Bronopol (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

; chemical name 2-bromo-2-nitropropane-1,3-diol) is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

that is used as an

antimicrobial An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat. For example, antibiotics are used aga ...

. It is a white solid although commercial samples appear yellow. The first reported synthesis of bronopol was in 1897. Bronopol was invented by The Boots Company PLC in the early 1960s and first applications were as a

preservative A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or ...

for

pharmaceutical Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...

s. Due to its low

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

ian

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

at in-use levels and high activity against

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

, especially

Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

species, bronopol became popular as a preservative in many consumer products such as

shampoo Shampoo () is a hair care product, typically in the form of a viscous liquid, that is formulated to be used for cleaning (scalp) hair. Less commonly, it is available in solid bar format. (" Dry shampoo" is a separate product.) Shampoo is use ...

s and

cosmetics Cosmetics are substances that are intended for application to the body for cleansing, beautifying, promoting attractiveness, or altering appearance. They are mixtures of chemical compounds derived from either Natural product, natural source ...

. It was subsequently adopted as an antimicrobial in other industrial environments such as

paper mill A paper mill is a factory devoted to making paper from vegetable fibres such as wood pulp, old rags, and other ingredients. Prior to the invention and adoption of the Fourdrinier machine and other types of paper machine that use an endless belt ...

oil exploration Hydrocarbon exploration (or oil and gas exploration) is the search by petroleum geologists and geophysicists for hydrocarbon deposits, particularly petroleum and natural gas, in the Earth's crust using petroleum geology. Exploration methods V ...

, and production facilities, as well as cooling water disinfection plants.

Production

Bronopol is produced by the

bromination In chemistry, halogenation is a chemical reaction which introduces one or more halogens into a chemical compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs ...

of di(hydroxymethyl)nitromethane, which is derived from

nitromethane Nitromethane, sometimes shortened to simply "nitro", is an organic compound with the chemical formula . It is the simplest organic nitro compound. It is a polar liquid commonly used as a solvent in a variety of industrial applications such as in ...

by a

nitroaldol reaction The Henry reaction is a classic carbon–carbon bond formation reaction in organic chemistry. Discovered in 1895 by the Belgian chemist Louis Henry (1834–1913), it is the combination of a nitroalkane and an aldehyde or ketone in the presence ...

. World production increased from the tens of

tonne The tonne ( or ; symbol: t) is a unit of mass equal to 1,000 kilograms. It is a non-SI unit accepted for use with SI. It is also referred to as a metric ton in the United States to distinguish it from the non-metric units of the s ...

s in the late 1970s to current estimates in excess of 5,000 tonnes. Production today is the business of low cost producers, mainly in

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

Applications

Bronopol is used in consumer products as an effective preservative agent, as well as a wide variety of industrial applications (almost any industrial water system is a potential environment for bacterial growth, leading to

slime Slime or slimy may refer to: Science and technology Biology * Slime coat, the coating of mucus covering the body of all fish * Slime mold, an informal name for several eukaryotic organisms * Biofilm, or slime, a syntrophic community of micr ...

and

corrosion Corrosion is a natural process that converts a refined metal into a more chemically stable oxide. It is the gradual deterioration of materials (usually a metal) by chemical or electrochemical reaction with their environment. Corrosion engine ...

problems - in many of these systems bronopol can be a highly effective treatment). The use of bronopol in

personal care products Personal care products are consumer products which are applied on various external parts of the body such as Human skin, skin, hair, Nail (anatomy), nails, lips, external genital and anal areas, as well as Human tooth, teeth and mucous membrane of ...

(

toiletries Personal care products are consumer products which are applied on various external parts of the body such as skin, hair, nails, lips, external genital and anal areas, as well as teeth and mucous membrane of the oral cavity, in order to make th ...

) has declined since the late 1980s due to the potential formation of

nitrosamine Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...

s. While bronopol is not in itself a nitrosating agent, under conditions where it decomposes ''(

alkaline In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The ...

solution and/or elevated temperatures)'' it can liberate nitrite and low levels of formaldehyde and these decomposition products can react with any contaminant secondary amines or amides in a personal care formulation to produce significant levels of nitrosamines (due to the toxicity of these substances, the term 'significant' means levels as low as tens of parts per billion). Manufacturers of personal care products are therefore instructed by regulatory authorities to avoid the formation of nitrosamines which might mean removing amines or amides from the formulation, removing bronopol from a formulation, or using nitrosamine inhibitors. Bronopol has been restricted for use in cosmetics in Canada.

