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    • 专利摘要:
    Synthesis process of 9,10-bis (chloromethyl) anthracene, which comprises mixing the anthracene and 1,3,5-trioxane reagents, a phase transfer catalyst selected from the group consisting of quaternary ammonium salt and crown ether with hydrochloric acid and acetic acid. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2686136A1
    申请号:ES201730460
    申请日:2017-03-29
    公开日:2018-10-16
    发明作者:Francisco José ORTEGA HIGUERUELO；Fernando LANGA DE LA PUENTE
    申请人:Universidad de Castilla La Mancha；
    IPC主号:
    专利说明:

    SYNTHESIS PROCEDURE OF 9.10-BISICLOROMETILIANTRACENO
    5
    FIELD OF THE INVENTION
    the 15 The present invention relates to a synthesis method of 9,10bis (chloromethyl) anthracene. In the process, anthracene, 1,3,5-trioxane, the hexadecyltrimethylammonium bromide catalyst, hydrochloric acid and acetic acid are mixed. 9, 10bis (chloromethyl) anthracene is a compound used in specific recognition, molecular electronic machines, drug carriers and catalysts in organic synthesis, fluorescence optics, photodynamic therapy and optical data storage, microfabrication, precursor in the preparation of derivatives Bi-substituted meso of the anthracene.
    BACKGROUND OF THE INVENTION
    Compound 9.1 O-bis (chloromethyl) anthracene
    It is a compound of high interest as an intermediate in chemical synthesis processes where it is necessary to include a double substituted anthracene skeleton in a meso or benzyl position (CH2 adjacent to the aromatic ring).
    The document J. Am. Chem. Soco 1955, 77, 2845-2848 describes a process of anthracene chloromethylation as a versatile intermediate towards obtaining other derivatives by means of displacement reactions, that is, from 9,10-bis (chloromethyl ) Anthracene towards a wide range of functionalization on demand. In summary, the synthetic procedure described in this document consists in passing a stream of hydrogen chloride
    30 fresh, generated in situ and continuously, to a mixture of 1,4-dioxane, anthracene, pformaldehyde and smoking hydrochloric acid. The reaction crude is heated to reflux while maintaining the hydrogen chloride stream for several hours to, after
    interruption, continue with the system at reflux for 24 more hours. After abundant filtration and washing to remove impurities, the compound is finally obtained in solid form with a fairly moderate yield of 67%. As you can see, it is a very laborious experiment with a much better performance.
    Other synthetic procedures have been described in the state of the art, such as that described in RSC Adv. 2015, 5, 73951-73957, where the synthesis is carried out in the presence of an organic solvent (dioxane) and at high temperatures (100 OC).
    However, the inventors of the present application have encountered serious reproducibility problems in this procedure. When the inventors have reproduced the procedure, they have found that 9,10-bis (chloromethyl) anthracene is not obtained, as the scientific article states, despite having repeated this reaction several times, proving fruitless in all cases. Therefore, this route of synthesis has to be ruled out.
    9.1 O-bis (chloromethyl) anthracene can be purchased from different suppliers. Sigma-Aldrich, on its website, classifies this product within a collection of 'unusual and unique chemical reagents', thus justifying its price to be quite high. However, this compound is widely used in scientific works as a structural intermediate of anthracene, which is chemically derivatized for convenience, mainly seeking the appearance of calorimetric and fluorescent optical properties.
    Some of the applications of this compound have been published in the state of the art.
    The RSC document Adv. 2015, 5, 73951-73957 describes this compound as a skeleton of new photoactive cyclophanes with molecular rigidity to be used in specific recognition, molecular electronic machines, drug transporters and catalysts in organic synthesis.
    The Chem. Mater document. 2004, 16, 2783-2789 describes this compound as an organic material for application in fluorescence optics, photodynamic therapy and optical data storage and microfabrication through donor-bridge-acceptor or donor-bridge-bridging compounds.
    This compound acts as a valuable precursor in the preparation of biso-substituted meso derivatives of anthracene in positions 9 and 10, such as amines and their respective hydrochlorides, amides, isocyanates, alcohols, esters, ethers, thiols, nitriles, acids and phosphonates.
    5 DESCRIPTION OF THE INVENTION
    The problem in view of the state of the art is to provide a synthesis method of 9,10-bis (chloromethyl) anthracene with a higher yield than that obtained with the prior art procedures
    The solution to this problem is to provide the procedure described below, a much simpler scaling than those described so far and in accordance with the principles of "g reen chemistry" by using a catalytic process and an aqueous reaction medium without presence of organic solvents.
