CN101704723B - Preparation method of hydroxymethyl substitutent o-alkyl biphenyl and intermediate thereof - Google Patents
Preparation method of hydroxymethyl substitutent o-alkyl biphenyl and intermediate thereof Download PDFInfo
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Abstract
The invention provides a preparation method of hydroxymethyl substitutent o-alkyl biphenyl and intermediate thereof, which takes halogen o-alkyl biphenyl as a raw material to synthesize halogen o-alkyl biphenyl through diazonium coupling reaction. The raw materials and catalyst utilized by the invention are massively commercialized at home and abroad and all around the world with low price. The method of the invention has low production cost, short synthetic route, mild reaction condition, easy and feasible operation process, less three wastes (waste gas, waste water and industrial residue) generation, low cost of raw materials and high yield and purity, thereby being favorable to industrial volume production.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to the preparation method of hydroxymethyl substitutent o-alkyl biphenyl and intermediate thereof.
Background technology
In the hydroxymethyl substitutent o-alkyl biphenyl compound, outbalance be the 2-methyl-3-phenyl benzil alcohol, it is mainly used in the production of agricultural chemicals bifenthrin and the synthesis material of other pharmaceutical prod.
Introduced the method for preparing the 2-methyl-3-phenyl benzil alcohol at Chinese patent application CN200610096552.2 and CN200710130941.7.Wherein, the preparation method of halo o-alkyl biphenyl intermediate is: take dihalo alkyl benzene as raw material, it carries out coupling with bromination benzene and obtains the halo o-alkyl biphenyl behind solvents tetrahydrofurane back warp grignard reaction.Carry out grignard reaction and reduction reaction acquisition 2-methyl-3-phenyl benzil alcohol from described halo o-alkyl biphenyl intermediate again.
In the above-mentioned route, starting compound dihalo alkyl benzene is to come take the adjacent alkyl benzene amine of halo as raw material production.The method route is long, and cost of material is higher, needs strict waterless operation, causes production cost expensive.According to aforesaid method, be unfavorable for suitability for industrialized production, so that there are many difficulties in industrial realization.
In sum, this area shortage is a kind of directly to obtain the operational path of halo o-alkyl biphenyl from the adjacent alkyl benzene amine of halo, but obtains first dihalo alkyl benzene, the halo o-alkyl biphenyl of reentrying.
Therefore, this area is in the urgent need to developing a kind of operational path that directly obtains the halo o-alkyl biphenyl from the adjacent alkyl benzene amine of halo, and this operational path reacts with the industrial raw material of easily buying, and technique is simple, aftertreatment is easily gone, productive rate is high, is applicable to industrialization.
Summary of the invention
The first purpose of the present invention is to obtain a kind of operational path for preparing hydroxymethyl substitutent o-alkyl biphenyl from the adjacent alkyl benzene amine of halo, this operational path reacts with the industrial raw material of easily buying, technique is simple, aftertreatment is easily gone, productive rate is high, is applicable to industrialization.
The second purpose of the present invention is to obtain the operational path that a kind of intermediate formyl radical replaces o-alkyl biphenyl, and this operational path reacts with the industrial raw material of easily buying, and technique is simple, easily row, productive rate are high in aftertreatment, are applicable to industrialization.
The 3rd purpose of the present invention is to obtain a kind of operational path that directly obtains the halo o-alkyl biphenyl from the adjacent alkyl benzene amine of halo, and this operational path reacts with the industrial raw material of easily buying, technique is simple, aftertreatment is easily gone, productive rate is high, is applicable to industrialization.
A first aspect of the present invention provides a kind of preparation method of hydroxymethyl substitutent o-alkyl biphenyl, and it comprises the steps:
(a) provide take the adjacent alkyl benzene amine of the halo shown in the formula (I) as raw material:
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is F, Cl, Br or I;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent alkyl benzene amine of the halo of the described formula (I) of step (a) and benzene carry out the diazonium coupling reaction, obtain the halo o-alkyl biphenyl compound suc as formula (II):
R in its Chinese style (II) and the implication of X are identical with formula (I);
(c) the halo o-alkyl biphenyl product of described formula (II) carries out grignard reaction and carbonyl addition, and the formyl radical that obtains formula (III) replaces o-alkyl biphenyl:
The implication of R in its Chinese style (III) is identical with formula (I);
(d) formyl radical of described formula (III) replacement o-alkyl biphenyl carries out the formyl radical reduction reaction in the presence of metallic reducing agent, obtains the hydroxymethyl substitutent o-alkyl biphenyl shown in the formula (IV):
The implication of R in its Chinese style (IV) is identical with formula (I).
