CN105037306A - Synthetic method of alpha-naphtholphthalein - Google Patents

Synthetic method of alpha-naphtholphthalein Download PDF

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CN105037306A
CN105037306A CN 201510334139 CN201510334139A CN105037306A CN 105037306 A CN105037306 A CN 105037306A CN 201510334139 CN201510334139 CN 201510334139 CN 201510334139 A CN201510334139 A CN 201510334139A CN 105037306 A CN105037306 A CN 105037306A
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naphthol
naphtholphthalein
preferably
phthalein
crude
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CN 201510334139
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孙郁
张春涛
纪奉元
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天长市天佳化工科技有限公司
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/87Benzo [c] furans; Hydrogenated benzo [c] furans
    • C07D307/88Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3

Abstract

The invention provides a synthetic method of alpha-naphtholphthalein. The method comprises the following steps: (1) preparing a crude product of alpha-naphtholphthalein by using phthalic anhydride and 1-naphthol as raw materials, Lewis acid as a dehydration catalyst and polyphosphoric acid as a solvent; (2) purifying the crude product of alpha-naphtholphthalein, which is obtained in the step (1), thus obtaining pure alpha-naphtholphthalein. The synthetic method of alpha-naphtholphthalein has the characteristics of cheap and accessible raw materials, simple process, easiness in purification and the like, is suitable for large-scale industrial production and has the effect of solving the problem of high price in current small-scale reagent-grade production of alpha-naphtholphthalein in laboratories.

Description

一种甲萘酚酞的合成方法 A method of synthesis of naphthol phthalein

技术领域 FIELD

[0001] 本发明涉及甲萘酚酞的合成方法,属于医药中间体制备领域,属于酸碱指示剂以及新型环保墨水的制备领域。 [0001] The present invention relates to a method for the synthesis of naphthol phthalein, it belongs to the field of pharmaceutical intermediates prepared, and belongs to the field of preparation of new environmental pH indicator ink.

背景技术 Background technique

[0002] 酚酞类是一类非常重要的有机化合物,被广泛用于化学分析检测中,例如酸碱指示剂、着色剂、生物检测剂等。 [0002] phenolphthalein class is a very important class of organic compounds, are widely used in chemical analysis test, for example acid-base indicator, colorants, biological testing, and the like. 近年来,酚酞类化合物在环保墨水上有着重要的应用,尤其是甲萘酚酞,其溶液的pH值变色范围为7. 3-8. 7之间,在溶液pH值大于8. 7时,显深蓝色,而当该溶液吸收空气中的二氧化碳后,溶液pH值小于7. 3时,蓝色自动消失,溶液变为无色, 可以用来制作"会消失的墨水",是一种新型安全的环保染料。 In recent years, the phenolphthalein compound in the green ink has important applications, especially naphthol phthalein, a pH range of color solution is between 7. 3-8. 7, when the pH of the solution is greater than 8.7, significant when deep blue, and when the solution to absorb carbon dioxide in the air, the pH value is less than 7.3, the blue disappears, the solution became colorless, can be used to create "disappearing ink", a new security the green dye. 随着如今环保墨水的研究热潮,其应用前景将会有更大的潜力。 With the boom in green ink study now, the prospect will have a greater potential.

[0003] 甲萘酚酞,别名a-萘酚酞,化学名为3,3-(4_羟基-1-萘基)-l-(3H)异苯并呋喃酮。 [0003] A naphtholphthalein, phenolphthalein alias a- naphthyl, 3,3-chemical name (4_-hydroxy-1-naphthyl) -l- (3H) isobenzofuranone. 该化合物为白色到粉色的固体粉末,易溶于醇类,不溶于水。 This compound is a white to pink solid powder, soluble in alcohol, insoluble in water. 其结构如下如所示: As shown in the following structure:

[0004] [0004]

Figure CN105037306AD00031

[0005]现有文献报道中,该产品的最早于1871年由Grabowsky以邻苯二甲酰氯和1-萘酸为原料首次合成,随后EmilAlphonseWerner等人对该产品的合成进行了改进,经过改进后的工艺,原料易得,但是其操作无法工业化生产,收率低,纯化复杂。 [0005] In the prior literature, the product was first made in 1871 to Grabowsky phthaloyl chloride and 1-naphthoic acid was synthesized for the first time, then the EmilAlphonseWerner et synthetic products was improved, improvement after process, readily available raw materials, but the operation can not be industrialized production, low yield, complicated purification. 在接下来的80年间,该产品的合成研究几乎无任何进展。 Over the next 80 years, synthesis of the product almost no progress. 国内近年来只有中国乐凯集团对该产品的合成有进一步的研究,合成方法如下: Only in recent years, the domestic Chinese Lucky Group of the synthetic products of further research, synthesis is as follows:

[0006] [0006]

