1. Introduction of vitamin e
Vitamin E (VE) is a fat-soluble vitamin (soluble in fat and ethanol, etc., insoluble in water) and its hydrolysis product is tocopherol, which is one of the most important antioxidants. Vitamin E is stable to heat and acid, unstable to alkali, sensitive to oxygen, and insensitive to heat, but vitamin E activity is significantly reduced when fried. It is present in cooking oil, fruits, vegetables, and grains.
VE has now become one of the vitamin species with high market volume and great production and sales and is listed as one of the three pillars of the vitamin series together with vitamin C (VC) and vitamin (VA). Vitamin E is divided into two types, natural and synthetic, with the synthetic type being the main one. This article introduces the manufacturers of synthetic type vitamin E.
The main products of vitamin e are Vitamin e oil 98%, and vitamin e 50% powder (food grade and feed grade). Vitamin E is mainly used in feed, which accounts for more than 65%, and the others are food, pharmaceutical, and cosmetics.
2. Functions of vitamin e
a. It is a strong antioxidant, that can protect the stability of cell membrane by interrupting the chain reaction of free radicals, preventing the formation of lipofuscin on the membrane, and slowing down the aging of the body.
b. It can prevent the formation of carcinogens in various tissues in the body, stimulate the body’s immune system, kill the newly generated deformed cells, and can reverse some malignant tumor cells into normal cells.
c. Maintain the elasticity of connective tissue and promote blood circulation; regulate the normal secretion of hormones in the body
d. Maintain normal reproductive function, maintain the normal state of the muscle and peripheral blood vessel structure and function, and enhance immunity
e. Regulate energy metabolism and prevent myopia
3. Main manufacturers of vitamin e
At present, the main manufacturers of synthetic vitamin e are DSM, BASF, Zhejiang Medicine Co., Ltd, Zhejiang NHU Co., Ltd, Nenter & Co., Inc, and Jilin Beisha Pharmaceutical Co., Ltd.
In terms of 50% VE powder, the current global total production capacity is 280,600 tons, CR5=78.0%, and the start-up rate is above 75% in recent years. The production capacity ratio is shown in the following chart.
DSM and BASF are both famous comprehensive vitamin manufacturers. In 2019, Nenter and DSM formed a new company, which led to a new change in the pattern of vitamin e. After the restructuring, their vitamin E production capacity accounts for about 35% of the world’s supply.
Zhejiang Medicine Co., Ltd is an important API and preparation manufacturer in China, and an important national production base for vitamins, anti-drug resistant bacterial antibiotics, and quinolone products. The company has formed a specialized, large-scale production of fat-soluble vitamins, vitamin-like, quinolone antibiotics, anti-drug resistant antibiotics, and other series of products. The production of natural vitamin E is the largest in China and the third-largest in the world.
In 1994, Zhejiang NHU Co., Ltd conquered the technology of vitamin E production, and in 1999, it realized the large-scale production of vitamin A. In 2002, it successfully developed biotin, namely VB7, and in 2005, it was the first domestic manufacturer of astaxanthin, and in 2006, it was the first domestic manufacturer to successfully develop citral. It is a comprehensive vitamin manufacturer with R&D and innovation ability.
Nenter & Co., Inc is a wholly-owned subsidiary of the listed company Guanfu (stock code: 002102), which was established in 2006. Nenter was a supplier of VE main ring intermediates until 2016. Due to the emergence of the main ring isophorone process, the major VE manufacturers have started to self-match the main ring intermediates, Nenter’s capacity utilization rate has been low, so in 2016 they began to extend downstream. In 2017, their vitamin E products were sold to the public. In 2019, Nenter and DSM formed a new company, vitamin E supply pattern changed again.
Jilin Beisha Pharmaceutical Co., Ltd was established in July 2010 and is located in Jilin City. It has one production line with an annual capacity of 10,000 tons of vitamin E, one production line with a supporting annual capacity of 16,000 tons of vitamin E powder, one production line with an annual capacity of 2,000 tons of sulfonamide series products, one production line with an annual capacity of 180 tons of folic acid and one production line with an annual capacity of 3,000 tons of taurine.
