Some thoughts on the testing of indicators in phenol products

Experiment 1: pH Value and Solubility of Saturated Solutions of Phenol at Different Temperatures I. Objective of the experiment: To determine the relationship between the pH value and solubility of saturated solutions of phenol at different temperatures. II. Basic principles: ***phenol in solution exists in the following ionization equilibrium. The equilibrium concentrations of HR and H+ are denoted respectively, with K being the ionization constant. The saturated concentration of ***phenol can be determined by titration with a NaOH standard solution. The concentration of H+ ions resulting from its ionization can be calculated using the pH value of the phenol solution measured with a pH meter at a certain temperature, based on the relationship pH = –lg[H+]. Additionally, the values of C and other relevant quantities can be determined using the equations C = … and …; by substituting these values into Equation 1, it is possible to compare them with the standard Ki value in order to assess the accuracy of the data at 25°C. III. Instruments and reagents: p-cresol (pure), Leici PHS-3C pH meter, 50 mL alkaline burette, 10 mL pipette, 10 mL volumetric pipette, thermometer, constant temperature water bath. IV. Experimental procedure: Prepare a saturated solution of pure p-cresol by placing it in a water bath; set the constant temperature at 30°C. Stir the solution until the temperature stabilizes, then let it stand for 30 minutes. Use a calibrated pH meter to determine the pH value of the saturated p-cresol solution at 30°C. Weigh a certain amount of this saturated solution and titrate it using NaOH standard solution to determine the concentration of p-cresol in it; subsequently, calculate the density of this solution. The specific measurement data are as follows: Sequence Number, Temperature (°C), pH Value, Phenol Content (%), Solubility, Measured Value of LgKi. 1: 22.8, 4.03, 1.33, 1.35, 7.04; 2: 24.8, 4.02, 1.32, 1.34, 7.02; 3: 25.0, 3.98, 1.45, 1.47, 6.978; 4: 28.8, 3.94, 1.74, 1.77, 6.978; 5: 29.5, 3.93, 1.76, 1.79, 6.96; 6: 30.6, 3.91, 1.86, 1.90, 6.9465; 7: 31.2, 3.90, 1.97, 2.01, 6.9515; 8: 32.5, 3.89, 2.13, 2.18, 6.9654

Experiment 2: Determination of free acid in normally produced p-hydroxybenzene. I. Principle: Based on the data obtained from Experiment 1, the appropriate temperature for titrating free acid was determined to be 25°C at a pH of 3.98. Since the pH value of water-saturated solutions of phenol remains relatively constant within the range of 25–32°C, 25°C was chosen as the reference temperature. ) II. Steps: Weigh about 1.6 g of normally produced p-phenol sample, dissolve it in hot water, then cool it to 25°C, using a pH meter as the indicator to determine the endpoint. First, record the pH value of the phenol solution at the start. Titrate it using a 0.005 mol/L NaOH standard solution, with the endpoint set at pH=3.98; then record the volume of NaOH used. III. Calculation formula: Percentage of free acid (%) = (C × V × M) / 1000. Where V is the volume of the NaOH standard solution used, c is the concentration of the NaOH standard solution, M is the molecular weight of HCl (36.45), and m is the mass of p-hydroxybenzene weighed. The specific measurement data are as follows:

Batch Number | Appearance | Solution Temperature (°C) | pH before titration | Titration volume (ml) | Percentage of free acid%
-------------|------------|------------------------|---------------------|----------------------|--------------------------|
2-168B | Beige | 27.9 | 3.00 | 9.60 | 0.112 |
25.8 | Beige | 3.12 | 11.45 | 0.132 |
2-169B | Beige | 30.4 | 3.17 | 6.15 | 0.07 |
29.1 | Beige | 3.17 | 6.70 | 0.075 |
2-170B | Beige | 33.5 | 3.48 | 4.40 | 0.050 |
28.1 | Beige | 3.40 | 5.05 | 0.058 |
2-171B | Beige | 30.8 | 3.50 | 4.75 | 0.054 |
26.5 | Beige | 3.56 | 4.82 | 0.051 |
2-172B | Beige | 23.0 | 2.98 | 12.45 | 0.145 |
23.7 | Beige | 2.87 | 11.80 | 0.136 |
2-173B | Beige | 30.8 | 3.39 | 4.40 | 0.051 |
28.5 | Beige | 3.29 | 5.75 | 0.059 |
2-175B | Beige | 28.3 | 3.53 | 3.40 | 0.40 |
31.6 | Beige | 3.49 | 3.80 | 0.043 |
2-177B | Beige | 25.5 | 3.17 | 6.20 | 0.071 |
29.8 | Beige | 3.22 | 6.50 | 0.076 |
2-178B | Beige | 26.6 | 3.22 | 6.10 | 0.070 |
25.5 | Beige | 3.20 | 5.90 | 0.068 |
2-166B | Light green| 26.2 | 3.16 | 7.30 | 0.084 |
27.5 | Light green| 3.10 | 7.80 | 0.087 |
2-167B | Light green| 26.6 | 3.23 | 6.05 | 0.068 |
26.2 | Light green| 3.35 | 5.20 | 0.061 |
2-176B | Light green| 29.2 | 3.25 | 5.70 | 0.066 |
27.0 | Light green| 3.18 | 5.40 | 0.061 |
362B | Light green| 30.3 | 3.25 | 5.65 | 0.0655 |
31.6 | Light green| 3.14 | 7.55 | 0.0703 |
242B | Light green| 30.1 | 3.48 | 3.90 | 0.0447 |
32.1 | Light green| 3.36 | 5.45 | 0.0504 |
245B | Light green| 29.1 | 3.49 | 3.80 | 0.0437 |
30.1 | Light green| 3.41 | 4.95 | 0.0450 |

Determination of phenol and phenoxide products (liquid chromatography method) 1. Method summary: High-performance reverse-phase liquid chromatography is used, with methanol+water as the mobile phase; gradient elution is employed to separate the various components in the sample. Detection is carried out using a UV detector, and the contents of the main peak and various components are determined by area normalization. Note: Protocol design: 1.1 Under certain conditions, a phenol sample of a specific concentration was prepared and subjected to chromatographic analysis. Only one impurity peak was detected, with almost no trace of the expected impurities. Using pure substances as references, it was found that m-phenol and p-phenol could not be separated at all, while nitrobenzene, due to its low concentration and proximity to the main peak, was difficult to separate. (The spectra are shown in PAP01013–PAP01032.) 1.2 By adjusting the ratio of the mobile phase and the column flow rate, it is possible to separate m-cresol, o-cresol, and p-cresol. However, the retention time for nitrobenzene (o-nitrochlorobenzene) is too long; it takes 45 minutes to complete the analysis of one sample. (Spectra are shown in PAP01037–PAP01052.) 1.3 A gradient elution method is used to accelerate the analysis of the samples. (Spectra are shown in PAP01081–PAP01085) 1.4 This method still needs further improvement. 2. Instruments (HPLC1100) 2.1 Infusion pump: flow rate of 0–5 ml/min, maximum operating pressure of 400 bar ； 2.2 Detector: Variable-wavelength UV absorption detector ； 2.3 Automatic sampling valve or manual sampling valve with 10ul dosing tube ； 2.4 Chromatography column: 4.6×150mm ZORBAX SB-C18 2.5 Recording device: Chemical workstation ； 2.6 Solution filtration device: equipped with water-based and organic-based filtration membranes, sample filtration head ； 2.7 Ultrasonic generator ； 2.8 Micropipette: 10ul flat-tip pipette ； 3. Reagents 3.1 Methanol: chromatographic grade ； 3.2 Water: twice-distilled water ； 4. Chromatographic analysis conditions: The optimal analysis conditions are selected based on the specific instrument used. Taking an HPLC liquid chromatograph as an example, the analysis conditions are as follows: 4.1 Column temperature: 40℃ ； 4.2 Injection volume: 10ul ； 4.3 Detector wavelength: 254nm ； 4.4 The composition and flow rates of the mobile phase are as follows: Time (min) Phase A (water) Phase B (methanol) Flow rate (ml/min) 0.0 60.0 40.0 0.5 17.0 60.0 40.0 0.5 17.5 35.0 65.0 1.0 30.0 35.0 65.0 1.0 5. Preparation of standard samples 5.1 Weigh 0.0168 g of o-cresol, 0.0067 g of m-cresol, 0.0925 g of p-nitrochlorobenzene, 0.0157 g of o-nitrochlorobenzene, and 0.080 g of m-nitrochlorobenzene respectively, and place them in a 100 ml volumetric flask. Dilute with methanol to the mark, mix well, and set aside for use. As Solution A. 5.2 Weigh 6.1761 g of p-***phenol and transfer it into a 100 ml B volumetric flask. Transfer 15 ml of solution A into this B flask, dilute to the mark with methanol, mix well, and set aside for use. As Solution B. 5.3 Transfer 10 ml of Solution B into a 50 ml volumetric flask, dilute to the mark with methanol, seal the flask tightly, place it in an ultrasonic generator for vibration; after the sample is homogenized, filter it and then inject it. 6. Determination of the sample. Weigh 0.2 g of the sample and place it in a 25 ml volumetric flask; dilute with methanol to the mark, seal the flask, and place it in an ultrasonic generator for vibration. After the sample is well mixed, filter it and then use it as the sample for analysis.