    In a first aspect, the present invention provides a synthesis method of 9,10bis (chloromethyl) anthracene comprising mixing the anthracene reagents and 1,3,5-trioxane, a phase transfer catalyst selected from the group consisting of ammonium salt quaternary and crown ether with hydrochloric acid and acetic acid.
    In the present specification, a "phase transfer catalyst ~ is that chemical species that makes possible and catalyzes chemical reactions between two or more reagents located in two or more phases, so as to allow a reactivity that, in the absence of the catalyst of phase transfer would not be possible.The mode of action is based on the provision of
    Catalyst between the phases, allowing the physicochemical connection between the reagents that actively participate in the reaction.
    Another embodiment is the process according to the first aspect of the invention, where the concentration of the phase transfer catalyst is between 1 and 5 mol%.
    Another embodiment is the process according to the first aspect of the invention, where the concentration of hexadecyltrimethylammonium bromide is between 2 and 4 mol%.
    Another embodiment is the process according to the first aspect of the invention, wherein the concentration of hexadecyltrimethylammonium bromide is between 2 and 3 mol%.
    Another embodiment is the process according to the first aspect of the invention, wherein the 1, 3,5-trioxane: anthracene molar ratio is between 0.5 and 3.
    Another embodiment is the process according to the first aspect of the invention, where the5 molar ratio 1, 3,5-trioxane: anthracene is between 1 and 2.
    Another embodiment is the process according to the first aspect of the invention, which comprises the following additional steps:
    (c) filtering the mixture resulting from step (b), 10 (d) washing with water and
    (e) wash with ethanol.
    The process according to the first aspect of the invention can be carried out at room temperature or by heating at temperatures above room temperature.
    The 9,10-bis (chloromethyl) anthracene compound appears very quickly, within a few minutes. There is presence of this compound less than 10 minutes from the start of the process according to the first aspect of the invention.
    The method according to the first aspect of the invention has a series of advantages over the methods described in the state of the art, such as:
    the absence of any organic solvent in the synthesis process, the medium being exclusively aqueous, which means avoiding the need for treatment of
    25 organic solvents; the absence of accessory streams of gaseous supply to the process; the high reaction yield measured as the mass of purified final product
    in solid state; the need for high temperatures in the synthesis, since it is not necessary to bring the solvent to reflux; the need for no further purification of the final product by recrystallization as it had been done; the outstanding reproducibility of the method.
    35 BRIEF DESCRIPTION OF THE FIGURES
    Figure 1. 400 MHz NMR spectrum of proton in deuterated chloroform and at room temperature of 9.1 O-bis (chloromethyl) anthracene.
    PE REAliZACiÓN MOPOS DESCRIPTION
    Reagents used
    The reagents used in the synthesis procedure were used from the commercial compound without purification or enrichment thereof before synthesis.
    10 Anthracene reagents (Anthracene ReagentPlus®, 99%, trade code 141062-25G, € 56.00, Spain), acetic acid (Acetic acid ReagentPlus®, ~ 99%, trade code A-62831L, € 43.60, Spain ) and 1,3,5-trioxane (1,3,5-trioxane, .99%, commercial code T81108-100G, € 23.30, Spain) were purchased from Sigma-Aldrich. Hydrochloric acid (Hydrochloric acid
    15 reagent grade, 37%, 1 L, € 28.23) was supplied by Scharlab. Finally, hexadecyltrimethylammonium bromide (Hexadecyltrimethylammonium bromide, ~ 96%, commercial code 52370-100G, € 32.00, Spain) comes from Fluka.
    Br or 1
    'N ~ x
    ) lOH + I -J14 HClaq
    Anthracene Acetic acid 1,3,5-trioxane Hexadecyltrimethylammonium bromide Chloric acid [drico
    Synthesis procedure of 9.10-bis (chloromethyl) anthracene
    In general, the experimental procedure can be described as follows: in a spherical flask the solid reagents (anthracene, 1,3,5-trioxane and bromide of
    25 hexadecyltrimethylammonium as a catalyst) without an established order of priority. To the mixture is added first hydrochloric acid and then acetic acid, all at room temperature and under constant and vigorous stirring (1500 rpm). Subsequently, the mixture is exposed to different temperatures so that the reaction takes place during a certain period of time, in which the medium turns yellow and looks
    Powdery, without dissolution of the solid present. After the set reaction time, the contents of the flask are filtered to collect the yellow precipitate and washed thoroughly with water to remove traces of trioxane, catalyst and acidic species present in the
    means, medium. As a final step, the solid obtained is washed with ethanol to remove the remains of water from the wash and allowed to dry at 70 oC in an oven for 2 hours until completely dry.
