PRODUCTS

E355 – ADIPIC ACID

E355 Adipic acid or hexanedioic acid is an organic compound with the chemical formula C6H10O4.
E355 Adipic acid is a white crystalline powder at standard temperature and pressure.
From an industrial perspective, E355 Adipic acid is the most important dicarboxylic acid at about 2.5 billion kilograms produced annually, mainly as a precursor for the production of nylon.

CAS:   124-04-9
MF:   C6H10O4
MW:   146.14
EINECS:   204-673-3

Synonyms
RARECHEM AL BO 0180;AKOS BBS-00004308;ADIPIC ACID;adipinic acid;1,6-HEXANEDIOIC ACID;BUTANE-1,4-DICARBOXYLIC ACID;DICARBOXYLIC ACID C6;HEXANDIOIC ACID

E355 Adipic acid otherwise rarely occurs in nature, but it is known as manufactured E number food additive E355.
Salts and esters of E355 Adipic acid are known as adipates.
E355 Adipic acid is a crystalline powder with practically no odor.
E355 Adipic acid has the lowest acidity of any of the acids commonly used in foods and has excellent buffering capacity in the range of pH 2.5 to 3.0.
Like succinic and fumaric acid, E355 Adipic acid is practically nonhygroscopic.
E355 Adipic acid's addition to foods imparts a smooth, tart taste.
In grape-flavored products, E355 Adipic acid adds a lingering supplementary flavor and gives an excellent set to food powders containing gelatin.
As a result, E355 Adipic acid has found a wide number of uses as an accidulant in dry powdered food mixtures, especially in those products having delicate flavors and where addition of tang to the flavor is undesirable.
E355 Adipic acid's aqueous solutions have the lowest acidity of any of the common food acids.
For concentrations from 0.5 to 2.4 g/100 mL, the pH of its solution varies less than half a unit.

Hence, E355 Adipic acid can be used as a buffering agent to maintain acidities within the range of 2.5 to 3.0.
E355 Adipic acid is highly desirable in certain foods, yet the pH is low enough to inhibit the browning of most fruits and other foodstuffs.
An alpha,omega-dicarboxylic acid that is the 1,4-dicarboxy derivative of butane.
E355 Adipic acid is a white crystalline solid.
E355 Adipic acid is insoluble in water.
The primary hazard is the threat to the environment.
Immediate steps should be taken to limit its spread to the environment.
E355 Adipic acid is used to make plastics and foams and for other uses.
E355 Adipic acid is a glycol ether that is used as an extraction solvent.
E355 Adipic acid has been shown to be a good solvent for the separation of organic acids and aromatic compounds, such as malonic acid and caproic acid.
E355 Adipic acid has also been shown to be a good solvent for the removal of sulfur and nitrogen compounds from water vapor.
E355 Adipic acid can also be used as an oxidation catalyst in the chemical industry.
E355 Adipic acid is stable in acidic and alkaline environments, but not in basic environments.

E355 Adipic acid Chemical Properties
Melting point: 151-154 °C(lit.)
Boiling point: 265 °C100 mm Hg(lit.)
density: 1,36 g/cm3
bulk density: 700kg/m3
vapor density: 5 (vs air)
vapor pressure: 1 mm Hg ( 159.5 °C)
refractive index: 1.4880
FEMA: 2011 | ADIPIC ACID
Fp: 385 °F
storage temp.: Store below +30°C.
solubility methanol: 0.1 g/mL, clear, colorless
form: Solid
pka: 4.43(at 25℃)
color: White
Odor: wh. monoclinic prisms, pract. odorless
PH: 3.74(1 mM solution);3.22(10 mM solution);2.71(100 mM solution);
biological source: synthetic
Water Solubility: 1.44 g/100 mL (15 ºC)
JECFA Number: 623
Merck: 14,162
BRN: 1209788
Henry's Law Constant: 6.6×107 mol/(m3Pa) at 25℃, Burkholder et al. (2019)
Dielectric constant: 1.8（Ambient）
Exposure limits ACGIH: TWA 5 mg/m3
Stability: Stable. Substances to be avoided include ammonia, strong oxidizing agents.
Major Application: flavors and fragrances
Cosmetics Ingredients Functions: FRAGRANCE BUFFERING
Cosmetic Ingredient Review (CIR): Adipic acid (124-04-9)
InChI: 1S/C6H10O4/c7-5(8)3-1-2-4-6(9)10/h1-4H2,(H,7,8)(H,9,10)
InChIKey: WNLRTRBMVRJNCN-UHFFFAOYSA-N
LogP: 0.09 at 25℃
CAS DataBase Reference: 124-04-9(CAS DataBase Reference)
NIST Chemistry Reference: E355 Adipic acid(124-04-9)
EPA Substance Registry System: E355 Adipic acid (124-04-9)

