ESTERIFICATION

step 1

In the first step, the ethanoic acid takes a proton (a hydrogen

ion) from the concentrated sulphuric acid. The proton becomes
attached to one of the lone pairs on the oxygen which is double-
bonded to the carbon.

The transfer of the proton to the oxygen gives it a positive

charge, but it is actually misleading to draw the structure in this
way (although nearly everybody does!).

The positive charge is delocalised over the whole of the right-

hand end of the ion, with a fair amount of positiveness on the
carbon atom. In other words, you can think of an electron pair
shifting to give this structure:

You could also imagine another electron pair shift producing a

third structure:

So which of these is the correct structure of the ion formed?

None of them! The truth lies somewhere in between all of them.
One way of writing the delocalised structure of the ion is like this:
 The double headed arrows are telling you that each of the
individual structures makes a contribution to the real structure of
the ion. They don't mean that the bonds are flipping back and
forth between one structure and another. The various structures
are known as resonance structures or canonical forms.

There will be some degree of positive charge on both of the

oxygen atoms, and also on the carbon atom. Each of the bonds
between the carbon and the two oxygens will be the same -
somewhere between a single bond and a double bond.

Step 2

The positive charge on the carbon atom is attacked by one of

the lone pairs on the oxygen of the ethanol molecule.

step 3

What happens next is that a proton (a hydrogen ion) gets transferred from the
bottom oxygen atom to one of the others. It gets picked off by one of the other
substances in the mixture (for example, by attaching to a lone pair on an
unreacted ethanol molecule), and then dumped back onto one of the oxygens
more or less at random.

The net effect is:

Step 4

Now a molecule of water is lost from the ion.

The product ion has been drawn in a shape to reflect the product which we
are finally getting quite close to!

The structure for the latest ion is just like the one we discusssed at length
back in step 1. The positive charge is actually delocalised all over that end of
the ion, and there will also be contributions from structures where the charge
is on the either of the oxygens:

It is easier to follow what is happening if we keep going with the structure with
the charge on the carbon.

Step 5

The hydrogen is removed from the oxygen by reaction with the

hydrogensulphate ion which was formed way back in the first step.
And there we are! The ester has been formed, and the sulphuric acid catalyst
has been regenerated.

2.

THE MECHANISM FOR THE ACID

CATALYSED HYDROLYSIS OF ESTERS

This page looks in detail at the mechanism for the hydrolysis of

esters in the presence of a dilute acid (such as hydrochloric acid
or sulphuric acid) acting as the catalyst. It uses ethyl ethanoate
as a typical ester.

The mechanism for the hydrolysis of ethyl ethanoate

A reminder of the facts

Ethyl ethanoate is heated under reflux with a dilute acid such as

dilute hydrochloric acid or dilute sulphuric acid. The ester reacts
with the water present to produce ethanoic acid and ethanol.

Because the reaction is reversible, an equilibrium mixture is

produced containing all four of the substances in the equation.
In order to get as much hydrolysis as possible, a large excess of
water can be used. The dilute acid provides both the acid
catalyst and the water.

The mechanism

Warning! This is a fairly complex mechanism, and is definitley NOT

required for any UK A level (or equivalent) syllabus. I have included it in
case it is of use to my many non-UK visitors.

All the steps in the mechanism below are shown as one-way

reactions because it makes the mechanism look less confusing.
The reverse reaction is actually done sufficiently differently that it
affects the way the mechanism is written. You will find a link to
the esterification reaction further down the page if you are
interested.

Note: The explanation assumes that you know about the use of curly
arrows in organic reaction mechanisms. If you aren't happy about these
follow this link before you go any further. (To be honest, if you are that
unsure about the conventions used in reaction mechanisms, you
probably shouldn't be reading this page anyway - you will find it distinctly
scary!)

Use the BACK button on your browser to return to this page.

Step 1

The actual catalyst in this case is the hydroxonium ion, H3O+,

present in all solutions of acids in water.

In the first step, the ester takes a proton (a hydrogen ion) from
the hydroxonium ion. The proton becomes attached to one of
the lone pairs on the oxygen which is double-bonded to the
carbon.