For phenol (gas chromatography): 1. Method summary: Gas chromatography is used to separate the various components in the sample; detection is performed using a hydrogen flame ionization detector, and the concentrations of the main peak and various components are calculated by area normalization. 1.1 Exploration of conditions: ① Selection of an appropriate solvent: Given that phenols are readily soluble in alcohols and ethers, methanol was chosen as the solvent; however, since there are too many impurities in alcohols, chromatography using methanol is necessary. The spectra are shown in (1) and (2). ②Searching for the optimal analysis conditions A; Detector temperature: 250℃ ； Vaporization chamber temperature: 250℃ ； Column temperature: Programmed heating – initially at 40°C for 2 minutes; then from 40°C to 100°C at a rate of 40°C/min. At 100°C, the temperature was held for 0.5 minutes; from 100°C to 140°C at a rate of 2°C/min; and from 140°C to 250°C at a rate of 30°C/min. Injection volume: 0.4 ul. The spectrum is shown in (3). The baseline is unstable, the main peak appears after 27.415 minutes, while the impurity peaks appear only after 140°C. B. Detector temperature: 250℃ ； Vaporization chamber temperature: 250℃ ； Column temperature: Programmed heating from an initial temperature of 120°C to 230°C, with a heating rate of 10°C/min. Injection volume: 0.4 ul. The spectra are shown in (4). As can be seen from spectra (3) and (4), there are few organic impurities in the phenol; no low-boiling or high-boiling substances are present, so a lower column temperature is sufficient, and programmed heating is not necessary. C. Detector temperature: 250℃ ； Vaporization chamber temperature: 250℃ ； Column temperature: 150°C D, Detector temperature: 250℃ ； Vaporization chamber temperature: 250℃ ； Column temperature: 180°C. The spectrum is shown in (5). 1.2 Qualitative identification of impurity peaks: Possible impurities present in phenol include o-***phenol ； m-***phenol ； o-Nitrochlorobenzene ； m-Nitrochlorobenzene ； p-Nitrochlorobenzene. The spectrum is shown in (6). 2. Instruments: HP6820 2.1 Gas supply (H2, Air, carrier gas); 2.2 Gas chromatograph; 2.3 Chromatographic column (DB-5, length 30 m, diameter 0.45 mm); 2.4 Voltage stabilizer; 2.5 Chemical workstation; 2.6 Injector (1 ul). 3. Reagents: Methanol (chromatographically pure). 4. Chromatographic analysis conditions: The optimal analysis conditions are selected based on the specific instrument; here, the 6820 gas chromatograph is used as an example. 4.1 Detector temperature: 250℃ ； 4.2 Vaporization chamber temperature: 250℃ ； 4.3 Column temperature: 180℃ ； 4.4 Column flow rate: 4.02 ml/min 4.5 H2 flow rate: 50.4 ml/min 4.6 Air flow rate: 431 ml/min 4.7 Split flow rate: 83.3 ml/min 5. Preparation of standard samples: 5.1 Weigh 0.0168 g of o-***phenol, 0.0067 g of m-***phenol, 0.0925 g of p-nitrochlorobenzene, 0.0157 g of o-nitrochlorobenzene, and 0.080 g of m-nitrochlorobenzene respectively, and place them in a 100 ml volumetric flask. Dilute with methanol to the mark, mix well, and set aside for use. As Solution A. 5.2 Weigh 6.1761 g of p-***phenol and transfer it into a 100 ml B volumetric flask. Take 15 ml of solution A and add it to the B volumetric flask, then dilute to the mark with methanol. After mixing well, the sample is prepared for analysis. The spectrum is shown in (7). 6. Sample analysis: Weigh 0.5 g of the sample and place it in a 25 ml volumetric flask; dilute it with methanol to the mark, seal the flask, and after the sample is well mixed, proceed with sampling. The spectrum is shown in ()

