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, J.; ...
, an α-haloketone is a
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 ...
consisting of a
ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
group or more generally a
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
group with an α-
halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this group is ...
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 ...
. α-haloketones are
alkylating agent
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
s. Prominent α-haloketones include
phenacyl bromide and
chloroacetone
Chloroacetone is a chemical compound with the chemical formula, formula . At Standard conditions for temperature and pressure, STP it is a colourless liquid with a pungent odour. On exposure to light, it turns to a dark yellow-amber colour. It wa ...
.
Structure
The general structure is RR′C(X)C(=O)R where R is an alkyl or aryl residue and X any one of the halogens.
The preferred
conformation of a haloketone is that of a
cisoid with the halogen and carbonyl sharing the same plane as the
steric hindrance
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
with the carbonyl alkyl group is generally larger.
Haloketone synthesis
Haloketones and halo carbonyl compounds in general are synthesized by reaction of
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
compounds with sources of X
+ (X = halogen), which is provided using
halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this group is ...
s:
[
:RC(O)CH3 + X2 → RC(O)CH2X + HX
Specialized sources of electrophilic halogenating agents include ''N''-Bromosuccinimide and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH). In the ]Nierenstein reaction
The Nierenstein reaction is an organic reaction describing the conversion of an acid chloride into a haloketone with diazomethane. It is an insertion reaction in that the methylene group from the diazomethane is inserted into the carbon-chlorine b ...
an acyl chloride reacts with diazomethane
Diazomethane is the chemical compound CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow gas; thus, it is almost u ...
Asymmetric synthesis
Efforts are reported in asymmetric synthesis
Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...
of halocarbonyls through organocatalysis
In organic chemistry, organocatalysis is a form of catalysis in which the rate of a chemical reaction is increased by an organic catalyst. This "organocatalyst" consists of carbon, hydrogen, sulfur and other nonmetal elements found in organic com ...
. In one study an acid chloride
In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
is converted into an α-halo-ester with a strong base (sodium hydride
Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in co ...
), a bromine donor and an organocatalyst based on proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
and quinine
Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg cr ...
:
In the proposed reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.
A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...
the base first converts the acid chloride to the ketene
In organic chemistry, a ketene is an organic compound of the form , where R and R' are two arbitrary monovalent chemical groups (or two separate substitution sites in the same molecule). The name may also refer to the specific compound ethen ...
, the organocatalyst then introduces chirality
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
through its quinonoid 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 substituent such a ...
, forming a ketene adduct.
Reactions
Haloketones take part in several reaction types, especially since they are bifunctional, with two electrophilic sites (alpha carbon and carbonyl carbon). In one manifestation of this duality, they are precursors to heterocycles. Aminothiazoles are produced by reaction of chloroketones with thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), except that the oxygen atom is replaced by a sulfur atom (as implied by the ''thio-'' prefix); however, the properties of urea ...
and with thioamides. Pyrroles by reaction of haloketones with dicarbonyls and ammonia the Hantzsch pyrrole synthesis The Hantzsch Pyrrole Synthesis, named for Arthur Rudolf Hantzsch, is the chemical reaction of β-ketoesters (1) with ammonia (or primary amines) and α-haloketones (2) to give substituted pyrroles (3).
Pyrroles are found in a variety of natural pr ...
.
Illustrative of their alkylating activity are reactions with potassium iodide
Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are u ...
in acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
, chloroacetone
Chloroacetone is a chemical compound with the chemical formula, formula . At Standard conditions for temperature and pressure, STP it is a colourless liquid with a pungent odour. On exposure to light, it turns to a dark yellow-amber colour. It wa ...
reacts faster than 1-chloropropane by a factor of 36,000. Haloketones react with phosphites in the Perkow reaction
The Perkow reaction is an organic reaction in which a trialkyl phosphite ester reacts with a haloketone to form a dialkyl vinyl phosphate and an alkyl halide.
In the related Michaelis–Arbuzov reaction the same reactants are known to form a be ...
.
Due to the presence of two electron withdrawing group
In chemistry, an electron-withdrawing group (EWG) is a substituent that has some of the following kinetic and thermodynamic implications:
*with regards to electron transfer, electron-withdrawing groups enhance the oxidizing power tendency of ...
s (carbonyl and halide), The alpha-C-H center is acidic. This property is exploited in the Favorskii rearrangement
The Favorskii rearrangement is principally a rearrangement of cyclopropanones and α-halo ketones that leads to carboxylic acid derivatives. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction. This ...
, where base abstracts first an acidic α-proton and the resulting carbanion
In organic chemistry, a carbanion is an anion in which carbon is trivalent (forms three bonds) and bears a formal negative charge (in at least one significant resonance form).
Formally, a carbanion is the conjugate base of a carbon acid:
:R3C ...
then displaces the halogen.
In crossed aldol reaction
The aldol reaction is a means of forming carbon–carbon bonds in organic chemistry.
Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872, the reaction combines two carb ...
s between haloketones 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 ...
s the initial reaction product is a halohydrin
In organic chemistry a halohydrin (also a haloalcohol or β-halo alcohol) is a functional group in which a halogen and a hydroxyl are bonded to adjacent carbon atoms, which otherwise bear only hydrogen or hydrocarbyl groups (e.g. 2-chloroethan ...
which can subsequently form an oxirane
Ethylene oxide is an organic compound with the formula . It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly swe ...
in the presence of base.
The halogroup can be removed in reductive dehalogenation of halo ketones
In organic chemistry, α-halo ketones can be Organic redox reaction, reduced with loss of the halogen atom to form enolates. The α-halo ketones are readily prepared from ketones by various ketone halogenation reactions, and the products are reacti ...
. Alpha-haloketones can also be converted to alkenes by treatment with hydrazine.
As a ketone, an α-haloketones can react with amines to form an α-haloimine, which can be converted back to the parent haloketone by hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
, so that haloimines may be used as masked versions of haloketones. This allows some chemical transformations to be achieved that is not possible on the parent haloketones directly.
References
{{Reflist
Functional groups