In
chemistry
Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...
, an amine oxide, also known as an amine ''N''-oxide or simply ''N''-oxide, is a
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
that contains the
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
, a nitrogen-oxygen
coordinate covalent bond
In coordination chemistry, a coordinate covalent bond, also known as a dative bond, dipolar bond, or coordinate bond is a kind of two-center, two-electron covalent bond in which the two electrons derive from the same atom. The bonding of metal io ...
with three additional hydrogen and/or
substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
-group
side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a l ...
s attached to N. Sometimes it is written as →O or, incorrectly, as .
In the strict sense, the term ''amine oxide'' applies only to
oxide
An oxide () is a chemical compound that contains at least one oxygen atom and one other element in its chemical formula. "Oxide" itself is the dianion of oxygen, an O2– (molecular) ion. with oxygen in the oxidation state of −2. Most of the E ...
s of tertiary
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
s. Sometimes it is also used for the analogous derivatives of primary and secondary amines.
Examples of amine oxides include
pyridine-''N''-oxide, a water-soluble crystalline solid with
melting point
The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends ...
62–67 °C, and
''N''-methylmorpholine ''N''-oxide, which is an oxidant.
Applications
Amine oxides are surfactants commonly used in consumer products such as shampoos, conditioners, detergents, and hard surface cleaners.
Alkyl dimethyl amine oxide (chain lengths C10–C16) is the most commercially used amine oxide.
They are considered a high production volume class of compounds in more than one member country of the Organisation for Economic Co-operation and Development, Organisation for Economic Co-operation and Development (
OECD
The Organisation for Economic Co-operation and Development (OECD; french: Organisation de coopération et de développement économiques, ''OCDE'') is an intergovernmental organisation with 38 member countries, founded in 1961 to stimulate e ...
); with annual production over in the US, Europe, and Japan, respectively.
[ In North America, more than 95% of amine oxides are used in home cleaning products.] They serve as stabilizers, thickeners, emollients, emulsifiers, and conditioners with active concentrations in the range of 0.1–10%.[ The remainder (< 5%) is used in personal care, institutional, commercial products] and for unique patented uses such as photography.[
]
Properties
Amine oxides are used as protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In many ...
for amines and as chemical
A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wi ...
intermediates. Long-chain alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...
amine oxides are used as amphoteric
In chemistry, an amphoteric compound () is a molecule or ion that can react both as an acid and as a base. What exactly this can mean depends on which definitions of acids and bases are being used.
One type of amphoteric species are amphiproti ...
surfactant
Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...
s and foam
Foams are materials formed by trapping pockets of gas in a liquid or solid.
A bath sponge and the head on a glass of beer are examples of foams. In most foams, the volume of gas is large, with thin films of liquid or solid separating the reg ...
stabilizers.
Amine oxides are highly polar molecule
In chemistry, polarity is a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end.
Polar molecules must contain one or more polar ...
s and have a polarity
Polarity may refer to:
Science
*Electrical polarity, direction of electrical current
*Polarity (mutual inductance), the relationship between components such as transformer windings
* Polarity (projective geometry), in mathematics, a duality of ord ...
close to that of quaternary ammonium salt
In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium cations ...
s. Small amine oxides are very hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are no ...
and have an excellent water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...
solubility
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubil ...
and a very poor solubility in most organic solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
s.
Amine oxides are weak bases with a p''K''b of around 4.5 that form R3N+−OH, cation
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
ic hydroxylamine
Hydroxylamine is an inorganic compound with the formula . The material is a white crystalline, hygroscopic compound.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–43 ...
s, upon protonation
In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...
at a pH below their p''K''b.
Synthesis
Almost all amine oxides are prepared by the oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
of either tertiary aliphatic amines or aromatic ''N''-heterocycle
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis ...
s. Hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
is the most common reagent both industrially and in academia, however peracid
A peroxy acid (often spelled as one word, peroxyacid, and sometimes called peracid) is an acid which contains an acidic –OOH group. The two main classes are those derived from conventional mineral acids, especially sulfuric acid, and the peroxy ...
s are also important. More specialised oxidising agents can see niche use, for instance Caro's acid
Peroxymonosulfuric acid, , also known as persulfuric acid, peroxysulfuric acid, or Caro's acid. In this acid, the S(VI) center adopts its characteristic tetrahedral geometry; the connectivity is indicated by the formula HO–O–S(O)2–OH. It i ...
or ''m''CPBA. Spontaneous or catalysed reactions using molecular oxygen are rare. Certain other reactions will also produce amine oxides, such as the Cope elimination
The Cope reaction or Cope elimination, developed by Arthur C. Cope, is an elimination reaction of the N-oxide to form an alkene and a hydroxylamine.
Mechanism and applications
The reaction mechanism involves an intramolecular 5-membered cyclic tr ...
, however they are rarely employed.
Reactions
Amine oxides exhibit many kinds of reactions.
*Pyrolytic elimination. Amine oxides, when heated to 150–200 °C eliminate a hydroxylamine, resulting in an alkene
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
. This pyrolytic
The pyrolysis (or devolatilization) process is the thermal decomposition of materials at elevated temperatures, often in an inert atmosphere. It involves a change of chemical composition. The word is coined from the Greek-derived elements ''pyr ...
syn-elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 ...
is known under the name Cope reaction
The Cope reaction or Cope elimination, developed by Arthur C. Cope, is an elimination reaction of the N-oxide to form an alkene and a hydroxylamine.
Mechanism and applications
The reaction mechanism involves an intramolecular 5-membered cyclic t ...
