Synthesis method of meso-position diarylamino substituted heptamethine

Abstract

The invention discloses a synthesis method of meso-position diarylamino substituted heptamethine, and belongs to the technical field of organic synthesis. Cyclopentanone is used as a raw material, and the meso-position diarylamino substituted heptamethine cyanine dye is obtained after two condensation, boronation and coupling steps. The synthesis route avoids the imine intermediate in the traditional route, thereby avoiding the generation of high-toxicity and high-corrosivity hydrogen fluoride gas and being more beneficial to industrialization. The whole synthetic route is subjected to four-step reaction, the reaction condition is mild, the operation is easy, and the total yield of cyclopentanone exceeds 30%.

Description

Technical Field

[0001] This invention relates to a method for synthesizing heptamethine with a meso-diarylamine group substituted at the meso-position, belonging to the field of organic synthesis technology. Background Technology

[0002] In computer-to-plate (CTP) printing technology, heptamethrin-based cyanine dyes play an irreplaceable role as near-infrared intensifiers. In current mainstream thermal CTP technologies, IR830 is used as an intensifier. Its main principle is that after IR830 absorbs near-infrared light, the thermal energy generated during the relaxation of its electronically excited state decomposes the resin, producing components soluble in the washing solution. This allows the printed image to remain on the plate after the washing process. The main problem with this technology is that the additional washing process increases costs and generates a large amount of waste liquid. As an alternative, post-exposure, no-washing technology is undoubtedly more attractive.

[0003]

[0004] Chinese patent CN200610125748.X discloses a treatment-free CTP technology that uses a meso-diarylamine-substituted heptamethine as an additive to replace IR830. Unlike traditional IR830-based thermal CTP, this treatment-free CTP technology uses a meso-diarylamine-substituted heptamethine to alter the hydrophilicity and oleophilicity of the printing plate coating through exposure, thus creating the printed image. Since only the oleophilic printed image can absorb ink, there is no need to wash away the hydrophilic and non-ink-absorbing background coating. Therefore, this treatment-free CTP technology has the advantages of lower cost and greater environmental friendliness.

[0005] As a core component of the coating for treatment-free CTP plates, the current synthesis route of this type of compound is represented by the following reaction equation:

[0006]

[0007] The problem with this synthetic method is that the first step uses tetrafluoroboric acid as the starting material, and the reaction is carried out under acidic, high-temperature conditions at 130-140°C. Under such conditions, tetrafluoroboric acid decomposes in large quantities, producing highly corrosive hydrogen fluoride, which poses a serious threat to operators and equipment, making it difficult to industrialize. Furthermore, the yield of this route is low; based on cyclopentanone, the overall yield of heptamethylaluminate after four steps is only about 10%. Summary of the Invention

[0008] To overcome the aforementioned technical deficiencies, this invention provides a novel synthetic method for meso-diarylamine-substituted heptamethine cyanide dyes that is easily industrialized. Using cyclopentanone as a starting material, the method involves two condensation, boration, and coupling steps to obtain meso-diarylamine-substituted heptamethine cyanide dyes. This synthetic route avoids the imine intermediate found in traditional routes, thus preventing the generation of highly toxic and corrosive hydrogen fluoride gas, and is more conducive to industrialization. The entire synthetic route involves four steps, with mild reaction conditions and easy operation, achieving an overall yield exceeding 30% based on cyclopentanone.

[0009] The method for synthesizing the meso-diarylamine-substituted heptamethine cyanine dye of the present invention includes the following steps: using cyclopentanone as a raw material, a condensing agent is first synthesized via a Vilsmeier-Haack reaction, followed by condensation with a 2,3,3-trimethylindole quaternary ammonium salt to obtain a meso-chlorosubstituted cyanine, then undergoing lithium-mediated boronization to obtain a meso-borinated cyanine, and finally reacting with a diarylamine via a Chan-Lam reaction in the presence of a copper catalyst to obtain the meso-diarylamine-substituted heptamethine cyanine dye. The reaction equation is as follows:

[0010]

[0011] Wherein: R1 is selected from hydrogen, C1-C5 alkyl, halogen, or C1-C5 alkoxy; R2 is selected from C1-C5 alkyl or C1-C5 alkyl (ether group) containing an oxygen atom; R3 and R4 are each independently selected from hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, sulfonic acid group, cyano group, nitro group, or amino group; A is selected from halogen. The halogens are all fluorine, chlorine, bromine, or iodine.

