Organic Reaction Intermediates by Ajnish Kumar Gupta & Bharti Gupta

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Reaction intermediates
Electronegativity of the atoms has a great role in deciding the type of organic reactions shown by the any compound. On the basis of this electronegativity difference between two atoms forming the covalent bonds in a compound the nature of organic reactions & nature of attacking reagents are decided. On the basis of electronegativity difference only, a covalent bond of organic compound is broken by two different ways to generate different types of short lived species which are commonly called as reaction intermediates.

First ways When electronegativity between two bonding atom is same or nearly same then on breaking of bond, one electron of the bonding pair goes with each of the leaving atom. Such type of bond breaking is called as homolytic breaking, hemolytic cleavage, homolytic fission or homolysis. Ex
A B A

Homolysis always give rise to free radicals. If carbon acquires such arrangement then it is called as carbon free radical. Homolysis in organic chemistry is mainly seen in alkanes where electronegativity of carbon-carbon bond is same and that of carbon-hydrogen bond is nearly same. Such species are very reactive and the reactions which proceed through hemolytic fission are known as free radical reactions. These free radicals are transitory and react with other radicals or molecules by gaining one or more electron to restore the stable bonding pair. This homolytic fission generally take place either in presence of light, heat or in presence of peroxides.

Second ways
When electronegativity between two bonding atoms are not same then on breaking of bond, both the bonding electron goes to one of the atom. Such breaking is called as heterolytic breaking, heterolytic cleavage, heterolytic fission or heterolysis. Ex
A B A
+

+
or

BB
+

A-

Heterolysis always gives anion & cation. If carbon acquires positive charge then it is called as carbocation & if carbon acquires negative charge then it is called as carbanion.

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These organic reaction intermediates are very short lived species and are tries to quickly convert itself into stable molecule. They differ in their stabilities, half life times and reactivities. Their half lives range from fractions of seconds to several minutes. Their existence can be proved by spectroscopy which is a modern method to find out the existence of any molecules. They can be generally isolated during the course of reaction from reaction container. They are the reaction intermediates which are observed in many organic reactions such as of alkyl halide, alcohol, ether, alkenes, alkynes, aromatic compounds, carbonyl compounds, carboxylic acid and its derivatives, carbohydrates, amino acids etc. Reactions which involve heterolytic fission are called as polar or ionic reactions. Those reactions in which carbanion is formed as an intermediate are said to proceed with carbanionic mechanism and similarly those reactions in which carbocation is formed as an intermediate are said to proceed with carbocationic mechanism

Types of Organic reaction intermediates

Organic reaction intermediates are mainly of six types. 1. Carbocations 2. Carbanions 3. Carbon free radicals 4. Carbenes 5. Nitrenes 6. Benzynes

1. Carbocations
Carbocations are those organic reaction intermediate which is trivalent in nature with carbon having positive charge & have 6 electrons in its octet. Let us take an example of heterolytic fission of the C-X bond present in an organic molecule. If X atom have greater electronegativity than carbon, then during cleavage X will take away both the bonding electron pair and itself becomes negatively charged while the carbon atom develops positive charge and the fragment formed with positively charged carbon is called as carbocation.
R1 R2 R3 X Heterolytic Fission R1 C R2 Carbocation
+

R3

X-

For many years carbocations were called as Carbonium ion but now it is more correctly called as carbocations because -onium ion usually refers higher covalency than that of neutral atom such as ammonium ion for NH4+ but in carbocations the covalency of positively carbon is only 3 such as CH3+. Carbocations may be primary, secondary, or tertiary depending upon the nature of carbon (Primary, Secondary or tertiary) which bears positive charge. CH3+, CH3CH2+ (Primary), (CH3)2CH+ (Secondary), (CH3)3C+ (Tertiary)

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Carbocations are very reactive organic reaction intermediate because the positively charged central carbon atom has only sextet in valence shell and has marked tendency to complete octet. The octet may be completed by anion species like OH-, CN-, X- etc. or neutral nucleophiles like H2O, NH3 etc. or by losing an atom without its bonding pair of electrons such as proton from its adjacent carbon.

