Hofmann elimination

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Hofmann elimination
Named after August Wilhelm von Hofmann
Reaction type Elimination reaction
Identifiers
Organic Chemistry Portal hofmann-elimination
RSC ontology ID RXNO:0000166

Hofmann elimination is an elimination reaction of an amine to form alkenes. The least stable alkene (the one with the fewest substituents on the carbons of the double bond), called the Hofmann product, is formed. This tendency, known as the Hofmann alkene synthesis rule, is in contrast to usual elimination reactions, where Zaitsev's rule predicts the formation of the most stable alkene. It is named after its discoverer, August Wilhelm von Hofmann. [1] [2]

Contents

The reaction starts with the formation of a quaternary ammonium iodide salt by treatment of the amine with excess methyl iodide (exhaustive methylation), followed by treatment with silver oxide and water to form a quaternary ammonium hydroxide. When this salt is decomposed by heat, the Hofmann product is preferentially formed due to the steric bulk of the leaving group causing the hydroxide to abstract the more easily accessible hydrogen.

Example of the Hofmann Elimination Reaction.png

In the Hofmann elimination, the least substituted alkene is typically favored due to intramolecular steric interactions. The quaternary ammonium group is large, and interactions with alkyl groups on the rest of the molecule are undesirable. As a result, the conformation necessary for the formation of the Zaitsev product is less energetically favorable than the conformation required for the formation of the Hofmann product. As a result, the Hofmann product is formed preferentially. The Cope elimination is very similar to the Hofmann elimination in principle, but occurs under milder conditions. It also favors the formation of the Hofmann product, and for the same reasons. [3]

An example of a Hofmann elimination (not involving a contrast between a Zaitsev product and a Hofmann product) is the synthesis of trans-cyclooctene. [4] The trans isomer is selectively trapped as a complex with silver nitrate (in this diagram the trans form looks like a cis form, but see the trans-cyclooctene article for better images):

Trans-cycloocteneSynthesis.svg

In a related chemical test, known as the Herzig–Meyer alkimide group determination, a tertiary amine with at least one methyl group and lacking a beta-proton is allowed to react with hydrogen iodide to the quaternary ammonium salt which when heated degrades to methyl iodide and the secondary amine. [5]

See also

Related Research Articles

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 as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine.

<span class="mw-page-title-main">Alkene</span> Hydrocarbon compound containing one or more C=C bonds

In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or in the terminal position. Terminal alkenes are also known as α-olefins.

<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">Elimination reaction</span> Reaction where 2 substituents are removed from a molecule in a 1 or 2 step mechanism

An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 reaction. The numbers refer not to the number of steps in the mechanism, but rather to the kinetics of the reaction: E2 is bimolecular (second-order) while E1 is unimolecular (first-order). In cases where the molecule is able to stabilize an anion but possesses a poor leaving group, a third type of reaction, E1CB, exists. Finally, the pyrolysis of xanthate and acetate esters proceed through an "internal" elimination mechanism, the Ei mechanism.

<span class="mw-page-title-main">Williamson ether synthesis</span> Method for preparing ethers

The Williamson ether synthesis is an organic reaction, forming an ether from an organohalide and a deprotonated alcohol (alkoxide). This reaction was developed by Alexander Williamson in 1850. Typically it involves the reaction of an alkoxide ion with a primary alkyl halide via an SN2 reaction. This reaction is important in the history of organic chemistry because it helped prove the structure of ethers.

<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.

The Cope reaction or Cope elimination, developed by Arthur C. Cope, is an elimination reaction of the N-oxide to form an alkene and a hydroxylamine.

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<span class="mw-page-title-main">Quaternary ammonium cation</span> Polyatomic ions of the form N(–R)₄ (charge +1)

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<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.

Organopalladium chemistry is a branch of organometallic chemistry that deals with organic palladium compounds and their reactions. Palladium is often used as a catalyst in the reduction of alkenes and alkynes with hydrogen. This process involves the formation of a palladium-carbon covalent bond. Palladium is also prominent in carbon-carbon coupling reactions, as demonstrated in tandem reactions.

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.

In organic chemistry, the Menshutkin reaction converts a tertiary amine into a quaternary ammonium salt by reaction with an alkyl halide. Similar reactions occur when tertiary phosphines are treated with alkyl halides.

<span class="mw-page-title-main">2,3-sigmatropic rearrangement</span> Class of chemical reaction

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In organic chemistry, the Ei mechanism, also known as a thermal syn elimination or a pericyclic syn elimination, is a special type of elimination reaction in which two vicinal (adjacent) substituents on an alkane framework leave simultaneously via a cyclic transition state to form an alkene in a syn elimination. This type of elimination is unique because it is thermally activated and does not require additional reagents, unlike regular eliminations, which require an acid or base, or would in many cases involve charged intermediates. This reaction mechanism is often found in pyrolysis.

<i>trans</i>-Cyclooctene Chemical compound

trans-Cyclooctene is a cyclic hydrocarbon with the formula [–(CH2)6CH=CH–], where the two C–C single bonds adjacent to the double bond are on opposite sides of the latter's plane. It is a colorless liquid with a disagreeable odor.

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<span class="mw-page-title-main">2-Chlorobutane</span> Chemical compound

2-Chlorobutane is a compound with formula C4H9Cl. It is also called sec-butyl chloride. It is a colorless, volatile liquid at room temperature that is not miscible in water.

References

  1. Hofmann, A. W. (1851). "Researches into the molecular constitution of the organic bases". Philosophical Transactions of the Royal Society of London . 141: 357–398. Bibcode:1851RSPT..141..357H. doi:10.1098/rstl.1851.0017. S2CID   108453887.
  2. Aug. Wilh. von Hofmann (1851). "Beiträge zur Kenntniss der flüchtigen organischen Basen" [Contribution to [our] knowledge of volatile organic bases]. Annalen der Chemie und Pharmacie (in German). 78 (3): 253–286. doi:10.1002/jlac.18510780302.
  3. Wade, p. 903.
  4. Arthur C. Cope; Robert D. Bach (1973). "trans-Cyclooctene". Organic Syntheses .; Collective Volume, vol. 5, p. 315
  5. J. Herzig; H. Meyer (1894). "Ueber den Nachweis und die Bestimmung des am Stickstoff gebundenen Alkyls". Berichte der deutschen chemischen Gesellschaft . 27 (1): 319–320. doi:10.1002/cber.18940270163.