A synthetic process for the preparation of 2,3,3,5-tetramethylindole

Abstract

This invention relates to the field of chemical synthesis technology, specifically a method for preparing 2,3,3,5-tetramethylindole. The method comprises using p-methylphenylhydrazine hydrochloride and 3-pentanone as raw materials, generating 2,3,3,5-tetramethylindole through a one-step condensation-cyclization reaction in acetic acid medium, followed by further processing steps. This synthetic method offers significant advantages: First, it is highly efficient, with a one-step condensation-cyclization reaction, a molar yield of 60-68%, HPLC endpoint control, and a total processing time of one day, making it suitable for industrial production. Second, it operates under mild conditions, using acetic acid as both solvent and catalyst, with a reaction temperature of 112℃, allowing the use of ordinary enamel-lined reactors and avoiding corrosion from traditional strong acid equipment. Third, it achieves excellent purity, with no isomers and a purity exceeding 99%, offering flexible purification at low cost. Fourth, it is more environmentally friendly, with a dichloromethane recovery rate ≥90%, and wastewater with a near-neutral pH for easy treatment. Fifth, it is easily scaled up, with quantitative formulas for parameters and flexible process adjustments, adaptable to various production fields.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to a method for preparing 2,3,3,5-tetramethylindole. Background Technology

[0002] Indole compounds are an important branch of nitrogen-containing heterocyclic compounds. Due to their unique molecular structure, they are widely used in the fields of medicine, pesticides, dyes and functional materials. Among them, 2,3,3,5-tetramethylindole, due to the methyl substitution at a specific position, has both good chemical stability and biological activity. It is a core intermediate for the synthesis of antidepressants, organic photoconductors and high-performance dyes, and there is an urgent market demand for it.

[0003] Current methods for synthesizing indole derivatives mainly include Fisher's indole synthesis and transition metal-catalyzed cyclization. However, for polysubstituted indoles such as 2,3,3,5-tetramethylindole, traditional processes have significant drawbacks: First, the reaction conditions are harsh, requiring high temperatures above 150°C or strong acid catalysis such as concentrated hydrochloric acid or polyphosphoric acid, resulting in high energy consumption and strong corrosion of equipment, increasing production costs and maintenance difficulties. Second, the regioselectivity is poor, easily generating positional isomers such as 2,3,5-trimethylindole, making product separation and purification complex. Third, the yield is low, with multiple reaction steps often resulting in an overall yield of less than 50%, leading to low production efficiency. Fourth, it is environmentally unfriendly, using large amounts of volatile organic solvents such as toluene and chloroform, and the wastewater contains strong acids and bases, making treatment difficult and causing serious pollution.

[0004] Currently, there is no synthetic process for 2,3,3,5-tetramethylindole that can simultaneously achieve high efficiency, mildness, high selectivity, and environmental friendliness. Therefore, it is necessary to propose a synthetic method for preparing 2,3,3,5-tetramethylindole. Summary of the Invention

[0005] To address the problems in the prior art, the present invention provides a synthetic method for preparing 2,3,3,5-tetramethylindole.

[0006] The technical solution adopted by this invention to solve its technical problem is: a synthetic method for preparing 2,3,3,5-tetramethylindole, comprising using p-methylphenylhydrazine hydrochloride and 3-pentanone as raw materials, generating 2,3,3,5-tetramethylindole through a one-step condensation-cyclization reaction in acetic acid medium, and a post-processing step for further treatment. The reaction equation is as follows: The post-processing steps are as follows: (1) Cooling and dilution: Cool the reaction solution to 25-30℃, add deionized water, the amount of water being twice the volume of the reaction solution; (2) Neutralization: use 20% Adjust the pH of the solution to 6-7 and control the temperature to ≤40℃; (3) Extraction: Extract three times with dichloromethane, with the volume of the extractant in each extraction being 1.5 times the volume of the organic phase; (4) Concentration: After drying the organic phase with anhydrous sodium sulfate (5% of the organic phase mass), the crude product is obtained by vacuum concentration. Purification: The crude product was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent (volume ratio 10:1~5:1), or, when a purity of ≥95% was required, by vacuum distillation (120-130℃, 2...). ).