Physical and chemical properties

Appearance

Bronopol is supplied as

crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macros ...

s or crystalline powder, which may vary from white to pale yellow in colour depending on the grade. The yellow coloration is due to chelation of iron during the manufacturing process.

Melting point

As a pure material, bronopol has a

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state of matter, state from solid to liquid. At the melting point the solid and liquid phase (matter), phase exist in Thermodynamic equilib ...

of about 130 °C. However, due to its polymorphic characteristics, bronopol undergoes a

lattice Lattice may refer to: Arts and design * Latticework, an ornamental criss-crossed framework, an arrangement of crossing laths or other thin strips of material * Lattice (music), an organized grid model of pitch ratios * Lattice (pastry), an or ...

rearrangement at 100 to 105 °C and this can often be wrongly interpreted as the melting point. At temperatures above 140 °C, bronopol decomposes

exothermic In thermodynamics, an exothermic process () is a thermodynamic process or reaction that releases energy from the system to its surroundings, usually in the form of heat, but also in a form of light (e.g. a spark, flame, or flash), electricity (e ...

ally releasing

hydrogen bromide Hydrogen bromide is the inorganic compound with the formula . It is a hydrogen halide consisting of hydrogen and bromine. A colorless gas, it dissolves in water, forming hydrobromic acid, which is saturated at 68.85% HBr by weight at room temper ...

and

oxides of nitrogen Nitrogen oxide may refer to a binary compound of oxygen and nitrogen, or a mixture of such compounds: Charge-neutral *Nitric oxide (NO), nitrogen(II) oxide, or nitrogen monoxide *Nitrogen dioxide (), nitrogen(IV) oxide * Nitrogen trioxide (), or ...

Solubility

Bronopol is readily soluble in water; the dissolution process is

endothermic An endothermic process is a chemical or physical process that absorbs heat from its surroundings. In terms of thermodynamics, it is a thermodynamic process with an increase in the enthalpy (or internal energy ) of the system.Oxtoby, D. W; Gillis, ...

. Solutions containing up to 28% w/v are possible at

ambient temperature Room temperature, colloquially, denotes the range of air temperatures most people find comfortable indoors while dressed in typical clothing. Comfortable temperatures can be extended beyond this range depending on humidity, air circulation, and ...

. Bronopol is poorly soluble in non-polar

solvent A solvent (from the Latin language, Latin ''wikt:solvo#Latin, solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a Solution (chemistry), solution. A solvent is usually a liquid but can also be a solid, a gas ...

s but shows a high affinity for polar organic solvents.

Partition coefficient

Study of the solubility data shows that bronopol has a high affinity for polar rather than non-polar environments. In two-phase systems, bronopol partitions preferentially into the polar (usually aqueous) phase.

Stability in aqueous solution

In aqueous solutions, bronopol is most stable when the pH of the system is on the

acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...

side of neutral. Temperature also has a significant effect on stability in alkaline systems.

Degradation

Under extreme alkaline conditions, bronopol decomposes in aqueous solution and very low levels of formaldehyde are produced. Liberated formaldehyde is not responsible for the biological activity associated with bronopol. Other decomposition products detected after bronopol breakdown are

bromide ion A bromide ion is the negatively charged form (Br−) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retardant ...

, nitrite ion, bromonitroethanol and 2-hydroxymethyl-2-nitropropane-1,3-diol.

Allergy

In 2005–2006, it was the 15th-most-prevalent

allergen An allergen is an otherwise harmless substance that triggers an allergic reaction in sensitive individuals by stimulating an immune response. In technical terms, an allergen is an antigen that is capable of stimulating a type-I hypersensitivi ...

patch test A patch test is a diagnostic method used to determine which specific substances cause allergic inflammation of a patient's skin. Patch testing helps identify which substances may be causing a delayed-type allergic reaction in a patient and ...

s (3.4%) of people with suspected allergic contact dermatitis. It is used as a substitute for formaldehyde, a disinfectant and preservative, in solvents. It is prevalent in skin and personal care products and topical medications.

References

{{Reflist

External links

Material Safety Data Sheet for Bronopol
Organobromides Nitro compounds Diols