What has been provided above is not a corporate standard; it’s something I came up with on my own. Corporate standards only determine the content levels

Preface: This standard applies to p-***phenol, which is produced by the hydrolysis and acidification of p-nitrochlorobenzene. The formatting of this standard is prepared in accordance with the relevant provisions of GB/T 1.1-2002 and GB/T 1.2-2002. This standard is formulated with reference to domestic manufacturers in the same industry as well as the production and actual usage requirements of our own factory. The physical and chemical parameters, testing methods, sampling methods, packaging, labeling, transportation, and storage specified in this standard remain in line with the contents of the relevant standards. This standard adds 7.5 Safety Usage Provisions. As of the date of implementation of this standard, the enterprise standard “Regarding *** Phenol” shall be repealed simultaneously. This standard was first published in July 2000, revised for the first time in August 2003, and revised for the second time in August 2006. The main drafter of this standard is: For ***phenol 1: This standard specifies the physical and chemical parameters of ***phenol, sampling methods, testing procedures, inspection rules, as well as requirements regarding labeling, packaging, transportation, storage, and safety. This standard applies to p-***phenol, which is produced by the hydrolysis and acidification of p-nitrochlorobenzene. Chemical name: 4-***phenol Molecular formula: C6H5NO3 Structural formula: Relative molecular weight: 139.11 (based on the international relative atomic masses of 1991). ) 2 Normative reference standards The provisions of the following documents become provisions of this standard through standard references. For any referenced documents dated, all subsequent amendment sheets (excluding corrections) or revised versions are not applicable to this standard; however, parties reaching an agreement under this standard are encouraged to consider whether the latest versions of such documents can be used. For reference documents without a date, the latest version applies to this standard. GB190 – Marking for packaging of dangerous goods; GB/T601 – Chemical reagents – Preparation of standard titration solutions; GB/T602 – Chemical reagents – Preparation of standard solutions for the determination of impurities; GB/T603 – Chemical reagents – Preparation of preparations and products used in test methods; GB/T6679 – General rules for sampling of solid chemical products; GB/T6682 – Specifications and test methods for water used in analytical laboratories. Requirements: 3.1 The physicochemical parameters of ***phenol shall meet the requirements specified in Table 1. Table 1: Parameter | Specification | First-class product | Conforming product; Appearance: Light yellow to light brown crystals; Content of ***phenol, %: ≥ 92.00, 88.00. Sampling: In accordance with GB/T6679, samples shall be taken from 40% of the packaging bags of each batch of products (with each reaction unit considered as one batch). Samples are taken from the upper, middle, and lower parts of the packaging bags using a stainless steel probe, mixed evenly, and then placed in two clean and dry plastic bags or wide-mouth bottles with stoppers (the total sample weight shall be no less than 250 g). The containers are sealed, and labels are attached indicating the manufacturer’s name, product name, batch number, and sampling date. One set of samples is used for testing by the inspection department, while another set is stored for three months for future reference. 5 Test Methods Unless otherwise specified, only analytically pure reagents and water of grade 3 as specified in GB/T6682 or water of equivalent purity shall be used in the analysis. The standard solutions, preparations, and products required for the tests shall be prepared in accordance with the provisions of GB/T601 and GB/T603 unless otherwise specified. 5.1 Appearance: Determined by visual inspection. 5.2 Determination of ***phenol content 5.2.1 Reagents and solutions 5.2.1.1 Standard sodium hydroxide titration solution: C(NaOH) = 0.1000 mol/L standard solution ； 5.2.1.2 Thymol blue–phenolphthalein mixed indicator solution: Weigh 0.12 g of thymol blue and 0.34 g of phenolphthalein, and dissolve them in 100 ml of 60% alcohol solution. 5.2.2 Instruments: General laboratory instruments. 5.2.3 Analysis procedure: Weigh about 0.2 g of the sample (with precision to 0.0001 g), place it in a 250 ml beaker, and dissolve it using 80 ml of hot water. After cooling, add four drops of thymol blue-phthalein mixed indicator, and titrate with a standard sodium hydroxide solution until the color changes from green to orange, indicating the end point. 5.2.4 Calculation of results The mass percentage X of ***phenol content is calculated as follows: X = C(NaOH) × V × 0.1391 × 100% / m, where C(NaOH) is the concentration of the standard sodium hydroxide titrant solution, in mol/l ； V — Volume of the sodium hydroxide standard titrant used, in ml ； m —— mass of the sample, in g; 0.1391 —— mass of ***phenol expressed in g, equivalent to 1 ml of standard sodium hydroxide titrant solution [C(NaOH=1.0000]]. 5.2.5 Allowable difference: The absolute difference between the results of two parallel measurements shall not be greater than 0.2%. The arithmetic mean of the parallel test results is used as the reported value. 6 Inspection Rules 6.1 For the determination of the quality criteria for ***phenol in this standard, the \"rounding value comparison method\" specified in GB/T1250 is adopted. 6.2 All the inspection items specified in this standard are type inspection items and factory inspection items. 6.3 The ***phenol is inspected by the company’s quality control department, to ensure that all ***phenol shipped from the factory meets the requirements of this standard. Each batch of *** phenol shipped from the factory shall be accompanied by a quality certificate, which shall include the name of the manufacturer, product name, batch number, production date, standard number applied, and quality specifications. 6.4 The user has the right to inspect the received *** phenol in accordance with the provisions of this standard, to determine whether its quality meets the requirements of this standard. 6.5 If any one of the test results does not meet the requirements of this standard, sampling from twice the amount of packaging should be carried out for retesting. If even one parameter in the retest results does not meet the requirements of these standards, the entire batch of products is considered unqualified. 7 Marking, Packaging, Transportation, Storage and Safe Use Regulations 7.1 Marking The outer packaging of products leaving the factory shall bear clear and durable markings indicating: the name of the manufacturer, the product name, the registered trademark, the net weight, the production date, the batch number, the applicable standards, and the grade; in addition, a “Toxic” marking shall be applied in accordance with the relevant provisions of GB190. 7.2 Packaging: The product is packaged in inner plastic bags, with a net weight of 50 kg ± 0.20 kg per bag; other forms of packaging can also be used as per the customer’s requirements. 7.3 Transportation During transportation, it should be protected from fire, rain, and exposure to direct sunlight. 7.4 Storage: The products should be stored in a cool, well-ventilated, and dry warehouse; exposure to direct sunlight must be avoided. It must not be stored together with flammable materials, and should be kept away from sources of fire and heat. 7.5 Safety Usage Instructions: The product is highly toxic; therefore, care must be taken to avoid contact with the skin, eyes, or inhalation during use and handling, and strict safety measures must be observed. Those in contact should wear protective gear such as gloves.

