having disclosed a kind of method by diazonium coupling introduces amino on phenyl ring, obtain key intermediate 3-oxyethyl group-4-oxygen in last of the ten Heavenly stems base aniline, but this method reaction conditions is comparatively harsh, the commercial supply of raw material is less, and cost an arm and a leg, and aftertreatment more complicated, yield and product purity are all undesirable, therefore are unfavorable for suitability for industrialized production.
Summary of the invention
The present invention is in order to solve the problems of the technologies described above, provide a kind of reaction conditions gentleness, technology and equipment simple, be convenient to operate, raw material sources are extensive and the preparation method of the intermediate 3-oxyethyl group-4-decyloxy nitrobenzene of the anticoccidial drug 4-hydroxyl of harmless environment-6-oxygen in last of the ten Heavenly stems base-7-oxyethyl group-3-quinoline carboxylic acid ethyl ester (decoquinate premix).
Above-mentioned technical problem of the present invention is mainly solved by following technical proposals: 3-oxyethyl group of the present invention-4-decyloxy nitrobenzene is with formula (I) expression, and the preparation method of 3-oxyethyl group-4-decyloxy nitrobenzene obtains according to following steps:
A.2, the preparation of 2-dimethyl piperonyl cyclonene:
In reactor, add 2～10 parts in acetone, 0.005～0.01 part of 1 times of pyrocatechol and condensing agent, stirring and refluxing reaction, reaction finish the back removal of solvent under reduced pressure and obtain with 2 of formula (II) expression, 2-dimethyl piperonyl cyclonene;
B.5-nitro-2, the preparation of 2-dimethyl piperonyl cyclonene:
In reactor, add 2,1 part of 2-dimethyl piperonyl cyclonene, 5～6 parts of glacial acetic acids, under cooling and agitation condition, drip 1.5～3 parts in certain density nitric acid, during stirring reaction finished to fall back, solid collected by filtration obtained the 5-nitro-2 with formula (III) expression, 2-dimethyl piperonyl cyclonene;
C.3, the preparation of 4-dihydroxyl oil of mirbane:
In reactor, add 5-nitro-2,1 part of 2-dimethyl piperonyl cyclonene, 5～20 parts of 10～15 parts of ethanol and dilute hydrochloric acid solutions, stirring and refluxing is reacted, and reaction finishes postcooling to 25 degree, filters the collection consubstantiality and obtains with 3 of formula (IV) expression, 4-dihydroxyl oil of mirbane;
D.3-the preparation of hydroxyl-4-decyloxy nitrobenzene:
In reactor, add 3,1～1.5 part of 1 part in 4-dihydroxyl oil of mirbane, 10～15 parts of ethanol, 0.01～0.02 part of benzyltriethylammoinium chloride and bromo-decane, stirring next time, stream carries out substitution reaction, removal of solvent under reduced pressure after reaction is finished, freezing and crystallizing, solid collected by filtration obtain 3-hydroxyl-4-decyloxy nitrobenzene of representing with formula V;
E.3-the preparation of oxyethyl group-4-decyloxy nitrobenzene:
In reactor, add 1～1.2 part of 3-hydroxyl-1 part of 4-decyloxy nitrobenzene, 1～2 part of organic solvent, 1～2 part of 30% aqueous sodium hydroxide solution, 0.003～0.01 part of sodium iodide and ethylization reagent, stir next time that stream carries out substitution reaction, obtain 3-oxyethyl group-4-decyloxy nitrobenzene.
As preferably, used condensing agent is p-methyl benzenesulfonic acid or Vanadium Pentoxide in FLAKES in the described A step, is excellent with Vanadium Pentoxide in FLAKES, and the reaction times is 24～48 hours, is excellent with 36 hours, and the acetone consumption is 7 parts.
As preferably, used concentration of nitric acid is 30～65% in the described B step, and 65% to be excellent, temperature of reaction is-15～0 ℃, is excellent with-5 ℃.
As preferably, the concentration of used dilute hydrochloric acid solution is 1～5% in the described C step, is excellent with 2%.
As preferably, used bromo-decane consumption is 3 in the described D step, 1.1 times of 4-dihydroxyl oil of mirbane.
As preferably, used organic solvent is any one in the rudimentary saturated alcohol in the described E step, can be methyl alcohol or ethanol, and ethylization reagent is ethyl sulfate or monobromethane.
