Atherton–Todd reaction

Last updated
Atherton–Todd reaction
Named afterFrank R. Atherton
Alexander R. Todd
Reaction type Substitution reaction
Identifiers
RSC ontology ID RXNO:0000690

The Atherton-Todd reaction is a name reaction in organic chemistry, which goes back to the British chemists F. R. Atherton, H. T. Openshaw and A. R. Todd. These described the reaction for the first time in 1945 as a method of converting dialkyl phosphites into dialkyl chlorophosphates. [1] The dialkyl chlorophosphates formed are often too reactive to be isolated, though. For this reason, the synthesis of phosphates or phosphoramidates can follow the Atherton-Todd reaction in the presence of alcohols or amines. The following equation gives an overview over the Atherton-Todd reaction using the reactant dimethyl phosphite as an example:

Contents

Atherton-Todd-Reaktion Atherton Todd reaction (Dimethyphosphite).svg
Atherton-Todd-Reaktion

The reaction takes place after the addition of tetrachloromethane and a base. This base is usually a primary, secondary or tertiary amine. Instead of methyl groups other alkyl or benzyl groups may be present.

Reaction mechanism

A possible reaction mechanism for the Atherton-Todd reaction is presented here for the example of dimethylphosphite, just like in the overview reaction: [2]

Erster Teil des Reaktionsmechanismus der Atherton-Todd-Reaktion Atherton Todd Reaction part 1 MV1.svg
Erster Teil des Reaktionsmechanismus der Atherton-Todd-Reaktion

First, a tertiary amine is used to cleave a methyl group of dimethyl phosphite. The intermediate 1 results from this reaction step.

Zweiter Teil des Reaktionsmechanismus der Atherton-Todd-Reaktion Atherton Todd Reaction part 2 MV1.svg
Zweiter Teil des Reaktionsmechanismus der Atherton-Todd-Reaktion

Subsequently, the intermediate 1 deprotonates the starting compound dimethylphosphite, so that intermediates 2a and intermediates 2b are formed. The intermediate 1 is then regenerated from the intermediate 2a.

Dritter Teil des Reaktionsmechanismus der Atherton-Todd-Reaktion Atherton Todd Reaction part 3 MV1.svg
Dritter Teil des Reaktionsmechanismus der Atherton-Todd-Reaktion

Finally, intermediate 2b is chlorinated by tetrachloromethane and dimethyl chlorophosphate 3 is formed.

Possible subsequent reactions

After the synthesis of the dimethyl chlorophosphate, a further reaction (for example with a primary amine like aniline) is possible by the following reaction equation: [3]

Weiterer Reaktionsverlauf durch Zugabe von Anilin Atherton Todd Reaction FV1.svg
Weiterer Reaktionsverlauf durch Zugabe von Anilin

Atom economy

In this reaction, in addition to the starting compound dialkyl phosphite, tetrachloromethane and a base (an amine) are used in stoichiometric amounts. Only chloroform, which occurs after two reaction steps from tetrachloromethane, is relevant as a waste product for the assessment of the atomic economy. It should furthermore be kept in mind that the product of the reaction has a greater molar mass than the starting compound. The atom economy of this reaction can therefore be classified as relatively good.

See also

The Atherton-Todd reaction is related to the Appel reaction. In the Appel reaction, tetrachloromethane is used for chlorination as well. [2]

Related Research Articles

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

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)–. The simplest ketone is acetone, with the formula CH3C(O)CH3. Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula CH3. In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many organic compounds. It is a very stable group in most molecules. While the methyl group is usually part of a larger molecule, bounded to the rest of the molecule by a single covalent bond, it can be found on its own in any of three forms: methanide anion, methylium cation or methyl radical. The anion has eight valence electrons, the radical seven and the cation six. All three forms are highly reactive and rarely observed.