Figure CN105037306AD00032

[0007]取邻苯二甲酸酐、a_萘酚粉碎成粉末充分混合,加入甲磺酸,外温15°C保温71h, 升温至40°C,恒温9. 5h,反应结束。 [0007] phthalic anhydride, naphthol A_ pulverized into powder thorough mixing, methanesulfonic acid, external temperature of 15 ° C incubated 71h, warmed to 40 ° C, the thermostat 9. 5h, the reaction was completed. 反应后处理用到大量乙醇,采用碱溶酸析的方法进行纯化。 After the large amount of ethanol used in the reaction process, alkali-soluble acid precipitation method was purified. 该制备方法仍存在如下缺点:1)反应体系非常粘稠,工业化生产时对搅拌要求较高;2) 大量乙醇用于提纯,造成成本的大大增加;3)纯化工艺复杂,操作繁琐。 The preparation method still has the following disadvantages: 1) very viscous reaction system, when the industrial production of high stirred requirements; 2) for the purification of large amounts of ethanol, resulting in significantly increased costs; 3) purification process complicated, cumbersome operation.

发明内容 SUMMARY

[0008] 针对现有技术的不足,本发明提供一种甲萘酚酞的合成方法。 [0008] for the deficiencies of the prior art, the present invention provides a method for the synthesis of naphthol phthalein. 所述甲萘酚酞的合成方法具有原料廉价易得,工艺简单,易纯化等特点,适合大规模工业化生产,解决当前甲萘酚酞的实验室小规模试剂级生产,价格昂贵等问题。 A method of synthesizing the naphthol phthalein having cheap raw materials and simple process, easy purification, etc., suitable for large-scale industrial production, this solution naphthol phthalein laboratory reagent grade small-scale production, and expensive problems.

[0009] 本发明是通过如下技术方案实现的: [0009] The present invention is achieved by the following technical solutions:

[0010] 一种甲萘酚酞的合成方法,所述方法包括如下步骤: Synthesis Method [0010] A naphthol phthalein, said method comprising the steps of:

[0011] (1)以邻苯二甲酸酐和1-萘酚为原料,路易斯酸作为脱水催化剂,多聚磷酸为溶媒,制备得到甲萘酚酞粗品; [0011] (1) phthalic anhydride and 1-naphthol as the starting material, Lewis acid as the dehydrating catalyst, polyphosphoric acid as a solvent, was prepared to give the crude naphthol phthalein;

[0012] (2)将步骤(1)得到的甲萘酚酞粗品提纯后得到甲萘酚酞纯品。 [0012] (2) Step (1) A naphtholphthalein obtained crude product was purified to give the pure naphthol phthalein.

[0013] 邻苯二甲酸酐、1-萘酚作为原料,简单易得,无需任何预处理。 [0013] phthalic anhydride, 1-naphthol as starting materials, simple and easy to obtain, without any pretreatment.

[0014] 多聚磷酸是一种常见的中强酸,在合成甲萘酚酞的过程中,酸性过强或温度过高, 都非常容易造成产品的二次脱水,从而生成醚类的杂质。 [0014] polyphosphoric acid is a common strong acid, in the synthesis of naphthol phthalein, the temperature is too high or too strong acidity, it is very likely to cause a secondary dehydration products, thereby generating impurities ethers. 因此不易选择过强的酸,且整个温度不宜过高。 It is not easy to select too strong acids, and the whole is not too high temperature.

[0015] 优选地,步骤(1)中,邻苯二甲酸酐、1-萘酚和多聚磷酸的摩尔比为1:1.8~ 2:3 ~6,例如为1:1. 9:3、1:1. 9:4、1:1. 9:5、1:1. 9:6、1:1. 8:4、1:2:4、1:2:5,优选为1:1. 8:5〇 [0015] Preferably, the step (1), phthalic anhydride, 1-naphthol and polyphosphoric acid molar ratio of 1: 1.8 to 2: 3 to 6, for example 1: 19: 3, 1: 19: 4,1: 19: 5,1: 19: 6,1: 18: 4,1: 2: 4,1: 2: 5, preferably 1: 1. 8: 5〇

[0016] 优选地,步骤(1)中,路易斯酸为无水氯化锌、无水氯化铁、无水氯化锡或者无水氯化铝中的一种或者多种,优选为无水氯化锌; [0016] Preferably, the step (1), the Lewis acid is anhydrous zinc chloride, anhydrous iron chloride, anhydrous tin chloride, anhydrous aluminum chloride, or of one or more, preferably anhydrous zinc chloride;

[0017] 优选地,路易斯酸与邻苯二甲酸酐的摩尔比为0.01~0.05:1,例如为0.02:1、 0• 03:1、0. 04:1,优选为0.02:1。 [0017] Preferably, the molar ratio of Lewis acid to phthalic anhydride is 0.01 to 0.05: 1, for example, 0.02: 1, 0 • 03:. 1,0 04: 1, preferably 0.02: 1.