The invention has the beneficial effects as follows:
1. adopt brand-new synthetic route, the volume production of this product is had important theory directive significance and actually operating meaning.
The raw material that adopts of each step be commercially available, wide material sources, in liberal supply.
3. gentleness and technology are simple relatively for this reaction conditions, and each step reaction is routine operation, obtains product through the reaction of five steps, is easy to control, need not complex apparatus, greatly reduces the pollution to environment.
Embodiment
Below by embodiment, and in conjunction with the accompanying drawings, technical scheme of the present invention is described in further detail.
Embodiment 1: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, carry out according to following steps:
A.2, the preparation of 2-dimethyl piperonyl cyclonene
In the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus is housed, add pyrocatechol (55g, 0.5mol), acetone (380ml) and Vanadium Pentoxide in FLAKES (0.3g), heated solution keeps oil temperature 80 degree, refluxes 36 hours, leave standstill cooling, removal of solvent under reduced pressure acetone, remaining oily matter are 2, the crude product (51.2g) of 2-dimethyl piperonyl cyclonene, content is greater than 96% (GC), yield 68.3%, crude product do not need purifying, can be directly used in next step reaction.
B.5-nitro-2, the preparation of 2-dimethyl piperonyl cyclonene
Reflux condensing tube is being housed, constant pressure funnel, add 2 in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 2-dimethyl piperonyl cyclonene crude product (15g, about 0.1mol), Glacial acetic acid (65ml), waiting to dissolve the back is cooled to about-5 ℃ with ice-water bath, slowly dropping concentration is 65% concentrated nitric acid (22g), the reaction process controlled temperature remains on about-5 ℃, and concentrated nitric acid drips and finishes the water-bath of recession deicing, and room temperature continues to stir 1 hour, have a large amount of solids to separate out this moment, reaction solution is poured in the cold water (300ml), filtered, precipitation washes (100ml * 4) with water, oven dry, obtain 5-nitro-2,2-dimethyl piperonyl cyclonene (18.1g), yield 92.8%.86-88 ℃ of product fusing point.
C.3, the preparation of 4-dihydroxyl oil of mirbane
In being housed, the 1000ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds 5-nitro-2,2-dimethyl piperonyl cyclonene (19.5g, 0.1mol), concentration is 2% dilute hydrochloric acid solution (200ml) and ethanol (250ml), be heated to backflow, keeping oil bath temperature is 100 ℃ of back flow reaction, and TLC (tlc) shows 5-nitro-2,2-dimethyl piperonyl cyclonene reacts completely, about 12 hours, leave standstill cooling, precipitation is separated out, filter, precipitation washes (100ml * 4) with water, and oven dry obtains 3,4-dihydroxyl oil of mirbane (12.6g), yield 80.3%.174-176 ℃ of product fusing point.
D.3-the preparation of hydroxyl-4-decyloxy nitrobenzene
Thermometer is being housed, in the 500ml three neck round-bottomed flasks of division box and magnetic stirring apparatus, add 3, and 4-dihydroxyl oil of mirbane (15.7g, 0.1mol), sodium hydroxide (4g, 0.1mol) and benzene (200ml), heating reflux reaction is until the water of telling theoretical yield (theoretical is 1.8ml), benzene is removed in decompression, obtains single sodium phenolate.
In being housed, the 500ml round-bottomed flask of reflux condensing tube puts into the sodium phenolate that the front has made then, add ethanol (170ml) again, bromo-decane (23.2g, 0.11mol) and benzyltriethylammoinium chloride (0.2g), reflux, under reflux state, slowly add less water, until dissolving fully, continued back flow reaction 15～18 hours, TLC (tlc) shows raw material 3, and 4-dihydroxyl oil of mirbane disappears, cooling, most of solvent is removed in decompression, and crystallization obtains crude product under 0 ℃ of left and right sides environment.Crude product recrystallization in methyl alcohol obtains 3-hydroxyl-4-decyloxy nitrobenzene (21.2g), yield 71.6%.