The transfer of the proton to the oxygen gives it a positive

charge, but the charge is actually delocalised (spread around)
much more widely than this shows.

One way of representing this delocalisation is to draw a number

of structures called resonance structures or canonical
formsjoined by double-headed arrows. You could, if you
wished, put in some curly arrows to show the movements of
electrons which change one of these structures into the next.
None of these formulae represents the true structure of the ion -
but each gives you some information about it. For example,
notice where the positive charge is in the three structures. What
this means in reality is that the positive charge is spread around
over those three atoms - the two oxygens and the carbon.

Note: If you haven't come across canonical forms as a way of

representing delocalisation, don't worry about it particularly. It is
important, however, that you don't imagine that the molecule is rapidly
flipping from one structure to another. The double-headed arrows mean
something different.

A mule is a hybrid of a donkey and a horse. In this notation, you could

represent a mule by writing donkey and horseconnected by a double-
headed arrow. Neitherdonkey norhorse accurately represents what a
mule looks like, but with a bit of imagination you could build up a fairly
good picture of a mule by combining together the characteristics of both
donkey and horse. But a mule obviously doesn't spend its time rapidly
changing back and forth between being a donkey and a horse!

The next stage of the mechanism involves an attack on the

carbon, and so it is convenient to use the structure showing the
positive charge on that carbon in the next step.

Step 2

The positive charge on the carbon atom is attacked by one of

the lone pairs on the oxygen of a water molecule.
 Note: You could work out precisely why that particular oxygen carries
the positive charge on the right-hand side. On the other hand, you could
realise that there has to be a positive charge somewhere (because you
started with one), and that particular oxygen doesn't look right - it has too
many bonds. Put the charge on there!

That's a quick rough-and-ready reasoning which works every time I use

it!

Step 3

What happens next is that a proton (a hydrogen ion) gets

transferred from the bottom oxygen atom to one of the others. It
gets picked off by one of the other substances in the mixture (for
example, by attaching to a lone pair on a water molecule), and
then dumped back onto one of the oxygens more or less at
random.

Eventually, by chance, it will join to the oxygen with the ethyl

group attached. When that happens, the net effect is:

Step 4

Now a molecule of ethanol is lost from the ion. That's one of the
products of the reaction.

The structure for the latest ion is just like the one we discusssed
at length back in step 1. The positive charge is actually
delocalised all over that end of the ion. The real structure will be
 a hybrid of these:

It is easier to follow what is happening if we keep going with the

structure with the charge on the carbon.

Step 5

The hydrogen is removed from the oxygen by reaction with a

water molecule.

And there we are! We have produced the ethanoic acid (the

other product of the reaction) and the hydroxonium ion catalyst
has been regenerated.

What is Lemieux-Johnson reaction?

The Lemieux–Johnson oxidation (Lemieux-Johnson reagent is NaIO4 + OsO4) of
alkenes gives aldehyde or ketones and therefore is equivalent to that of (reductive)
ozonolysis. If strong oxidizing conditions like KMnO4 in place of OsO4 is used,
permanganate causes cis-hydroxylation easily and further in the last step it oxidises any
aldehyde formed into carboxylic acids.
Reference: Advanced Organic Chemistry: Reaction Mechanisms by Reinhard
Bruckner (Page-567–568)

This is one of the several methods of oxidation of alkenes. This reaction takes place in
two step.The first step is vicinal syn-hydroxylation of the alkene by OsO4 followed by
oxidative cleavage of 1,2-diols by (IO4)-, periodate into two carbonyl compounds.

 In the second step, NaIO4 forms bonds with 1,2-diols to the iodine and Vicinal-
diols form a cyclic periodate ester.
 Then reverse cycloaddition occurs (similar to what happens when an ozonide
breaks down). The periodate ester undergoes rearrangement of the electrons,
cleaving the C-C bond, and forming two C=O (aldehydes or ketones
products are determined by the substituents on the diol.). (IO4)- is
reduced from iodine(VII) to iodine(V). In this respect, it’s the same as periodic
acid (HIO4) and lead tetra-acetate [Pb(OAc)4].
  Excess periodate is used to regenerate the osmium tetroxide by reoxidation of
Os(VI) to Os(VIII), allowing it to be used in catalytic amounts.