[0007] Specifically, the molar ratio of p-methylphenylhydrazine hydrochloride to 3-pentanone is 1:2.3, and the amount of acetic acid used is based on a p-methylphenylhydrazine hydrochloride mass: acetic acid volume = 1:10. The calculation is as follows: ,in , This represents the amount of p-methylphenylhydrazine hydrochloride.

[0008] Specifically, the conditions for the condensation-cyclization reaction are: reaction temperature 112℃ (acetic acid reflux temperature), reaction time 2.5-3 h, and the conversion rate of p-methylphenylhydrazine hydrochloride is monitored by HPLC during the reaction. The conversion rate is calculated using the following formula: The reaction was terminated when the conversion rate was ≥98% and the peak area of ​​2,3,3,5-tetramethylindole was ≥95%.

[0009] Specifically, propionic acid or butyric acid can be used instead of acetic acid as the reaction medium, with reaction temperatures of 141℃ or 163℃ respectively, and product yields of 60-65%.

[0010] Specifically, p-toluenesulfonic acid can be added to the reaction system at a dosage of 5% of the mass of p-methylphenylhydrazine hydrochloride, shortening the reaction time to 2 hours, and requiring the addition of saturated... Solution washing steps.

[0011] Specifically, the product 2,3,3,5-tetramethylindole has a purity ≥95%, a molar yield of 60-68%, and its structure is confirmed by the following methods: (1) Nuclear magnetic resonance hydrogen spectrum ( , As a solvent, Detection conditions): Chemical shift satisfy: , , , , , ,in Represents a double peak, Represents a single peak. The coupling constant; (2) Infrared spectrum ( Detection conditions for tablet compression method): wavenumber of characteristic absorption peak satisfy: (Corresponding to NH bond stretching vibration) (Corresponding to CH bond stretching vibration) (Corresponding to benzene ring skeleton vibration); (3) Purity and yield calculations must conform to the following formulas: ①Purity The area was calculated using the high-performance liquid chromatography (HPLC) area normalization method, and the formula is as follows: ,in, The HPLC peak area for 2,3,3,5-tetramethylindole is... This is the total area of ​​all chromatographic peaks in the HPLC chromatogram (including the target product peak and impurity peaks). ②Molar yield The formula is as follows: Based on p-methylphenylhydrazine hydrochloride. in, The mass of purified 2,3,3,5-tetramethylindole (in g). =175.27 The molar mass of 2,3,3,5-tetramethylindole The mass of p-methylphenylhydrazine hydrochloride added (unit: g). =161.63 This represents the molar mass of p-methylphenylhydrazine hydrochloride; ③ Weight yield The formula for characterizing the mass of the target product corresponding to a unit mass of raw material p-methylphenylhydrazine hydrochloride is: in, , Define the formula for yield per molar, and in this method... The value ranges from 0.70 to 0.74 (corresponding to a molar yield of 60-68%).

[0012] The beneficial effects of this invention: The synthetic method for preparing 2,3,3,5-tetramethylindole described in this invention... High efficiency: The condensation-cyclization reaction is completed in one step, with a molar yield of 60-68% (traditional <50%). The reaction endpoint is monitored in real time by HPLC to avoid waste of raw materials. The total working time is only 1 day, which is suitable for industrial production.

[0013] Mild conditions: Using acetic acid as both solvent and catalyst, the reaction temperature is 112℃ (no high temperature and high pressure required), and ordinary enamel-lined reactors can be used, reducing equipment investment and maintenance costs and avoiding the strong corrosion problems of traditional strong acids on equipment.

[0014] High purity: The raw materials have a high degree of structural matching and no positional isomer byproducts, with a product purity of over 99%; Flexible purification: Purity ≥95% can be directly distilled under reduced pressure, while silica gel column chromatography can be used for high purity requirements, resulting in low separation costs.

[0015] More environmentally friendly: Dichloromethane recovery rate ≥90%, reducing solvent waste; the pH of the neutralized wastewater is close to neutral, making treatment simple and significantly reducing pollution and wastewater treatment costs compared to traditional processes.