E355 Adipic acid is the organic compound with the formula (CH2)4(COOH)2.
From the industrial perspective, E355 Adipic acid is the most important dicarboxylic acid: About 2.5 billion kilograms of this white crystalline powder are produced annually, mainly as a precursor for the production of nylon.
E355 Adipic acid otherwise rarely occurs in nature.

Physical properties
E355 Adipic acid is a straight-chain dicarboxylic acid that exists as a white crystalline compound at standard temperature and pressure.
E355 Adipic acid is one of the most important industrial chemicals and typically ranks in the top 10 in terms of volume used annually by the chemical industry.

Uses
E355 Adipic acid’s main use is in the production of 6,6 nylon.
E355 Adipic acid is also used in resins, plasticizers, lubricants, polyurethanes, and food additives.
E355 Adipic acid is primarily used in the synthesis of nylon.
E355 Adipic acid has been used as a reagent in the solid-state polymerization of nylon analogs.
E355 Adipic acid is an acidulant and flavoring agent.
E355 Adipic acid is characterized as stable, nonhygroscopic, and slightly soluble, with a water solubility of 1.9 g/100 ml at 20°c.
E355 Adipic acid has a ph of 2.86 at 0.6% usage level at 25°c.
E355 Adipic acid is used in powdered drinks, beverages, gelatin desserts, loz- enges, and canned vegetables.
E355 Adipic acid is also used as a leavening acidulant in baking powder.
E355 Adipic acid can be used as a buffering agent to maintain acidities within a range of ph 2.5–3.0.
E355 Adipic acid is occasionally used in edi- ble oils to prevent rancidity.
About 60% of the 2.5 billion kg of E355 Adipic acid produced annually is used as monomer for the production of nylon by a polycondensation reaction with hexamethylene diamine forming nylon 66.
Other major applications also involve polymers; E355 Adipic acid is a monomer for production of polyurethane and its esters are plasticizers, especially in PVC.

In medicine
E355 Adipic acid has been incorporated into controlled-release formulation matrix tablets to obtain pH-independent release for both weakly basic and weakly acidic drugs.
E355 Adipic acid has also been incorporated into the polymeric coating of hydrophilic monolithic systems to modulate the intragel pH, resulting in zero-order release of a hydrophilic drug.
The disintegration at intestinal pH of the enteric polymer shellac has been reported to improve when E355 Adipic acid was used as a pore-forming agent without affecting release in the acidic media.
Other controlled-release formulations have included adipic acid with the intention of obtaining a late-burst release profile.

In foods
Small but significant amounts of E355 Adipic acid are used as a food ingredient as a flavorant and gelling aid.
E355 Adipic acid is used in some calcium carbonate antacids to make them tart.
As an acidulant in baking powders, E355 Adipic acid avoids the undesirable hygroscopic properties of tartaric acid.
E355 Adipic acid, rare in nature, does occur naturally in beets, but this is not an economical source for commerce compared to industrial synthesis.

