Oxazole is the parent compound for a vast class of
heterocyclic
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
aromatic
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
s. These are
azole
Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring.
Their names originate from the Hantzsch–Widman nomenclature. T ...
s with an oxygen and a nitrogen separated by one carbon. Oxazoles are
aromatic compound
Aromatic compounds, also known as "mono- and polycyclic aromatic hydrocarbons", are organic compounds containing one or more aromatic rings. The parent member of aromatic compounds is benzene. The word "aromatic" originates from the past grouping ...
s but less so than the thiazoles. Oxazole is a weak base; its
conjugate acid has a
p''K''a of 0.8, compared to 7 for
imidazole.
Preparation
Classical oxazole synthetic methods in
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...
are
* the
Robinson–Gabriel synthesis
The Robinson–Gabriel synthesis is an organic reaction in which a 2-acylamino-ketone reacts intramolecularly followed by a dehydration to give an oxazole. A cyclodehydrating agent is needed to catalyze the reaction It is named after Sir Robert Ro ...
by dehydration of 2-acylaminoketones
* the
Fischer oxazole synthesis from cyanohydrins and aldehydes
* the
Bredereck reaction with α-
haloketone
In organic chemistry, an α-haloketone is a functional group consisting of a ketone group or more generally a carbonyl group with an α-halogen substituent. α-haloketones are alkylating agents. Prominent α-haloketones include phenacyl bromide ...
s and
formamide
* the
Van Leusen reaction with aldehydes and
TosMIC
Other methods:
* Oxazolines can also be obtained from cycloisomerization of certain
propargyl amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s. In one study oxazoles were prepared via a
one-pot synthesis consisting of the condensation of
propargyl amine and
benzoyl chloride
Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula . It is a colourless, fuming liquid with an irritating odour, and consists of a benzene ring () with an acyl chloride () substituent. It is ...
to the
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
, followed by a
Sonogashira coupling of the terminal
alkyne end with another equivalent of benzoylchloride, and concluding with
''p''-toluenesulfonic acid catalyzed
cycloisomerization:
:
*In one reported oxazole synthesis the reactants are a
nitro-substituted
benzoyl chloride
Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula . It is a colourless, fuming liquid with an irritating odour, and consists of a benzene ring () with an acyl chloride () substituent. It is ...
and an
isonitrile
An isocyanide (also called isonitrile or carbylamine) is an organic compound with the functional group –. It is the isomer of the related nitrile (–C≡N), hence the prefix is ''isocyano''.IUPAC Goldboo''isocyanides''/ref> The organic fragme ...
:
:
Biosynthesis
In
biomolecules
A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include lar ...
, oxazoles result from the cyclization and oxidation of
serine or
threonine nonribosomal
peptides:
:
Oxazoles are not as abundant in
biomolecules as the related
thiazole
Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular fo ...
s with oxygen replaced by a sulfur atom.
Reactions
With a pK
a of 0.8 for the conjugate acid, oxazoles are far less basic than imidazoles (pK
a = 7).
[Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England,
1997. 414 pp. .]
*
Deprotonation
Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju. ...
of oxazoles at C2 is often accompanied by ring-opening to the isonitrile.
*
Electrophilic aromatic substitution
Electrophilic aromatic substitution is an organic reaction in which an atom that is attached to an aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitutions are aromatic n ...
takes place at C5 requiring
activating groups.
*
Nucleophilic aromatic substitution
A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. Aromatic rings are usually nucleophilic, but some aromatic compou ...
takes place with leaving groups at C2.
*
Diels–Alder reactions with oxazole dienes can be followed by loss of oxygen to form
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a ...
s.
* The
Cornforth rearrangement of 4-acyloxazoles is a thermal
rearrangement reaction with the organic acyl residue and the C5 substituent changing positions.
* Various
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 ...
reactions. One study
["Ceric Ammonium Nitrate Promoted Oxidation of Oxazoles", David A. Evans, Pavel Nagorny, and Risheng Xu. '' Org. Lett.''; 2006; 8(24) pp 5669 - 5671; (Letter) ] reports on the oxidation of 4,5-diphenyloxazole with 3 equivalents of
CAN to the corresponding
imide and
benzoic acid
Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, ...
:
:
: In the balanced
half-reaction
A half reaction (or half-cell reaction) is either the oxidation or reduction reaction component of a redox reaction. A half reaction is obtained by considering the change in oxidation states of individual substances involved in the redox reaction. ...
three equivalents of water are consumed for each equivalent of oxazoline, generating 4 protons and 4 electrons (the latter derived from Ce
IV).
See also
*
Isoxazole, an analog with the
nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
atom
Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons.
Every solid, liquid, gas, ...
in position 2.
*
Imidazole, an analog with 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 ...
replaced by a nitrogen.
*
Thiazole
Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular fo ...
, an analog with the oxygen replaced by a sulfur.
*
Benzoxazole, where the oxazole is fused to another aromatic ring.
*
Pyrrole, an analog without the oxygen atom.
*
Furan, an analog without the nitrogen atom.
*
Oxazoline, which has one double bond reduced.
*
Oxazolidine
An oxazolidine is a five-membered ring compound consisting of three carbon atoms, a nitrogen atom and an oxygen atom. The O atom and NH group are the 1 and 3 positions, respectively. In oxazolidine derivatives, there is always a carbon atom betwee ...
, which has both double bonds reduced.
*
Oxadiazoles Oxadiazoles are a class of heterocyclic aromatic chemical compound of the azole family; with the molecular formula C2H2N2O. There are four isomers of oxadiazole:
File:1,2,3-oxadiazole.svg, 1,2,3-oxadiazole
File:1,2,4-oxadiazole.svg, 1,2,4-oxadiazo ...
with two nitrogens instead of one (e.g.
furazan
Furazan, or 1,2,5-oxadiazole, is a heterocyclic aromatic organic compound consisting of a five-atom ring containing 1 oxygen and 2 nitrogen atoms. The furazan ring system is also found in the steroid furazabol. Furazan and its derivatives are ob ...
).
*
Oxazolone, an analog with a carbonyl group
References
{{reflist
Simple aromatic rings