In a specific embodiment of the present invention,
The adjacent alkyl benzene amine of the halo of described formula (I) is the 3-chloro-2-methyl aniline;
The halo o-alkyl biphenyl compound of described formula (II) is 3-chloro-2-methyl biphenyl;
It is 2-methyl-3-phenyl phenyl aldehyde that the formyl radical of described formula (III) replaces o-alkyl biphenyl,
The hydroxymethyl substitutent o-alkyl biphenyl of described formula (IV) is the 2-methyl-3-phenyl benzil alcohol.
In a specific embodiment of the present invention,
Metal catalyst in the step (b) is selected from fe and trivalent or bivalent compound, Z 250, elemental copper and monovalence or bivalent compound, zinc salt, sal epsom, nickel compound, Palladous chloride, cobalt chloride, Cobaltous diacetate, Manganse Dioxide, Tai-Ace S 150, tin tetrachloride, zirconium tetrachloride, ammonium tungstate, ammonium molybdate or its combination;
More specifically,
Described fe and trivalent thereof or bivalent compound are iron(ic) chloride, ferric oxide, ferric sulfate, iron protoxide, iron protochloride or ferrous sulfate;
Described elemental copper and monovalence or bivalent compound are cupric chloride, cupric oxide, copper sulfate, Red copper oxide, cuprous chloride or cuprous sulfate;
Described zinc salt is zinc chloride, zinc sulfate or zinc acetate;
Described nickel compound is nickelous chloride, nickelous nitrate or single nickel salt.
In a specific embodiment of the present invention,
Acids promotor in the step (b) is carboxylic acid, sulfonic acid, phosphoric acid or derivatives thereof;
More specifically,
Described carboxylic acid is selected from acetic acid, trichoroacetic acid(TCA), trifluoroacetic acid, propionic acid, oxalic acid, vinylformic acid or its combination;
Described sulfonic acid is selected from methylsulfonic acid;
The derivative of described carboxylic acid or sulfonic acid is selected from triethyl orthoformate.
In a specific embodiment of the present invention,
Nitrous acid ester in the step (b) is the Fatty Alcohol(C12-C14 and C12-C18) nitrous acid ester;
More specifically, described nitrous acid ester is nitrous acid isopropyl esters, nitrous acid n-butyl, nitrous acid isobutyl, nitrous acid tertiary butyl ester, nitrous acid n-pentyl ester, nitrous acid isopentyl ester or its combination.
In a specific embodiment of the present invention, described step (b) meets the one or more of following reaction conditions:
(i) the diazonium coupling temperature of reaction is 20-80 ℃;
(ii) consumption of described metal catalyst is the 0.001-1.0 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo;
(iii) consumption of described acids promotor is the 0.001-1.2 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo;
(iv) consumption of described nitrous acid ester is the 1.0-3.0 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo;
(v) consumption of described benzene is the 1-150 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo.
A second aspect of the present invention provides a kind of method for preparing halo o-alkyl biphenyl intermediate, and it comprises the steps:
(a) provide take the adjacent alkyl benzene amine of the halo shown in the formula (I) as raw material:
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is F, Cl, Br or I;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent alkyl benzene amine of the halo of the described formula (I) of step (a) and benzene carry out the diazonium coupling reaction, obtain the halo o-alkyl biphenyl compound suc as formula (II):
In a specific embodiment of the present invention, the adjacent alkyl benzene amine of the halo of described formula (I) is the 3-chloro-2-methyl aniline;
The halo o-alkyl biphenyl compound of described formula (II) is 3-chloro-2-methyl biphenyl.
In a preference, the metal catalyst in the step (b) is selected from fe and trivalent or bivalent compound, Z 250, elemental copper and monovalence or bivalent compound, zinc salt, sal epsom, nickel compound, Palladous chloride, cobalt chloride, Cobaltous diacetate, Manganse Dioxide, Tai-Ace S 150, tin tetrachloride, zirconium tetrachloride, ammonium tungstate, ammonium molybdate or its combination;
More specifically,
Described fe and trivalent thereof or bivalent compound are iron(ic) chloride, ferric oxide, ferric sulfate, iron protoxide, iron protochloride or ferrous sulfate;
Described elemental copper and monovalence or bivalent compound are cupric chloride, cupric oxide, copper sulfate, Red copper oxide, cuprous chloride or cuprous sulfate;
Described zinc salt is zinc chloride, zinc sulfate or zinc acetate;
Described nickel compound is nickelous chloride, nickelous nitrate or single nickel salt.
