Glycidol: both an epoxide and an alcohol

Introduction

Glycidol is an epoxide and an alcohol, and as such is a highly reactive compound. It is miscible with water but also reacts with it. It decomposes when distilled at atmospheric pressure. In 1909, chemist Nikolai Prilezhaev at the Warsaw University of Technology prepared glycidol by epoxidizing allyl alcohol with peroxybenzoic acid. This reaction was a breakthrough at the time and became known as the Prilezhaev oxidation. Glycidol is still manufactured in much the same way; but in 2018, a group of companies built a pilot plant in Teesside, UK, to make it via a "green" process. Glycidol has a chiral center, but it is generally produced and used as the racemic mixture. It is used as a chemical intermediate and in the production of detergents, healthcare products, and industrial paints and coatings.

Synthesis of Glycidol

The method for preparing the glycidol comprises the steps of:(1) with a pump to the mixing kettleInto the 95% ethanol 1600kg,The condensed water is cooled to 15 ° C, and then 325 kg of solid NaOH is added in portions under stirring to control the kettle temperature of 10 ° C to 15 ° C to obtain solution A;(2) 990 kg of ethanol and 925 kg of 3-chloro-1,2-propanediol were introduced into the mixing kettle 2 at the same time,Chloro-1,2-propanediol to NaOH at a molar ratio of 1: 0.97) and cooled to -5 ° C with ice brine to give solution B;(3) The prepared solution A is then added dropwise to solution B and the temperature of the mixing kettle 2 is controlled to -5 ± 3 ° C toAt the end of the reaction time 6h, the reaction solution after the reaction is deducted from ethanol, the composition of 3-chloro-1,2-propanediol 0.5%, glycidol 94.3%, other impurities 5.2%(4) removing the solid solution by centrifuging the reaction solution obtained in the step (3) to obtain crude glycidol;Glycerin crude pH = 7.8;(5) Subsequently, the crude glycidol obtained in step (4) is evaporated by a thin film, and most of the ethanol is distilled off for recovery.[1]

The moisture content of the film is 54%, the vacuum degree is -93KPa, the moisture content of the heavy component after evaporation of the film is 4.0%; the weight of the heavy component (water is not included) is 4.9% ethanol, 90.7% of glycidol, Chlorine-1,2-propanediol 0.3%, other impurities 4.1%;(6) The concentrated liquid after the light component of step (5) is distilled off is further subjected to a short-range distillation to remove the remainingOf the ethanol and the recovery of the use of a short-range distillation of the water back to the temperature of 35 , vacuum -94KPa, a short-range distillation of the heavy component of water 2.9%; heavy component (water excluded) for the ethanol 0.3 %, Glycidol 94.7%, 3-chloro-1,2-propanediol 0.6%, other impurities 4.4%;(7) The heavy component obtained in step (6) is subjected to secondary short-range distillation to obtain a glycidol product,The water temperature of the secondary short-range distillation is 54 , the vacuum degree is -97KPa, the water content of the product obtained by the second-stage short-range distillation is 1.4%, the pH is 6.5; the product content (not included in the water) is ethanol 0 %, Glycidol 98.5%, 3-chloro-1,2-propanediol 0.1%, other impurities 1.4%.

Cancer Studies in Experimental Animals

Oral exposure to glycidol caused tumors at many different tissue sites in mice and rats. Administration of glycidol by stomach tube increased the incidences of benign and/or malignant tumors of the mammary gland (adenoma, fibroadenoma, or adenocarcinoma) in rats of both sexes and female mice, the forestomach (papilloma or carcinoma) in rats of both sexes and male mice, the thyroid gland (follicular-cell adenoma or carcinoma) and the brain (glioma) in rats of both sexes, the Harderian gland (adenoma or adenocarcinoma) in mice of both sexes, and the skin (squamous-cell papilloma or carcinoma, basal-cell tumors, or sebaceous-gland adenoma or adenocarcinoma) in mice of both sexes and male rats. Also observed in rats were cancer of the Zymbal gland (carcinoma) and testis (mesothelioma of the tunica vaginalis) and intestinal tumors (adenomatous polyps or adenocarcinoma) in males and tumors of the mammary gland (fibroadenoma or adenocarcinoma), oral cavity (papilloma or carcinoma), and clitoral gland (adenoma, adenocarcinoma, or carcinoma) in females. In mice, oral exposure to glycidol also caused cancer of the uterus (carcinoma or adenocarcinoma) and subcutaneous tissue (sarcoma or fibrosarcoma) in females and tumors of the lung (alveolar/bronchiolar adenoma or carcinoma) and the liver (mainly carcinoma) in males. Also possibly related to glycidol exposure were cancer of the glandular stomach (fibrosarcoma) in female rats and cancer of the urinary bladder (carcinoma) and testis (sarcoma of the epididymis) in male mice.[2]

