Description
Succinic acid (butanedioic acid) is a dicarboxylic acid. It is a common intermediate in the metabolic pathway of several anaerobic and facultative micro-organisms.
Succinic acid is used as a dietary supplement for symptoms related to menopause such as hot flashes and irritability. It is used as a flavoring agent for food and beverages. It is used to manufacture polyurethanes, paints and coatings, adhesives, sealants, artificial leathers, cosmetics and personal care products, biodegradable plastics, nylons, industrial lubricants, phthalate-free plasticizers, and dyes & pigments. In the pharmaceutical industry, it is used in the preparation of active calcium succinate, as a starting material for active pharmaceutical ingredients (adipic acid, N-methyl pyrrolidinone, 2-pyrrolidinone, succinate salts, etc.), as an additive in drug formation, for medicines of sedative, antispasmer, antiplegm, antiphogistic, anrhoter, contraception and cancer curing, in the preparation of vitamin A and anti-Inflammatory, and as antidote for toxic substance.
Chemical Properties
Succinic acid is a normal constituent of almost all plant and animal tissues. Succinic anhydride is the dehydration product of the acid. Succinic acid was first obtained as the distillate from amber (Latin, Succinum) for which it is named. It occurs in beet, brocoli, rhubarb, sauerkraut, cheese, meat, molasses, eggs, peat, coal, fruits, honey, and urine (Gardner, 1972; Winstrom, 1978; Doores, 1989). It is formed by the chemical and biochemical oxidation of fats, by alcoholic fermentation of sugar, and in numerous catalyzed oxidation processes. Succinic acid is also a major byproduct in the manufacture of adipic acid.
Succinic acid, a dicarboxylic acid, is a relatively new nonhygroscopic product approved for food uses. Its apparent taste characteristics in foods appear to be very similar to the other acidulants of this type, although pure aqueous solutions tend to have a slightly bitter taste (Monsanto Chemical Co, 1970; Gardner, 1972). Succinic anhydride, in contrast, is the only commercially available anhydride for food uses (Gardner, 1972).
Occurrence
Succinic acid is found in all plant and animal materials as a result of the central metabolic role played by this dicarboxylic acid in the Citric Acid Cycle. Succinic acid concentrations are monitored in the manufacture of numerous foodstuffs and beverages, including wine, soy sauce, soy bean flour, fruit juice and dairy products (e.g. cheese). The ripening process of apples can be followed by monitoring the falling levels of succinic acid. The occurrence of > 5 mg/kg of this acid in egg and egg products is indicative of microbial contamination. Apart from use as a flavouring agent in the food and beverage industries, succinic acid finds many other non-food applications, such as in the production of dyes, drugs, perfumes, lacquers, photographic chemicals and coolants.
Succinic acid is widely distributed in almost all plants, animals and microorganisms where it is a common intermediate in the intermediary metabolism. A way to utilise this is with fermentation of biomass by microorganisms. Succinic acid is therefore a good candidate for biobased industrial production. A concept for a large scale production plant is patented by the company Diversified Natural Products. The plant consists of a fermentation stage and a separation stage. During the separations the succinate produced in the fermenter is crystallised to the final product, succinic acid.
Uses
Succinic acid (COOH(CH2)2COOH) is a carboxylic acid used in food (as an acidulant), pharmaceutical (as an excipient), personal care (soaps) and chemical (pesticides, dyes and lacquers) industries. Bio-based succinic acid is seen as an important platform chemical for the production of biodegradable plastics and as a substitute of several chemicals (such as adipic acid).
Succinic Acid is widely used in the food industry as a chelating agent and as a pH adjuster. The FDA has granted Succinic Acid with the GRAS status (Generally Recognised as Safe Substance). Studies conducted within the food industry show Succinic Acid has anti-oxidant properties: even though this does not imply the same will be exerted when the substance is applied topically, it gives an indication that suitable tests could be carried out to understand whether Succinic Acid maintain such effect once formulated in a cosmetic product. Succinic Acid is also used as an intermediate to manufacture several chemicals, amongst which raw materials for the cosmetic and personal-care industry, e.g. emollients, surfactants and emulsifiers.
Preparation
Succinic acid can also be manufactured by catalytic hydrogenation of malic or fumaric acids. It has also been produced commercially by aqueous acid or alkalihydrolysis of succinonitrile derived from ethylene bromide and potassium cyanide (Gergel and Revelise, 1952; Gardner, 1972).
Today succinic acid is mainly produced from fossil resources through maleic acid hydrogenation. It can also be produced through fermentation of sugars. In that case, in addition to succinic acid, other carboxylic acids (such as lactic acid, formic acid, propionic acid) and alcohols (such as ethanol) are also obtained.