In a preference, the acids promotor in the step (b) is carboxylic acid, sulfonic acid, phosphoric acid or derivatives thereof;
More specifically,
Described carboxylic acid is selected from acetic acid, trichoroacetic acid(TCA), trifluoroacetic acid, propionic acid, oxalic acid, vinylformic acid or its combination;
Described sulfonic acid is selected from methylsulfonic acid;
The derivative of described carboxylic acid or sulfonic acid is selected from triethyl orthoformate.
In a preference, the nitrous acid ester in the step (b) is the nitrous acid hydrocarbyl carbonate;
More specifically, described nitrous acid ester is nitrous acid isopropyl esters, nitrous acid n-butyl, nitrous acid isobutyl, nitrous acid tertiary butyl ester, nitrous acid n-pentyl ester, nitrous acid isopentyl ester or its combination.
A third aspect of the present invention provides a kind of formyl radical to replace the preparation method of o-alkyl biphenyl, and it comprises the steps:
(a) provide take the adjacent alkyl benzene amine of the halo shown in the formula (I) as raw material:
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is F, Cl, Br or I;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent alkyl benzene amine of the halo of the described formula (I) of step (a) and benzene carry out the diazonium coupling reaction, obtain the halo o-alkyl biphenyl compound suc as formula (II):
R in its Chinese style (II) and the implication of X are identical with formula (I);
(c) the halo o-alkyl biphenyl product of described formula (II) carries out grignard reaction and carbonyl addition, and the formyl radical that obtains formula (III) replaces o-alkyl biphenyl:
The implication of R in its Chinese style (III) is identical with formula (I).
In a specific embodiment of the present invention,
The adjacent alkyl benzene amine of the halo of described formula (I) is the 3-chloro-2-methyl aniline;
The halo o-alkyl biphenyl compound of described formula (II) is 3-chloro-2-methyl biphenyl;
It is 2-methyl-3-phenyl phenyl aldehyde that the formyl radical of described formula (III) replaces o-alkyl biphenyl.
Embodiment
The inventor is through extensive and deep research, by improving preparation technology, a class novel reaction scheme, catalyzer and promotor have been used, this reaction scheme, catalyzer and promotor are cheap, voltinism stable and be difficult for moisture absorption decomposes, the utmost point is applicable to the diazonium coupling reaction, and its productive rate is not less than the productive rate of existing technique simultaneously.Simultaneously, obtained a kind of operational path of new hydroxymethyl substitutent o-alkyl biphenyl, and find that this technique is simple, easily row, productive rate are high in aftertreatment, are applicable to industrialization.Finished on this basis the present invention.
Herein, described " alkyl " except as otherwise noted, refers to the straight or branched alkane that contains 1-5 carbon atom.For example, alkyl includes but not limited to methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl.
Herein, described " Fatty Alcohol(C12-C14 and C12-C18) " except as otherwise noted, refers to the straight or branched Fatty Alcohol(C12-C14 and C12-C18) that contains 1-5 carbon atom.For example, the fatty group in the Fatty Alcohol(C12-C14 and C12-C18) includes but not limited to methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl.
Design of the present invention is as follows:
Adopt novel reaction scheme, catalyzer and promotor, obtained halo o-alkyl biphenyl intermediate; The operational path of following a kind of new hydroxymethyl substitutent o-alkyl biphenyl also is provided simultaneously:
Specify such as nothing, various raw materials of the present invention all can obtain by commercially available; Or prepare according to the ordinary method of this area.For example, the adjacent alkyl benzene amine of halo of the present invention can be synthetic by marketable material and traditional chemical transform mode.
Unless otherwise defined or explanation, same meanings of being familiar with of all specialties used herein and scientific words and those skilled in the art.Any method similar or impartial to described content and material all can be applicable in the inventive method in addition.
Below describe in detail to various aspects of the present invention.
Halo o-alkyl biphenyl intermediate
The preparation method of halo o-alkyl biphenyl intermediate of the present invention comprises the steps:
(a) provide take the adjacent alkyl benzene amine of the halo shown in the formula (I) as raw material:
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is F, Cl, Br or I;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent alkyl benzene amine of the halo of the described formula (I) of step (a) and benzene carry out the diazonium coupling reaction, obtain the halo o-alkyl biphenyl compound suc as formula (II):
R in its Chinese style (II) and the implication of X are identical with formula (I).