2.
OZONOLYSIS:

Sodium Periodate-Potassium
Permanganate
 NaIO4-KMnO4

(NaIO4)

[7790-28-5] · INaO4 · Sodium Periodate-Potassium Permanganate · (MW

213.89) (KMnO4)

[7722-64-7] · KMnO4 · Sodium Periodate-Potassium Permanganate · (MW 158.04)

(oxidant for the cleavage of carbon-carbon double bonds1)

Physical Data: NaIO4: mp 300 °C (dec); specific gravity 3.865. KMnO4: mp 240 °C
(dec); specific gravity 2.703.

Solubility: NaIO4: sol H2SO4, HNO3, MeCO2H, hot water; slightly sol cold water.
KMnO4: sol MeOH, acetone, hot water; slightly sol cold water.

Form Supplied in: NaIO4: white to colorless efflorescent solid. KMnO4: dark purple
crystals. Both reagents are widely available and can be used as supplied.

Handling, Storage, and Precautions: gloves and safety goggles must be worn during
handling; avoid inhalation of dust and contact with combustible matter.

Introduction.
The oxidative cleavage of carbon-carbon double bonds to give carboxylic acids using
a catalytic amount of Potassium Permanganate in the presence of Sodium
Periodate was first reported by Lemieux and von Rudloff.2 The reaction is usually
carried out under buffered reaction conditions and, depending on the pH of the
solution, either a 1,2-diol (at pH 9-10) or a 1,2-ketol (at pH 7-8) is initially formed.
Oxidative cleavage of either of these intermediates by periodate yields the
corresponding aldehyde, which is oxidized by permanganate to give the carboxylic
acid. Permanganate is continually being regenerated from its reduced state
(manganate) by the periodate. The reaction can be carried out in an aqueous medium
or in mixed solvents (e.g. t-BuOH-H2O, pyridine-H2O) and proceeds optimally in the
pH range between 7 and 10. Ketones and esters are not oxidized by NaIO 4-KMnO4,
whereas alcohols are oxidized slowly to carboxylic acids. Acyclic and cyclic alkenes
are efficiently oxidized by NaIO4-KMnO4 to the carboxylic acids (eqs 1 and 2).1,3 ,-
Unsaturated ketones are oxidized smoothly to give keto acids with loss of one carbon
atom (eq 3).4
Double bonds located in the side chain of a ring are more easily oxidized than those
situated in the ring (eq 4).5 Also, double bonds in hydroxy alkenes can be selectively
cleaved in the presence of a hydroxyl group.5b,c Thus (R)-(+)-citronellol is oxidized
with NaIO4-KMnO4 to give (R)-(+)-6-hydroxy-4-methylhexanoic acid (eq 5).5c The
oxidation of cyclic conjugated dienes6 with NaIO4-KMnO4 can lead to products arising
from hydroxylation7 and epoxidation5a of the double bonds, as well as the expected
oxidative cleavage of the double bonds (eq 6).7a
1. Suga, T.; von Rudloff, E. CJC 1969, 47, 3682.
2. (a) Lemieux, R. U.; von Rudloff, E. CJC 1955, 33, 1701. (b) von Rudloff,
E. CJC 1965, 43, 1784. (c) von Rudloff, E. CJC 1956, 34, 1413.
3. von Rudloff, E. CJC 1965, 43, 2660.
4. Back, T. G. JOC 1981, 46, 1442.
5. (a) ApSimon, J. W.; Chau, A. S. Y.; Craig, W. G.; Krehm, H. CJC 1967, 45, 1439.
(b) Bernassau, J.-M.; Fetizon, M. S 1975, 795. (c) Overberger, C. G.; Kaye,
H. JACS 1967, 89, 5640.
6. von Rudloff, E. TL 1966, 993.
7. (a) Boncza-Tomaszewski, Z. CJC 1987, 65, 656. (b) Nace, H. R.; Rieger, A.
L. JOC 1970, 35, 3846.

