The Reimer–Tiemann reaction is a

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

used for the '' ortho''-

formylation Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds (for example the conversion of benzene to benz ...

phenols In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl groups (− O H) bonded directly to an aromatic hydrocarbon group. The simplest is phenol, . Phenolic compounds ar ...

. with the simplest example being the conversion of

phenol Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire. The molecule consists of a phenyl group () ...

salicylaldehyde Salicylic aldehyde (2-hydroxybenzaldehyde) is an organic compound with the formula . Along with 3-hydroxybenzaldehyde and 4-hydroxybenzaldehyde, it is one of the three isomers of hydroxybenzaldehyde. This colorless oily liquid has a bitter almo ...

. The reaction was first reported by Karl Reimer and Ferdinand Tiemann. Reimer-Tiemann Reaction Scheme

Reaction mechanism

Chloroform Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and po ...

(1) is deprotonated by a strong base (normally

hydroxide Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. It ...

) to form the chloroform carbanion (2) which will quickly alpha-eliminate to give

dichlorocarbene Dichlorocarbene is the reactive intermediate with chemical formula CCl2. Although this chemical species has not been isolated, it is a common intermediate in organic chemistry, being generated from chloroform. This bent diamagnetic molecule rapi ...

(3); this is the principal reactive species. The hydroxide will also deprotonate the phenol (4) to give a negatively charged phenoxide (5). The negative charge is delocalised into the aromatic ring, making it far more nucleophilic. Nucleophilic attack on the dichlorocarbene gives an intermediate dichloromethyl substituted phenol (7). After basic hydrolysis, the desired product (9) is formed.

Selectivity

By virtue of its two

electron-withdrawing An electron-withdrawing group (EWG) is a group or atom that has the ability to draw electron density toward itself and away from other adjacent atoms. This electron density transfer is often achieved by resonance or inductive effects. Electron-with ...

chlorine groups, the carbene (3) is highly electron deficient and is attracted to the electron rich phenoxide (5). This interaction favors selective ''ortho''-formylation, consistent with other

electrophilic aromatic substitution Electrophilic aromatic substitution (SEAr) is an organic reaction in which an atom that is attached to an aromatic ring, aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitut ...

reactions.

Reaction conditions

Hydroxides are not readily soluble in chloroform, thus the reaction is generally carried out in a biphasic solvent system. In the simplest sense this consists of an aqueous hydroxide solution and an organic phase containing the chloroform. Therefore, the two reagents are separated and must be brought together for the reaction to take place. This can be achieved by rapid mixing,

phase-transfer catalyst In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the Phase transition, transition of a reactant from one phase (matter), phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of cat ...

s, or an

emulsifying An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Although ...

agent such as 1,4-dioxane as solvent. The reaction typically needs to be heated to initiate the process; however, once started, the Reimer–Tiemann Reaction can be highly exothermic. This combination of properties makes it prone to

thermal runaway Thermal runaway describes a process that is accelerated by increased temperature, in turn releasing Thermal energy, energy that further increases temperature. Thermal runaway occurs in situations where an increase in temperature changes the cond ...

Scope

The Reimer–Tiemann reaction is effective for other hydroxy-aromatic compounds, such as

naphthol Naphthol may refer to: * 1-Naphthol 1-Naphthol, or α-naphthol, is an organic compound with the formula . It is a fluorescent white solid. 1-Naphthol differs from its isomer 2-naphthol by the location of the hydroxyl group on the naphthalene ...

s. Electron rich heterocycles such as

pyrroles Pyrrole is a heterocyclic, Aromaticity, aromatic, organic compound, a five-membered Ring (chemistry), ring with the chemical formula, formula . It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives a ...

and

indoles Indole is an organic compound with the formula . Indole is classified as an aromatic Heterocyclic compound, heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are d ...

are also known to react. Dichlorocarbenes can react with alkenes and amines to form dichlorocyclopropanes and

isocyanide 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 ...

s respectively. As such the Reimer–Tiemann reaction may be unsuitable for substrates bearing these functional groups. In addition, many compounds can not withstand being heated with hydroxide.

Comparison to other methods

The direct

of aromatic compounds can be accomplished by various methods such as the

Gattermann reaction The Gattermann reaction (also known as the Gattermann formylation and the Gattermann salicylaldehyde synthesis) is a chemical reaction in which aromatic compounds are formylated by a mixture of hydrogen cyanide (HCN) and hydrogen chloride (HCl) ...

Gattermann–Koch reaction The Gattermann reaction (also known as the Gattermann formylation and the Gattermann salicylaldehyde synthesis) is a chemical reaction in which aromatic compounds are formylated by a mixture of hydrogen cyanide (HCN) and hydrogen chloride (HCl) ...

Vilsmeier–Haack reaction The Vilsmeier–Haack reaction (also called the Vilsmeier reaction) is the chemical reaction of a substituted formamide (1) with phosphorus oxychloride and an electron-rich arene (3) to produce an aryl aldehyde or ketone (5): : HArZ + POCl3 ...

, or

Duff reaction The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source. The method is generally inefficient. The reaction is named after J ...

; however, in terms of ease and safety of operations, the Reimer–Tiemann reaction is often the most advantageous route chosen in chemical synthesis. Of the reactions mentioned before, the Reimer–Tiemann reaction is the only route not requiring

acidic An acid is a molecule or ion capable of either donating a proton (i.e. hydrogen cation, H+), known as a Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis acid. The first category of acids are the ...

and/or

anhydrous A substance is anhydrous if it contains no water. Many processes in chemistry can be impeded by the presence of water; therefore, it is important that water-free reagents and techniques are used. In practice, however, it is very difficult to achie ...

conditions. Additionally the Gattermann—Koch reaction is not applicable to phenol substrates.

Variations

Using

carbon tetrachloride Carbon tetrachloride, also known by many other names (such as carbon tet for short and tetrachloromethane, also IUPAC nomenclature of inorganic chemistry, recognised by the IUPAC), is a chemical compound with the chemical formula CCl4. It is a n ...

instead of chloroform gives a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

product instead of an aldehyde. For example, this reaction variant with phenol would yield

salicylic acid Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or white), bitter-tasting solid, it is a precursor to and a active metabolite, metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been lis ...

Historical references

Reimer and Tiemann published several papers on the subject. The early work has been reviewed.

References

{{DEFAULTSORT:Reimer-Tiemann reaction Addition reactions Carbon-carbon bond forming reactions Name reactions Formylation reactions