E.3-the preparation of oxyethyl group-4-decyloxy nitrobenzene
Reflux condensing tube is being housed, add 3-hydroxyl-4-decyloxy nitrobenzene (29.6g in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 0.1mol), 30% aqueous sodium hydroxide solution (15ml, about 0.15mol), ethanol (50ml) and sodium iodide (0.1g), heated solution, (21.8g 0.2mol) and the mixed solution of ethanol (30ml), keeps oil temperature 70 degree slowly to splash into monobromethane again, refluxed 15～18 hours, TLC (tlc) shows that 3-hydroxyl-4-decyloxy nitrobenzene reacts completely, and leaves standstill cooling, tells the upper strata oil reservoir, unreacted monobromethane of pressure reducing and steaming and etoh solvent obtain crude product with the crystallization under 0 ℃ of left and right sides environment of remaining oily matter.Crude product recrystallization in methyl alcohol obtains 3-oxyethyl group-4-decyloxy nitrobenzene (29.3g), yield 90.4%.53-55 ℃ of product fusing point.1H?NMR(CDCl
3，500MHz)δ：0.93(3H，t)，1.28-1.35(17H，m)，1.87(2H，q)，4.16(2H，t)，4.27(2H，q)，7.23(1H，s)，7.54-7.68(2H，d)。m/z：356.490(M+H)+。
Embodiment 2: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 2 of A step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
In the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus is housed, add pyrocatechol (55g, 0.5mol), acetone (380ml) and Vanadium Pentoxide in FLAKES (0.3g), heated solution keeps oil temperature 80 degree, refluxes 24 hours, leave standstill cooling, removal of solvent under reduced pressure acetone, remaining oily matter are 2, the crude product (46.7g) of 2-dimethyl piperonyl cyclonene, content is greater than 96% (GC), yield 62.3%, crude product do not need purifying, can be directly used in next step reaction.
Embodiment 3: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 2 of A step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
In the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus is housed, add pyrocatechol (55g, 0.5mol), acetone (380ml) and Vanadium Pentoxide in FLAKES (0.3g), heated solution keeps oil temperature 80 degree, refluxes 48 hours, leave standstill cooling, ketone in the removal of solvent under reduced pressure, remaining oily matter is 2, the crude product (45.5g) of 2-dimethyl piperonyl cyclonene, content is greater than 96% (GC), yield 60.7%, crude product do not need purifying, can be directly used in next step reaction.
Embodiment 4: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 2 of A step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
In the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus is housed, add pyrocatechol (55g, 0.5mol), acetone (180ml) and Vanadium Pentoxide in FLAKES (0.3g), heated solution keeps oil temperature 80 degree, refluxes 36 hours, leave standstill cooling, removal of solvent under reduced pressure acetone, remaining oily matter are 2, the crude product (47.8g) of 2-dimethyl piperonyl cyclonene, content is greater than 96% (GC), yield 63.7%, crude product do not need purifying, can be directly used in next step reaction.
Embodiment 5: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 2 of A step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
In the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus is housed, add pyrocatechol (55g, 0.5mol), acetone (570ml) and Vanadium Pentoxide in FLAKES (0.3g), heated solution keeps oil temperature 80 degree, refluxes 36 hours, leave standstill cooling, removal of solvent under reduced pressure acetone, remaining oily matter are 2, the crude product (49.3g) of 2-dimethyl piperonyl cyclonene, content is greater than 96% (GC), yield 65.7%, crude product do not need purifying, can be directly used in next step reaction.
Embodiment 6: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 2 of A step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
In the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus is housed, add pyrocatechol (55g, 0.5mol), acetone (380ml) and p-methyl benzenesulfonic acid (0.3g), heated solution, keep oil temperature 80 degree, refluxed 36 hours, leave standstill cooling, removal of solvent under reduced pressure acetone, remaining oily matter is 2, the crude product (34.3g) of 2-dimethyl piperonyl cyclonene, and content is greater than 92% (GC), yield 45.7% need be further purified just and can be used for next step reaction.
Embodiment 7: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are the 5-nitro-2 of B step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 2 in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 2-dimethyl piperonyl cyclonene crude product (15g, about 0.1mol), Glacial acetic acid (65ml), waiting to dissolve the back is cooled to about-5 ℃ with ice-water bath, slowly dropping concentration is 45% concentrated nitric acid (33g), the reaction process controlled temperature remains on about-5 ℃, and concentrated nitric acid drips and finishes the water-bath of recession deicing, and room temperature continues to stir 1 hour, have a large amount of solids to separate out this moment, reaction solution is poured in the cold water (300ml), filtered, precipitation washes (100ml * 4) with water, oven dry, obtain 5-nitro-2,2-dimethyl piperonyl cyclonene (17.3g), yield 88.7%.86-88 ℃ of product fusing point.
