TW201217368A - characterized by adopting a mixed dehydrating agent containing hydrochloric acid and organic acid, thereby being mild and easy to control, synthesizing a high-purity product and safely discharging waste liquid due to no addition of pollutants - Google Patents

Abstract

The present invention provides an one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, which belongs to the field of organic synthesis and includes: reacting o-phenylenediamine with the compound represented by formula III in the presence of a mixed dehydrating agent in one step synthesis. Wherein, the mixed dehydrating agent is a mixture of hydrochloric acid and organic acid. The organic acid can act as a phase-transfer catalyst, a dehydrating agent and a buffering agent to reduce the polymerization of the compound represented by formula III and side reaction. This synthesis method is mild and easy to control, synthesizes a high-purity product, and safely discharges the waste liquid due to no addition and production of pollutants. By adopting a ketone solvent in the post-treatment, this synthesis method can reduce separation step and product loss to increase the yield.

Description

201217368 VI. Description of the invention: [Technical field to which the invention pertains] The present invention relates to the field of organic synthesis, and in particular to the efficient synthesis of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrene Method 0 of the porphyrin [Prior Art] 1,10-morpholine compound is one of the most widely studied nitrogen-containing heterocyclic chelating agents. As an important ligand, many of its complexes play an important role in many fields (P. G.

Sammes, G. Yahioglu, Chem. Sov. ν·, 1994, 23, 327). Complexes with 1 '10-phenanthroline derivatives as ligands have good optical properties' can be used as photosensitizers and photocatalysts (r. Sahai, L. M〇rgan, DP Killema, Inorg. Chem) 1988, 27 , 3,495). Especially the symmetrically substituted 1,10-phenanthroline derivatives, because these substances can maintain the two-part symmetry of the coordination element, can avoid the stereoisomerism when complexed with the metal. Therefore, it is a class of compounds that are particularly important and worthy of study. 2' 9 · Dimercapto-4, 7-diphenyl-bu 10_phenanthroline is an important one in the i,1〇· _ 琳 琳 derivative Compounds can be used to detect copper ions and can also be used in photovoltaic materials. 2,9-Dimethyl·4,7- 201217368 Diphenyl-1,10-phenanthroline has a melting point of up to 288. (:, energy level 3.3eV, so it is commonly used as an exciton/hole blocking material in OLEDs. But 2,9-dimethyl-4,7-dipyridyl·J,1〇-phenanthroline The synthesis is not very satisfactory. The current synthesis of such materials is mainly Skraup and Doebner-von Miller synthesis, which requires the use of sulphuric acid or arsenic pentoxide (Case F. H·, Brennan JA, J. Org. Chem., 1954, 19, 919.); requires three steps of reaction, the reaction is very intense, the yield is only a few percent 'not suitable for industrialization. The disadvantages of these methods are the intermediate product, the yield Very low, only a small amount of product is required to report the time of the report, and the steps are complicated, and the benefits are poor from the perspective of economic efficiency. Czech patent CS146030 proposes to synthesize 2 '9-dimercapto- 4 by one-step method. 7-Diphenyl-1,10-phenanthroline, although the synthetic route was changed from three steps to one step, saving a lot of manpower, but still arsenic as an oxidant, environmental pollution is also very heavy; and repeat & Post-treatment is also very complicated, so it is necessary to find a synthetic route that does not use arsenic compounds as oxidants. Czech patent CS226921 mentions the use of tetrahydroanthracene, DDQ, etc. as an oxidant to synthesize 1'10-formula compound, although this method is rid of The use of arsenic compounds is a problem encountered in the industrialization process. Tetrachlorohydroquinone is insoluble in acidic solutions and organic solvents after the reaction, and is difficult to handle; Lost, the yield is only less than the root 201217368 According to the synthesis method that has been reported so far, it is necessary to find a method that is both environmentally friendly and yieldable. [Summary of the Invention] 2,9-Dimethyl-4, 7-diphenyl- 1,10-phenanthroline is synthesized by the Skraup and Doebner-von Miller methods, and has the problems of low yield and high pollution; the present invention selects non-polluting reaction raw materials and improves at the same time from the reaction mechanism of synthesis of such compounds. The reaction condition 'improves the reaction, the post-treatment is easy, and the reaction yield is improved, and the product purity is high. One-step synthesis of 2'9-dimethyl-4,7-diphenyl-1,1〇-phenanthroline (as in Formula I), the conditions of the adjacent diamine and the formula 111 in the mixing of the water shrinking agent Synthetic reaction obtained, the combined shrinking agent is a mixture of hydrochloric acid and an organic acid,