[0016] Easy to scale up: Parameters such as raw material ratio and solvent dosage are all quantified, and the stability is strong from laboratory small-scale tests to industrial pilot-scale tests; it can also flexibly replace solvents and add catalysts to adapt to the production needs of multiple fields such as pharmaceuticals and optoelectronic materials. Attached Figure Description

[0017] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0018] Figure 1 A schematic diagram of the synthetic method for preparing 2,3,3,5-tetramethylindole provided by the present invention; Figure 2 A reaction route diagram for the synthesis of 2,3,3,5-tetramethylindole provided by the present invention; Figure 3 An analytical report diagram illustrating a synthetic method for preparing 2,3,3,5-tetramethylindole provided by this invention. Detailed Implementation

[0019] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0020] like Figures 1-2 As shown, the present invention provides the following technical solution: Example 1: A synthetic method for preparing 2,3,3,5-tetramethylindole, comprising using p-methylphenylhydrazine hydrochloride and 3-pentanone as raw materials, generating 2,3,3,5-tetramethylindole through a one-step condensation-cyclization reaction in acetic acid medium, and further processing steps. The reaction equation is as follows: The post-processing steps are as follows: (1) Cooling and dilution: Cool the reaction solution to 25-30℃, add deionized water, the amount of water being twice the volume of the reaction solution; (2) Neutralization: use 20% Adjust the pH of the solution to 6-7 and control the temperature to ≤40℃; (3) Extraction: Extract three times with dichloromethane, with the volume of the extractant in each extraction being 1.5 times the volume of the organic phase; (4) Concentration: After drying the organic phase with anhydrous sodium sulfate (5% of the organic phase mass), the crude product is obtained by vacuum concentration. Purification: The crude product was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent (volume ratio 10:1~5:1), or, when a purity of ≥95% was required, by vacuum distillation (120-130℃, 2...). ).

[0021] Wherein, the molar ratio of p-methylphenylhydrazine hydrochloride to 3-pentanone is 1:2.3, and the amount of acetic acid used is based on the ratio of p-methylphenylhydrazine hydrochloride mass to acetic acid volume = 1:10. The calculation is as follows: ,in , This represents the amount of p-methylphenylhydrazine hydrochloride.

[0022] The condensation-cyclization reaction conditions were: reaction temperature 112℃ (acetic acid reflux temperature), reaction time 2.5-3 h. The conversion rate of p-methylphenylhydrazine hydrochloride was monitored by HPLC during the reaction, and the conversion rate was calculated using the following formula: The reaction was terminated when the conversion rate was ≥98% and the peak area of ​​2,3,3,5-tetramethylindole was ≥95%.

[0023] Propionic acid or butyric acid can be used instead of acetic acid as the reaction medium, with reaction temperatures of 141℃ or 163℃ respectively, and product yields of 60-65%.

[0024] In this process, p-toluenesulfonic acid can be added to the reaction system at a concentration of 5% of the mass of p-methylphenylhydrazine hydrochloride. This shortens the reaction time to 2 hours and requires the addition of saturated... Solution washing steps.

[0025] The product 2,3,3,5-tetramethylindole has a purity ≥95%, a molar yield of 60-68%, and its structure is confirmed by the following methods: (1) Nuclear magnetic resonance hydrogen spectrum ( , As a solvent, Detection conditions): Chemical shift satisfy: , , , , , ,in Represents a double peak, Represents a single peak. The coupling constant; (2) Infrared spectrum ( Detection conditions for tablet compression method): wavenumber of characteristic absorption peak satisfy: (Corresponding to NH bond stretching vibration) (Corresponding to CH bond stretching vibration) (Corresponding to benzene ring skeleton vibration); (3) Purity and yield calculations must conform to the following formulas: ①Purity The area was calculated using the high-performance liquid chromatography (HPLC) area normalization method, and the formula is as follows: ,in, The peak area is for 2,3,3,5-tetramethylindole. This is the total area of ​​all chromatographic peaks in the HPLC chromatogram (including the target product peak and impurity peaks). ②Molar yield The formula is as follows: Based on p-methylphenylhydrazine hydrochloride. in, The mass of purified 2,3,3,5-tetramethylindole (in g). =175.27 The molar mass of 2,3,3,5-tetramethylindole The mass of p-methylphenylhydrazine hydrochloride added (unit: g). =161.63 This represents the molar mass of p-methylphenylhydrazine hydrochloride; ③ Weight yield The formula for characterizing the mass of the target product corresponding to a unit mass of raw material p-methylphenylhydrazine hydrochloride is: in, , Define the formula for yield per molar, and in this method... The value ranges from 0.70 to 0.74 (corresponding to a molar yield of 60-68%).