Embodiment 8: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are the 5-nitro-2 of B step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 2 in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 2-dimethyl piperonyl cyclonene crude product (15g, about 0.1mol), Glacial acetic acid (65ml), waiting to dissolve the back is cooled to about-5 ℃ with ice-water bath, slowly dropping concentration is 30% concentrated nitric acid (47g), the reaction process controlled temperature remains on about-5 ℃, and concentrated nitric acid drips and finishes the water-bath of recession deicing, and room temperature continues to stir 1 hour, have a large amount of solids to separate out this moment, reaction solution is poured in the cold water (300ml), filtered, precipitation washes (100ml * 4) with water, oven dry, obtain 5-nitro-2,2-dimethyl piperonyl cyclonene (16.3g), yield 83.6%.86-88 ℃ of product fusing point.
Embodiment 9: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are the 5-nitro-2 of B step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 2 in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 2-dimethyl piperonyl cyclonene crude product (15g, about 0.1mol), Glacial acetic acid (65ml), waiting to dissolve the back is cooled to about-5 ℃ with ice-water bath, slowly dropping concentration is 65% concentrated nitric acid (22g), the reaction process controlled temperature remains on about-15 ℃, and concentrated nitric acid drips and finishes the water-bath of recession deicing, and room temperature continues to stir 1 hour, have a large amount of solids to separate out this moment, reaction solution is poured in the cold water (300ml), filtered, precipitation washes (100ml * 4) with water, oven dry, obtain 5-nitro-2,2-dimethyl piperonyl cyclonene (18.0g), yield 92.3%.86-88 ℃ of product fusing point.
Embodiment 10: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are the 5-nitro-2 of B step, and the preparation method of 2-dimethyl piperonyl cyclonene is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 2 in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 2-dimethyl piperonyl cyclonene crude product (15g, about 0.1mol), Glacial acetic acid (65ml), waiting to dissolve the back is cooled to about-5 ℃ with ice-water bath, slowly dropping concentration is 65% concentrated nitric acid (22g), the reaction process controlled temperature remains on about-15 ℃, and concentrated nitric acid drips and finishes the water-bath of recession deicing, and room temperature continues to stir 1 hour, have a large amount of solids to separate out this moment, reaction solution is poured in the cold water (300ml), filtered, precipitation washes (100ml * 4) with water, oven dry, obtain 5-nitro-2,2-dimethyl piperonyl cyclonene (17.7g), yield 90.8%.86-88 ℃ of product fusing point.
Embodiment 11: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 3 of C step, and the preparation method of 4-dihydroxyl oil of mirbane is as follows:
In being housed, the 1000ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds 5-nitro-2,2-dimethyl piperonyl cyclonene (19.5g, 0.1mol), concentration is 1% dilute hydrochloric acid solution (400ml) and ethanol (250ml), be heated to backflow, keeping oil bath temperature is 100 ℃ of back flow reaction, and TLC (tlc) shows 5-nitro-2,2-dimethyl piperonyl cyclonene reacts completely, about 12 hours, leave standstill cooling, precipitation is separated out, filter, precipitation washes (100ml * 4) with water, and oven dry obtains 3,4-dihydroxyl oil of mirbane (10.4g), yield 66.2%.174-176 ℃ of product fusing point.
Embodiment 12: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, are 3 of C step, and the preparation method of 4-dihydroxyl oil of mirbane is as follows:
In being housed, the 1000ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds 5-nitro-2,2-dimethyl piperonyl cyclonene (19.5g, 0.1mol), concentration is 5% dilute hydrochloric acid solution (100ml) and ethanol (250ml), be heated to backflow, keeping oil bath temperature is 100 ℃ of back flow reaction, and TLC (tlc) shows 5-nitro-2,2-dimethyl piperonyl cyclonene reacts completely, about 12 hours, leave standstill cooling, precipitation is separated out, filter, precipitation washes (100ml * 4) with water, and oven dry obtains 3,4-dihydroxyl oil of mirbane (11.1g), yield 70.7%.174-176 ℃ of product fusing point.