(III)201217368

The organic acid of ch3 is one or more of formic acid, acetic acid, propionic acid, butyric acid, and valeric acid. The volume ratio of the hydrochloric acid to the organic acid mixture is 1: -9 9:1 · The volume ratio of the hydrochloric acid to the organic acid mixture is 3: 7-7: 3. The synthesis reaction comprises the following steps: 1) Adding concentrated hydrazine to o-phenylenediamine in a concentrated solution of hydrochloric acid, reacting at 50-90 ° C for 2-10 hours; 2) adding organic acid at 90-110 ° C 'returning reaction at 2-10 hours . • The step (the reaction conditions of hydrazine are: 7〇-85°C, the reaction is 2-8 hours, and the reaction condition of the step (2) is: 9〇-l〇〇°C' reflux reaction in 2- 8 hours. The step (1) is carried out by adding hydrochloric acid to the reaction vessel, and the o-diamine is added to the reaction flask in portions at room temperature, and after stirring for 1-6 hours, the reaction is carried out by adding the formula 111. The synthesis reaction also includes Post-treatment step, the post-treatment step 10 201217368 is to add the final reaction solution to the ammonia water at 〇-5 ° C, adjust the pH = 10-13, remove the water layer, add the ketone solvent, precipitate the solid; , washing the strip, drying. The ketone solvent is one or more of acetone, methyl acetone, methyl ethyl ketone, 2, 5-hexanyl. According to the prior art, 2,9-dimethyl-4, A one-step synthesis of 7-diphenyl-1,10-phenanthroline (formula I), the synthesis route is as follows:

The reaction uses ortho-diphenylamine (the formula II shown in the above figure is a hydrochloride structure) as a starting material, and needs to be converted into a hydrochloride salt in an acidic environment ' 11 201217368; in an acidic environment, The amine group undergoes an addition reaction with hydrazine to form !V, which is rapidly converted to ν, and an amine group in compound V, which continues to react with the dish to give compound I. In fact, the reaction mechanism is that o-phenylenediamine reacts with the olefinic structure to synthesize 1,10·phenanthroline structure. The previous synthesis process uses concentrated sulfuric acid and concentrated phosphoric acid as a water shrinking agent, and arsenic oxide or tannic acid is used.