[0012] Furthermore, in the above technical solution, the first step of the condensation reaction: phosphorus oxychloride and DMF are used as formylation reagents, and the reaction temperature is 30-100℃, preferably 40-60℃.

[0013] Furthermore, in the above technical solution, the first step of the condensation reaction involves a molar ratio of cyclopentanone, phosphorus oxychloride, and DMF of 1:3-6:3-6.

[0014] Furthermore, in the above technical solution, the second step of the condensation reaction: acetic anhydride is used as the solvent, and the reaction temperature is 50-100℃, preferably 60-80℃.

[0015] Furthermore, in the above technical solution, the second step of the condensation reaction involves a molar ratio of the condensing agent to 2,3,3-trimethylindole quaternary ammonium salt of 1:2-2.5.

[0016] Furthermore, in the above technical solution, the third step of the borylation reaction is carried out in tetrahydrofuran, diethyl ether or 2-methyltetrahydrofuran solvent, at a reaction temperature of -78°C to -10°C, preferably -40°C to -20°C.

[0017] Furthermore, in the above technical solution, the third step of the borylation reaction involves a molar ratio of the chloro-substituted cyanine, lithium metal, and trimethyl borate of 1:2-2.2:1-2.5.

[0018] Furthermore, in the above technical solution, the fourth step of the coupling reaction involves using copper acetate as a catalyst, triethylamine as a co-catalyst, and dichloromethane as a solvent, with a reaction temperature of 15-50℃, preferably 20-30℃.

[0019] Furthermore, in the above technical solution, the fourth coupling reaction involves a molar ratio of the meso-boronine, diarylamine, and copper catalyst of 1:1-3:0.02-0.1.

[0020] Studies have shown that it is feasible to directly replace the anthocyanin chlorine atom with aliphatic primary or secondary amines, as well as aromatic primary amines, but it is unsuccessful to replace the anthocyanin chlorine atom with a diarylamine. This invention employs a strategy of first borylation and then substitution, that is, to synthesize heptamethrin-type anthocyanin dyes with a diarylamine substituted mesoside based on a Chan-Lam type reaction.

[0021] After optimizing the reaction of special substrates such as meso-boronized heptamethine with diarylamines, it was found that the reaction can proceed smoothly in the range of 15-50℃ using copper acetate as catalyst, triethylamine as co-catalyst, and dichloromethane as solvent.

[0022] Beneficial effects of the present invention

[0023] 1. The synthetic route avoids the imine intermediate in the traditional route, thus avoiding the generation of highly toxic and corrosive hydrogen fluoride gas, which is more conducive to industrialization.

[0024] 2. The yield of this invention is significantly higher than that of traditional routes, which is beneficial for improving production efficiency and reducing costs. The entire synthetic route involves four reaction steps, with mild reaction conditions and easy operation, achieving an overall yield of over 30% based on cyclopentanone. Attached Figure Description

[0025] Figure 1 The HNMR spectrum of Cy7-P-1 with a meso-diphenylamino group substituted in the middle position was obtained in Example 4;

[0026] Figure 2 The HNMR spectrum of Cy7-P-2 with a mid-diphenylamino group substituted in the middle position was obtained in Example 7. Detailed Implementation

[0027] Example 1:

[0028]

[0029] A mixture of 365 g (5 mol) of N,N-dimethylformamide and 400 mL of dichloromethane was cooled to -6 °C, and then 613 g (4 mol) of phosphorus oxychloride was added dropwise while maintaining the temperature below 0 °C. After the addition was complete, 84 g (1 mol) of cyclopentanone was added dropwise. The resulting yellow reaction solution was heated to 50 °C and reacted for 3 hours. After cooling, the reaction solution was poured into 200 g of crushed ice, kept at 0-5 °C and stirred for 1 hour. The mixture was then filtered and dried to obtain 127 g of condensing agent A, a yellow solid, with a yield of 80%. 1 The HNMR results are consistent with the literature data.