    Several reaction protocols with different reaction temperature values, time and excess 1,3,5-trioxane have been tested as a source of formaldehyde with respect to the limiting amount of anthracene.
    Examples 1-4 describe the different synthesis procedures of 9,10bis (chloromethyl) anthracene tested.
    Example 1. Synthesis procedure of 9.1 O-bis (chloromethyl) anthracene
    he
    1,3,5-lrioxane (2 eq)
    Hexadecyltrimelilamonium bromide (2.5 mol%)HCI conc. + AcOH conc.
    24 h, 100 ° C
    he
    15 Description of quantities of reagents used: Anthracene -4,500 mg, 2.8 mmol. 1.3.5-lrioxane ~ 504 mg. 2 eq (5.6 mmol). Hexadecyltrimethylammonium bromide -4 25 mg, 0.07 mmol (2.5 mol%) Hydrochloric acid 37% -4 10 ml
    20 Acetic acid 99% _ 2.5 mi Reaction yield: 89%
    Example 2. Synthesis procedure of 9.1 O-bis (chloromethyl) anthracene
    1,3,5-trioxane (2 eq) Hexadecyltrimethylammonium bromide (2.5 mol%)
    HCI conc. + AcOH conc.
    24 h, 60 oC
    he
    25 Description of quantities of reagents used: Anthracene _ 500 mg, 2.8 mmol. 1.3.5-lrioxane ~ 504 mg. 2 eq (5.6 mmol). 1,3,5-trioxane molar ratio: anthracene: 2
    Hexadecyltrimethylammonium bromide -4 25 mg, 0.07 mmol (2.5 mol%)Hydrochloric acid 37% -4 10 miAcetic acid 99% -4 2.5 miReaction yield: 96%.
    Example 3. Synthesis procedure of 9.1 O-bis (chloromethyl) anthracene
    1,3,5-trioxane (2 eq) Hexadecyltrimethylammonium bromide (2.5 mol%)
    HCI conc. + AcOH conc.
    14h, 60 ° C
    Description of quantities of reagents used:
    10 Anthracene -4,500 mg, 2.8 mmol. 1,3,5-trioxane ~ 504 mg, 2 eq (5.6 mmol). Molar ratio 1,3,5-trioxane: anthracene: 2 Hexadecyltrimethylammonium bromide -4 25 mg, 0.07 mmol (2.5 mol%) Hydrochloric acid 37% -4 10 mi
    15 Acetic acid 99% -4 2.5 mi Reaction yield: 93%.
    Example 4. Synthesis procedure of 9.1 O-bis (chloromethyl) anthracene
    1,3,5-trioxane (1 eq) Hexadecyltrimethylammonium bromide (2.5 mol%)
    HCI conc. + AcOH conc.
    24 h, 60 oC
    he
    20 Description of quantities of reagents used: Anthracene -4,500 mg, 2.8 mmol. 1,3,5-trioxane ~ 504 mg, 1 eq (2, 8 mmol). Molar ratio 1,3,5-trioxane: anthracene: 1 Hexadecyltrimethylammonium bromide -4 25 mg, 0.07 mmol (2.5 mol%)
    25 Hydrochloric acid 37% -4 10 ml Acetic acid 99% -4 2.5 ml Reaction yield: 97% of solid that does not correspond by NMR analysis with pure product, but there is presence of unreacted anthracene.
    Next, in Table 1, an informative table is presented as a summary of the previous results according to the variables.
    Table 1
    Variables Example 1 Time (h) 24 Temperature 100 ('e) Molar ratio 1,3,52 trioxane: anthracene Weighing yield (%) 89 Example 2 24 60 2 96Example 3 14 60 2 93Example 4 24 60 1 97Example 5 24 25 2 74
    The 9.1 O-bis (chloromethyl) anthracene synthesized in Examples 1-4 was characterized by proton nuclear magnetic resonance (NMR) experiments on a Bruker 400 MHz 10 NMR spectrometer, performing temperature measurements ambient and using deuterated chloroform (CDCb) as solvent in the analyzes.