Use

Glycidol is a member of a class of chiral molecules that are important intermediates in the industrial synthesis of pharmaceutical products and other biologically active substances and in production of flavoring and sweetening agents and insecticides. It has been used in the pharmaceutical industry since the 1970s; before then, it was used solely for research purposes. Glycidol is used as a stabilizer in the manufacture of vinyl polymers and natural oils and as an intermediate in the synthesis of glycerol, glycidyl ethers, and amines. It is also used as an alkylating agent, demulsifier, and dye-leveling agent and for sterilizing milk of magnesia. The glycidol structure is present in two commercially important groups of derivatives, glycidyl ethers and glycidyl esters, neither of which is prepared directly from glycidol. In 2009, was available from 19 suppliers worldwide, including 12 U.S. suppliers. Annual combined U.S. production and imports of glycidol reported to the U.S. Environmental Protection Agency were in the range of 10,000 to 500,000 lb from 1986 through 1998 and exceeded 500,000 lb in 2006. No more recent production data and no data specifically on U.S. imports or exports of glycidol were found.

Exposure

The primary routes of potential human exposure to glycidol are inhalation, eye and dermal contact, and ingestion. Heating causes the dehydration of glycol configurations in glycerol and sugars to form glycidol; however, the quantities formed during cooking are assumed to be low (Hindsø Landin et al. 2000). Glycidol is a metabolite of 3-monochloropropane-1,2-diol (Jones 1975), a chloropropanol found in many foods and food ingredients, including soy sauce and hydrolyzed vegetable protein. Glycidol was detected in the urine of rats exposed to 1-bromopropane by inhalation (Ishidao et al. 2002). Occupational exposure to glycidol could occur through inhalation. The National Occupational Exposure Survey (conducted from 1981 to 1983) estimated that 4,872 workers (in 88 facilities and 10 occupations in the Chemicals, Allied Products and Fabricated Metal Products industries), including 580 women, potentially were exposed to glycidol.

Oral administration

Groups of 50 male and 50 female B6C3F1 mice, nine weeks of age, were administered 0, 25 or 50 mg/kg bw of glycidol (94% purity, with the primary impurity, as determined by gas chromatography, being diglycidyl ether at a concentration of 2.8%, and 3-methoxy-1,2-propanediol (1.2%), 2,6-dimethanol-1,4-dioxane (1.1%), 3chloro-1,2-propanediol (0.4%) and methanol (0.1%) as lesser impurities) in distilled water by gavage on five days per week for 103 weeks. Groups of 50 male and 50 female Fischer 344 rats, eight weeks of age, were administered 0, 37.5 or 75 mg/kg bw of glycidol (purity, 94%, with the main impurities being those listed in distilled water by gavage on five days per week for 103 weeks. Survival of rats was significantly lower in the treated groups in both males and females than in the control groups, with the mean survival being 92, 82 and 66 weeks for the control, mid- and high-dose males, respectively, and 97, 85 and 78 weeks for the female dose groups. As shown, there was a statistically significant increase in the incidence of mesotheliomas of the tunica vaginalis/peritoneum in males at both 37.5 and 75 mg/kg bw. [3]

References

[1] SHANDONG GP NATURAL PRODUCTS - CN106588820, 2017, A

[2] National Toxicology Program. 15th Report on Carcinogens [Internet]. Research Triangle Park (NC): National Toxicology Program; 2021 Dec 21. Glycidol: CAS No. 556-52-5.

[3] Lijinsky W., Kovatch R.M. A study of the carcinogenicity of glycidol in Syrian hamsters. Toxicol. ind. Health. 1992;8:267–271.

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