Amino in above-mentioned diazonium coupling reaction Chinese style (I) compound is by diazonium coupling, thus the formula of obtaining (II) compound.
In a preference, the adjacent alkyl benzene amine of the halo of described formula (I) is the 3-chloro-2-methyl aniline; The halo o-alkyl biphenyl compound of described formula (II) is 3-chloro-2-methyl biphenyl.
Herein, " diazonium coupling reaction " of the present invention refer to: the amino in the adjacent alkyl benzene amine of the halo of following formula (I) is by diazonium coupling:
Wherein R is C
nH
2n+1, n=1,2,3,4,5;
X is F, Cl, Br, I.
There is not yet the route that the adjacent alkyl benzene amine of play-by-play halo prepares the adjacent alkyl benzene amine of halo in the prior art, therefore following counterweight nitrogen coupling reaction describes in detail:
Metal catalyst
The activeconstituents of metal catalyst of the present invention is metal ion.Metal catalyst of the present invention can directly adopt, and also metal catalyst can be loaded on the inert support as activeconstituents.
The metal ion of metal catalyst of the present invention is unrestricted, can be fe and trivalent thereof or bivalent compound, Z 250, elemental copper and monovalence or bivalent compound, zinc salt, magnesium salts, nickel compound or its combination.Preferably, described metal catalyst is: iron(ic) chloride, ferric oxide, ferric sulfate, iron protoxide, iron protochloride, ferrous sulfate, cupric chloride, cupric oxide, copper sulfate, Red copper oxide, cuprous chloride, cuprous sulfate, zinc chloride, zinc sulfate, zinc acetate, sal epsom, nickelous chloride, nickelous nitrate, single nickel salt, Palladous chloride, cobalt chloride, Cobaltous diacetate, Manganse Dioxide, Tai-Ace S 150, tin tetrachloride, zirconium tetrachloride, ammonium tungstate, ammonium molybdate or its combination.Particularly preferably, described metal catalyst is iron trichloride.
Described supported catalyst can adopt the load method preparation, also can adopt direct method preparation in synthetic inert support to contain the material of active ingredient.
The present invention adopts the metal catalyst of catalytic amount to get final product.Described catalytic amount is not particularly limited, only otherwise goal of the invention of the present invention is produced restriction to be got final product.For example be the 0.001-1.0 mol ratio particularly, calculate with the adjacent alkyl benzene amine 1mol amount of halo.
The acids promotor
Acids promotor of the present invention can be carboxylic acid, sulfonic acid, phosphoric acid or derivatives thereof.Preferably, described acids promotor is triethyl orthoformate, methylsulfonic acid, acetic acid, p-methyl benzenesulfonic acid, trifluoroacetic acid, trichoroacetic acid(TCA), oxalic acid, propionic acid, vinylformic acid, phosphoric acid or its combination.Particularly preferably, described acids promotor is acetic acid.
The consumption of acids promotor of the present invention is preferably the 0.001-1.2 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo.
Nitrous acid ester
Nitrous acid ester of the present invention is unrestricted.Preferably, described nitrous acid ester is isopropyl esters, n-butyl, isobutyl, tertiary butyl ester, n-pentyl ester, isopentyl ester or its combination.Particularly preferably, described nitrous acid ester is nitrous acid isopropyl ester.
The consumption of nitrous acid ester of the present invention for example is the 1.0-3.0 mol ratio particularly, calculates with the adjacent alkyl benzene amine 1mol amount of halo.
Diazonium coupling temperature of reaction of the present invention is generally 20-80 ℃.
After finishing, above reaction adopts conventional post-treating method (extraction, suction filtration, washing, drying, precipitation etc.).
Target product can adopt ultimate analysis, ebulliometry, and the methods such as gas-chromatography or gaseous mass spectrum detect proof.
The raw material of not complete reaction of the present invention can reclaim and carry out circulating reaction, until reach required productive rate.
Above-mentioned metal catalyst, acids promotor, nitrous acid ester also are applicable to prepare o-alkyl biphenyl.Particularly, comprise the steps:
(a) provide adjacent alkyl benzene amine as raw material;
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is H;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent amyl aniline of step (a) and benzene carry out the diazonium coupling reaction, obtain adjacent pentylbiphenyl.