Hell-Volhard-Zelinsky Reaction

Treatment with bromine and a catalytic amount of phosphorus leads to the selective α-bromination of
carboxylic acids.

Mechanism of the Hell-Volhard-Zelinsky Reaction

Phosphorus reacts with bromine to give phosphorus tribromide, and in the first step this converts the
carboxylic acid into an acyl bromide.

An acyl bromide can readily exist in the enol form, and this tautomer is rapidly brominated at the α-
carbon. The monobrominated compound is much less nucleophilic, so the reaction stops at this stage.
This acyl intermediate compound can undergo bromide exchange with unreacted carboxylic acid via the
anhydride, which allows the catalytic cycle to continue until the conversion is complete.
Why isn’t conc. h2so4 used for the dehydration of
carboxylic acids to anhydrides? What is special in
p2o5?
ANS:

Dehydration of carboxylic acids with phosphorus pentoxide (P2O5) yields acid

anhydrides,because it strong dehydrated anhydride ;P2O5 itself reacts with water
molecules to form phosphoric acid. That enables it to remove free water molecules by a
simple hydrolysis reaction,

The OH group is not a very good leaving group. Even in simpler reactions like the
dehydration of an alcohol to an olefin we often first convert the hydroxyl group into a
better leaving group by protonation with acid or conversion to an inorganic ester (for
example using thionyl chloride or phosphorus pentoxide). The same thing takes place
here - we are converting the acid's hydroxyl group into a better leaving group.

& also H2SO4 Is given the dehydration of carboxilic acid.. But Is should not give easily
protonation. Thn it’s form ester … then esterification do not give enough dehydration as
comparison to P2O5.

Reduction with LiAlH4

Haloform test. The reagent used here is NaOH and Halogen(X2), where X can be Cl, Br
or I. Traditionally I2 is used.
One added advantage of using I2 is that Iodoform (HCI3) precipitates out in the
solution, making it cloudy. While Bromoform and Chloroform are liquids and that too
colourless making it difficult to recognise whether the test was positive or negative.

On the other side Benzaldehyde doesnt have the Alpha methyl group so it fails this test.

2.) Also Acetaldehyde will react with Fehling’s solution giving a red precipitate of
Copper(I) oxide or cuprous oxide(Cu₂O) while Benzaldehyde won’t give the test and
thus NO red precipitate will be formed here.

Schotten-Baumann Reaction
Schotten-Baumann Conditions
The use of added base to drive the equilibrium in the formation of amides from amines and acid chlorides.

The acylation of amines with carboxylic acid chlorides leads to the production of one equivalent acid,
which will form a salt with unreacted amine and diminish the yield. The addition of an additional
equivalent of base to neutralise this acid is a way to optimise the conditions. Normally, aqueous base is
slowly added to the reaction mixture.

In general, the use of biphasic aqueous basic conditions is often named "Schotten-Baumann conditions".

Mechanism of the Schotten-Baumann Reaction

Recent Literature

Practical Synthesis of Aryl Triflates under Aqueous Conditions

D. E. Frantz, D. G. Weaver, J. P. Carey, M. H. Kress, U. H. Dolling, Org. Lett., 2002, 4, 4717-4718.

Schmidt Reaction
The acid-catalysed reaction of hydrogen azide with electrophiles, such as carbonyl compounds, tertiary
alcohols or alkenes. After a rearrangement and extrusion of N2, amines, nitriles, amides or imines are
produced.

Mechanism of the Schmidt Reaction

Reaction of carboxylic acids gives acyl azides, which rearrange to isocyanates, and these may be
hydrolyzed to carbamic acid or solvolysed to carbamates. Decarboxylation leads to amines.

The reaction with a ketone gives an azidohydrin intermediate, which rearranges to form an amide:
Alkenes are able to undergo addition of HN3 as with any HX reagent, and the resulting alkyl azide can
rearrange to form an imine:

Tertiary alcohols give substitution by azide via a carbenium ion, and the resulting alkyl azide can
rearrange to form an imine.