Embodiment 13: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, and just the preparation method of the 3-hydroxyl-4-decyloxy nitrobenzene of D step is as follows:
Thermometer is being housed, in the 500ml three neck round-bottomed flasks of division box and magnetic stirring apparatus, add 3, and 4-dihydroxyl oil of mirbane (15.7g, 0.1mol), sodium hydroxide (4g, 0.1mol) and benzene (200ml), heating reflux reaction is until the water of telling theoretical yield (theoretical is 1.8ml), benzene is removed in decompression, obtains single sodium phenolate.
In the 500ml round-bottomed flask of reflux condensing tube is housed, put into the sodium phenolate that the front has made then, add ethanol (170ml) again, bromo-decane (21.1g, 0.1mol) and benzyltriethylammoinium chloride (0.2g), reflux slowly adds less water under reflux state, until dissolving fully, continued back flow reaction 15-18 hour, TLC (tlc) shows raw material 3, and 4-dihydroxyl oil of mirbane disappears, cooling, most of solvent is removed in decompression, and crystallization obtains crude product under 0 ℃ of left and right sides environment.Crude product recrystallization in methyl alcohol obtains 3-hydroxyl-4-decyloxy nitrobenzene (19.7g), yield 66.5%.
Embodiment 14: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, and just the preparation method of the 3-hydroxyl-4-decyloxy nitrobenzene of D step is as follows:
Thermometer is being housed, in the 500ml three neck round-bottomed flasks of division box and magnetic stirring apparatus, add 3, and 4-dihydroxyl oil of mirbane (15.7g, 0.1mol), sodium hydroxide (4g, 0.1mol) and benzene (200ml), heating reflux reaction is until the water of telling theoretical yield (theoretical is 1.8ml), benzene is removed in decompression, obtains single sodium phenolate.
In being housed, the 500ml round-bottomed flask of reflux condensing tube puts into the sodium phenolate that the front has made then, add ethanol (170ml) again, bromo-decane (31.7g, 0.15mol) and benzyltriethylammoinium chloride (0.2g), reflux, under reflux state, slowly add less water, until dissolving fully, continued back flow reaction 15-18 hour, TLC (tlc) shows raw material 3, and 4-dihydroxyl oil of mirbane disappears, cooling, most of solvent is removed in decompression, and crystallization obtains crude product under 0 ℃ of left and right sides environment.Crude product recrystallization in methyl alcohol obtains 3-hydroxyl-4-decyloxy nitrobenzene (16.1g), yield 54.4%.
Embodiment 15: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, and just the preparation method of the 3-oxyethyl group-4-decyloxy nitrobenzene of E step is as follows:
Reflux condensing tube is being housed, add 3-hydroxyl-4-decyloxy nitrobenzene (29.6g in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 0.1mol), 30% aqueous sodium hydroxide solution (15ml, about 0.15mol), methyl alcohol (50ml) and sodium iodide (0.1g), heated solution, (43.6g 0.2mol) and the mixed solution of methyl alcohol (30ml), keeps oil temperature 70 degree slowly to splash into monobromethane again, refluxed 15～18 hours, TLC (tlc) shows that 3-hydroxyl-4-decyloxy nitrobenzene reacts completely, and leaves standstill cooling, tells the upper strata oil reservoir, unreacted monobromethane of pressure reducing and steaming and etoh solvent obtain crude product with the crystallization under 0 ℃ of left and right sides environment of remaining oily matter.Crude product recrystallization in methyl alcohol obtains 3-oxyethyl group-4-decyloxy nitrobenzene (29.7g), yield 91.7%.53～55 ℃ of product fusing points.
Embodiment 16: the preparation method of a kind of 3-oxyethyl group-4-decyloxy nitrobenzene of present embodiment, and other steps are identical with embodiment 1, and just the preparation method of the 3-oxyethyl group-4-decyloxy nitrobenzene of E step is as follows:
Reflux condensing tube is being housed, add 3-hydroxyl-4-decyloxy nitrobenzene (29.6g in the 250ml three-necked bottle of thermometer and magnetic stirring apparatus, 0.1mol), 30% aqueous sodium hydroxide solution (15ml, about 0.15mol), methyl alcohol (80ml) and sodium iodide (0.1g), heated solution, (30.8g 0.2mol), keeps oil temperature 70 degree slowly to splash into ethyl sulfate again, refluxed 15～18 hours, TLC (tlc) shows that 3-hydroxyl-4-decyloxy nitrobenzene reacts completely, and leaves standstill cooling, tells the upper strata oil reservoir, unreacted monobromethane of pressure reducing and steaming and etoh solvent obtain crude product with the crystallization under 0 ℃ of left and right sides environment of remaining oily matter.Crude product recrystallization in methyl alcohol obtains 3-oxyethyl group-4-decyloxy nitrobenzene (29.2g), yield 90.1%.53～55 ℃ of product fusing points.