4. Manufacturing process of vitamin E
The existing industrial synthesis method of vitamin E is basically made from trimethylhydroquinone and isophytol by a one-step condensation reaction, so trimethylhydroquinone and isophytol are the key intermediates of vitamin E. The synthesis route of both is long and the technical barriers are high.
The traditional vitamin E production process requires nearly 20 steps of chemical reactions, which is technically complex and requires strong technical strength. From the perspective of safety production, chemical production involves flammable and explosive substances and involves reactions with certain dangers such as format reactions and hydrogenation reactions, which have very high requirements on production processes, engineering equipment, production safety norms, and management procedures, and production experience. The synthesis process is long and complex, and only by scaling up can we effectively reduce production costs and dilute equipment costs. Scale and integration, on the one hand, the company’s technical level and management level put forward higher requirements, on the other hand, requires a high initial investment, and the industry has high capital barriers to entry. The Vitamin E industry requires raw materials such as m-cresol, methyl acetoacetate, or difenesinone, which requires related industry chain support, and raw materials are scarce to a certain extent.
4.1 Isophytol synthesis methods
Isophanol total synthesis method basically needs to go through methylheptenone, linalool, geranylacetone, farnesylacetone, and other key intermediates, the synthesis process is actually the process of carbon chain growth. Methylheptenone is also a key intermediate of citral. In fact, the Roche method and BASF method which are often mentioned in the synthesis of isophytol are the Roche method and BASF method for the synthesis of methylheptenone. Except for Nenter, other manufacturers use the above methods to produce isophytol.
Nenter has developed a fermentation method to synthesize isophytol in cooperation with Amyris. In fact, this fermentation method is a semi-fermentation method in which sugar and ethanol are used as raw materials and fermented by modified yeast, and farnesene can be extracted from the fermentation mixture. Subsequently, isophytol can be produced from farnesene by going through only 1 large cycle, and the synthesis path is significantly shortened compared with total synthesis. This technology has great cost advantages and is greener.
4.2 Synthesis of trimethylhydroquinone
The classical synthesis method of trimethylhydroquinone is the m-methylphenol method, which undergoes methanolic o-methylation to 2,3,6-trimethylphenol, followed by oxidation to 2,3,5-trimethylbenzoquinone, and finally hydrogenation to obtain trimethylhydroquinone. This process is short, with high product yield and low pollution, and is currently the main synthetic route for trimethylhydroquinone.
Nenter has developed a route from p-tert-butylphenol to 2,3,6-trimethylphenol, after obtaining 2,3,6-trimethylphenol, trimethylhydroquinone can be finally obtained by the aforementioned oxidation-reduction method. This process uses the more readily available p-tert-butylphenol as raw material, which has good economic benefits in the current situation of m-cresol raw material shortage.
The other is the isophorone route, which is an efficient and environmentally friendly production process with cheap and easy to obtain raw materials, simple processes and low pollution. Acetone is first polymerized to α-isophorone, followed by rearrangement to β-isophorone, and then oxidized to theophyllone (KIP, oxo-isophorone), or directly from α-isophorone oxidation to KIP, KIP followed by rearrangement acylation, saponification hydrolysis to obtain trimethylhydroquinone.
Among the existing manufacturers, only BASF still adopts the old process of crotonaldehyde, ZMC adopts the m-cresol route, Nenter uses its own developed special process, and NHU adopts the isophorone route and m-cresol route.
5. Summary
Vitamin e producers include DSM, BASF, NHU, ZMC, Nenter, and Beisha, among which Nenter has some technical and cost advantages. Trimethylhydroquinone and isophytol are the key raw materials for its synthesis and are scarce. It has both financial and technical barriers, and it is difficult to find new entrants.