Recent Literature

Chemoselective Schmidt Reaction Mediated by Triflic Acid: Selective Synthesis of Nitriles from Aldehydes
B. V. Rokade, J. R. Prabhu, J. Org. Chem., 2012, 77, 5364-5370.

Efficient, One-Pot, BF3·OEt2-Mediated Synthesis of Substituted N-Aryl Lactams

D. Caturvedi, A. K. Chaturvedi, N. Mishra, V. Mishra, Synlett, 2012, 23, 2627-2630.
Gold(I)-Catalyzed Intramolecular Acetylenic Schmidt Reaction
D. J. Gorin, N. R. Davis, F. D. Toste, J. Am. Chem. Soc., 2005, 127, 11260-11261.

Curtius Rearrangement

The Curtius Rearrangement is the thermal decomposition of carboxylic azides to produce an isocyanate.
These intermediates may be isolated, or their corresponding reaction or hydrolysis products may be
obtained.

The reaction sequence - including subsequent reaction with water which leads to amines - is named the
Curtius Reaction. This reaction is similar to the Schmidt Reaction with acids, differing in that the acyl
azide in the present case is prepared from the acyl halide and an azide salt.

Mechanism of the Curtius Rearrangement

Preparation of azides:

Decomposition:

Reaction with water to the unstable carbamic acid derivative which will undergo spontaneous
decarboxylation:
Isocyanates are versatile starting materials:

Isocyanates are also of high interest as monomers for polymerization work and in the derivatisation of
biomacromolecules.

Recent Literature

Propylphosphonic Anhydride (T3P®)-Mediated One-Pot Rearrangement of Carboxylic Acids to

Carbamates
J. K. Augustine, A. Bombrun, A. B. Mandal, P. Alagarsamy, R. N. Atta, P. Selvam, Synthesis, 2011, 1477-
1483.

Boc-Protected Amines via a Mild and Efficient One-Pot Curtius Rearrangement

H. Lebel, O. Leogane, Org. Lett., 2005, 7, 4107-4110.
One-Pot Synthesis of Ureido Peptides and Urea-Tethered Glycosylated Amino Acids Employing Deoxo-
Fluor and TMSN3
H. P. Hemantha, G. Chennakrishnareddy, T. M. Vishwanatha, V. V. Sureshbabu, Synlett, 2009, 407-410.

Radical Azidonation of Aldehydes

L. Marinescu, J. Thinggaard, I. B. Thomsen, M. Bols, J. Org. Chem., 2003, 68, 9453-9455.

Iodobenzene Dichloride in Combination with Sodium Azide for the Effective Synthesis of Carbamoyl
Azides from Aldehydes
X.-Q. Li, X.-F. Zhao, C. Zhang, Synthesis, 2008, 2589-2593.

Radical Azidonation of Aldehydes

L. Marinescu, J. Thinggaard, I. B. Thomsen, M. Bols, J. Org. Chem., 2003, 68, 9453-9455.

An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal
Protecting Groups
E. A. Englund, H. N. Gopi, D. H. Appella, Org. Lett., 2004, 6, 213-215.

Lossen rearrangement is the conversion of a hydroxamic acid to an isocyanate via

the formation of an O-acyl, sulfonyl, or phosphoryl intermediate hydroxamic acid O-
derivative (2) and then conversion to its conjugate base. Here, 4-Toluenesulfonyl
chloride is used to form a sulfonyl O-derivative of hydroxamic acid.
The isocyanate can be used further to generate ureas in the presence of amines or
generate amines in the presence of H2O.
The mechanism below begins with an O-acylated hydroxamic acid derivative that is
treated with base to form an isocyanate that generates an amine and CO2 gas in the
presence of H2O. The hydroxamic acid acid derivative is first converted to its conjugate
base by abstraction of a hydrogen by a base. Spontaneous rearrangement kicks off a
carboxylate anion to produce the isocyanate intermediate. The isocyanate in the
presence H2O hydrolyzes and then decarboxylation via abstraction of a hydrogen by a
base generates an amine and CO2 gas.