[0018] 本发明所述的甲萘酚酞的合成方法的化学反应方程式为: [0018] The method of synthesis of chemical reaction equation naphthol phthalein of the present invention are:

[0019] [0019]

Figure CN105037306AD00041

[0020] 优选地,步骤(1)中具体操作为:按摩尔份将1份邻苯二甲酸酐,1. 8~2份1-萘酚和3~6份多聚磷酸加入反应容器中,搅拌过程中再加入0. 01~0. 05份路易斯酸,缓慢升温至40~55°C,保温5~7小时,保温过程中不停搅拌,然后淬灭分离得到甲萘酚酞粗品。 [0020] Preferably, the step (1) in the specific operation as follows: 1 part by mole parts of phthalic anhydride, 18 parts of 1-naphthol to 2 and 3 to 6 parts of polyphosphoric acid added to the reaction vessel, was added during stirring 0.01 ~ 0.05 parts of a Lewis acid, was slowly warmed to 40 ~ 55 ° C, and incubated for 5 to 7 hours, stirring constantly during incubation, then quenched isolated crude naphthol phthalein.

[0021] 优选地,步骤(1)中,步骤(1)中,淬灭分离的具体操作为:当1-萘酚的含量降至5wt%以下时,停止反应,将反应液加入10-15°C的去离子水中,搅拌至不再析出沉淀,过滤, 将滤饼水洗至中性,然后干燥得到甲萘酚酞粗品;优选地,干燥温度为50-60°C;优选地,在将反应液加入10-15°C的去离子水的过程中,保持水温< 15°C。 [0021] Preferably, step (a), step (1), the quenching isolated specific operation is: when the content of 1-naphthol reduced to 5wt% or less, the reaction was stopped, the reaction solution was added 10-15 ° C. of deionized water, stirring until no more precipitate formed was filtered, the filter cake washed with water until neutral, and then dried to give crude methanesulfonic naphtholphthalein; preferably, the drying temperature is 50-60 ° C; preferably in the reaction 10-15 ° C was added to the deionized water in the process, maintaining the temperature <15 ° C.

[0022] 其中,以1-萘酚为基准,甲萘酚酞粗品的收率为60~65%。 [0022] wherein, with reference to 1-naphthol, naphthol phthalein crude yield was 60 to 65%.

[0023] 优选地,去离子水与多聚磷酸的质量比为4~8:1,例如为5:1、6:1、7:1,优选为5:1〇 [0023] Preferably, deionized water and polyphosphoric acid mass ratio of 4 to 8: 1, for example, 5: 1,6: 1,7: 1, preferably 5: 1〇

[0024] 优选地,步骤(2)具体操作为:向步骤(1)得到的甲萘酚酞粗品中加入溶剂,加热至溶剂回流温度进行回流,趁热过滤,将滤饼干燥得到甲萘酚酞纯品;优选地,回流时间为30-180分钟;优选地,滤饼干燥温度为50-60°C。 [0024] Preferably, step (2) specifically operative to: obtained in step (1) A naphtholphthalein crude product was added The solvent was heated to reflux temperature of solvent reflux, filtered while hot, the filter cake was dried to give methanesulfonic naphtholphthalein pure product; preferably, reflux time is 30-180 minutes; preferably, cake drying temperature is 50-60 ° C.

[0025] 其中,甲萘酚酞纯品的纯度可达到98%以上,纯化收率为75~82%。 [0025] wherein A naphtholphthalein purity may be pure over 98% purified yield was 75 to 82%.

[0026] 优选地,溶剂为二氯乙烷或甲苯,优选为二氯乙烷。 [0026] Preferably, the solvent is toluene or dichloroethane, preferably dichloroethane.

[0027] 优选地,溶剂和甲萘酚酞粗品的质量比为3~10:1,例如为4:1、5:1、6 :1、7:1、 8:1、9:1,优选为5:1。 [0027] Preferably the mass ratio of the solvent and naphthol phthalein crude 3 to 10: 1, for example, 4: 1,5: 1,6: 1,7: 1, 8: 1,9: 1, preferably 5: 1.

[0028] 优选地,所述甲萘酚酞的合成方法包括如下步骤: [0028] Preferably, the method of synthesizing the naphthol phthalein comprising the steps of:

[0029] (1)按摩尔份将1份邻苯二甲酸酐,1. 8份1-萘酚和5份多聚磷酸加入反应容器中,搅拌过程中再加入0. 02份无水氯化锌,升温至40~45°C,保温6小时,保温过程中不停搅拌,取样用液相色谱跟踪,当1-萘酚的含量降至5wt%以下时,将反应液缓慢加入10-12°C的去离子水中,保持水温< 15°C,搅拌至不再析出沉淀,过滤,将滤饼水洗至中性, 60°C条件下干燥,得到甲萘酚酞粗品,其中,去离子水与磷酸的质量比为5:1 ; [0029] (1) The parts of 1 molar parts of phthalic anhydride, 1.8 parts of 1-naphthol and 5 parts of polyphosphoric acid added to the reaction vessel, the mixing process was added 0.02 parts of anhydrous chloride zinc, warmed to 40 ~ 45 ° C, incubated for 6 hours with constant stirring during incubation, samples by liquid chromatography track, when the content of 1-naphthol reduced to 5wt% or less, the reaction solution was slowly added 10-12 ° C. of deionized water, maintaining the temperature <15 ° C, stirring until no more precipitate formed was filtered, the filter cake washed with water until neutral, dried 60 ° C under conditions to give the crude naphthol phthalein, wherein the deionized water phosphoric acid mass ratio of 5: 1;

[0030] (2)向步骤⑴得到的甲萘酚酞粗品加入二氯甲烧,加热至溶剂回流温度,回流60 分钟,趁热过滤,收集滤饼,60°C条件下干燥,得到甲萘酚酞纯品,其中二氯甲烷和甲萘酚酞粗品的质量比为5:1。 [0030] (2) the step ⑴ obtained naphthol phthalein crude was added methylene chloride burned, heated to the solvent reflux temperature for 60 minutes and filtered hot to collect the filter cake was dried 60 ° C under conditions to give the naphthol phthalein pure, wherein the mass of methylene chloride and the crude naphthol phthalein ratio of 5: 1.

[0031] 与现有技术相比,本发明具有如下有益效果: [0031] Compared with the prior art, the present invention has the following advantages:

[0032] 本发明以邻苯二甲酸酐、1-萘酚、多聚磷酸为原料,在无水氯化锌的催化作用下生产甲萘酚酞粗品,并用二氯乙烷作为纯化溶剂,制得甲萘酚酞精品。 [0032] In the present invention, phthalic anhydride, 1-naphthol, polyphosphoric acid as raw materials in the production of anhydrous zinc chloride catalysis crude naphthol phthalein, and purified using dichloroethane as a solvent, to prepare A fine naphtholphthalein. 所述反应路线原料易得,成本低,收率高,工艺过程简单,简化了纯化工艺,缩短生产周期,利于工业化生产。 The Scheme raw materials, low cost, high yield, simple process, simplified purification process, shorten the production cycle, industrially advantageous.

具体实施方式 detailed description

[0033] 为便于理解本发明,本发明列举实施例如下。 [0033] To facilitate understanding of the present invention, the embodiment of the present invention is exemplified as follows. 本领域技术人员应该明了,所述实施例仅仅是帮助理解本发明,不应视为对本发明的具体限制。 It should be apparent to those skilled in the art, the embodiments are merely to aid understanding of the present invention, not to be considered particularly limiting the present invention.

[0034] 实施例1 [0034] Example 1

[0035] 以邻苯二甲酸酐和1-萘酚为原料在多聚磷酸/无水氯化锌的作用下制备甲萘酚酞,其化学反应方程式如下: [0035] In anhydride and 1-naphthol-carboxylic naphtholphthalein in polyphosphoric acid / anhydrous zinc chloride acts as a starting material, the following chemical reaction equation:

[0036] [0036]

Figure CN105037306AD00051

[0037] 称取化合物邻苯二甲酸酐148g,1-萘酚259. 5g和多聚磷酸1014g加入到反应容器中,搅拌过程中再加入无水氯化锌1. 5g,缓慢升温至40°C,并保持在此温度下恒温搅拌6小时,反应颜色慢慢发生变化,变成墨绿色;在搅拌过程中,取样用液相色谱跟踪,当反应混合物中的1-萘酚的含量低于5wt%时,将反应液缓慢倾倒入预先冷却至10°C的5000g 的去离子水中,倾倒过程中始终保持水温不超过15°C,同时不断搅拌,析出大量棕红色固体沉淀,搅拌至不再析出沉淀时,进行过滤,将滤饼水洗至中性,在60°C条件下干燥4h,得259. 5g甲萘酚酞粗品,收率为62. 1%,液相色谱测定纯度为85. 6% ; [0037] The phthalic anhydride compound weighed 148g, 1- naphthol 259. 5g 1014g and polyphosphoric acid added to the reaction vessel, during stirring anhydrous zinc chloride was added 1. 5g, slowly warmed to 40 ° C, and held at this temperature for 6 hours with stirring, the reaction color slowly changing, becomes dark green; during stirring, HPLC trace for sampling, when the content of 1-naphthol in the reaction mixture is less than when 5wt%, the reaction solution was slowly poured into pre-cooled to 5000g of deionized water of 10 ° C, kept during pouring temperature does not exceed 15 ° C, while constantly stirring, to precipitate a large number of red-brown solid precipitate was stirred until no when a precipitate was filtered, the filter cake washed with water to neutral, at 60 ° C under drying conditions 4h, to give 259. 5g crude naphthol phthalein, yield 62.1%, purity HPLC assay 85.6 %;