[0030] Example 2:

[0031]

[0032] 60.5 g (0.2 mol) of 1-ethyl-2,3,3-trimethyl-5-chloroindole bromide and 15.8 g (0.1 mol) of condensing agent A were added to a three-necked flask, followed by 200 mL of acetic anhydride and 16.4 g (0.2 mol) of sodium acetate. The mixture was heated to 70 °C and reacted for 1 hour. After the reaction was complete, the reaction solution was poured into a saturated potassium iodide aqueous solution, stirred, filtered, and the filter cake was washed successively with water and methyl tert-butyl ether. After drying, 52.7 g of a metallic solid, Cy7-Cl-1, was obtained, with a yield of 76%. 1 HNMR(400MHz,CD3OD):1.28-1.42(m,12H),1.78(s,6H),3.05(s,4H),4.01-4.11(m,4H),5.36(d,1H),5.59(s,1 H),6.18(s,1H),6.58(s,1H),6.64(t,1H),7.17(dd,1H),7.44(dd,1H),7.57(d,1H),7.65(d,1H),8.86(d,1H).

[0033] Comparative Examples

[0034] Under a nitrogen atmosphere, 50 mL of N,N-dimethylformamide, 6.94 g (0.01 mol) of Cy7-Cl-1 and 2.79 g (0.03 mol) of aniline were added to a reaction flask, and the mixture was heated to 90 °C and stirred for 8 hours. No reaction occurred.

[0035]

[0036] Under a nitrogen atmosphere, 50 mL of N,N-dimethylformamide, 16.94 g (0.01 mol) of Cy7-Cl-, and 2.55 g (0.03 mol) of piperidine were added to a reaction flask, and the mixture was heated to 90 °C and reacted for 2 hours. After the reaction was complete, the reaction solution was added to 150 mL of 20% KI aqueous solution, stirred for 10 min, filtered, and the filter cake was collected, dried under vacuum, and recrystallized from acetone to give 3.86 g of a blue solid, which was the compound Cy7-NP. 1 H NMR(400MHz, CDCl3):1.28-1.38(t,6H),1.47(m,6H),1.51-1.63(m,6H),1.82(s,6H),2.94(t,4H),3.02(s,4H),4.11-4.17(m,4H),5 .35(d,1H),5.62(s,1H),6.19(s,1H),6.57(s,1H),6.62(t,1H),7.20(dd,1H),7.44(dd,1H),7.51(d,1H),7.62(d,1H),8.85(d,1H).

[0037] Under a nitrogen atmosphere, 50 mL of N,N-dimethylformamide, 6.94 g (0.01 mol) of Cy7-Cl-1, and 5.1 g (0.03 mol) of diphenylamine were added to a reaction flask. The mixture was heated to 90 °C and stirred. Samples were taken every 2 hours for monitoring. After 6 hours, TLC showed no reaction. 3.03 g (0.03 mol) of triethylamine was added as an acid-binding agent, and the reaction was continued for 2 hours. TLC still showed no reaction.

[0038] Example 3:

[0039]