[0026] When using it, the following steps are included: Step 1: Pre-production preparation: Raw materials and reagents: p-methylphenylhydrazine hydrochloride (purity ≥98%), 3-pentanone (purity ≥99%), acetic acid (analytical grade). =1.049 ), 20% (quality fraction) Solution, dichloromethane (analytical grade) =1.326 Anhydrous sodium sulfate (analytical grade), silica gel (for column chromatography, 200-300 mesh), petroleum ether (boiling range 60-90℃), ethyl acetate (analytical grade); Equipment verification: Electronic balance: accuracy 0.01g, calibrated with standard weights; pH meter: accuracy ±0.01, calibrated with standard buffer solutions of pH=4.00 and 7.00; High-performance liquid chromatography (HPLC): equipped with a C18 column (250mm × 4.6mm, 5) The recovery rate should be 98%-102% when verified using 2,3,3,5-tetramethylindole standard with a purity of 99.9%. Reactor: 100L enamel-lined reactor (with stirrer, reflux condenser, and thermometer), airtightness test pressure fluctuation ≤0.01. ; Step 2: Feeding and Reaction Control Feeding procedure: Add 16.2L of acetic acid to a 100L reactor and start stirring (200-300r / min). Then slowly add 1616.3g of p-methylphenylhydrazine hydrochloride and stir for 15min until completely dissolved to form a clear solution. Then control the temperature inside the reactor to ≤30℃. Then slowly add 1980.99g of 3-pentanone through a dropping funnel over 30-40min to avoid local overheating. Heating and Holding: Turn on the jacket heating, with a heating rate of 5-8℃ / min. When the temperature reaches 110℃, adjust the rate to 1℃ / min until it stabilizes. =112℃ (acetic acid reflux temperature), record the reaction start time. ; Thermal reaction =3h, 5mL sampled every 30min, and the conversion rate of p-methylphenylhydrazine hydrochloride was detected by HPLC. The calculation formula is as follows: in, This represents the HPLC peak area of ​​p-methylphenylhydrazine hydrochloride at the initial stage of the reaction. for Measure the peak area of ​​p-methylphenylhydrazine hydrochloride at specific times; if the conversion rate is ≥98%, the reaction can be terminated early; if the conversion rate is <95% after 3 hours, add 5% 3-pentanone (approximately 99g) and continue the reaction for 30 minutes; Determining the endpoint of a reaction: The reaction can be terminated when the following two conditions are met: p-Methylphenylhydrazine hydrochloride conversion rate ≥98%; The peak area of ​​p-methylphenylhydrazine hydrochloride in the HPLC chromatogram is ≥95% (total impurity peak area ≤5%), and the reaction solution is a clear brownish-red color. Step 3: Post-processing (neutralization, extraction, concentration): Cooling and Dilution: Turn off the heating, turn on the jacket cooling water, and lower the temperature of the reaction solution to 25-30℃ at a rate ≤10℃ / min. Then add deionized water to dilute the solution, calculating the water volume as "twice the volume of the reaction solution": reaction solution volume ≈ , For the volume of 3-pentanone, according to calculate, =0.183 ,in =1980.99 / 0.813≈2437mL, therefore the water volume is: =2×(16200+2437)=37274mL (actually 37.3L was taken), stir for 10min; Neutralization and adjustment: Turn on the stirrer (150 rpm), and add 20% of the mixture dropwise using a peristaltic pump. For the solution, drop at a rate of 50-80 mL / min, and monitor the pH value in real time. When the pH approaches 5, adjust the dropping rate to 10-20 mL / min until the pH stabilizes at 6-7 (the neutralization process is exothermic, so the temperature inside the vessel must be controlled ≤40℃; if the temperature exceeds the limit, turn on the cooling water). After neutralization, stir for 15 min, let stand for 30 min, and the system will separate into layers (the upper layer is the aqueous phase, and the lower layer is the organic phase). Dichloromethane extraction: Extractant dosage: calculated as "1.5 times the volume of the organic phase", extracted in 3 stages, with the volume of extractant per stage being... ; First extraction: Add Stir for 20 minutes (250 r / min), let stand for 40 minutes, and release the lower organic phase into the storage tank; repeat the operation 2 times, and combine the organic phases 3 times. Drying: Add anhydrous sodium sulfate to the combined organic phases at a rate of 5% of the organic phase mass, calculated as follows: ,in (Density of dichloromethane mixed with 2,3,3,5-tetramethylindole), stir for 30 min, let stand for 2 h to dry; Vacuum Concentration: Transfer the dried organic phase to a vacuum concentration tank, turn on the vacuum pump, control the vacuum degree to -0.095~-0.098MPa, and the jacket heating temperature to 50-60℃; collect the fraction (mainly dichloromethane, recovery rate ≥90%) under these conditions. When no obvious fraction flows out, stop the concentration to obtain a brown oily crude product, which is then weighed. Calculate the crude product yield: , ,in =10 × 175.27 = 1752.7g. If the actual crude product obtained is 1820g, then... =1820 / 1752.7≈103.8% (Due to the presence of a small amount of solvent, the yield of the crude product may be slightly higher than 100%). Step 4: Purification Silica gel column chromatography purification: Column packing: Wet packing is used, and the amount of silica gel is "20 times the crude mass" (as shown in the example). =20×1820=36400g), balance the column with petroleum ether; Sample loading: Dissolve the crude product in a small amount of dichloromethane (about 50 mL) and load the sample slowly; Elution: The eluent was a mixture of petroleum ether and ethyl acetate with an initial volume ratio of 10:1. The ratio was adjusted according to TLC monitoring (Rf value controlled between 0.3 and 0.5), and the eluent containing 2,3,3,5-tetramethylindole was collected. Product concentration: The collected eluent is concentrated under reduced pressure (under the same conditions as before) to obtain a brownish-red oily product, which is then weighed. Calculate the final yield and purity: Molar yield: ; Weight yield: ; Purity: determined by HPLC area normalization method, formula: ,in The peak area is for 2,3,3,5-tetramethylindole. The total area of ​​all peaks; Step 5, Results: In the example, 1710g of 2,3,3,5-tetramethylindole product with a purity of 99% was finally obtained. Therefore: (After deducting purification losses, the actual industrial yield is stable at around 68%) (The yield was 0.74% by weight in the laboratory pilot test. The yield increased slightly after industrial scale-up due to improved equipment efficiency.)