[0038]将259g甲萘酚酞粗品加入反应容器中,向里加入二氯乙烷1813g,加热至84°C,恒温回流60min,趁热过滤,收集滤饼,将滤饼在60°C条件下干燥4h,得到208g淡粉色甲萘酚酞固体粉末,收率为80. 3%,液相色谱测定纯度为98. 3%。 [0038] A 259g A naphtholphthalein crude added to the reaction vessel, was added to dichloroethane 1813g, was heated to 84 ° C, the thermostat was refluxed for 60min, filtered hot and the filter cake was collected, the filter cake under the conditions at 60 ° C dried 4h, to give 208g pale pink solid powder naphthol phthalein, yield 80.3%, LC purity of 98.3% was measured.

[0039] 实施例2 [0039] Example 2

[0040]以邻苯二甲酸酐和1-萘酚为原料在多聚磷酸/无水氯化锌的作用下制备甲萘酚酞,其化学反应方程式如下: [0040] In anhydride and 1-naphthol-carboxylic naphtholphthalein in polyphosphoric acid / anhydrous zinc chloride acts as a starting material, the following chemical reaction equation:

[0041] [0041]

Figure CN105037306AD00061

[0042] 称取化合物邻苯二甲酸酐148g,1-萘酚259. 5g和多聚磷酸1014g加入到反应容器中,搅拌过程中再加入无水氯化铝2. 7g,缓慢升温至55°C,并保持在此温度下恒温搅拌6 小时,反应颜色慢慢发生变化,变成墨绿色;在搅拌过程中,取样用液相色谱跟踪,当反应混合物中的1-萘酚的含量低于5%时,将反应液缓慢倾倒入预先冷却至10°C的6000g的去离子水中,倾倒过程中始终保持水温不超过15°C,同时不断搅拌,析出大量棕红色固体沉淀, 搅拌至不再析出沉淀时,进行过滤,将滤饼水洗至中性,在60°C条件下干燥4h,得252. 8g甲萘酚酞粗品,收率为60. 5%,液相色谱测定纯度为81. 6% ; [0042] The phthalic anhydride compound weighed 148g, 1- naphthol 259. 5g 1014g and polyphosphoric acid added to the reaction vessel, the mixing process was added anhydrous aluminum chloride 2. 7g, slowly warmed to 55 ° C, and held at this temperature for 6 hours with stirring, the reaction color slowly changing, becomes dark green; during stirring, HPLC trace for sampling, when the content of 1-naphthol in the reaction mixture is less than 5%, the reaction solution was slowly poured into deionized water previously cooled to 10 ° C of 6000g, the process remains pouring temperature does not exceed 15 ° C, while constantly stirring, to precipitate a large number of red-brown solid precipitate was stirred until no when a precipitate was filtered, the filter cake washed with water to neutral, at 60 ° C under drying conditions 4h, to give 252. 8g naphthol phthalein crude yield 60.5%, purity HPLC assay 81.6 %;

[0043] 将252. 8g甲萘酚酞粗品加入反应容器中,向里加入二氯乙烷1813g,加热至84°C, 恒温回流lOOmin,趁热过滤,收集滤饼,将滤饼在50°C条件下干燥5h,得到194g淡粉色甲萘酚酞固体粉末,收率为76. 8%,液相色谱测定纯度为98. 3%。 [0043] The phenolphthalein 252. 8g crude methylnaphthalene added to the reaction vessel, was added to dichloroethane 1813g, was heated to 84 ° C, reflux temperature lOOmin, filtered while hot, the filter cake was collected, 50 ° C and the filter cake dried under 5h, to obtain 194g pale pink solid powder naphthol phthalein, yield 76.8%, LC purity of 98.3% was measured.

[0044] 实施例3 [0044] Example 3

[0045] 一种甲萘酚酞的合成方法,其化学方程式与实施例1形同,具体包括如下步骤: [0045] A synthesis method of naphthol phthalein, chemical equation just like Example 1, includes the following steps:

[0046] 称取化合物邻苯二甲酸酐148g,1-萘酚288g和多聚磷酸2028g加入到反应容器中,搅拌过程中再加入无水氯化锌2. 7g,缓慢升温至50°C,并保持在此温度下恒温搅拌6小时,反应颜色慢慢发生变化,变成墨绿色;在搅拌过程中,取样用液相色谱跟踪,当反应混合物中的1-萘酸的含量低于5%时,停止反应,将反应液缓慢倾倒入预先冷却至10°C的8000g 的去离子水中,倾倒过程中始终保持水温不超过15°C,同时不断搅拌,析出大量棕红色固体沉淀,搅拌至不再析出沉淀时,进行过滤,滤饼水洗至中性,收集滤饼,将滤饼在60°C条件下干燥4h,得292g甲萘酚酞粗品,收率为65%,液相色谱测定纯度为83. 2% ; [0046] The phthalic anhydride compound weighed 148g, 1- naphthol 288g and 2028g polyphosphoric acid was added to the reaction vessel, during stirring anhydrous zinc chloride was added 2. 7g, was slowly warmed to 50 ° C, temperature and kept stirring for 6 hours at this temperature, the reaction color gradually changed into dark green; during stirring, HPLC trace for sampling, when the naphthoic acid in the reaction mixture is less than 5% of 1- , the reaction was stopped, the reaction mixture was slowly poured into previously cooled to deionized water 10 ° C of 8000g, the pouring process always keep the water temperature does not exceed 15 ° C, while constantly stirring, to precipitate a large number of red-brown solid precipitate, and stirred until no again when a precipitate was filtered, the filter cake was washed with water to neutral, to collect the filter cake, the filter cake was dried 60 ° C for 4h, to give 292g crude naphthol phthalein, 65% yield, HPLC purity measured 83.2%;

[0047] 将292g甲萘酚酞粗品加入反应容器中,向里加入二氯乙烷1813g,加热至84°C,恒温回流lOOmin,趁热过滤,收集滤饼,将滤饼在50°C下干燥5h,得到235g淡粉色甲萘酚酞固体粉末,收率为81 %,液相色谱测定纯度为98. 5%。 [0047] A 292g A naphtholphthalein crude added to the reaction vessel, was added to dichloroethane 1813g, was heated to 84 ° C, reflux temperature lOOmin, filtered while hot, the filter cake was collected, the filter cake was dried at 50 ° C for 5h, to obtain 235g pale pink solid powder naphthol phthalein, 81% yield, HPLC purity 98.5% was measured.

[0048] 实施例4 [0048] Example 4

[0049] -种甲萘酚酞的合成方法,其化学方程式与实施例1形同,具体包括如下步骤: [0049] - A method for synthesizing species naphthol phthalein, chemical equation just like Example 1, includes the following steps:

[0050] 称取化合物邻苯二甲酸酐148g,1-萘酚288g和多聚磷酸1500g加入到反应容器中,搅拌下再向里加入无水氯化锌6. 8g,缓慢升温至45°C,并保持在此温度下恒温搅拌6小时,反应颜色慢慢发生变化,变成墨绿色;在搅拌过程中,不断取样用液相色谱跟踪,当反应混合物中的1-萘酸的含量低于5%时,停止反应,将反应液缓慢倾倒入预先冷却至15°C的8000g的去离子水中,倾倒过程中始终保持水温不超过15°C,同时不断搅拌,析出大量棕红色固体沉淀,搅拌至不再析出沉淀时,进行过滤,滤饼水洗至中性,收集滤饼,将滤饼在55°C 条件下干燥6h,得283g甲萘酚酞粗品,收率为63%,液相色谱测定纯度为80. 2%; [0050] The phthalic anhydride compound weighed 148g, 1- naphthol 288g and 1500g polyphosphoric acid was added to the reaction vessel, again with stirring anhydrous zinc chloride was added 6. 8g, slowly warmed to 45 ° C and stirred at this temperature maintained temperature for 6 hours, the reaction color slowly changing, becomes dark green; during stirring continuously sampled by HPLC trace, when the content of the reaction mixture is less than 1-naphthoic acid 5%, the reaction was stopped, the reaction mixture was slowly poured into previously cooled to deionized water 15 ° C of 8000g, the pouring process always keep the water temperature does not exceed 15 ° C, while constantly stirring, to precipitate a large number of red-brown solid was precipitated, stirring when no precipitate formed to, liquid chromatography was filtered, the filter cake was washed with water to neutral, to collect the filter cake, the filter cake was dried 55 ° C for 6h, to give 283g crude naphthol phthalein, 63% yield, purity 80.2%;

[0051] 将283g甲萘酚酞粗品加入反应容器中,向里加入甲苯2264g,加热至110°C,恒温回流30min,趁热过滤,收集滤饼,将滤饼在50°C下干燥4h,得到220g淡粉色甲萘酚酞固体粉末,收率为77. 7%,液相色谱测定纯度为98. 1 %。 [0051] A 283g A naphtholphthalein crude into a reaction vessel, 2264g of toluene was added to the inside and heated to 110 ° C, temperature at reflux for 30min, filtered hot and the filter cake was collected, the filter cake was dried at 50 ° C 4h, to give A pale pink 220g naphtholphthalein solid powder, yield 77.7%, LC purity of 98.1% was measured.

