Due to its wide application, the demand for allantoin has been increasing year by year . The chemical synthesis method of allantoin appeared in foreign countries in the 1940s. But it was not until the late 1970s and early 1980s that Japan and West Germany put it into industrial production. The development of domestic allantoin synthesis started relatively late, and research and development began in the late 1970s. At present, only a few domestic companies have achieved pilot or mass production . Because there are few manufacturers, the market is extremely tight. Due to the special physical and chemical properties of allantoin, allantoin derivatives have variety types and are widely used. Until today, allantoin and its derivatives are still continue to send development .
Allantoin, chemical name is 1-urea-m-diazocene – [2,4]; Acetaldehyde Tetraaza cyclopentadiene; (2,5-dioxocene-4-m-diazopentyl) urea; 5-urea hydantoin etc. It belongs to the imidazole heterocyclic compound, molecular formula is C4H6N4O3, molecular weight is 158.12 g/mol. Allantoin is a crystal or crystalline powder which color between colorless and white, and it is odorless and tasteless. The melting point of allantoin range of 220 ~ 238 ℃. Allantoin is insoluble in water, alcohol, ether and chloroform, soluble in hot water, dilute ethanol, and propan- triols. The saturated aqueous solution (0.6%) was slightly acidic, pH =. 6. In an aqueous solution of pH = 4 to 9, it remains stable, and in a non-aqueous solvent and drying air is stable , even in the 80 ~ 90 ℃ 30 min under heat also remained unchanged.
But it can not withstand high temperatures (above 100 ℃), a strong base, or a long time of the boiling and sunlight . Allantoin has isomers, and the structural formula is as follows:
The alcohol conjugated system is the reason for the formation of acidic groups and can stabilize the molecules. The existence of OH– may cause some people to think that allantoin is a binary acid compound. However, generally speaking, the hydrogen on C(4) has a very low activity and weak dissociation constant. The acid at the position of carbon (2) is stronger, and the dissociation constant is 1.17 × 10-9. Therefore, only a single series of salts, acid salts or basic salts can be formed. Therefore, allantoin is a monobasic acid-base amphoteric compound. Both alcohol and ketone forms can exist. As an amphoteric compound, allantoin is not only a basic compound, but also a weak acid, and also a weak base for acid salt compounds. Therefore, allantoin can form metal salts and adducts with many substances. These metal salts and adducts not only maintain the properties of allantoin itself, but also do not lose the inherent properties of the added substances. Next, we will list some physical and chemical properties of allantoin aluminum compounds as an example.
Allantoin aluminum compounds provide a wide range of effective functions for the treatment of skin diseases. Because the convergence of aluminum ion and the ideal characteristics of allantoin are fully combined. The presence of allantoin improves the effect of aluminum salt and eliminates the irritation of some patients with aluminum salt allergy. Animal experiments also showed that allantoin aluminum salt had no irritation and allergy. Several common forms are as follows:
1. Alluminum dihydroxy allantoinate
Alluminum dihydroxy allantoinate has a molecular formula of Al(OH)2C4H5N4O3. It is a white powder, insoluble in water and other solvents, such as ethanol, ether and chloroform. Its international trade name is “aldioxa”.The composition of Alluminum dihydroxy allantoinate is as follows: aluminum oxide (22.0 ± 5)%, allantoin (55.0 ± 5)%, pH value (4% suspension) is 6-5.8.
Alluminum dihydroxy allantoinate’s molecular formula is [Al2(OH)4ClC4H5N4O3]C3H8O2. It is a white powder, in molecular state or modified form, and is used as a deodorant, a wetting agent and skin astringent .
3. Aluminum chlorhy dro xy allantoinate
The formula of Aluminum chlorhy dro xy allantoinate is Al2(OH)4ClC4H5N4O3. Aluminum chlorhy dro xy allantoinate is pure white powder, soluble in water, slightly soluble in ethanol, insoluble in ether and chlorine imitation. The international trade name of Aluminum chlorhy dro xy allantoinate is “alcloxa”.The composition is as follows: Aluminum oxide (28.0 ± 3)%, allantoin (40.0 ± 3)%, chlorine (9.5 ± 1.5)%, nitrogen (14.2 ± 1.5)%.
At the same time, the composition of modified chloroaluminum allantoin is as follows : Aluminum oxide (45.61 ± 2.0)%, allantoin (1.25 ± 0.3)%, chlorine (15.60 ± 1.5). The pH value of 10% solution of Aluminum chlorhy dro xy allantoinate is about 4.3 .
According to the literature reports, the main synthetic methods of allantoin are as follows:
1. Reaction of uric acid with potassium permanganate
Uric acid and potassium permanganate are oxidized in alkaline medium, and the products are decarboxylated with acetic acid. The oxidants can also be lead dioxide, potassium ferricyanide, oxygen, ozone, manganese dioxide, hydrogen peroxide, etc. The reaction process is as follows:
First, oxidation reaction. Uric acid and potassium permanganate react.
Then, decarboxylation ring opening reaction get the final product.
This is the earliest process route, which is limited to small batch production because of the shortage of raw materials, high price, large equipment volume and high cost.
2. Electrolytic oxidation of lithium urate
Allantoin was synthesized by condensation of glyoxylic acid and urea under electricity.
Although the yield of this method is slightly higher than that of uric acid oxidation method, it also has the above problems and has less industrial application.
3. Electrolytic oxidation of oxalic acid
This is a new process developed in recent years, and this production line has been established in China. The raw materials are easy to obtain, but the power consumption is large. According to the literature, the process is not mature and needs to be improved.
4. Oxidation of glyoxal
Because glyoxylic acid can be prepared by partial oxidation of glyoxal and the process conditions are mild, this synthetic route is often used in industry. However, this method uses nitric acid to oxidize, which causes serious environmental pollution.
First, partial oxidation of glyoxal to get glyoxylic acid.
It has two side reactions giving below, so the yield of this way to get glyoxylic acid is about 83%.
Then, synthesis of allantoin by condensation of glyoxylic acid and urea under heating and acid condition.
The conversion of glyoxylic acid by this way is 52% ～ 58%. According to all the reactions, counted by glyoxal, the allantoin yield is 38% – 40% of the theoretical value.
5. Reaction of urea with dichloroacetic acid
It is prepared by heating 2 mol urea and 1 mol dichloroacetic acid. The reaction process is as follows:
In 1930’s, American patent reported that allantoin could be produced in ethylene glycol at 120 ℃ for 4 h, but the yield was low. The total yield of allantoin-p-dichloroacetic acid can reach 30.3%. Some researchers from China have studied the process, and made the total yield of allantoin over 40%. The whole routine is as follows.
At present, other ways of technology development and research are also very active, trying to achieve success at a lower cost, such as acetylene method, carbon dioxide, carbon monoxide and other high content waste gas recovery methods. However, so far no report has been put into production. As an important industrial product, allantoin needs more synthetic research to support.
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