The oxidizing agent, the ring-closing and dehydrogenation conditions are severe, so the yield is low and the side reactions are many. To control the yield, it is necessary to maintain a two-step continuous reaction to select a suitable deuteration agent and a dehydrating agent, and to lower the reaction conditions. The selection is due to the presence of a double bond, which is prone to polymerization under a strong acid environment. Add to reaction (iv) to reduce the formation of by-products. Adding the compound dish to maintain the temperature unchanged, the compound iv, v is obtained, and the addition acid promotes the condensation reaction and also plays the role of phase transfer. The organic invention mixed water shrinking agent reduces the reflux temperature and reduces the side reaction. . The product obtained by the end of the reaction is required to be released in the form of the hydrochloride salt, the ammonia water is very transferred and the mixture is effectively treated with hydrazine, and the by-product is dissolved in _solvent to form a high-purity product. The ketone solvent is one or more selected from the group consisting of propylene glycol, methyl ketone, and bismuth 2, 5-hexanedione.峒, melons are added at intervals of severe hours 'appropriate time during the entire reaction process, Π, affecting product yield, time interval 1~6 12 201217368 2~4 hours. The melon addition temperature can be controlled at 50-90 ° C, suitable for temperature 60-90 ° C, and the optimum temperature is 70-85 ° C. The synthesis process of this patent can be carried out as follows: (1) Hydrochloric acid is added to the reaction vessel, and the reaction flask is added to the reaction flask in portions at room temperature, stirred for 1-6 hours, and converted into the hydrochloride form. (2) Add hydrazine at 70-85 ° C, react at this temperature for 2-8 hours, convert the hydrazine hydrochloride to IV, V, and add the organic acid in portions. • (3) Raise the temperature at reflux, the temperature is between 90 and 100 ° C, and the reaction ends at 2-8 hours. (4) The reaction solution is dropwise added with ammonia water at 0-5 ° C, pH = 8-10, the aqueous layer is removed, a ketone solvent is added, and the solid is stirred and precipitated; suction filtration, washing, and drying. The process provided above solves the current low yield, many by-products, and reduces environmental pollution, and has the following advantages: • O-phenylenediamine hydrochloride is converted into IV and V by reaction with hydrazine under hydrochloric acid conditions, and the organic acid acts as a phase. Transferring catalyst and shrinking agent action 'Organic acid as a buffering agent, reducing the polymerization reaction of hydrazine, making the by-products of the reaction less, high purity, mild and easy to control. Because non-polluting substances are added and produced, waste liquid can be safely discharged. Ketone solvent reduction separation step 'reduced product loss' increased production 13 [S3·201217368 rate [Embodiment] Hereinafter, embodiments of the present invention will be described by way of specific embodiments, and those skilled in the art can use the present specification. Other advantages and utilities of the present invention are readily apparent from the disclosure. The present invention will be further described in detail below with reference to the embodiments. • Preparation of raw materials Μ : (Preparation of crotonyl gas) First, lkg (lmol) of crotonic acid is put into a 5L reaction flask, and 1650ml (1.5mol) of chlorinated sulfite is slowly added under mixing, which will produce a large amount of HC1. The reaction was stirred at room temperature until the gas no longer violently occurred and the temperature was slowly warmed to reflux. After the end of the reaction, the mixture was steamed at a constant pressure to collect 871 g of a fraction of 116_124 ° C, and the yield was 72%. • 1-2: (Preparation of compound m) Benzene 461 was added to a 100 L reaction flask, and anhydrous = 21.75 kg of vaporized aluminum was added in portions to the reaction flask under mixing. After cooling to 〇_5〇c, 11.6 kg of crotonyl chloride was added dropwise, maintaining the temperature below 5 ,, and a large amount of bright yellow solid appeared in the reaction flask and gradually increased. After the addition of the acid gas, the temperature is maintained at 5-1 (the reaction is stirred until the Ηα gas is no longer produced; the reactants are poured into ice and concentrated hydrochloric acid (3:1) in batches. ί Si 14 201217368 Medium, bright yellow solid dissolved. Static layering, the upper layer is light yellow organic layer, the lower layer is slightly turbid water layer. The water layer is extracted twice with ethyl acetate 201, and the benzene layer and ethyl acetate are washed with saturated brine 501. The organic layer was washed with a 10% aqueous sodium hydroxide solution, and washed twice with saturated brine, dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo to remove low-boiling solvent, and then distilled under reduced pressure to collect 144-164 ° C fraction. .5kg, yield 66%, a pale yellow oily liquid, yield 80%. • Example 1: (Method of the invention) First, add 6.51 concentrated hydrochloric acid, stir and pass nitrogen for half an hour. Then add o-benzene in batches. 470 g of diamine, stirred at 60 ° C for 2 hours, added with 0.7 kg of phenylpropenyl ketone at 70-85 ° C, stirred for 3 hours, and added 51 acetic acid in portions during the stirring. Slowly warmed to reflux at about 94 ° C, refluxing for 8 h. , the reaction solution is brown. Stop heating, reduce to room temperature, cool in ice bath, stir 6 kg of ice cubes were added to the reaction solution in portions, and the solution was slowly added with ammonia to adjust the pH to 8-10' to separate the upper aqueous layer. 61 acetone was added to the black viscous material and stirred for 1 hour, and filtered to obtain 300 g of a yellow filter cake. Recrystallization, product 230 g purity 99 ° / 〇, yield 14% HNMR (CDC 13, 400 MHz) δ (ppm): 3.1 (s, 3H), 7.56 (s, lH), 7.62 (m, 5H), 7.86 (s, lH) MS (El) 360 Example 2: (according to patent amplification) 15 [si 201217368 According to the method of Example 1, the magnification is 10 times larger, the yield is 14-20%, and the reaction waste liquid is not Containing harmful substances can be discharged. Comparative Example 1: (provided by the literature on the five-oxidation method) ° First add 101 concentrated hydrochloric acid, mix and pass nitrogen for half an hour. Then add o-phenylenediamine 885g in batches, 6 (rc stir for 2 hours) , 7〇85〇c