Formyl radical replaces o-alkyl biphenyl intermediate and hydroxymethyl substitutent o-alkyl biphenyl thereof
After obtaining described halo o-alkyl biphenyl intermediate, can prepare derived product according to ordinary method, for example formyl radical replaces the o-alkyl biphenyl intermediate, prepares hydroxymethyl substitutent o-alkyl biphenyl again.Replace o-alkyl biphenyl as adopting step (c) to prepare formyl radical particularly, or adopt step (d) to prepare hydroxymethyl substitutent o-alkyl biphenyl:
(c) the halo o-alkyl biphenyl product of described formula (II) carries out Ge Shi and carbonyl addition, and the formyl radical that obtains formula (III) replaces o-alkyl biphenyl:
(d) formyl radical of described formula (III) replacement o-alkyl biphenyl carries out the formyl radical reduction reaction in the presence of metallic reducing agent, obtains the hydroxymethyl substitutent o-alkyl biphenyl shown in the formula (IV):
The grignard reaction of above-mentioned steps (c) and step (d) can be carried out according to the reaction conditions of prior art.For example shown in Chinese patent application CN200610096552.2 and the CN200710130941.7.
Particularly, described form and carbonyl addition, by 1mol, the magnesium chips consumption is the 1.1-2mol ratio in the halo o-alkyl biphenyl, and the tetrahydrofuran solvent consumption is the 10-100mol ratio, and temperature of reaction is 20-65 ℃, reaction times 4-20 hour.Used DMF amount is the 1-2mol ratio, and temperature of reaction is 20-65 ℃, reaction times 1-3 hour.
Particularly, described formyl radical reduction reaction replaces o-alkyl biphenyl by 1mol in formyl radical, and the POTASSIUM BOROHYDRIDE consumption is the 0.25-1mol meter, and temperature of reaction 20-65 ℃, reaction times 2-10 hour.
The reaction parameter of described step (c) and step (d) has all been passed through play-by-play, does not give unnecessary details herein.It will be understood by those skilled in the art that obtaining described halo o-alkyl biphenyl intermediate, can prepare according to the ordinary method of this area formyl radical and replace the o-alkyl biphenyl intermediate, prepare again hydroxymethyl substitutent o-alkyl biphenyl.
Beneficial effect
(1) the adjacent alkyl benzene amine of the used main raw material halo of the present invention is lower than the employed dihalo alkyl of available technology adopting form coupling method benzene cost, have significant price advantage, other used supplementary materials of the present invention reach in the world all large-scale commercial and cheap at home.
(2) in the reaction process of the present invention without any need for organic solvent, reactant benzene is not only made solvent but also make reagent, and recovery is simply easy, can also reduce last handling process, almost without side reaction.
(3) method therefor of the present invention does not have anhydrous requirement to starting material.Reduced production cost, method therefor mild condition of the present invention, easy and simple to handle, with short production cycle, good product purity, yield is high, and three waste discharge is a kind of method that is suitable for scale operation of clean environment firendly seldom.
Above-mentioned synthetic method is the synthetic route of part of compounds of the present invention, and according to above-mentioned example, those skilled in the art can synthesize other compounds of the present invention by adjusting diverse ways.Synthetic compound can further be further purified by modes such as column chromatography, high performance liquid chromatography or crystallizations.
Below in conjunction with specific embodiment, further illustrate the present invention.Should be understood that these embodiment only to be used for explanation the present invention and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example usually according to normal condition, for example is " condition in the smooth organic chemistry handbook of Bel Si (Chemical Industry Press, 1996), or the condition of advising according to manufacturer.Ratio and per-cent are based on weight, unless stated otherwise.
Unless otherwise defined or explanation, same meanings of being familiar with of all specialties used herein and scientific words and those skilled in the art.Any method similar or impartial to described content and material all can be applicable in the inventive method in addition.
Embodiment 1
Drop into 3-chloro-2-methyl aniline (71g, 0.5mol) in the 1000ml four-hole boiling flask, benzene (300ml, 3.38mol) is opened and is stirred.Iron trichloride (2g, 0.012mol), triethyl orthoformate (55g, 0.34mol) are put in the reactor.Oil bath control temperature of reaction joins nitrous acid isopropyl ester (80g, 0.9mol) and benzene (200mL, 2.25mol) in the constant pressure funnel in 40 ℃, under 40 ℃ of conditions of maintenance reaction constant temperature, is added drop-wise in the reactor.After dripping nitrous acid isopropyl ester, stirred 2 hours at 40 ℃.Be cooled to room temperature, drop into urea (50g) and 30% hydrochloric acid (200g).After the phase-splitting, organic layer carries out rectifying.Reclaim first benzene, it is 99.5% that continuation rectifying obtains purified product 3-chloro-2-methyl biphenyl (76g, 0.37mol) gas chromatographic analysis purity, yield 75%.
