The Beckmann Rearrangement

5/20/2018 The Beckmann Rearrangement

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The Beckmann rearrangement, named after the German chemistErnst Otto Beckmann(1853

1923), is anacid-catalyzedrearrangementof anoximeto anamide.[1][2][3]

Cyclic oximes yield

lactams.

This example reaction[4]

starting withcyclohexanone,forming thereaction intermediatecyclohexanone oxime and resulting incaprolactamis one of the most important applications of

the Beckmann rearrangement, as caprolactam is the feedstock in the production ofNylon 6.

The Beckmann solutionconsists ofacetic acid,hydrochloric acidandacetic anhydride,and was

widely used to catalyze the rearrangement. Other acids, such assulfuric acidorpolyphosphoric

acid,can also be used.sulfuric acidis the most commonly used acid for commercial lactamproduction due to its formation of an ammonium sulfate by-product when neutralized with

ammonia.Ammonium sulfateis a common agriculturalfertilizerproviding nitrogen and sulfur.

Contents

Reaction mechanism

Thereaction mechanismof the Beckmann rearrangement is in general believed to consist of analkylmigration with expulsion of the hydroxyl group to form anitrilium ionfollowed by

hydrolysis:
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In one study,[5]the mechanism is establishedin silicotaking into account the presence ofsolventmolecules and substituents. The rearrangement of acetone oxime in the Beckmann solution

involves three acetic acid molecules and one proton (present as anoxonium ion). In thetransition

stateleading to the iminium ion (-complex), the methyl group migrates to the nitrogen atom inaconcerted reactionand the hydroxyl group is expulsed. The oxygen atom in the hydroxyl group

is stabilized by the three acetic acid molecules. In the next step the electrophilic carbon atom in

the nitrilium ion is attacked by water and the proton is donated back to acetic acid. In the

transition state leading to the N-methyl acetimidic acid, the water oxygen atom is coordinated to4 other atoms. In the third step, an isomerization step protonates the nitrogen atom leading to the

amide.
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The same computation with ahydroxoniumion and 6 molecules of water has the same result,

but, when the migrating substituent is phenyl in the reaction of acetophenone oxime withprotonated acetic acid, the mechanism favors the formation of an intermediate three-membered

-complex. This -complex is again not found in the H3O+(H2O)6.
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With the cyclohexanone-oxime, the relief ofring strainresults in a third reaction mechanism,

leading directly to the protonated caprolactam in a single concerted step without the intermediate

formation of a -complex or -complex.

Cyanuric chloride assisted Beckmann reaction

Beckmann reaction is known to be catalyzed bycyanuric chlorideandzinc chlorideco-catalyst.For example, cyclododecanone can be converted to the correspondinglactam,amonomerfor the

production ofNylon 12.[6][7]

Thereaction mechanismfor this reaction is based on acatalytic cyclewith cyanuric chloride

activating thehydroxylgroup via anucleophilic aromatic substitution.The reaction product isdislodged and replaced by new reactant via an intermediateMeisenheimer complex.
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Beckmann fragmentation

When the oxime has aquaternary carbon atomin an anti position to the hydroxyl group afragmentation occurs forming anitrile:

The fluorine donor in this fragmentation reaction is diethylaminosulfur trifluoride (DAST):[8]

SemmlerWolff reaction

The oxime ofcyclohexenonewith acid formsanilinein a dehydrationaromatizationreactioncalled the SemmlerWolff reactionor Wolff aromatization

[9][10][11][12]
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Fries rearrangementFrom Wikipedia, the free encyclopedia

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The Fries rearrangement, named for the German chemistKarl Theophil Fries,is arearrangement reactionof aphenylesterto ahydroxyarylketonebycatalysisofLewisacids.

[1][2][3][4]

It involves migration of anacylgroup ofphenyl estertobenzenering. The reaction isortho andpara selectiveand one of the two products can be favoured by changing reaction conditions, such

astemperatureandsolvent.

Contents

Mechanism

Despite many efforts a definitivereaction mechanismfor the Fries rearrangement is not

available. Evidence for inter- andintramolecularmechanisms have been obtained by so-calledcross-experiments with mixed reactants. Reaction progress is not dependent onsolventor

substrate.A widely accepted mechanism involves acarbocationintermediate.