Note: Since the determination of the content in this standard relies on conventional titration with an indicator to determine the endpoint, it is difficult to identify this endpoint accurately, resulting in large errors in the measurement results. Therefore, a pH meter is used to determine the endpoint, thereby improving the method for determining the main content of p-cresol. 1. Previously, a mixed indicator (thymol blue-phenolphthalein) was used to determine the endpoint when measuring the main content of p-cresol; the disadvantages of this method were that the endpoint was not very distinct, there was poor reproducibility between duplicate samples, and errors were significant. To enable accurate analysis of the p-cresol content, a pH meter is now used to indicate the endpoint. 2. Principle: The determination of p-cresol involves titrating it with the standard solution NaOH; this is essentially an acid-base titration. Since p-cresol is a very weak acid with a low dissociation constant, the range of change during titration with a base is also small. A solution of a known concentration is prepared using p-phenol (1 g/100 ml), and it is titrated with a 0.5N sodium hydroxide standard solution. Calculations show that the pH of the solution at the theoretical endpoint is 8.68; this pH value is used to determine the titration endpoint for the sample. 3. Sample Analysis 3.1 Reagents and Solutions Sodium hydroxide standard titration solution: C(NaOH) = 0.5000 mol/L standard solution ； 3.2 Instruments: pH meter, general laboratory instruments. 3.3 Analysis procedure: Weigh approximately 1.2 g of the sample (with precision to 0.0001 g), place it in a 250 ml beaker, dissolve it using 80 ml of hot water, then bring the volume to 100 ml. After cooling, use a pH meter to determine the endpoint, and titrate with 0.5 N sodium hydroxide standard solution until the pH reaches 8.68. A blank test is also conducted simultaneously. Result calculation: The mass percentage X of ***phenol content is calculated as follows: C(NaOH) × (V1–V2) × 0.1391, where X = ×100/m. Here, C(NaOH) is the concentration of the standard sodium hydroxide titrant solution, in mol/l ； V1 —— Volume of the sodium hydroxide standard titrant solution used in the titration of the sample, in ml ； V2 —— Volume of sodium hydroxide standard titrant used in the blank titration, ml ； m —— mass of the sample, g ； 0.1391 —— the mass of ***phenol in grams, equivalent to 1 ml of standard sodium hydroxide titrant solution [C(NaOH=1.0000]. Allowable difference: The absolute value of the difference between two parallel test results shall not be greater than 0.2%. The arithmetic mean of the parallel test results is used as the reported value. The specific statistical data are as follows: Table 1 (determining the titration endpoint using a pH meter) Batch Number, Sample Weight (g), pH Value, Percentage Content%. Batch Number, Sample Weight (g), pH Value, Percentage Content%. 9-1: 1.199, 8.68, 93.35; 9-5: 1.2054, 8.68, 93.31; 1.1944, 8.68, 93.30; 1.2521, 8.68, 93.14. 9-2: 1.2093, 8.68, 94.44; 9-6: 1.1956, 8.68, 92.93; 1.1988, 8.68, 94.60; 1.1973, 8.68, 93.08. 9-3: 1.2012, 8.68, 93.41; 9-7: 1.2022, 8.68, 92.01; 1.2019, 8.68, 93.36; 1.1989, 8.68, 92.14. 9-4: 1.2000, 8.68, 93.16; 9-8: 1.2031, 8.68, 93.03; 1.2008, 8.68, 93.10; 1.1983, 8.68, 93.29. Table 2 (determining the titration endpoint using a mixed indicator) Batch Number, Sample Weight (g), Percentage Content%. Batch Number, Sample Weight (g), Percentage Content%. 9-1: 0.2025, 93.35; 9-5: 0.2069, 92.86; 0.2103, 92.86; 0.1989, 93.18. 9-2: 0.2015, 93.54; 9-6: 0.2052, 93.93; 0.2006, 94.05; 0.2041, 92.56. 9-3: 0.1998, 92.86; 9-7: 0.1991, 92.35; 0.2139, 94.02; 0.2051, 92.96. 9-4: 0.2046, 92.95; 9-8: 0.2043, 93.23; 0.1994, 93.13; 0.2058, 92.95