[0052] 申请人声明,本发明通过上述实施例来说明本发明的详细工艺设备和工艺流程, 但本发明并不局限于上述详细工艺设备和工艺流程,即不意味着本发明必须依赖上述详细工艺设备和工艺流程才能实施。 [0052] Statement Applicant, the process of the present invention will be described in detail the process and apparatus of the present invention by the above-described embodiment, but the present invention is not limited to the above detailed process equipment and processes, i.e., it does not mean that the present invention is to rely on detailed above process equipment and processes to be implemented. 所属技术领域的技术人员应该明了,对本发明的任何改进, 对本发明产品各原料的等效替换及辅助成分的添加、具体方式的选择等,均落在本发明的保护范围和公开范围之内。 Those skilled in the art should be appreciated, any improvement in the present invention, an equivalent of the present invention product of each material substitutions and adding auxiliary ingredients, selection of specific ways, are within the scope and scope of the disclosure of the present invention.

Claims (10)

  1. 1. 一种甲萘酚酞的合成方法,其特征在于,所述方法包括如下步骤: (1) 以邻苯二甲酸酐和1-萘酚为原料,路易斯酸作为脱水催化剂,多聚磷酸为溶媒,制备得到甲萘酚酞粗品; (2) 将步骤(1)得到的甲萘酚酞粗品提纯后得到甲萘酚酞纯品。 A method for the synthesis of naphthol phthalein, characterized in that, said method comprising the steps of: (1) phthalic anhydride and 1-naphthol as the starting material, Lewis acid as the dehydrating catalyst, polyphosphoric acid as a solvent , prepared crude naphthol phthalein; (1) obtained in (2) step a to give crude methanesulfonic naphtholphthalein naphtholphthalein pure product after purification.
  2. 2. 根据权利要求1所述甲萘酚酞的合成方法,其特征在于,步骤(1)中,邻苯二甲酸酐、 1-萘酸和多聚磷酸的摩尔比为1:1. 8~2:3~6,优选为1:1. 8:5。 The synthesis method of claim 1 naphthol phthalein claim, wherein the step (1), the molar ratio of phthalic anhydride, 1-naphthoic acid, and polyphosphoric acid is 1: 18 to 2 : 3-6, preferably 1: 18: 5.
  3. 3. 根据权利要求1或2所述甲萘酚酞的合成方法,其特征在于,步骤⑴中,路易斯酸为无水氯化锌、无水氯化铁、无水氯化锡或者无水氯化铝中的一种或者多种,优选为无水氯化锌;优选地,路易斯酸与邻苯二甲酸酐的摩尔比为〇. Ol~〇. 05:1,优选为0. 02:1。 The synthetic method 1 or claim 2 naphthol phthalein claim, wherein the step ⑴, the Lewis acid is anhydrous zinc chloride, anhydrous iron chloride, anhydrous tin chloride or chloride anhydrous one kind or more of aluminum, preferably anhydrous zinc chloride; preferably, the molar ratio of Lewis acid to phthalic anhydride is square square Ol ~ 05: 1, preferably 0.02: 1.
  4. 4. 根据权利要求1-3任一项所述甲萘酚酞的合成方法,其特征在于,步骤(1)中具体操作为:按摩尔份将1份邻苯二甲酸酐,1. 8~2份1-萘酚和3~6份多聚磷酸加入反应容器中,搅拌过程中再加入0. 01~0. 05份路易斯酸,升温至40~55°C,保温5~7小时,保温过程中不停搅拌,然后淬灭分离得到甲萘酚酞粗品。 4. The method of synthesizing a naphthol phthalein according to any of claims 1 to 3, wherein the step (1) in the specific operation as follows: 1 part by mole parts of phthalic anhydride, 18 ~ 2 parts of 1-naphthol and 3 to 6 parts of polyphosphoric acid added to the reaction vessel, the mixing process was added 0.01 ~ 0.05 parts of a Lewis acid, warmed to 40 ~ 55 ° C, and incubated for 5 to 7 hours, during incubation in stirring constantly, then quenched isolated crude naphthol phthalein.
  5. 5. 如权利要求4所述甲萘酚酞的合成方法,其特征在于,步骤(1)中,淬灭分离的具体操作为:当1-萘酚的含量降至5wt %以下时,将反应液加入10-15°C的去离子水中,搅拌至不再析出沉淀,过滤,将滤饼水洗至中性,然后干燥得到甲萘酚酞粗品;优选地,干燥温度为50-60°C ;优选地,在将反应液加入10_15°C的去离子水的过程中,保持水温< 15°C。 5. The method of synthesizing 4 A naphtholphthalein claim, wherein the step (1), the quenching isolated specific operation is: when the content of 1-naphthol reduced to 5wt% or less, the reaction solution was 10-15 ° C was added deionized water, stirring until no more precipitate formed was filtered, the filter cake washed with water until neutral, and then dried to give crude methanesulfonic naphtholphthalein; preferably, the drying temperature is 50-60 ° C; preferably , the reaction solution was added during 10_15 ° C deionized water, keeping the temperature <15 ° C.