In the first reaction step aLewis acidfor instancealuminium chlorideAlCl

3co-ordinates to thecarbonyloxygen atom of theacylgroup. This oxygen atom is moreelectron
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oxylhttp://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/wiki/Phenylhttp://en.wikipedia.org/wiki/Rearrangement_reactionhttp://en.wikipedia.org/wiki/Karl_Theophil_Frieshttp://en.wikipedia.org/wiki/Fries_rearrangement#p-searchhttp://en.wikipedia.org/wiki/Fries_rearrangement#mw-navigation


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rich than thephenolicoxygen atom and is the preferredLewis base.This interactionpolarizesthe

bondbetween the acyl residue and the phenolic oxygen atom and the aluminium chloride group

rearranges to the phenolic oxygen atom. This generates a freeacyliumcarbocationwhich reactsin a classicalelectrophilic aromatic substitutionwith the aromatic ring. The abstracted proton is

released ashydrochloric acidwhere the chlorine is derived from aluminium chloride. The

orientation of the substitution reaction is temperature dependent. A low reaction temperaturefavorspara substitutionand with high temperatures theorthoproduct prevails, this can berationalised as exhibiting classicThermodynamic versus kinetic reaction controlas the ortho

product can form a more stable bidentate complex with the Aluminium.[5]

Formation of the ortho

product is also favoured in non-polar solvents; as the solvent polarity increases, the ratio of thepara product also increases.

[6]

Scope

Phenolsreact toestersbut do not react to hydroxyarylketones with acylhalogen compounds

underFriedel-Crafts acylationreaction conditions and therefore this reaction is of industrial

importance for the synthesis of hydroxyarylketones which are important intermediates forseveral pharmaceutics such asparacetamolandsalbutamol.As an alternative toaluminium

chloride,otherLewis acidssuch asboron trifluorideandbismuthtriflateor strong protic acids

such ashydrogen fluorideandmethanesulfonic acidcan also be used. In order to avoid the use ofthese corrosive and environmentally unfriendlycatalystsaltogether research into alternative

heterogeneouscatalysts is actively pursued.

Limits

In all instances onlyesterscan be used with stable acyl components that can withstand the harsh

conditions of the Fries rearrangement. If the aromatic or the acyl component is heavilysubstituted then thechemical yieldwill drop due tostericconstraints. Deactivating meta-directing groups on the benzene group will also have an adverse effect as can be expected for a

FriedelCrafts acylation.

Photo-Fries rearrangement

In addition to the ordinary thermal phenyl ester reaction a so-calledphotochemicalPhoto-Fries

rearrangementexists[7]

that involves aradicalreaction mechanism.This reaction is also

possible with deactivatingsubstituentson the aromatic group. Because the yields are low this

procedure is not used in commercial production. However, photo-Fries rearrangement may occur

naturally, for example when a plastic bottle made of polyethylene terephthalate (PET) is exposedto the sun, particular to UV light at a wavelength of about 310 nm, if the plastic has been heated

to 40 degrees Celsius or above (as might occur in a car with windows closed on a hot summer

day). In this case, photolysis of the ester groups would lead to leaching of phthalate from theplastic.