I’ve learned that formulating standards is a very complex task; I hope what the original poster has done will contribute to the establishment of national standards.

I also hope that users can express their opinions freely; the focus is on communication. I believe there is no perfect solution, only better ones

The design of Experiment 1 and Experiment 2 by the original poster involves some clever techniques that provide a basis for determining the titration endpoint of the free acid; it’s really good. I have two suggestions regarding the improvement of the method for determining the main content of ***phenol: First, if there is a good automatic titrator available, it might be worth giving it a try to see if it can automatically determine the endpoint of the titration and compare it with the theoretical endpoint; automatic titrators are more convenient to use ； Secondly, when using a pH meter to determine the titration endpoint, since the theoretical endpoint is 8.68 and the actual titration endpoint is also 8.68, there is no so-called endpoint error. If the water used in the analysis laboratory is of qualified quality, then a blank test is not necessary; however, the value of free acid should be subtracted when calculating the results. This post was last edited by xwtsq on 2009-2-12 12:05.]

Thank you for your suggestion; I will take it into account

Personally, for phenol, the following tests are recommended: 1. Main content: titrimetric analysis; 2. Free acid: titrimetric analysis, to determine the amount of sodium chloride present; 3. Chloride ions: titrimetric analysis, to determine the quantity of chloride ions; 4. Moisture: Karl Fischer titration, to assess the manufacturing process; 5. Organic purity: gas chromatography or liquid chromatography, to evaluate the quality of the product