Toxicology
Succinic acid is moderately toxic by subcutaneous route (Lewis, 1989). It is also a severe eye irritant. When heated to decomposition, succinic acid emits acrid smoke and irritating fumes.
Dye et al. (1944) conducted short-term studies on rats who received daily subcutaneous injections of 0.5 mg succinic acid. These doses were increased gradually up to 2.0 mg/day at 4 weeks, and the studies continued at this level for 100 days. When compared with the control animals, the test animals did not show any abnormalities in reproduction, hair appearance, tooth eruption, or eye opening.
Dye et al. (1944) also found no abnormalities in the development of chick embryos when comparable dosages were administered into the air sacs.
Since it occurs naturally in small amounts in several fruits and vegetables and as an intermediate in the Krebs cycle, no limit has been set on the acceptable daily intake of succinic acid in the human diet.
References
[1] https://en.wikipedia.org/wiki/Succinic_acid
[2] http://www.webmd.com
[3] http://chemicalland21.com
Description
Succinic acid is a dicarboxylic acid with a pair of carboxylic acid functional groups. The terminal carboxylic acid groups can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond.
Chemical Properties
Succinic acid,C02H(CH2)2C02H, also known as butanedioic acid,butane diacid, and amber acid, is a colorless odorless prisms or white crystalline powder that melts at 185°C (364 of). Soluble in water and alcohol, it is used as a chemical intermediate, Succinic acid is used in lacquers,medicine,dyes,and as a taste modifier.
Uses
Succinic Acid was identified in essential oil from Saxifraga stolonifera and has antibacterial activity.
Uses
Succinic Acid is an acidulant that is commercially prepared by the
hydrogenation of maleic or fumaric acid. it is a nonhygroscopic acid
but is more soluble in 25°c water than fumaric and adipic acid. it
has low acid strength and slow taste build-up; it is not a substitute
for normal acidulants. it combines with proteins in modifying the
plasticity of bread dough. it functions as an acidulant and flavor
enhancer in relishes, beverages, and hot sausages.
Uses
succinic acid is widely use as organic intermediates for the pharmaceutical, engineering plastics, resins etc.. For the synthesis of sedatives, contraceptives and cancer drugs in the pharmaceutical industry. In the chemical industry for the production of dyes, alkyd resin, glass fiber reinforced plastics, ion exchange resins and pesticides.
Definition
ChEBI: An alpha,omega-dicarboxylic acid resulting from the formal oxidation of each of the terminal methyl groups of butane to the corresponding carboxy group. It is an intermediate metabolite in the citric acid cycle.
Definition
A crystalline carboxylic
acid, HOOC(CH
2)
2COOH, that occurs in
amber and certain plants. It forms during
the fermentation of sugar (sucrose).
Biotechnological Production
Traditionally, succinic acid is produced by petrochemical synthesis using the
precursor maleic acid. However, there are some microorganisms that are
able to produce succinic acid (e.g. Actinobacillus succinogenes, Anaerobiospirillum
succiniciproducens and Mannheimia succiniciproducens). Maximum product
concentrations of 106 g.L-1 with a yield of 1.25 mol of succinic acid per mole of
glucose and a productivity of 1.36 g.L-1.h-1 have been achieved by growing A.
succinogenes on glucose . A high productivity of 10.40 g.L-1.h-1 has been
reached with A. succinogenes growing on a complex medium with glucose in a
continuous process with an integrated membrane bioreactor-electrodialysis process.
In this process, the product concentration has been 83 g.L-1 . Moreover,
metabolic engineering methods were used to develop strains (e.g. C.
glutamicum, E. coli, S. cervisiae and Y. lipolytica) with high productivity and titer
as well as low byproduct formation. For example, growing C.
glutamicum strain DldhA-pCRA717 on a defined medium with glucose, a high
productivity of 11.80 g.L-1.h-1 with a yield of 1.37 mol of succinic acid per mole
of glucose and a titer of 83 g.L-1 has been reported after 7 h. An extended
cultivation resulted in a product concentration of 146 g.L-1 after 46 h.
General Description
White crystals or shiny white odorless crystalline powder. pH of 0.1 molar solution: 2.7. Very acid taste.
Air & Water Reactions
Slightly water soluble.
Reactivity Profile
Succinic acid reacts exothermically to neutralize bases, both organic and inorganic. Can react with active metals to form gaseous hydrogen and a metal salt. Such reactions are slow in the dry, but systems may absorb water from the air to allow corrosion of iron, steel, and aluminum parts and containers. Reacts slowly with cyanide salts to generate gaseous hydrogen cyanide. Reacts with solutions of cyanides to cause the release of gaseous hydrogen cyanide. May generate flammable and/or toxic gases and heat with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. May react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Can be oxidized exothermically by strong oxidizing agents and reduced by strong reducing agents. May initiate polymerization reactions.