[8]
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note-8http://en.wikipedia.org/wiki/Fries_rearrangement#cite_note-8http://en.wikipedia.org/wiki/Substituenthttp://en.wikipedia.org/wiki/Reaction_mechanismhttp://en.wikipedia.org/wiki/Radical_%28chemistry%29http://en.wikipedia.org/wiki/Fries_rearrangement#cite_note-7http://en.wikipedia.org/wiki/Photochemistryhttp://en.wikipedia.org/wiki/Friedel-Crafts_reactionhttp://en.wikipedia.org/wiki/Steric_hindrancehttp://en.wikipedia.org/wiki/Chemical_yieldhttp://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/wiki/Heterogeneous_catalysishttp://en.wikipedia.org/wiki/Catalysthttp://en.wikipedia.org/wiki/Methanesulfonic_acidhttp://en.wikipedia.org/wiki/Hydrogen_fluoridehttp://en.wikipedia.org/wiki/Triflatehttp://en.wikipedia.org/wiki/Bismuthhttp://en.wikipedia.org/wiki/Boron_trifluoridehttp://en.wikipedia.org/wiki/Lewis_acidhttp://en.wikipedia.org/wiki/Aluminium_chloridehttp://en.wikipedia.org/wiki/Aluminium_chloridehttp://en.wikipedia.org/wiki/Salbutamolhttp://en.wikipedia.org/wiki/Paracetamolhttp://en.wikipedia.org/wiki/Friedel-Crafts_acylationhttp://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/wiki/Phenolhttp://en.wikipedia.org/wiki/Fries_rearrangement#cite_note-6http://en.wikipedia.org/wiki/Fries_rearrangement#cite_note-5http://en.wikipedia.org/wiki/Thermodynamic_versus_kinetic_reaction_controlhttp://en.wikipedia.org/wiki/Arene_substitution_patternshttp://en.wikipedia.org/wiki/Arene_substitution_patternshttp://en.wikipedia.org/wiki/Hydrochloric_acidhttp://en.wikipedia.org/wiki/Electrophilic_aromatic_substitutionhttp://en.wikipedia.org/wiki/Carbocationhttp://en.wikipedia.org/wiki/Acyliumhttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Chemical_polarityhttp://en.wikipedia.org/wiki/Lewis_basehttp://en.wikipedia.org/wiki/Phenol


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Benzidine(trivial name), also called 4,4'-diaminobiphenyl(systematic name), is the solidorganic compoundwith theformula(C6H4NH2)2. Thisaromaticamineis a component of a test

forcyanideand also in theproductionofdyes.Benzidine has been linked tobladderand

pancreatic cancer.[1]

Since August 2010 benzidine dyes are included in the EPA's List ofChemicals of Concern.

[2]

Contents

Synthesis and propertiesBenzidine is prepared in a two step process fromnitrobenzene.First, the nitrobenzene is

converted to 1,2-diphenylhydrazine, usually using iron powder as the reducing agent. Treatmentof this hydrazine with mineral acids induces arearrangement reactionto 4,4'-benzidine. Smaller

amounts of other isomers are also formed.[3]

The benzidine rearrangement, which proceeds

intramolecularly, is a classicmechanisticpuzzle inorganic chemistry.[4]

The conversion is described as a [5,5]sigmatropic reaction.[5][6]

In terms of its physical properties, 4,4'-benzidine is poorly soluble in cold water but can berecrystallized from hot water, where it crystallises as the monohydrate. It is dibasic, the

deprotonated species hasKavalues of 9.3 1010

and 5.6 1011

. Its solutions react withoxidizing agents to give deeply coloured quinone-related derivatives.
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Applications

As with some otheraromatic aminessuch as2-Naphthylamine,benzidine has been significantly

withdrawn from use in most industries because it is so carcinogenic.

In the past, benzidine was used to test forblood.Anenzymein blood causes the oxidation ofbenzidine to a distinctivelyblue-coloured derivative.

The test forcyaniderelies on similar reactivity.

Such applications have largely been replaced by methods usingphenolphthalein/hydrogen

peroxideandluminol.

he pinacol rearrangementor pinacolpinacolone rearrangementis a method for converting a

1,2-diolto acarbonylcompound inorganic chemistry.This1,2-rearrangementtakes place underacidic conditions. The name of the reaction comes from the rearrangement ofpinacolto

pinacolone.

This reaction was first described byWilhelm Rudolph Fittigin 1860.[1]

Contents

An overview of mechanism(discussion)

In the course of thisorganic reaction,protonation of one of theOH groups occurs and acarbocationis formed. If both theOH groups are not alike, then the one which yields a more

stable carbocation participates in the reaction. Subsequently, analkylgroup from the adjacentcarbon migrates to the carbocation center. The driving force for this rearrangement step is

believed to be the relative stability of the resultant oxonium ion, which has complete octet

configuration at all centers (as opposed to the preceding carbocation). The migration of alkylgroups in this reaction occurs in accordance with their usualmigratory aptitude,i.e.Aryl>>>>

hydride>Phenyl> tertiary carbocation (if formed by migration) > secondary carbocation (if
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formed by migration) > methyl cation . The conclusion which group stabilizes carbocation more

effectively is migrated

Stereochemistry of the rearrangement

In cyclic systems, the reaction presents more features of interest. In these reactions, thestereochemistryof the diol plays a crucial role in deciding the major product. An alkyl group

which is situated trans- to the leavingOH group alone may migrate. If otherwise, ring

expansion occurs, i.e. the ring carbon itself migrates to the carbocation centre. This reveals

another interesting feature of the reaction, viz. that it is largely concerted. There appears to be aconnection between the migration origin and migration terminus throughout the reaction.