Embodiment 2～embodiment 9
Amount of metal catalyst or kind are changed, and other are with embodiment 1, and it the results are shown in Table 1
Table 1
| Embodiment | Metal catalyst | Consumption (g) | Content (%) | Yield (%) |
| 2 | Iron(ic) chloride | 1.6 | 99.45 | 76.2 |
| 3 | Iron protoxide | 0.4 | 99.33 | 73.7 |
| 4 | Cupric sulfate pentahydrate | 0.6 | 99.25 | 74.8 |
| 5 | Zinc acetate dihydrate | 11 | 99.64 | 72.2 |
| 6 | Six water nickelous nitrates | 0.15 | 99.23 | 71.3 |
| 7 | Cobalt diacetate tetrahydrate | 0.6 | 99.31 | 70.5 |
| 8 | Manganse Dioxide | 22 | 99.42 | 72.3 |
| 9 | Anhydrous magnesium sulfate | 60 | 99.56 | 75.1 |
Embodiment 10～embodiment 17
Acids promotor kind or consumption are changed, the other the same as in Example 1, it the results are shown in Table 2
Table 2
| Embodiment | The acids promotor | Consumption (g) | Content (%) | Yield (%) |
| 10 | Triethyl orthoformate | 40 | 99.55 | 76.4 |
| 11 | Trichoroacetic acid(TCA) | 98 | 99.73 | 72.3 |
| 12 | Methylsulfonic acid | 48 | 99.51 | 74.2 |
| 13 | Acetic acid | 3 | 99.42 | 71.2 |
| 14 | Vinylformic acid | 0.36 | 99.38 | 70.1 |
| 15 | Trifluoroacetic acid | 0.3 | 99.14 | 71.0 |
| 16 | Phosphoric acid | 2.45 | 99.23 | 73.2 |
| 17 | P-methyl benzenesulfonic acid | 0.1 | 99.62 | 74.5 |
Embodiment 18～embodiment 21
Change temperature of reaction, the other the same as in Example 1, it the results are shown in Table 3
Table 3
| Embodiment | Temperature of reaction (℃) | Content (%) | Yield (%) |
| 18 | 20 | 99.55 | 76.4 |
| 19 | 40 | 99.73 | 72.3 |
| 20 | 60 | 99.23 | 71.2 |
| 21 | 80 | 99.12 | 70.5 |
Embodiment 22～embodiment 26
Change kind or the consumption of nitrous acid ester, the other the same as in Example 1, it the results are shown in Table 4
Table 4
| Embodiment | Nitrous acid ester | Consumption (g) | Content (%) | Yield (%) |
| 22 | The nitrous acid isopropyl esters | 111.25 | 99.75 | 74.9 |
| 23 | The nitrous acid methyl ester | 91.5 | 99.64 | 74.2 |
| 24 | The nitrous acid ethyl ester | 75 | 99.35 | 73.8 |
| 25 | The nitrous acid tertiary butyl ester | 77.25 | 99.24 | 72.2 |
| 26 | Nitrous acid n-pentyl ester | 58.6 | 99.15 | 70.8 |
Embodiment 27～embodiment 33
Change the consumption of benzene, the other the same as in Example 1, it the results are shown in Table 5
Table 5
| Embodiment | The consumption of benzene (g) | Content (%) | Yield (%) |
| 27 | 195.3 | 99.75 | 74.9 |
| 28 | 1952.7 | 99.34 | 77.2 |
| 29 | 4686.6 | 99.72 | 72.7 |
| 30 | 39.1 | 99.61 | 71.2 |
| 31 | 390.6 | 99.79 | 72.9 |
| 32 | 3905.5 | 99.74 | 74.5 |
| 33 | 5858.3 | 99.73 | 75.7 |
Embodiment 34～embodiment 38
Change the kind of the adjacent alkyl benzene amine of halo, the other the same as in Example 1, it the results are shown in Table 6 embodiment 34～37; Embodiment 38 is the example of adjacent alkyl benzene amine:
Table 6
| Embodiment | The adjacent alkyl benzene amine of halo | Obtain the amount (g) of halo o-alkyl biphenyl | Content (%) | Yield (%) |
| 34 | 3-chloro o-toluidine | 77.8 | 99.79 | 76.8 |
| 35 | 3-bromo o ethyl aniline | 97.4 | 99.64 | 74.6 |
| 36 | The adjacent propyl group aniline of 3-fluoro | 77.2 | 99.35 | 73.4 |
| 37 | The adjacent butylaniline of 3-iodo | 121.2 | 99.22 | 72.1 |
| 38 | Adjacent amyl aniline | 79.6 | 99.15 | 71.0 |
Embodiment 39
In the 1000ml four-hole boiling flask, drop into 3-chloro-2-methyl biphenyl (162.4g, 0.8mol), monobromethane (4g, 0.036mol), magnesium chips (25g, 1.04mol), tetrahydrofuran (THF) 600ml is heated to 50 ℃ of reactions 16 hours.In above-mentioned reaction solution, drop into DMF (65.8g, 0.9mol) again, 50 ℃ of lower reactions 1 hour.Be cooled to room temperature, drop into 15% hydrochloric acid and be hydrolyzed, go to separating funnel and divide the sub-cloud water layer, obtaining upper organic phase is 3-formyl radical-2-methyl diphenyl tetrahydrofuran solution.Be neutralized to neutrality with 10% sodium bicarbonate aqueous solution, add POTASSIUM BOROHYDRIDE (20g under the room temperature, 0.37mol), obtaining 3-methylol-2-methyl diphenyl through precipitation, filtration, drying (also is 2-methyl-3-phenyl phenyl aldehyde, 142.7g, 0.72mol), gas chromatographic purity is 99.5%, yield 90%.