[0040] 600 mL of tetrahydrofuran and 52.7 g (0.076 mol) of Cy7-Cl-1 were added to a three-necked flask filled with nitrogen. The temperature was lowered to below -25 °C, and 1.09 g of lithium metal (0.1558 mol) was added. After about 5 minutes, the temperature of the system was observed to rise to -20 °C. The reaction was continued to be stirred for 30 minutes, and the temperature of the system was lowered back to below -25 °C. 10.4 g of trimethyl borate (0.1 mol) dissolved in 15 mL of tetrahydrofuran solution was added dropwise while maintaining the internal temperature below -20 °C. After the addition was completed, the reaction was kept at this temperature for 30 minutes. 10% hydrochloric acid was added dropwise to adjust the pH to 5-6 while maintaining the internal temperature below 0 °C. The mixture was concentrated to remove most of the tetrahydrofuran while maintaining the temperature below 30 °C. 100 mL of saturated ammonium fluoroborate solution was added, and the mixture was stirred for 15 minutes. The mixture was filtered, and the filter cake was washed successively with water and tert-butyl methyl ether. After vacuum drying, 33 g of the borated product Cy7-B-1 was obtained, with a yield of 65%. 1HNMR(400MHz,DMSO-d6):1.34-1.45(m,12H),1.72(s,6H),3.05(s,4H),4.09-4.21(m,4H),5.31(d,1H),5.60(s,1H),6 .27(s,1H),6.51(s,1H),6.63(t,1H),7.23(dd,1H),7.47(dd,1H),7.49(s,2H),7.51(d,1H),7.64(d,1H),8.87(d,1H).

[0041] Example 4:

[0042]

[0043] 150 mL of dichloromethane was added to a three-necked flask, and 33 g (0.05 mol) of the borylated product Cy7-B-1, 10.1 g (0.06 mol) of diphenylamine, 0.45 g (5 mol%) of copper acetate, and 7.6 g (0.075 mol) of triethylamine were added sequentially with stirring. The mixture was kept at 25 °C for 12 h. The reaction solution was washed with 50 mL of water, the organic phase was separated, and then washed again with 50 mL of water. The organic phase was concentrated, and the residue was recrystallized from isopropanol to give 32.8 g of heptamethylamine Cy7-P-1 with a median diphenylamino substituted form, in 80% yield. 1 HNMR(400MHz,CD3OD):1.12(s,12H),1.34(t,6H),2.96(s,4H),3.97(q,4H),5.75(d,2H),6.92(d,2H) ,7.08(t,2H),7.12(d,2H),7.23-7.28(m,6H),7.38(t,4H),7.48(d,2H).UV-VIS:λmax=795nm(CH3OH).

[0044] Example 5:

[0045]

[0046] 76 g (0.2 mol) of 1-methoxyethyl-2,3,3-trimethyl-5-chloroindole iodide and 15.8 g (0.1 mol) of condensing agent A were added to a three-necked flask, followed by 200 mL of acetic anhydride and 16.4 g (0.2 mol) of sodium acetate. The mixture was heated to 70 °C and reacted for 1 hour. After the reaction was complete, the reaction solution was poured into 600 mL of saturated potassium iodide aqueous solution, stirred, filtered, and the filter cake was washed with water and methyl tert-butyl ether, respectively. After drying, 62 g of solid Cy7-Cl-2 with a metallic luster was obtained, with a yield of 82%. 1HNMR(400MHz,DMSO-d6):1.41(s,6H),1.76(s,6H),3.05(m,4H),3.07(s,2H),3.20(s,3H),3.24(s,3H),3.45(t,2H),3.61(t,2H),4.24(t, 2H),5.37(d,1H),5.63(s,1H),6.20(s,1H),6.50(s,1H),6.63(t,1H),7.24(dd,1H),7.41(dd,1H),7.54(d,1H),7.67(d,1H),8.85(d,1H).

[0047] Example 6:

[0048]

[0049] Add 600 mL of tetrahydrofuran and 62 g (0.082 mol) of Cy7-Cl-2 to a nitrogen-filled three-necked flask. Cool to below -25 °C, then add 1.17 g of lithium metal (0.168 mol). After about 5 minutes, the system temperature rises to -20 °C. Continue stirring for 30 minutes, then cool the system temperature back to below -25 °C. Controlling the internal temperature below -20 °C, add 13 g of trimethyl borate (0.125 mol) dissolved in 20 mL of a tetrahydrofuran mixture. After the addition is complete, maintain the temperature for 30 minutes. Controlling the internal temperature below 0 °C, add 10% hydrochloric acid to adjust the pH to 5-6. Controlling the temperature below 30 °C, concentrate to remove most of the tetrahydrofuran. Add 100 mL of saturated ammonium fluoroborate solution, stir for 15 minutes, filter, and wash the filter cake successively with water and tert-butyl methyl ether. Dry under vacuum to obtain 39 g of the borated product Cy7-B-2, with a yield of 66%. 1 HNMR(400MHz,DMSO-d6):1.43(s,6H),1.74(s,6H),3.02-3.05(m,6H),3.24(s,3H),3.27(s,3H),3.44(t,2H),3.62(t,2H),4.24(t,2H),5.30 (d,1H),5.64(s,1H),6.27(s,1H),6.52(s,1H),6.66(t,1H),7.23(dd, 1H),7.40(dd,1H),7.48(s,2H),7.52(d,1H),7.66(d,1H),8.88(d,1H).