    Figure 1 shows the 400 MHz NMR spectrum of proton in deuterated chloroform and at room temperature. This spectrum is identical for the compound obtained in the Examples
    15 1-4. The spectrum is coincident with the spectrum described in the prior art (OH 400 MHz, eDel,: 5.77 ppm, singlet, 4H; 7.74-7.77 ppm, multiplet, 4H; 8.53-8, 55 ppm, multiplet, 4H).
    Example 5. Synthesis procedure of 9.1 O-bis (chloromethyl) anthracene 20
    1, 3,5-trioxane (2 eq)Hexadecyltrimethylammonium bromide (2.5 mol%)
    HCI conc. + AcOH conc.
    24 h, 25 oC
    The Description of quantities of reagents used: Anthracene --- t 500 mg, 2.8 mmol. 1,3,5-trioxane ~ 504 mg, 2 eq (5.6 mmol).
    1,3,5-trioxane molar ratio: anthracene: 2Hexadecyltrimethylammonium bromide -25 mg, 0.07 mmol (2.5 mol%)Hydrochloric acid 37% _ 10 miAcetic acid 99% _ 2.5 mi
    5 Reaction yield: 74% solid.
    Example 6. Non-thesis procedure of 9.1 O-bis (chloromethyl) anthracene
    In this example, the following phase transfer catalysts were used:
    Tetrabutylammonium BromideTetrabutylammonium FluorideTetramethylammonium NitrateTetrabutylammonium Hexafluorophosphate
    15 Tetrabutylammonium perchlorate Benzyltrimethylammonium chloride Corona ether 4-carboxybenzo-18-crown-6 (1,4,7,10,13, 16-Hexaoxacyclooctadecane 1,4,7,10,13,16-Hexaoxacyclooctadecane) Crown ether 18- crown-6 (carboxylic acid 18-2,3,5.6.8.9.1 1.12.14.15
    20 decahydrobenzo [b] [1, 4,7,10,13, 16] hexaoxacyclooctadecin 2.3.5.6.8.9.11.12.14.15decahydrobenzo [b] [1,4, 7,10,13, 16] hexaoxacyclooctadecine-18-carboxylic acid)
    Table 2 shows reaction parameters and performance obtained in the experiments of this example:
    Table 2
    Fa transfer catalyst was used Reaction time temperature ('C)(h) JWeighing performance of pure product ('lo)
    Tetrabutylammonium Bromide 24/6083
    Tetrabutylammonium Fluoride 24/6080
    Tetramethylammonium Nitrate 24/6071
    Tetrabutylammonium Hexafluorophosphate 24/6070
    Tetrabutylammonium perchlorate 24/6075
    Benzyltrimethylammonium Chloride 24/6070
    Ether crown carboxybenzo-18-crown-6 4 24/6067
    Ether crown 18-crown-6 24/6063
    权利要求:
    Claims (3)
    [1]
    1. A synthesis procedure of 9.1 O-bis (chloromethyl) anthracene comprising mixing the anthracene reagents and 1,3,5-trioxane, a selected phase transfer catalyst
    5 of the group consisting of quaternary ammonium salt and crown ether with hydrochloric acid and acetic acid.
    [2]
    2. The process according to claim 1, characterized in that the concentration of the phase transfer catalyst is between 1 and 5 mol%.
    [3]
    3. The method according to claim 1 or 2, characterized in that the molar ratio 10 1, 3,5-trioxane: anthracene is between 0.5 and 3.
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    引用文献:
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    JPH03188029A|1989-12-15|1991-08-16|Harima Chem Inc|Preparation of bis-chloromethyl-substituted aromatic compound|
    JP3836541B2|1996-09-13|2006-10-25|新日鐵化学株式会社|Method for producing 4,4'-bis biphenyl|
    KR100220645B1|1997-07-04|1999-09-15|구광시|Process for producing benzene derivatives|
    KR100610406B1|2000-02-22|2006-08-09|브레우어 사이언스 인코포레이션|Organic polymeric antireflective coatings deposited by chemical vapor deposition|
    CN101870657A|2009-04-23|2010-10-27|北京化工大学|Method for synthesizing novel anthracene-based electroluminescent material compound|
    CN103570499B|2011-08-02|2016-04-13|浙江永太科技股份有限公司|A kind of preparation method of 2-halogeno-5-trifluoromethyl benzyl alcohol|
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