Embodiment 40
In the 1000ml four-hole boiling flask, drop into 3-chloro-2-methyl biphenyl (162.4g, 0.8mol), monobromethane (4g, 0.036mol), magnesium chips (30g, 1.25mol), tetrahydrofuran (THF) 700ml is heated to 40 ℃ of reactions 20 hours.In above-mentioned reaction solution, drop into DMF (73.1g, 1mol) again, 40 ℃ of lower reactions 2 hours.Be cooled to room temperature, drop into 15% hydrochloric acid and be hydrolyzed, go to separating funnel and divide the sub-cloud water layer, obtaining upper organic phase is 3-formyl radical-2-methyl diphenyl tetrahydrofuran solution.Be neutralized to neutrality with 10% sodium bicarbonate aqueous solution, add POTASSIUM BOROHYDRIDE (15g under the room temperature, 0.28mol), obtaining 3-methylol-2-methyl diphenyl through precipitation, filtration, drying (also is the 2-methyl-3-phenyl benzil alcohol, 145.5g, 0.73mol), gas chromatographic purity is 99.5%, yield 92%.
All quote in this application as a reference at all documents that the present invention mentions, just as each piece document is quoted separately as a reference.Should be understood that in addition after having read foregoing of the present invention, those skilled in the art can make various changes or modifications the present invention, these equivalent form of values fall within the application's appended claims limited range equally.
Claims (10)
1. the preparation method of a hydroxymethyl substitutent o-alkyl biphenyl is characterized in that, comprises the steps:
(a) provide take the adjacent alkyl benzene amine of the halo shown in the formula (I) as raw material:
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is F, Cl, Br or I;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent alkyl benzene amine of the halo of the described formula (I) of step (a) and benzene carry out the diazonium coupling reaction, obtain the halo o-alkyl biphenyl compound suc as formula (II):
R in its Chinese style (II) and the implication of X are identical with formula (I);
(c) the halo o-alkyl biphenyl product of described formula (II) carries out grignard reaction and carbonyl addition, and the formyl radical that obtains formula (III) replaces o-alkyl biphenyl:
The implication of R in its Chinese style (III) is identical with formula (I);
(d) formyl radical of described formula (III) replacement o-alkyl biphenyl carries out the formyl radical reduction reaction in the presence of metallic reducing agent, obtains the hydroxymethyl substitutent o-alkyl biphenyl shown in the formula (IV):
The implication of R in its Chinese style (IV) is identical with formula (I).
2. the method for claim 1 is characterized in that,
The adjacent alkyl benzene amine of the halo of described formula (I) is the 3-chloro-2-methyl aniline;
The halo o-alkyl biphenyl compound of described formula (II) is 3-chloro-2-methyl biphenyl;
It is 2-methyl-3-phenyl phenyl aldehyde that the formyl radical of described formula (III) replaces o-alkyl biphenyl,
The hydroxymethyl substitutent o-alkyl biphenyl of described formula (IV) is the 2-methyl-3-phenyl benzil alcohol.
3. the method for claim 1, it is characterized in that, the metal catalyst in the step (b) is selected from fe and trivalent or bivalent compound, elemental copper and monovalence or bivalent compound, zinc salt, sal epsom, nickel compound, Palladous chloride, cobalt chloride, Cobaltous diacetate, Manganse Dioxide, Tai-Ace S 150, tin tetrachloride, zirconium tetrachloride, ammonium tungstate, ammonium molybdate or its combination.