<span class="mw-page-title-main">Haloalkane</span> Group of chemical compounds derived from alkanes containing one or more halogens

The haloalkanes 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 used commercially. They are used as flame retardants, fire extinguishants, refrigerants, propellants, solvents, and pharmaceuticals. Subsequent to the widespread use in commerce, many halocarbons have also been shown to be serious pollutants and toxins. For example, the chlorofluorocarbons have been shown to lead to ozone depletion. Methyl bromide is a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to the ozone layer, but fluorinated volatile haloalkanes in theory may have activity as greenhouse gases. Methyl iodide, a naturally occurring substance, however, does not have ozone-depleting properties and the United States Environmental Protection Agency has designated the compound a non-ozone layer depleter. For more information, see Halomethane. Haloalkane or alkyl halides are the compounds which have the general formula "RX" where R is an alkyl or substituted alkyl group and X is a halogen.

<span class="mw-page-title-main">Alkylation</span> Transfer of an alkyl group from one molecule to another

Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene. Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline. In medicine, alkylation of DNA is used in chemotherapy to damage the DNA of cancer cells. Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents.

<span class="mw-page-title-main">Enamine</span>

An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates.

<span class="mw-page-title-main">Imine</span> Organic compound or functional group containing a C=N bond

In organic chemistry, an imine 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 bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.

<span class="mw-page-title-main">Appel reaction</span>

The Appel reaction is an organic reaction that converts an alcohol into an alkyl chloride using triphenylphosphine and carbon tetrachloride. The use of carbon tetrabromide or bromine as a halide source will yield alkyl bromides, whereas using carbon tetraiodide, methyl iodide or iodine gives alkyl iodides. The reaction is credited to and named after Rolf Appel, it had however been described earlier. The use of this reaction is becoming less common, due to carbon tetrachloride being restricted under the Montreal protocol.

In organic chemistry, ozonolysis is an organic reaction where the unsaturated bonds of alkenes, alkynes, or azo compounds are cleaved with ozone. Alkenes and alkynes form organic compounds in which the multiple carbon–carbon bond has been replaced by a carbonyl group while azo compounds form nitrosamines. The outcome of the reaction depends on the type of multiple bond being oxidized and the work-up conditions.

<span class="mw-page-title-main">Hydrohalogenation</span> Electrophilic addition of hydrohalic acids to alkenes

A hydrohalogenation reaction is the electrophilic addition of hydrohalic acids like hydrogen chloride or hydrogen bromide to alkenes to yield the corresponding haloalkanes.

<span class="mw-page-title-main">Michaelis–Arbuzov reaction</span>

The Michaelis–Arbuzov reaction is the chemical reaction of a trivalent phosphorus ester with an alkyl halide to form a pentavalent phosphorus species and another alkyl halide. The picture below shows the most common types of substrates undergoing the Arbuzov reaction; phosphite esters (1) react to form phosphonates (2), phosphonites (3) react to form phosphinates (4) and phosphinites (5) react to form phosphine oxides (6).

In organic chemistry, hydroboration refers to the addition of a hydrogen-boron bond to certain double and triple bonds involving carbon. This chemical reaction is useful in the organic synthesis of organic compounds.

<span class="mw-page-title-main">Knorr pyrrole synthesis</span> Chemical reaction

The Knorr pyrrole synthesis is a widely used chemical reaction that synthesizes substituted pyrroles (3). The method involves the reaction of an α-amino-ketone (1) and a compound containing an electron-withdrawing group α to a carbonyl group (2).

<span class="mw-page-title-main">Camphorsulfonic acid</span> Chemical compound

Camphorsulfonic acid, sometimes abbreviated CSA or 10-CSA is an organosulfur compound. Like typical sulfonic acids, it is a relatively strong acid that is a colorless solid at room temperature and is soluble in water and a wide variety of organic substances.