Moreover, if the migrating alkyl group has a chiral center as its key atom, the configuration atthis center is retainedeven after migration takes place.

HistoryAlthough Fittig first published about the pinacol rearrangement,it was not Fittig butAleksandr

Butlerovwho correctly identified the reaction products involved.[2]

In a 1859 publicationWilhelm Rudolph Fittigdescribed the reaction ofacetonewithpotassium

metal...[3]

Fittig wrongly assumed amolecular formulaof (C3H3O)nfor acetone, the result of along standing atomic weight debate finally settled at theKarlsruhe Congressin 1860. He also

wrongly believed acetone to be an alcohol which he hoped to prove by forming a metal alkoxide

salt. The reaction product he obtained instead he called paraceton which he believed to be an

acetonedimer.In his second publication in 1860 he reacted paraceton withsulfuric acid(the

actual pinacol rearrangement).

Again Fittig was unable to assign a molecular structure to the reaction product which he assumed

to be another isomer or a polymer. Contemporary chemists who had already adapted to the new

atomic weight reality did not fare better. One of them,Charles Friedel,believed the reactionproduct to be theepoxidetetramethylethylene oxide[4]

in analogy with reactions ofethylene

glycol.Finally Butlerov in 1873 came up with the correct structures after he independently

synthesised the compound trimethylacetic acid which Friedel had obtained earlier by oxidizingwith adichromate.

[5]

Some of the problems during the determination of the structure are because carbon skeletal

rearrangements were unknown at that time and therefore the new concept had to be found.
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Butlerov theory allowed the structure of carbon atoms in the molecule to rearrange and with this

concept a structure for pinacolone could be found.

Hofmann rearrangement

From Wikipedia, the free encyclopedia

Jump to:navigation,search

The Hofmann rearrangementis theorganicreaction of a primaryamideto a primaryamine

with one fewercarbonatom.[1][2][3]

The reaction is named after its discoverer:August Wilhelm von Hofmann.This reaction is alsosometimes called the Hofmann degradationor the Harmon Process, and should not beconfused with theHofmann elimination.

Contents

Mechanism

The reaction ofbrominewithsodium hydroxideformssodiumhypobromitein situ,which

transforms the primary amide into an intermediateisocyanate.The intermediate isocyanate ishydrolyzed to a primary amine, giving offcarbon dioxide.

Variations

Several reagents can substitute for bromine.N-Bromosuccinimideand1,8-

diazabicyclo[5.4.0]undec-7-ene (DBU)can effect a Hofmann rearrangement. In the following