[0027] like Figure 3 As shown in the analysis report for 2,3,3,5-tetramethylindole: Chromatographic analysis conditions: Detector: FID (Flame Ionization Detector) Chromatographic column: C18 column (250mm × 4.6mm, 5) ); Mobile phase: methanol-water (volume ratio 80:20); Flow rate: 1.0 mL / min; Column temperature: 30℃; Detection wavelength: 254nm; The sample showed a main peak at a retention time of approximately 6.099 min, which was consistent with the characteristic retention time of 2,3,3,5-tetramethylindole. There were no obvious interference from other peaks, indicating that the main component peak of the product was well separated. Based on the peak table data, the product purity was calculated using the area normalization method. ; The 2,3,3,5-tetramethylindole sample (YF22169-221122-F1) analyzed in this study was found to have a purity of 99.73% by high performance liquid chromatography (HPLC), which is far higher than the industry standard (≥95%). The main peak was well separated and there was no significant impurity interference. The product quality meets the application requirements of high-end pharmaceutical and optoelectronic material intermediates.

[0028] Example 2: The technical solutions in this example that differ from Example 1 include: 1. Solvent substitution: Propionic acid can be used ( ) or butyric acid ( If acetic acid is substituted, the reaction temperature needs to be raised to 141℃ (propionic acid reflux) and 163℃ (butyric acid reflux), respectively, and the yield will drop to 60-65%, but the corrosion of the equipment can be reduced. 2. Catalyst addition: Adding p-toluenesulfonic acid (PTSA, at 5% of the mass of p-methylphenylhydrazine hydrochloride) to the reaction system can shorten the reaction time to 2 hours, but a neutralization step is required (using 20%). After adjusting the pH to 6-7, use additional saturated water. Wash once with the solution). 3. Purification Optimization: If the product purity requirement is ≥95% (e.g., for non-pharmaceutical applications), silica gel column chromatography can be omitted, and purification can be directly performed using vacuum distillation under the following conditions: temperature 120-130℃, vacuum degree 2. The distillation yield is ≥90%, and the process cost is reduced by 30%.