. The mechanism is similar to that of the Hofmann elimination
Hofmann elimination is an elimination reaction of an amine to form alkenes. The least stable alkene (the one with the least number of substituents on the carbons of the double bond), called the Hofmann product, is formed. This tendency, known as ...
.
*Reduction to amines. Amine oxides are readily converted to the parent amine by common reduction reagent
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
s including lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...
, sodium borohydride
Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds appli ...
, catalytic reduction, zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
/ acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...
, and iron / acetic acid. Pyridine ''N''-oxides can be deoxygenated by phosphorus oxychloride
Phosphoryl chloride (commonly called phosphorus oxychloride) is a colourless liquid with the formula . It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from phosp ...
* Sacrificial catalysis. Oxidants can be regenerated by reduction of ''N''-oxides, as in the case of regeneration of osmium tetroxide
Osmium tetroxide (also osmium(VIII) oxide) is the chemical compound with the formula OsO4. The compound is noteworthy for its many uses, despite its toxicity and the rarity of osmium. It also has a number of unusual properties, one being that the ...
by ''N''-methylmorpholine ''N''-oxide.
* ''O''-Alkylation. Pyridine ''N''-oxides react with alkyl halide
The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely ...
s to the ''O''-alkylated product
* Bis-''ter''-pyridine derivatives adsorbed on silver surfaces are discussed to react with oxygen to bis-''ter''-pyridine ''N''-oxide. This reaction can be followed by video-scanning tunneling microscopy
A scanning tunneling microscope (STM) is a type of microscope used for imaging surfaces at the atomic level. Its development in 1981 earned its inventors, Gerd Binnig and Heinrich Rohrer, then at IBM Zürich, the Nobel Prize in Physics in 1986. ...
with sub-molecular resolution.
* In the Meisenheimer rearrangement (after Jakob Meisenheimer
Jakob Meisenheimer (14 June 1876 – 2 December 1934) was a German chemist. He made numerous contributions to organic chemistry, the most famous being his proposed structure for a group of compounds now named Meisenheimer complex. He also pro ...
) certain ''N''-oxides R1R2R3N+O− rearrange to hydroxylamine
Hydroxylamine is an inorganic compound with the formula . The material is a white crystalline, hygroscopic compound.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–43 ...
s R2R3N−O−R1
: in a 1,2-rearrangement:
:
:or a 2,3-rearrangement:
:
* In the Polonovski reaction a tertiary ''N''-oxide is cleaved by acetic acid anhydride to the corresponding acetamide
Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound ''N'',''N''-dimeth ...
and aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
:
:
Metabolites
Amine oxides are common metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s of medication and psychoactive drug
A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...
s. Examples include nicotine
Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
, Zolmitriptan
Zolmitriptan, sold under the brand name Zomig among others, is a triptan used in the acute treatment of migraine attacks with or without aura and cluster headaches. It is a selective serotonin receptor agonist of the 1B and 1D subtypes.
It wa ...
, and morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
.
Amine oxides of anti-cancer drugs
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
have been developed as prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
s that are metabolized in the oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
-deficient cancer tissue to the active drug.
Human safety
Amine oxides (AO) are not known to be carcinogens, dermal sensitizers, or reproductive toxicants. They are readily metabolized and excreted if ingested. Chronic ingestion by rabbits found lower body weight, diarrhea, and lenticular opacities at a lowest observed adverse effect levels (LOAEL) in the range of 87–150 mg AO/kw bw/day. Tests of human skin exposure have found that after 8 hours less than 1% is absorbed into the body. Eye irritation due to amine oxides and other surfactants is moderate and temporary with no lasting effects.[
]
Environmental safety
Amine oxides with an average chain length of 12.6 have been measured to be water-soluble at ~410 g L−1. They are considered to have low bioaccumulation
Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...
potential in aquatic species based on log Kow data from chain lengths less than C14 (bioconcentration factor < 87%).[ Levels of AO in untreated influent were found to be 2.3–27.8 ug L−1, while in effluent they were found to be 0.4–2.91 ug L−1. The highest effluent concentrations were found in oxidation ditch and trickling filter treatment plants. On average, over 96% removal has been found with secondary activated sludge treatment.][ Acute toxicity in fish, as indicated by 96h LC50 tests, is in the range of 1,000–3,000 ug L−1 for carbon chain lengths less than C14. LC50 values for chain lengths greater than C14 range from 600 to 1400 ug L−1. Chronic toxicity data for fish is 420 ug/L. When normalized to C12.9, the NOEC is 310 ug L−1 for growth and hatchability.][
]
See also
* Functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
* Amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
, NR3
* Hydroxylamine
Hydroxylamine is an inorganic compound with the formula . The material is a white crystalline, hygroscopic compound.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–43 ...
, NR2OH
* Phosphine oxide, PR3=O
* Sulfoxide
In organic chemistry, a sulfoxide, also called a sulphoxide, is an organosulfur compound containing a sulfinyl () functional group attached to two carbon atoms. It is a polar functional group. Sulfoxides are oxidized derivatives of sulfides. E ...
, R2S=O
* Azoxy
In chemistry, azoxy compounds are a group of chemical compounds sharing a common functional group with the general structure . They are considered N-oxides of azo compounds. Azoxy compounds are 1,3-dipoles. They undergo 1,3-dipolar cycloaddit ...
, RN=N+(O−)R RN=N+RO−
* Aminoxyl group Radicals with the general structure R2N–O•
* :Amine oxides, containing all articles on specific amine-oxide compounds
References
External links
Chemistry of amine oxides
Surfactants, types and uses
(pdf)
{{DEFAULTSORT:Amine Oxide
Functional groups