<span class="mw-page-title-main">Phosphite ester</span> Organic compound with the formula P(OR)3

In organic chemistry, a phosphite ester or organophosphite usually refers to an organophosphorous compound with the formula P(OR)3. They can be considered as esters of an unobserved tautomer phosphorous acid, H3PO3, with the simplest example being trimethylphosphite, P(OCH3)3. Some phosphites can be considered esters of the dominant tautomer of phosphorous acid (HP(O)(OH)2). The simplest representative is dimethylphosphite with the formula HP(O)(OCH3)2. Both classes of phosphites are usually colorless liquids.

The Kornblum–DeLaMare rearrangement is a rearrangement reaction in organic chemistry in which a primary or secondary organic peroxide is converted to the corresponding ketone and alcohol under acid or base catalysis. The reaction is relevant as a tool in organic synthesis and is a key step in the biosynthesis of prostaglandins.

Organophosphines are organophosphorus compounds with the formula PRnH3−n, where R is an organic substituent. These compounds can be classified according to the value of n: primary phosphines (n = 1), secondary phosphines (n = 2), tertiary phosphines (n = 3). All adopt pyramidal structures. Organophosphines are generally colorless, lipophilic liquids or solids. The parent of the organophosphines is phosphine (PH3).

<span class="mw-page-title-main">Diethyl phosphorochloridate</span> Chemical compound

Diethyl chlorophosphate is an organophosphorus compound with the formula (C2H5O)2P(O)Cl. As an reagent in organic synthesis, it is use the convert alcohols to the corresponding diethylphosphate esters. It is a colorless liquid with a fruity odor. It is a corrosive, and as a cholinesterase inhibitor, highly toxic through dermal absorption. The molecule is tetrahedral.

Secondary is a term used in organic chemistry to classify various types of compounds or reactive intermediates. An atom is considered secondary if it has two 'R' Groups attached to it. An 'R' group is a carbon containing group such as a methyl. A secondary compound is most often classified on an alpha carbon or a nitrogen. The word secondary comes from the root word 'second' which means two.

<span class="mw-page-title-main">Diethylphosphite</span> Chemical compound

Diethylphosphite is the organophosphorus compound with the formula (C2H5O)2P(O)H. It is a popular reagent for generating other organophosphorus compounds, exploiting the high reactivity of the P-H bond. Diethylphosphite is a colorless liquid. The molecule is tetrahedral.

<span class="mw-page-title-main">Dimethylphosphite</span> Chemical compound

Dimethylphosphite is an organophosphorus compound with the formula (CH3O)2P(O)H, known as dimethyl hydrogen phosphite (DMHP). Dimethylphosphite, is a minor tautomer of the phosphorus(V) derivative. It is a reagent for generating other organophosphorus compounds, exploiting the high reactivity of the P-H bond. The molecule is tetrahedral. It is a colorless liquid. The compounds can be prepared by methanolysis of phosphorus trichloride or by heating diethylphosphite in methanol.

References

  1. F. R. Atherton, H. T. Openshaw, A. R. Todd (1945), "174. Studies on phosphorylation. Part II. The reaction of dialkyl phosphites with polyhalogen compounds in presence of bases. A new method for the phosphorylation of amines", Journal of the Chemical Society (Resumed) (in German), pp. 660–663, doi:10.1039/jr9450000660 {{citation}}: CS1 maint: multiple names: authors list (link)
  2. 1 2 Zerong Wang (2009), Comprehensive organic name reactions and reagents Volume 1 (in German), Hoboken (N.J.): John Wiley, pp. 114–118, ISBN   978-0-470-28662-3
  3. Stéphanie S. Le Corre, Mathieu Berchel, Hélène Couthon-Gourvès, Jean-Pierre Haelters, Paul-Alain Jaffrès (2014), "Atherton–Todd reaction: mechanism, scope and applications", Beilstein Journal of Organic Chemistry (in German), vol. 10, no. 1, pp. 1166–1196, doi:10.3762/bjoc.10.117, PMC   4077366 , PMID   24991268 {{citation}}: CS1 maint: multiple names: authors list (link)