[0029] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of protection claimed by the present invention. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A synthetic method for preparing 2,3,3,5-tetramethylindole, characterized in that, The reaction involves a one-step condensation-cyclization reaction of p-methylphenylhydrazine hydrochloride and 3-pentanone in acetic acid to produce 2,3,3,5-tetramethylindole, followed by a post-treatment step. The reaction equation is as follows: The post-processing steps are as follows: (1) Cooling and dilution: Cool the reaction solution to 25-30℃, add deionized water, the amount of water being twice the volume of the reaction solution; (2) Neutralization: use 20% Adjust the pH of the solution to 6-7 and control the temperature to ≤40℃; (3) Extraction: Extract three times with dichloromethane, with the volume of the extractant in each extraction being 1.5 times the volume of the organic phase; (4) Concentration: After drying the organic phase with anhydrous sodium sulfate, the crude product is concentrated under reduced pressure. Purification: The crude product was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent, at a volume ratio of 10:1 to 5:

1. Alternatively, when a purity of ≥95% was required, vacuum distillation was used at 120-130℃. .

2. The method for preparing 2,3,3,5-tetramethylindole according to claim 1, characterized in that: The molar ratio of p-methylphenylhydrazine hydrochloride to 3-pentanone is 1:2.

3. The amount of acetic acid used is calculated based on a p-methylphenylhydrazine hydrochloride mass: acetic acid volume = 1:10, using the formula: ,in , This represents the amount of p-methylphenylhydrazine hydrochloride.

3. The method for preparing 2,3,3,5-tetramethylindole according to claim 1, characterized in that: The conditions for the condensation-cyclization reaction were: reaction temperature 112℃ (the reflux temperature of acetic acid), reaction time 2.5-3 h, and the conversion rate of p-methylphenylhydrazine hydrochloride was monitored by HPLC during the reaction. The conversion rate was calculated using the following formula: The reaction was terminated when the conversion rate was ≥98% and the peak area of ​​2,3,3,5-tetramethylindole was ≥95%.

4. The method for preparing 2,3,3,5-tetramethylindole according to claim 1, characterized in that: Propionic acid or butyric acid can be used instead of acetic acid as the reaction medium, with reaction temperatures of 141℃ or 163℃ respectively, and product yields of 60-65%.

5. The method for preparing 2,3,3,5-tetramethylindole according to claim 1, characterized in that: Adding p-toluenesulfonic acid to the reaction system, at a dosage of 5% of the mass of p-methylphenylhydrazine hydrochloride, shortens the reaction time to 2 hours and requires increasing the saturation point. Solution washing steps.

6. The method for preparing 2,3,3,5-tetramethylindole according to claim 1, characterized in that: The product 2,3,3,5-tetramethylindole has a purity ≥95%, a molar yield of 60-68%, and its structure is confirmed by the following methods: (1) Proton nuclear magnetic resonance spectrum, , As a solvent, Detection conditions: chemical shift satisfy: , , , , , ,in Represents a double peak, Represents a single peak. The coupling constant; (2) Infrared spectrum, Tablet compression method detection conditions: wavenumber of characteristic absorption peak satisfy: : Corresponding to the stretching vibration of the NH bond, : Corresponding to CH bond stretching vibration, : Corresponds to the vibration of the benzene ring skeleton; (3) Purity and yield calculations must conform to the following formulas: ①Purity The area was calculated using the high-performance liquid chromatography (HPLC) area normalization method, and the formula is as follows: ,in, The HPLC peak area for 2,3,3,5-tetramethylindole is... This represents the total area of ​​all chromatographic peaks in the HPLC chromatogram, including the target product peak and impurity peaks. ②Molar yield The formula is as follows: Based on p-methylphenylhydrazine hydrochloride, the calculation is: in, The mass of purified 2,3,3,5-tetramethylindole. =175.27 The molar mass of 2,3,3,5-tetramethylindole For the mass of p-methylphenylhydrazine hydrochloride added, =161.63 This represents the molar mass of p-methylphenylhydrazine hydrochloride; ③ Weight yield The formula for characterizing the mass of the target product corresponding to a unit mass of raw material p-methylphenylhydrazine hydrochloride is: in, , Define the formula for yield per molar, and in this method... The value range is 0.70-0.74.

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