The Reformatsky reaction (sometimes misspelled Reformatskii reaction) is an organic reaction which

condenses Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor to ...

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 or ketones with α-halo

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

s using metallic

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 ...

to form β-hydroxy-esters: The

organozinc Organozinc compounds in organic chemistry contain carbon (C) to zinc (Zn) chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions.The Chemistry of Organozinc Compoun ...

reagent, also called a 'Reformatsky enolate', is prepared by treating an alpha-halo ester with zinc dust. Reformatsky enolates are less reactive than lithium enolates or Grignard reagents and hence nucleophilic addition to the ester group does not occur. The reaction was discovered by Sergey Nikolaevich Reformatsky. Some reviews have been published. In addition to aldehydes and ketones, it has also been shown that the Reformatsky enolate is able to react with acid chlorides,

imines In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...

nitriles In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix '' cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

(see

Blaise reaction The Blaise reaction is an organic reaction that forms a β-ketoester from the reaction of zinc metal with a α-bromoester and a nitrile. The reaction was first reported by Edmond Blaise (1872–1939) in 1901. The final intermediate is a metaloimin ...

), and nitrones. Moreover, metals other than zinc have also been used, including

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

iron Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...

cobalt Cobalt is a chemical element with the symbol Co and atomic number 27. As with nickel, cobalt is found in the Earth's crust only in a chemically combined form, save for small deposits found in alloys of natural meteoric iron. The free element, p ...

nickel Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow ...

, germanium,

cadmium Cadmium is a chemical element with the symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Like zinc, it demonstrates oxidation state +2 in most of ...

indium Indium is a chemical element with the symbol In and atomic number 49. Indium is the softest metal that is not an alkali metal. It is a silvery-white metal that resembles tin in appearance. It is a post-transition metal that makes up 0.21 parts ...

, barium, and

cerium Cerium is a chemical element with the symbol Ce and atomic number 58. Cerium is a soft, ductile, and silvery-white metal that tarnishes when exposed to air. Cerium is the second element in the lanthanide series, and while it often shows the +3 ...

. Additionally, metal salts are also applicable in place of metals, notably

samarium(II) iodide Samarium(II) iodide is an inorganic compound with the formula SmI2. When employed as a solution for organic synthesis, it is known as Kagan's reagent. SmI2 is a green solid and solutions are green as well. It is a strong one-electron reducing a ...

chromium(II) chloride Chromium(II) chloride describes inorganic compounds with the chemical formula, formula Chromium, CrChlorine, Cl2(H2O)n. The anhydrous solid is white when pure, however commercial samples are often grey or green; it is hygroscopic and readily disso ...

titanium(II) chloride Titanium(II) chloride is the chemical compound with the formula TiCl2. The black solid has been studied only moderately, probably because of its high reactivity. Ti(II) is a strong reducing agent: it has a high affinity for oxygen and reacts irre ...

, cerium(III) halides such as cerium(III) iodide, and titanocene(III) chloride.

Structure of the reagent

The crystal structures of the

THF Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...

complexes of the Reformatsky reagents ''tert''-butyl bromozincacetate and ethyl bromozincacetate have been determined. Both form cyclic eight-membered dimers in the solid state, but differ in stereochemistry: the eight-membered ring in the ethyl derivative adopts a tub-shaped conformation and has ''cis'' bromo groups and ''cis'' THF ligands, whereas in the ''tert''-butyl derivative, the ring is in a chair form and the bromo groups and THF ligands are ''trans''.

Reaction mechanism

Zinc metal is inserted into the carbon-halogen bond of the α-haloester by

oxidative addition Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxid ...

1. This compound dimerizes and rearranges to form two zinc enolates 2. The oxygen on an aldehyde or ketone coordinates to the zinc to form the six-member chair like transition state 3. A rearrangement occurs in which zinc switches to the aldehyde or ketone oxygen and a carbon-carbon bond is formed 4. Acid workup 5,6 removes zinc to yield zinc(II) salts and a β-hydroxy-ester 7.Kurti, L.; Czako, B. ''Strategic Applications of Named Reactions in Organic Synthesis''; Elsevier: Burlington, 2005.

Variations

In one variation of the Reformatsky reaction an iodolactam is coupled with an

with

triethylborane Triethylborane (TEB), also called triethylboron, is an organoborane (a compound with a B–C bond). It is a colorless pyrophoric liquid. Its chemical formula is or , abbreviated . It is soluble in organic solvents tetrahydrofuran and hexane. Pr ...

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) a ...

at -78 °C.

References

{{reflist Addition reactions Carbon-carbon bond forming reactions Organometallic chemistry Name reactions

Structure of the reagent

Reaction mechanism

Variations

See also

References