The above is preferred embodiment of the present invention only, is not to be used for limiting scope of the present invention, and is all according to equalization variation and modification that the present invention did, is all claim of the present invention and contains.
Claims (6)
1. the preparation method of 3-oxyethyl group-4-decyloxy nitrobenzene is characterized in that obtaining according to following steps with the 3-oxyethyl group-4-decyloxy nitrobenzene of formula (I) expression:
A.2, the preparation of 2-dimethyl piperonyl cyclonene:
In reactor, add 2～10 parts in acetone, 0.005～0.01 part of 1 times of pyrocatechol and condensing agent, stirring and refluxing reaction, reaction finish the back removal of solvent under reduced pressure and obtain with 2 of formula (II) expression, 2-dimethyl piperonyl cyclonene;
B.5-nitro-2, the preparation of 2-dimethyl piperonyl cyclonene:
In reactor, add 2,1 part of 2-dimethyl piperonyl cyclonene, 5～6 parts of glacial acetic acids, under cooling and agitation condition, drip 1.5～3 parts in certain density nitric acid, during stirring reaction finished to fall back, solid collected by filtration obtained the 5-nitro-2 with formula (III) expression, 2-dimethyl piperonyl cyclonene;
C.3, the preparation of 4-dihydroxyl oil of mirbane:
In reactor, add 5-nitro-2,1 part of 2-dimethyl piperonyl cyclonene, 5～20 parts of 10～15 parts of ethanol and dilute hydrochloric acid solutions, stirring and refluxing reaction, reaction finish postcooling to 25 degree, and solid collected by filtration obtains with 3 of formula (IV) expression, 4-dihydroxyl oil of mirbane;
D.3-the preparation of hydroxyl-4-decyloxy nitrobenzene:
In reactor, add 3,1～1.5 part of 1 part in 4-dihydroxyl oil of mirbane, 10～15 parts of ethanol, 0.01～0.02 part of benzyltriethylammoinium chloride and bromo-decane, stirring next time, stream carries out substitution reaction, removal of solvent under reduced pressure after reaction is finished, freezing and crystallizing, solid collected by filtration obtain 3-hydroxyl-4-decyloxy nitrobenzene of representing with formula V;
E.3-the preparation of oxyethyl group-4-decyloxy nitrobenzene:
In reactor, add 1～1.2 part of 3-hydroxyl-1 part of 4-decyloxy nitrobenzene, 1～2 part of organic solvent, 1～2 part of 30% aqueous sodium hydroxide solution, 0.003～0.01 part of sodium iodide and ethylization reagent, stir next time that stream carries out substitution reaction, obtain 3-oxyethyl group-4-decyloxy nitrobenzene.
2. the preparation method of a kind of 3-oxyethyl group according to claim 1-4-decyloxy nitrobenzene is characterized in that condensing agent used in the described A step is p-methyl benzenesulfonic acid or Vanadium Pentoxide in FLAKES, and the reaction times is 24～48 hours, and the acetone consumption is 7 parts.
3. the preparation method of a kind of 3-oxyethyl group according to claim 1-4-decyloxy nitrobenzene is characterized in that concentration of nitric acid used in the described B step is 30～65%, and temperature of reaction is-15～0 ℃.
4. the preparation method of a kind of 3-oxyethyl group according to claim 1-4-decyloxy nitrobenzene, the concentration that it is characterized in that dilute hydrochloric acid solution used in the described C step is 1～5%.
5. the preparation method of a kind of 3-oxyethyl group according to claim 1-4-decyloxy nitrobenzene is characterized in that bromo-decane consumption used in the described D step is 3,1.1 times of 4-dihydroxyl oil of mirbane.
6. the preparation method of a kind of 3-oxyethyl group according to claim 1-4-decyloxy nitrobenzene, it is characterized in that organic solvent used in the described E step is any one in the rudimentary saturated alcohol, can be methyl alcohol or ethanol, ethylization reagent be ethyl sulfate or monobromethane.
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