The synthesis and introduction of 1,4-Butanediol

General description

1,4-Butanediol  is an organic compound with molecular formula of c4h10o2 and molecular weight of 90.12. The appearance is colorless or light yellow oily liquid. Combustible, freezing point 20.1 ℃, refractive index 1.4461. It is soluble in methanol, ethanol, acetone and slightly soluble in ether. It has hygroscopicity, bitter smell and slightly sweet taste in the mouth. 1,4-Butanediol is not active in its own right; its mechanism of action stems from its identity as a prodrug of GHB, meaning that it is rapidly converted into GHB in the body. GHB is considered to be a safe and non-toxic substance when used responsibly or medically.

Application and Pharmacology

1,4 butanediol is an important organic chemical and fine chemical raw material. It is the basic raw material for the production of polybutylene terephthalate (PBT) engineering plastics and PBT fiber; PBT plastic is one of the five most promising engineering plastics. 1,4 butanediol is the main raw material for the production of tetrahydrofuran, which is an important organic solvent. Polytetramethylene glycol ether (PTMEG) obtained after polymerization is the basic raw material for the production of high elastic spandex (Lycra fiber). Spandex is mainly used to produce high elastic knitwear such as high-grade sportswear and swimming clothes. Downstream products of 1,4 butanediol γ- Butyrolactone is the raw material for the production of 2-pyrrolidone and N-methyl pyrrolidone products, from which a series of high value-added products such as vinyl pyrrolidone and polyvinylpyrrolidone are derived, which are widely used in the fields of pesticides, medicine, cosmetics and so on.

1.With the improvement of plastic pollution control from the original "plastic restriction" to "plastic prohibition", the main raw materials of degradable plastic PBAT are 1,4-butanediol, terephthalic acid and adipic acid. It needs 0.43 tons of 1,4-butanediol to produce 1 ton PBAT. Due to the huge market demand of 1,4-butanediol products, the rapid development of the industry has been promoted. 1,4-butanediol (BDO) is an important raw material for organic chemical industry and fine chemical industry. It is widely used in medicine, automobile, chemical industry and textile industry γ- Butylene glycol, tetrahydrofuran, poly (tetramethylene ether glycol), polyurethane and poly (butylene terephthalate glycol). 

2.Gamma-hydroxybutyrate (GHB), and its analogues 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), are common recreational ingestants. 1,4-BD is converted sequentially by alcohol dehydrogenase (ADH) to 1,4-butaraldehyde and aldehyde dehydrogenase to GHB (Figure 1). 1,4-BD appears to have no psychoactive effect on its own in both animals and humans in experiments when 1,4-BD was coadministered with an ADH blocker. Instead, sedation reflects the effect of the GHB metabolite. Similarly, GBL is also metabolised to GHB[1].

Figure The enzymatic metabolism of 1,4-BD to GHB[1].

Synthesis

1.1,4-butanediol (BDO) has been widely used as an important organic chemical and fine chemical raw material. In recent years, with the rapid development of biodegradable materials industry, BOD as an important raw material for the biodegradable materials, will have a huge market in the future. This paper introduces the process technology of sacetylene-formaldehyde process, maleic anhydride process, allyl alcohol process and butadiene process, analyzes the status of BDO industry in China, compares the production cost of sacetylene - formaldehyde process and maleic anhydride process, and prospects the BDO technology combined with national conditions[2]：

1. In acetylene method, 1,4-butynediol is prepared by reacting acetylene and formaldehyde in the presence of Cu Bi catalyst at 98kpa and 80-95 ℃. The latter is then catalyzed by skeleton nickel and hydrogenated to 1,4-maleate at 1.372-2.06mpa and 50-60 ℃, followed by Ni Cu Mn / Al2O3 further catalyzed hydrogenation (13.7-20.6mpa and 120-140 ℃) to 1,4-butanediol. After removing metal ions by ion exchange resin, the pure product is obtained by distillation and purification. 2. Maleic anhydride hydrogenation 3 In butadiene process, 1,3-butadiene reacts with acetic acid and oxygen to produce 1,4-diacetoxy-2-butene, which is prepared by hydrogenation and hydrolysis. 4.1,4-dichlorobutene process 1,4-dichlorobutene is the intermediate product of the production of chloroprene from butadiene. It is used as raw material to obtain 1,4-butanediol through hydrolysis and hydrogenation.[3]

2.Achievements and Perspectives in 1,4-Butanediol Production from Engineered Microorganisms[4]：1,4-Butanediol (1,4-BDO), a significant commodity chemical, is currently manufactured exclusively from a host of energy-intensive processes, accompanied by severe environmental issues, such as the greenhouse effect and air pollution. As a result of the ever-increasing global market demands and increasing applications of 1,4-BDO, attention has turned to the sustainable bioproduction of 1,4-BDO, and several bio-based approaches for 1,4-BDO production have been successfully established in engineered Escherichia coli, includingde novobiosynthesis and biocatalysis. Recent achievements in enhancing the accumulation of 1,4-BDO have been achieved by metabolic engineering strategies, such as improving precursor supply, enhancing activities of critical enzymes, and fewer byproduct synthesis. 

Figure 1 Metabolic pathway for 1,4-BDO production in E. coli

To date, a large number of heterologous metabolic pathways have been engineered to synthesize various chemicals, biofuels, and bioactive molecules;44however, there is still very little known about 1,4-BDO production in Cyanobacteria. In summary, we can expect that more advanced strategies will be developed for economical production of 1,4-BDO using photoautotrophic microbes, and heterologous enzyme reactions, which have been applied for 1,4-BDO production in E. coli, could also be considered for the efficient synthesis of 1,4-BDO in Cyanobacteria. Meanwhile, further optimization could contribute to commercially feasible processes.

Storage and Safety

1,4-Butanediol overdose mimicking toxic alcohol exposure：1,4-butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) analogue with a similarly narrow therapeutic window that is becoming a more common cause of recreational overdose. Reports of confirmed exposures are limited. 1,4-BD is a less well-recognised ingestant and cause of overdose with clinical features and pharmacokinetics that are less well-described than GHB. 1,4-BD is used as an industrial solvent and for the manufacture of plastics and other materials, so it is legal to import and sell in many jurisdictions worldwide, including Australia. 1,4-BD is uncommonly tested for specifically, and even more rarely is it detected in blood（GHB is predominantly an agonist at gamma aminobutyric acid (GABA) B receptors. GHB has a narrow therapeutic index which increases the probability of poisoning due to overdose. Well-known complications of overdose include reduced level of consciousness, seizures, hypoventilation, bradycardia and aspiration, with supportive care being the mainstay of treatment for such overdoses）. The highest blood concentration of 1,4-BD reported so far being 220 mg/L in a 42 year old female, post mortem.

Reference

1.Stefani M. & Roberts D. M., "1,4-Butanediol overdose mimicking toxic alcohol exposure," Clin Toxicol (Phila), Vol.58, No.3(2020), pp.204-207.

2.Huang Peipei: production status and development of 1,4-butanediol, contemporary chemical research, No. 01, 2022, pp. 48-50.

3.Xie Jun: analysis and Prospect of 1,4-butanediol production technology in China, Guangdong chemical industry, No. 21, 2021, pp. 111-113.

4.Cheng J., Li J. & Zheng L., "Achievements and Perspectives in 1,4-Butanediol Production from Engineered Microorganisms," Journal of Agricultural and Food Chemistry, Vol.69, No.36(2021), pp.10480-10485.