Pharmaceutical Applications
E355 Adipic acid is used as an acidifying and buffering agent in intramuscular, intravenous and vaginal formulations.
E355 Adipic acid is also used in food products as a leavening, pH-controlling, or flavoring agent.
E355 Adipic acid has been incorporated into controlled-release formulation matrix tablets to obtain pH-independent release for both weakly basicand weakly acidic drugs.
E355 Adipic acid has also been incorporated into the polymeric coating of hydrophilic monolithic systems to modulate the intragel pH, resulting in zero-order release of a hydrophilic drug.
The disintegration at intestinal pH of the enteric polymer shellac has been reported to improve when E355 Adipic acid was used as a pore-forming agent without affecting release in the acidic media.
Other controlled-release formulations have included E355 Adipic acid with the intention of obtaining a late-burst release profile.

Preparation and reactivity
E355 Adipic acid is produced by oxidation of a mixture of cyclohexanone and cyclohexanol, which is called KA oil, an abbreviation of ketone-alcohol oil.
Nitric acid is the oxidant.
The pathway is multistep.
Early in the reaction, the cyclohexanol is converted to the ketone, releasing nitrous acid:

HOCH(CH2)5 + HNO3 → O=C(CH2)5 + HNO2 + H2O
The cyclohexanone is then nitrosated, setting the stage for the scission of the C-C bond:

HNO2 + HNO3 → [NO+][NO3]− + H2O
O=C(CH2)5 + NO+ → O=C(CHNO)(CH2)4 + H+
Side products of the method include glutaric and succinic acids.
Nitrous oxide is produced in about one to one mole ratio to the adipic acid, as well, via the intermediacy of a nitrolic acid.
Related processes start from cyclohexanol, which is obtained from the hydrogenation of phenol.

Alternative methods of production
Several methods have been developed by carbonylation of butadiene. For example, the hydrocarboxylation proceeds as follows:

CH2=CH−CH=CH2 + 2 CO + 2 H2O → HO2C(CH2)4CO2H
Another method is oxidative cleavage of cyclohexene using hydrogen peroxide.
The waste product is water.

Auguste Laurent discovered E355 Adipic acid in 1837 by oxidation of various fats with nitric acid via sebacic acid and gave it the current name because of that (ultimately from Latin adeps, adipis – 'animal fat'; cf. adipose tissue).

Reactions
E355 Adipic acid is a diprotic acid (it has two acidic groups).
The pKa values for their successive deprotonations are 4.41 and 5.41.
With the carboxylate groups separated by four methylene groups, E355 Adipic acid is suited for intramolecular condensation reactions.
Upon treatment with barium hydroxide at elevated temperatures, E355 Adipic acid undergoes ketonization to give cyclopentanone.

Production Methods
E355 Adipic acid is prepared by nitric acid oxidation of cyclohexanol or cyclohexanone or a mixture of the two compounds.
Recently, oxidation of cyclohexene with 30% aqueous hydrogen peroxide under organic solvent- and halide-free conditions has been proposed as an environmentally friendly alternative for obtaining colorless crystalline adipic acid.
E355 Adipic acid can be manufactured using several methods, but the traditional and main route of preparation is by the two-step oxidation of cyclohexane (C6H12).
In the first step, cyclohexane is oxidized to cyclohexanone and cyclohexanol with oxygen or air.
This occurs at a temperature of approximately 150°C in the presence of cobalt or manganese catalysts.
The second oxidation is done with nitric acid and air using copper or vanadium catalysts.
In this step, the ring structure is opened and adipic acid and nitrous oxide are formed.
Other feedstocks such as benzene and phenol may be use to synthesize adipic acid.
E355 Adipic acid production used to be a large emitter of nitrous oxide, a greenhouse gas, but these have been controlled in recent years using pollution abatement technology.