2630 g of phenylpropenyl ketone was added and stirred for 3 hours, and l883 g of lanthanum pentoxide was added in portions during the stirring. The temperature was slowly raised to reflux at about u 〇 ° C, and refluxed for 8 h, and the reaction mixture was brown. The heating was stopped, the temperature was lowered to room temperature, and the mixture was cooled in an ice bath. 1 kg of ice was added to the reaction solution in portions, and then an aqueous ammonia solution was slowly added thereto to adjust the pH to 8-10, and the upper aqueous layer was separated. Add 101 acetone to the black thick material and mix for lh. After 遽, the yellow filter was obtained, and the cake was about 1.7 kg. Put the cake in a container and add dichloromethane 41, stir for 1 hour to filter 'steamed dichloromethane filtrate, evaporate and add acetone, and filter to obtain 287.68g of purity 96%, and purify more than 98% of the product. The rate is 8%. HNMR (CDC13, 400MHz) s

(ppm): 3.1 (s, 3H), 7.56 (s, lH), 7.62 (m, 5H), 7.86 (s, lH) ° MS (El) 360 Comparative Example 2: (tetrachlorohydroquinone method)

First, add 500 ml of concentrated hydrochloric acid, stir and pass nitrogen for half an hour. Then, 27 g of o-phenylenediamine was added in portions, and the mixture was stirred at 60 ° C for 2 hours, 7 〇 - 85 ° C, 16 m of 201217368 phenylpropenyl ketone 80 g, and stirred for 3 hours, and 135 g of tetrachlorohydroquinone was added in portions during the stirring. The temperature was slowly raised to reflux at about 94 ° C, and the reaction was refluxed for 8 h. The heating was stopped, the temperature was lowered to room temperature, and the mixture was cooled in an ice bath. Under stirring, 500 g of ice was added portionwise to the reaction liquid, and then an aqueous ammonia solution was slowly added thereto, and 8-10 was adjusted to separate the upper aqueous layer. 600 ml of acetone was added to the black viscous material and stirred for 1 hour, and filtered to obtain a yellow cake. Recrystallization, the product 13g purity 99%, yield 12%. H NMR (CDC 13 , 400 MHz) δ (ppm): 3.1 (s, 3H), 7.56 (s, 1H), 7.62 (m, 5H), 7.86 (s, lH). MS (El) 360 Comparative Example 3: (four-gas argon-helium method amplification) According to the method of Comparative Example 2, the amplification is 10 times, the agglomeration phenomenon occurs after cooling, and the solid cannot be dissolved by reheating; a large amount of insoluble solids are generated because The by-product of tetrachlorohydroquinone contains a large amount of organic gas, which pollutes the environment. While the foregoing description of the preferred embodiments of the invention, the embodiments of the invention The spirit and scope of the principles of the invention. It will be appreciated by those skilled in the art that the invention can be modified in many forms, structures, arrangements, ratios, materials, components and components. Therefore, the embodiments disclosed herein are to be considered as illustrative and not restrictive. The scope of the present invention is defined by the scope of the appended claims, and its legal equivalents are not limited to the foregoing description. * [Simple description of the scheme] Figure 1 shows the DSC spectrum of the compound of Example 1, the melting point of the product is 288.773⁄4.