Fire Hazard
Flash point data for Succinic acid are not available. Succinic acid is probably combustible.
Flammability and Explosibility
Non flammable
Biochem/physiol Actions
Succinic acid is a byproduct of anaerobic fermentation in microbes. It is a dicarboxylic acid and an intermediate in Kreb′s cycle. Polymorphism in succinate dehydrogenase leads to succinate accumulation. High levels of succinate impairs 2-oxoglutarate epigenetic signalling. Succinate levels may modulate tumor progression. Succinate inhibits histone demethylation and may contribute to epigenetic changes. Succinate is crucial for interleukin-1 β (IL-1β) synthesis during inflammation and immune signalling.
Biotechnological Applications
Succinic acid and its derivatives are used as flavoring agents for food and beverages. This acid could be used as feedstock for dyes, insecticides, perfumes, lacquers, as well as in the manufacture of clothing, paint, links, and fibers (McKinlay et al. 2007). Succinic acid is widely used in medicine as an antistress, antihypoxic, and immunity-improving agent, in animal diets, and as a stimulator of plant growth. It is also a component of bio-based polymers such as nylons or polyesters (Kamzolova et al. 2012b). Succinate esters are precursors for the known petrochemical products such as 1,4-butanediol, tetrahydrofuran, c-butyrolactone, and various pyrrolidinone derivatives (Bechthold et al. 2008).
Succinic acid production by Y. lipolytica was reported for the first time when it was grown on ethanol under aerobic conditions and nitrogen limitation. Succinic acid amount was 63.4 g/L as the major product of batch fermentation in this process. However, the disadvantage was low yield of succinic acid on ethanol (58 %), and a high cost of production (Kamzolova et al. 2009).
Kamzolova et al. developed a novel process for the production of succinic acid. It includes the synthesis of a-ketoglutaric acid by a thiamine-auxotrophic strain Y. lipolytica VKMY-2412 from n-alkanes, and subsequent oxidation of the acid by hydrogen peroxide to succinic acid. The concentration of succinic acid and its yield were found to be 38.8 g/L and 82.45 % of n-alkane consumed, respectively (Kamzolova et al. 2012b).
Succinic acid production was also studied by genetically modified strains using glucose and glycerol as substrates. Yuzbashev et al. constructed temperaturesensitive mutant strains with mutations in the succinate dehydrogenase encoding gene SDH1 by in vitro mutagenesis-based approach. Then, the mutants were used to optimize the composition of the media for selection of transformants with the deletion in the SDH2 gene. The defects of each succinate dehydrogenase subunit prevented the growth on glucose, but the mutant strains grew on glycerol and produced succinate in the presence of the buffering agent CaCO3. Subsequent selection of the strain with deleted SDH2 gene for increased viability was allowed to obtain a strain that is capable to accumulate succinate at the level of more than 450 g/L with buffering and more than 17 g/L without buffering. Therefore, a reduced succinate dehydrogenase activity can lead to an increased succinate production (Yuzbashev et al. 2010). Y. lipolytica is able to produce succinic acid at low pH values. High amounts of succinate can be achieved by genetic engineering (Otto et al. 2013).
Safety Profile
Moderately toxic by subcutaneous route. A severe eye irritant. Mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.
Carcinogenicity
Monosodium succinate was
given to groups of 50 male and 50 female Fischer 344 rats
in drinking water at levels of 0%, 1%, or 2% for 2 years. No
toxic lesion specifically caused by long-term administration
of monosodium succinate was detected, and no dose-related
increase was found in the incidence of tumors in any organ or
tissue. The incidence of C-cell tumors of the thyroid gland of
females that received 2% solution was apparently, but not
significantly, higher than that in controls. Because C-cell
tumors are commonly occurring spontaneous tumors in aging
female rats of this strain and the incidence of C-cell tumors in
the female control group was lower than that of historical
controls for the testing laboratory, the authors concluded that
this lesion was not treatment related.
Purification Methods
Wash it with diethyl ether. Crystallise it from acetone, distilled water, or tert-butanol. Dry it under vacuum over P2O5 or conc H2SO4. Also purify it by conversion to the disodium salt which, after crystallisation from boiling water (charcoal), is treated with mineral acid to regenerate the succinic acid. The acid is then recrystallised and dried in a vacuum. [Beilstein 2 H 606, 2 IV 1908.]
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