example, the intermediate isocyanate is trapped bymethanol,forming acarbamate.[4]
http://en.wikipedia.org/wiki/Hofmann_rearrangement#mw-navigationhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#mw-navigationhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#mw-navigationhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#p-searchhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#p-searchhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#p-searchhttp://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-1http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-1http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-3http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-3http://en.wikipedia.org/wiki/August_Wilhelm_von_Hofmannhttp://en.wikipedia.org/wiki/August_Wilhelm_von_Hofmannhttp://en.wikipedia.org/wiki/August_Wilhelm_von_Hofmannhttp://en.wikipedia.org/wiki/Hofmann_eliminationhttp://en.wikipedia.org/wiki/Hofmann_eliminationhttp://en.wikipedia.org/wiki/Hofmann_eliminationhttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Sodium_hydroxidehttp://en.wikipedia.org/wiki/Sodium_hydroxidehttp://en.wikipedia.org/wiki/Sodium_hydroxidehttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Hypobromitehttp://en.wikipedia.org/wiki/Hypobromitehttp://en.wikipedia.org/wiki/In_situhttp://en.wikipedia.org/wiki/In_situhttp://en.wikipedia.org/wiki/In_situhttp://en.wikipedia.org/wiki/Isocyanatehttp://en.wikipedia.org/wiki/Isocyanatehttp://en.wikipedia.org/wiki/Isocyanatehttp://en.wikipedia.org/wiki/Carbon_dioxidehttp://en.wikipedia.org/wiki/Carbon_dioxidehttp://en.wikipedia.org/wiki/Carbon_dioxidehttp://en.wikipedia.org/wiki/N-Bromosuccinimidehttp://en.wikipedia.org/wiki/N-Bromosuccinimidehttp://en.wikipedia.org/wiki/N-Bromosuccinimidehttp://en.wikipedia.org/wiki/1,8-Diazabicycloundec-7-enehttp://en.wikipedia.org/wiki/1,8-Diazabicycloundec-7-enehttp://en.wikipedia.org/wiki/1,8-Diazabicycloundec-7-enehttp://en.wikipedia.org/wiki/1,8-Diazabicycloundec-7-enehttp://en.wikipedia.org/wiki/Methanolhttp://en.wikipedia.org/wiki/Methanolhttp://en.wikipedia.org/wiki/Methanolhttp://en.wikipedia.org/wiki/Carbamatehttp://en.wikipedia.org/wiki/Carbamatehttp://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-4http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-4http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-4http://en.wikipedia.org/wiki/File:Hoffmann_rearrangement_mechanism.svghttp://en.wikipedia.org/wiki/File:Hofmann_Rearrangement_Scheme.pnghttp://en.wikipedia.org/wiki/File:Hoffmann_rearrangement_mechanism.svghttp://en.wikipedia.org/wiki/File:Hofmann_Rearrangement_Scheme.pnghttp://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-4http://en.wikipedia.org/wiki/Carbamatehttp://en.wikipedia.org/wiki/Methanolhttp://en.wikipedia.org/wiki/1,8-Diazabicycloundec-7-enehttp://en.wikipedia.org/wiki/1,8-Diazabicycloundec-7-enehttp://en.wikipedia.org/wiki/N-Bromosuccinimidehttp://en.wikipedia.org/wiki/Carbon_dioxidehttp://en.wikipedia.org/wiki/Isocyanatehttp://en.wikipedia.org/wiki/In_situhttp://en.wikipedia.org/wiki/Hypobromitehttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Sodium_hydroxidehttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Hofmann_eliminationhttp://en.wikipedia.org/wiki/August_Wilhelm_von_Hofmannhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-3http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-1http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-1http://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#p-searchhttp://en.wikipedia.org/wiki/Hofmann_rearrangement#mw-navigation


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In a similar fashion, the intermediate isocyanate can be trapped bytert-butanol,yielding thet-butoxycarbonyl(Boc)-protected amine.

A mild alternative to bromine is also(bis(trifluoroacetoxy)iodo)benzene.[5]
http://en.wikipedia.org/wiki/Tert-butanolhttp://en.wikipedia.org/wiki/Tert-butanolhttp://en.wikipedia.org/wiki/Tert-butanolhttp://en.wikipedia.org/wiki/Di-tert-butyl_dicarbonatehttp://en.wikipedia.org/wiki/Di-tert-butyl_dicarbonatehttp://en.wikipedia.org/wiki/Di-tert-butyl_dicarbonatehttp://en.wikipedia.org/wiki/Di-tert-butyl_dicarbonatehttp://en.wikipedia.org/wiki/%28bis%28trifluoroacetoxy%29iodo%29benzenehttp://en.wikipedia.org/wiki/%28bis%28trifluoroacetoxy%29iodo%29benzenehttp://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-5http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-5http://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-5http://en.wikipedia.org/wiki/File:Hoffmann_Rearrangement_NBS.pnghttp://en.wikipedia.org/wiki/Hofmann_rearrangement#cite_note-5http://en.wikipedia.org/wiki/%28bis%28trifluoroacetoxy%29iodo%29benzenehttp://en.wikipedia.org/wiki/Di-tert-butyl_dicarbonatehttp://en.wikipedia.org/wiki/Di-tert-butyl_dicarbonatehttp://en.wikipedia.org/wiki/Tert-butanol

Documents

The Beckmann Rearrangement