Preparation
E355 Adipic acid is produced from a mixture of cyclohexanol and cyclohexanone called "KA oil", the abbreviation of "ketone-alcohol oil."
The KA oil is oxidized with nitric acid to give E355 Adipic acid, via a multistep pathway.
Early in the reaction the cyclohexanol is converted to the ketone, releasing nitrous acid:
HOC6H11 + HNO3 → OC6H10 + HNO2 + H2O
Among its many reactions, the cyclohexanone is nitrosated, setting the stage for the scission of the C- C bond:
HNO2 + HNO3 → NO+NO3- + H2O
OC6H10 + NO+→ OC6H9-2 - NO + H+
Side products of the method include glutaric and succinic acids.
Related processes start from cyclohexanol, which is obtained from the hydrogenation of phenol.

Reactions
E355 Adipic acid is a dibasic acid (can be deprotonated twice).
Its pKa's are 4.41 and 5.41.
With the carboxylate groups separated by four methylene groups, E355 Adipic acid is suited for intramolecular condensation reactions.
Upon treatment with barium hydroxide at elevated temperatures, E355 Adipic acid undergoes ketonization to give cyclopentanone.

Biotechnological Production
E355 Adipic acid is industrially produced by chemical synthesis.
However, there are new efforts to develop an E355 Adipic acid production process using biorenewable sources.
A direct biosynthesis route has not yet been reported.
The possible precursors Z,Z-muconic acid and glucaric acid can be produced biotechnologically by fermentation.
Z,Z-muconic acid can be made from benzoate with concentrations up to 130 mM with a yield of close to 100 % (mol/mol) by Pseudomonas putida KT2440-JD1 grown on glucose.
Alternatively, E355 Adipic acid can be produced by engineered E. coli directly from glucose at up to 260 mM with a yield of 0.2 mol Z,Zmuconic acid per mole glucose.
The production of the second possible precursor, glucaric acid, by engineered E. coli growing on glucose has been reported.
However, the product titers were low (e.g. 4.8 and 12 mM.
To overcome the problem of low product concentrations, an alternative synthetic pathway has been suggested but not yet demonstrated .

In a hydrogenation process, Z,Z-muconic acid and glucaric acid could be converted chemically into E355 Adipic acid.
Therefore, bimetallic nanoparticles or platinum on activated carbon as catalysts have been studied.
In particular, nanoparticles of Ru10Pt2 anchored within pores of mesoporous silica showed high selectivity and conversion rates, greater than 0.90 mol adipic acid per mole Z,Zmuconicacid.
With platinum on activated carbon, conversion rates of 0.97 mol.mol-1 of Z,Z-muconic acid into adipic acid have been shown.
Another possibility would be the production of E355 Adipic acid from glucose via the a–aminoadipate pathway.
Finally, the production of adipic acid from longchain carbon substrates has been suggested.
The conversion of fatty acids into dicarboxylic acids by engineered yeast strains has been reported.

Reactivity Profile
E355 Adipic acid is a carboxylic acid.
Carboxylic acids donate hydrogen ions if a base is present to accept them.
They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat.
Neutralization between an acid and a base produces water plus a salt.
Carboxylic acids with six or fewer carbon atoms are freely or moderately soluble in water; those with more than six carbons are slightly soluble in water.
Soluble carboxylic acid dissociate to an extent in water to yield hydrogen ions.
The pH of solutions of carboxylic acids is therefore less than 7.0.
Many insoluble carboxylic acids react rapidly with aqueous solutions containing a chemical base and dissolve as the neutralization generates a soluble salt.
Carboxylic acids in aqueous solution and liquid or molten carboxylic acids can react with active metals to form gaseous hydrogen and a metal salt.
Such reactions occur in principle for solid carboxylic acids as well, but are slow if the solid acid remains dry.
Even "insoluble" carboxylic acids may absorb enough water from the air and dissolve sufficiently in E355 Adipic acid to corrode or dissolve iron, steel, and aluminum parts and containers.

Carboxylic acids, like other acids, react with cyanide salts to generate gaseous hydrogen cyanide.
The reaction is slower for dry, solid carboxylic acids.
Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide.
Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides.
Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat.
Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat.
Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents.
These reactions generate heat.
A wide variety of products is possible.
Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.
Behavior in Fire: Melts and may decompose to give volatile acidic vapors of valeric acid and other substances.