4. method as claimed in claim 3 is characterized in that, described fe and trivalent thereof or bivalent compound are Z 250, iron(ic) chloride, ferric oxide, ferric sulfate, iron protoxide, iron protochloride or ferrous sulfate;
Described elemental copper and monovalence or bivalent compound are cupric chloride, cupric oxide, copper sulfate, Red copper oxide, cuprous chloride or cuprous sulfate;
Described zinc salt is zinc chloride, zinc sulfate or zinc acetate;
Described nickel compound is nickelous chloride, nickelous nitrate or single nickel salt.
5. the method for claim 1 is characterized in that, the acids promotor in the step (b) is carboxylic acid, sulfonic acid, phosphoric acid or derivatives thereof.
6. method as claimed in claim 5 is characterized in that, described carboxylic acid is selected from acetic acid, trichoroacetic acid(TCA), trifluoroacetic acid, propionic acid, oxalic acid, vinylformic acid or its combination;
Described sulfonic acid is selected from methylsulfonic acid, p-methyl benzenesulfonic acid;
Described carboxylic acid derivative is selected from triethyl orthoformate.
7. the method for claim 1 is characterized in that, the nitrous acid ester in the step (b) is the Fatty Alcohol(C12-C14 and C12-C18) nitrous acid ester.
8. method as claimed in claim 7 is characterized in that, described nitrous acid ester is nitrous acid isopropyl esters, nitrous acid n-butyl, nitrous acid isobutyl, nitrous acid tertiary butyl ester, nitrous acid n-pentyl ester, nitrous acid isopentyl ester or its combination.
9. the method for claim 1 is characterized in that, described step (b) meets the one or more of following reaction conditions:
(i) the diazonium coupling temperature of reaction is 20-80 ℃;
(ii) consumption of described metal catalyst is the 0.001-1.0 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo;
(iii) consumption of described acids promotor is the 0.001-1.2 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo;
(iv) consumption of described nitrous acid ester is the 1.0-3.0 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo;
(v) consumption of described benzene is the 1-150 mol ratio, calculates with the adjacent alkyl benzene amine 1mol amount of halo.
10. the preparation method of a formyl radical replacement o-alkyl biphenyl is characterized in that, comprises the steps:
(a) provide take the adjacent alkyl benzene amine of the halo shown in the formula (I) as raw material:
Wherein R is C
nH
2n+1, n=1,2,3,4 or 5;
X is F, Cl, Br or I;
(b) in the presence of metal catalyst, acids promotor and nitrous acid ester, the adjacent alkyl benzene amine of the halo of the described formula (I) of step (a) and benzene carry out the diazonium coupling reaction, obtain the halo o-alkyl biphenyl compound suc as formula (II):
R in its Chinese style (II) and the implication of X are identical with formula (I);
(c) the halo o-alkyl biphenyl product of described formula (II) carries out grignard reaction and carbonyl addition, and the formyl radical that obtains formula (III) replaces o-alkyl biphenyl:
The implication of R in its Chinese style (III) is identical with formula (I).
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| CN102964217B (en) * | 2012-11-30 | 2014-10-01 | 江苏优嘉化学有限公司 | Method for preparing 2-methyl-3-biphenylmethyanol through continuous Grignard and hydroxylation reactions |
| CN105085288B (en) * | 2014-04-18 | 2017-03-08 | 四川安东油气工程技术服务有限公司 | A kind of preparation method of organic polycarboxylic acid |
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| CN108658725B (en) * | 2017-03-30 | 2022-06-10 | 石家庄圣泰化工有限公司 | Synthetic method of 2-fluorobiphenyl |
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| GB2087886A (en) * | 1979-12-19 | 1982-06-03 | Upjohn Co | Preparing biphenyl compounds by coupling |
| CN1935761A (en) * | 2006-09-27 | 2007-03-28 | 荆和祥 | Method for preparing 2-methyl-3-phenyl benzil alcohol |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2087886A (en) * | 1979-12-19 | 1982-06-03 | Upjohn Co | Preparing biphenyl compounds by coupling |
| CN1935761A (en) * | 2006-09-27 | 2007-03-28 | 荆和祥 | Method for preparing 2-methyl-3-phenyl benzil alcohol |
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| 陈恒昌等.合成联苯衍生物的改良方法.《有机化学》.1989,第9卷(第1期),49-50. * |
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