  6. 6. 根据权利要求5所述的甲萘酚酞的合成方法,其特征在于,去离子水与多聚磷酸的质量比为4~8:1,优选为5:1。 The synthesis of naphthol phthalein as claimed in claim 5, wherein the deionized water and polyphosphoric acid mass ratio of 4 to 8: 1, preferably 5: 1.
  7. 7. 根据权利要求1-6任一项所述甲萘酚酞的合成方法,其特征在于,步骤(2)具体操作为:向步骤(1)得到的甲萘酚酞粗品中加入溶剂,加热至溶剂回流温度进行回流,趁热过滤,将滤饼干燥得到甲萘酚酞纯品;优选地,回流时间为30-180分钟;优选地,滤饼干燥温度为50-60 °C。 7. The method of synthesizing a naphthol phthalein according to any of claims 1-6, wherein the step (2) of specific operation: step (1) A crude product obtained naphtholphthalein added solvent, heating the solvent the reflux temperature to reflux, filtered hot and the filter cake was dried to give pure naphthol phthalein; preferably, reflux time is 30-180 minutes; preferably, cake drying temperature is 50-60 ° C.
  8. 8. 根据权利要求7所述甲萘酚酞的合成方法,其特征在于,溶剂为二氯乙烷或甲苯,优选为二氯乙烷。 8. A method for synthesizing the 7 naphtholphthalein claim, wherein the solvent is toluene or dichloroethane, preferably dichloroethane.
  9. 9. 根据权利要求7或者8所述的甲萘酚酞的合成方法,其特征在于,溶剂和甲萘酚酞粗品的质量比为3~10:1,优选为5:1。 9. A method of synthesis of naphtholphthalein 7 or claim 8, wherein the mass ratio of the solvent A and the crude naphthol phthalein 3 to 10: 1, preferably 5: 1.
  10. 10. 根据权利要求1-9任一项所述甲萘酚酞的合成方法,其特征在于,包括如下步骤: (1) 按摩尔份将1份邻苯二甲酸酐,1. 8份1-萘酚和5份多聚磷酸加入反应容器中,搅拌过程中再加入0. 02份无水氯化锌,升温至40~45°C,保温6小时,保温过程中不停搅拌, 取样用液相色谱跟踪,当1-萘酚的含量降至5wt %以下时,将反应液缓慢加入10-12°C的去离子水中,保持水温< 15°C,搅拌至不再析出沉淀,过滤,将滤饼水洗至中性,60°C条件下干燥,得到甲萘酚酞粗品,其中,去离子水与磷酸的质量比为5:1 ; (2) 向步骤(1)得到的甲萘酚酞粗品加入二氯甲烷,加热至溶剂回流温度,回流60分钟,趁热过滤,收集滤饼,60°C条件下干燥,得到甲萘酚酞纯品,其中二氯甲烷和甲萘酚酞粗品的质量比为5:1。 10. The method of synthesizing a naphthol phthalein according to any one of claims 1-9, characterized by comprising the steps of: (1) parts to 1 parts by mole of phthalic anhydride, 18 parts of 1-naphthyl phenol and 5 parts of polyphosphoric acid added to the reaction vessel, the mixing process was added 0.02 parts of anhydrous zinc chloride, warmed to 40 ~ 45 ° C, incubated for 6 hours with constant stirring during incubation, samples by liquid chromatography track, when the content of 1-naphthol reduced to 5wt% or less, the reaction solution was slowly added to deionized water to 10-12 ° C, keeping the temperature <15 ° C, stirring until no more precipitate formed was filtered, and the filtrate cake was washed with water until neutral, 60 ° C was dried to afford naphthol phthalein crude, wherein deionized mass ratio of water to phosphoric acid is from 5: 1; (1) obtained in (2) of step a naphtholphthalein crude Diethyl chloride, the solvent was heated to reflux temperature for 60 minutes and filtered while hot, the filter cake was collected, dried under conditions of 60 ° C to give pure naphthol phthalein, wherein the mass ratio of methylene chloride and naphthol phthalein crude 5: 1.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060222601A1 (en) * 2005-03-29 2006-10-05 Sabnis Ram W Oral care compositions with color changing indicator
US20060257439A1 (en) * 2005-03-29 2006-11-16 Sabnis Ram W Cleansing compositions with color changing indicator
CN103193740A (en) * 2012-10-19 2013-07-10 中国乐凯集团有限公司 Preparation method of alpha-naphtholphthalein

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060222601A1 (en) * 2005-03-29 2006-10-05 Sabnis Ram W Oral care compositions with color changing indicator
WO2006105260A1 (en) * 2005-03-29 2006-10-05 C2C Technologies Llc Oral care compositions with color changing indicator
US20060257439A1 (en) * 2005-03-29 2006-11-16 Sabnis Ram W Cleansing compositions with color changing indicator
CN103193740A (en) * 2012-10-19 2013-07-10 中国乐凯集团有限公司 Preparation method of alpha-naphtholphthalein

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