Several reviews have been published.

Hydroxamic acids are commonly synthesized from their corresponding esters.

Hunsdiecker Reaction

The silver(I) salts of carboxylic acids react with halogens to give unstable intermediates which readily
decarboxylate thermally to yield alkyl halides. The reaction is believed to involve homolysis of the C-C
bond and a radical chain mechanism.
Mechanism of the Hunsdiecker Reaction

What is Hoffmann bromamide reaction?

When an amide is treated with bromine in an aqueous or ethanolic solution of sodium hydroxide,
degradation of amide takes place leading to the formation of primary amine. This reaction involving
degradation of amide and is popularly known as Hoffmann bromamide degradation reaction. The
primary amine thus formed contains one carbon less than the number of carbon atoms in that amide.

RCONH2 +Br2 + 4NaOH → R-NH2 + Na2CO3 + 2NaBr + 2H2O

What is the general mechanism of Hoffmann bromamide reaction?
The general mechanism of Hoffmann bromamide reaction includes following steps:

 A strong base (usually an alkali) attacks the amide, this leads to deprotonation generating an
anion.
 This anion reacts with bromine to form N-bromoamide. This reaction can be seen as α-
substitution reaction.
 Deprotonation of the bromoamide molecule to generate a bromoamide anion.
 The generated bromoamide anion undergoes rearrangement such that the R group attached
to the carbonyl carbon migrates to nitrogen. The bromide ion leaves the compound
simultaneously, leading to the formation of isocyanate.
 Water molecules are added to the isocyanateto form carbamic acid. This reaction is an
example of nucleophilic addition.
 Finally, the carbamic acid loses carbon dioxide, CO2 leading to the formation of primary
amine.
Which reference books can one follow for understanding Hoffmann bromamide reaction?
For understanding the Hoffmann bromamide degradation reaction, one must go through the NCERT
class 12thchemistry textbook part 2. A brisk walk through NCERT will give you a sound idea of this
reaction. Apart from this, you can follow a reference book to understand the detailed mechanism of
this reaction. Some authentic books for understanding the detailed mechanism of Hoffmann
bromamide reaction include organic chemistry books from authors like Solomons & Fryhle, Morrison
& Boyd. Once you have understood the reaction, you can practice questions from the books of
authors like M. S. Chauhan, etc.

Why doesn’t the carbylamine reaction work in

secondary and tertiary amines?
The carbyl amine test involves dichlorocarbene intermediate, which behaves as electrophile
(due to incomplete octet at carbon) hence attacked by a lone pair of amine(s).

During reaction with a (aliphatic or aromatic) primary amine (RNH2 or ArNH2), we get
stable foul-smelling isocyanide product.
  Reaction with tertiary amine would only provide a little yield of unstable
inner-salt R3NCCl2 (it cannot proceed further owing to the absence of
hydrogen directly bonded to nitrogen).
 Reaction with secondary amine would only provide a bit of R2NCHCl2 (it
cannot give elimination further).
 Acid amides fail carbyl amine test.
 With amino acids, like Glycine, anthranilic acid, sulphanilic acid etc,
no odour is detected due to non-volatility of acidic isocyanide in
alkaline solution (salt is formed).
 In the case of pyrrole, the major products are:

Carbylamine reaction is a reaction to detect primary amine and chloroform. This test is also
used to distinguish primary amine from secondary and tertiary amines. According to the
mechanism, this is one of the best examples of Alpha elimination reaction,in which
carbanion is formed in very first step which latter loses chloride Ion to form highly reactive
dichlorocarbene. Now remaining two chlorine atoms get removed in the form of HCL. For
that hydrogen is provided from the nitrogen in amine.
ALDOL:
The test is give by only 2 degree amine(both aliphatic and aromatic). 2 degree amine is
converted into nitroso amine by treating the amine with HNO2.On warming the phenol
and conc. H2SO4 brown red colour is formed at first, which changes to blue then
green.colour changes to red on dilution and further to greenish blue or violet on
treatment with alkali