Experimental apparatus: 2910MDSCV4.4E, detection conditions: 10 ° C / min, N 2 Figure 2 DSC spectrum of the compound of Comparative Example 1, product melting point 287.96 〇 C.

• Experimental instrument: 2910MDSCV4.4E, detection conditions: 10 ° C / min, N2 Figure 3 TGA spectrum of the compound of Example 1 Experimental instrument: TGA Q5000 V3.5 Build 252, detection conditions: l 〇 ° C / min, N2 Figure 4 TGA spectrum of the compound of Comparative Example 1. Experimental Instruments·· TGA Q5000 V3.5 Build 252, Detection conditions: l〇°C/min, N2 18 [S} 201217368 [Main component symbol description] None

[s] 19

Claims (1)

201217368 VII. Application for Patent Park: 1. A one-step synthesis method of 2'9-dimethyl-4'7-phenylene-1, phenothiline, which is obtained by synthesizing the reaction of o-phenylenediamine and formula III in the next step of mixing a water-reducing agent. The mixed water shrinking agent is a mixture of concentrated hydrochloric acid and an organic acid. (III) 2. A one-step synthesis method of 2'9-dimethyl-4,7-diphenyl 4,10-phenanthroline as described in claim 1, wherein the organic acid is selected from the group consisting of formic acid, acetic acid, and C Acid, butyric acid, valeric acid or a composition thereof. 3. A one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline as described in claim 1, wherein the volume ratio of the hydrochloric acid to the organic acid mixture is 1: 9-9: 1. 4. The one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline as described in claim 1, wherein the volume ratio of the hydrochloric acid to the organic acid mixture is 3: 7-7: 3. A one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline 4 according to claim 1, wherein the synthesis reaction comprises the following steps: A concentrated hydrochloric acid solution of stupid diamine is added to the hydrazine, and the reaction is carried out for 2-1 hr at 50-90 X:; the organic acid is added at 90 Hz, and the reaction is refluxed at 2-1 hr. 6 The one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-i, 10-phenanthroline 20 201217368 porphyrin according to claim 5, wherein the reaction condition of the step 1 is 7〇~85 °C, the reaction is 2 to 8 hours. 7. The one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-1,1〇-phenanthroline as described in claim 5, wherein the reaction condition of the second step is 9〇~1 〇〇°C 'Reflow reaction for 2 to 8 hours. 8. A one-step synthesis method of 2,9-dimethyl-4,7-diphenyl-1, ίο-phenanthroline as described in claim 5, wherein the concentrated hydrochloric acid of o-p-diamine in the first step ^ The solution was prepared by adding concentrated hydrochloric acid to the reaction vessel, and adding o-phenylenediamine to the reaction flask in portions at room temperature, and stirring for ～6 hours. 9. The one-step synthesis method of 2,9-dimethyl-4,7-dipyridyl-1,10-phenanthroline as described in claim 1, wherein the synthesis reaction further comprises a post-treatment step of post-treatment The procedure is to add the ammonia solution to the final reaction solution at the time of 〇_5^, adjust the PH-10-13 'removal of the water layer' and add the hydrazine solvent to precipitate the solid; suction filtration to wash and dry. 10. The one-step synthesis method of 2,9-dimethyl-4'7~diphenyl-1,10-•phenanthroline according to claim 9, wherein the ketone solvent is selected from the group consisting of acetone and methyl acetone , D-, 2,5-hexanedione or a composition thereof. Eight, schema: 21