[0050] Example 7:

[0051]

[0052] 150 mL of dichloromethane was added to a three-necked flask, and 39 g (0.054 mol) of the borylated product Cy7-B-2, 11 g (0.065 mol) of diphenylamine, 0.49 g (5 mol%) of copper acetate, and 8.2 g (0.081 mol) of triethylamine were added sequentially with stirring. The mixture was kept at 25 °C for 12 h. The reaction solution was washed with 50 mL of water, the organic phase was separated, washed again with 50 mL of water, the organic phase was concentrated, and the residue was recrystallized from acetone to give 37.5 g of heptamethylamine Cy7-B-2 with a median diphenylamine substituted, yield 82%. 1 HNMR(400MHz,DMSO-d6):1.12(s,12H),2.88(s,4H),3.23(s,6H),3.63(t,4H),4.22(t,4H),5.89(t,2 H),7.12(t,2H),7.25(dd,6H),7.36(dd,2H),7.44(m,6H),7.55(d,2H); UV-VIS: λmax=796nm(CH3OH).

[0053] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. For those skilled in the art, various improvements and modifications can be made without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing a meso-diarylamine-substituted heptamethine cyanine dye, characterized in that, The process includes the following steps: using cyclopentanone as a starting material, a condensing agent is first synthesized via a Vilsmeier-Haack reaction, followed by condensation with 2,3,3-trimethylindole quaternary ammonium salt to obtain a mesochlorosubstituted cyanine, then undergoes lithium-mediated borylation to obtain a mesoborinated cyanine, and finally reacts with a diarylamine via a Chan-Lam reaction in the presence of a copper catalyst to obtain a mesodiarylamine-substituted heptamethine cyanine dye; the equations are as follows: Wherein: R1 is selected from hydrogen, C1-C5 alkyl, halogen or C1-C5 alkoxy; R2 is selected from C1-C5 alkyl or C1-C5 alkyl (ether group) containing oxygen atom; R3 and R4 are each independently selected from hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, sulfonic acid group, cyano, nitro or amino; A is selected from halogen.

2. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the first step of the condensation reaction, phosphorus oxychloride and DMF are used as formylation reagents, and the reaction temperature is 30-100℃.

3. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the first step of the condensation reaction, the molar ratio of cyclopentanone, phosphorus oxychloride and DMF is 1:3-6:3-6.

4. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the second condensation reaction, acetic anhydride is used as the reaction solvent, and the reaction temperature is 50-100℃.

5. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the second condensation reaction, the molar ratio of the condensing agent to 2,3,3-trimethylindole quaternary ammonium salt is 1:2-2.

5.

6. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the third step of the borylation reaction, the reaction is carried out in tetrahydrofuran, diethyl ether or 2-methyltetrahydrofuran solvent, and the reaction temperature is -78℃ to -10℃.

7. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 6, characterized in that: In the third step of the borylation reaction, the molar ratio of the chlorosubstituted cyanine, lithium metal and trimethyl borate is 1:2-2.2:1-2.

5.

8. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the fourth coupling reaction, copper acetate was used as a catalyst, triethylamine as a co-catalyst, and dichloromethane as a solvent, with a reaction temperature of 15-50℃.

9. The method for synthesizing the meso-diarylamine-substituted heptamethine cyanide dye according to claim 1, characterized in that: In the fourth coupling reaction, the molar ratio of the meso-boronized anthocyanin, diarylamine, and copper catalyst is 1:1-3:0.02-0.1.

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