Formation of carbocations
Carbocation is the main organic reaction intermediate which are formed in many organic reactions. They may be formed by following general ways. 1. They are formed by direct ionization of alkyl halide in polar medium such as H2O, ROH or in presence of Lewis acids such as AlCl3, BF3, SbCl5 etc.
H3C H3C H3C H3C Cl O H3C Cl Cl H3C H3C C
+

CH3

+
CH2 O
+

Cl

+ +

AlCl 3

H3C

+ +

AlCl 4-

AlCl 3

H3C

AlCl 4-

2. By protonation on atom which have lone pairs of electron such as ROH, ROR.
H R OH

+ +

+ +

H2O

H H R O R H
+

ROH

3. By protonation on alkenes, alkynes, nitriles, carbonyl compounds etc which have double bond or triple bond.
H 3C CH 2 H 3C CH H 3C N O H 3C CH 3

+ + + +

H 3C

CH

CH 3 H
+

H 3C

CH 2 H
+

H 3C

NH OH H
+ +

H3C

CH 3

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4. By adding aqueous AgNO3 in solution of alkyl halide.

H3C H3C H3C N2Cl Heat Cl Aq. AgNO3 H3C C H3C
+

CH3

Cl

5. By decomposition of benzene diazonium salt.

+ +
N2

Stability of carbocations
Charged species are generally less stable than neutral one so carbocations are generally less stable than neutral molecule. The stability of all carbocations is not same for all but stability is relative term i.e. one carbocation is more stable than other one. Since the reactions proceed through most stable intermediate, it become essential to study the factors which affects the stability of intermediate.

Factors influencing stability of carbocationsThose factors which disperse the positive charge from carbon atom will increase the stability of carbocation. If the positive charge is localized then the carbocation is less stable but if positive charge is delocalized then it is more stable. These are some important factors which influence the stability of carbocation. 1. Aromaticity If positive charge of carbocation is present in aromaticity then stability of the carbocation is very high.

+ +
,

2. Resonance or M- Effect +M group such as OH, -NH2, -OR, -CH=CH2 etc always increases the stability of carbocation while M group such as NO2, -CN, C=O etc decreases the stability of carbocation.

+ +
( charge is dispersed through resonance thereby increasing the stability of carbocation)
+

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If compound have equivalent resonating structures then stability of carbocation will also increases.
H 2C
+

H 2C CH 2 CH 2
+

(Equivalent resonating structures)

3. Hyperconjugation If single bonded carbon directly attached carbocation have hydrogen then it will stabilize the carbocation through hyperconjugation.
H CH2 R1 R 2
+

R1 H R2

CH2

4. Inductive effect + I effect of alkyl group stabilizes the carbocation while I effect of any group destabilizes the carbocation.
CH3 H3C O N O
+ CH2

CH3 > H3C C

+

H > H3C C
+

H > H C
+

CH3 O N

H O <
+ CH2

H O < O N
+

H (Decrease in stability)

CH2

(Increase in stability)

5. Role of SolventCarbocations are more stable in polar medium because negative part of polar molecule stabilizes the carbocation while in non-polar medium no additional stability is observed.
H O H

H3C C
+

H O H

H3C
O H

CH3
H

6. Anti-Aromatic compound
If positive charge of carbocation is in anti-aromaticity then its stability will be least among all the carbocations known because anti-aromaticity is simply a theoretical concept and its existence in not known.

+
Anti-Aromatic compound

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General carbocations in decreasing order of stability-

+
>

+
>

+ +
CH3 C
+

>

+>
H3C > C
+

+ CH2

>

Ph-CH2

>

Ph C Ph
+

Ph
+ > > C CH3 Ph Ph Ph

H > H Ph H C
+

CH3 Ph CH3 >

+

CH3 H3C > Ph-CH2+ > C CH3

+

H2C H2C H

> CH3 H

> CH3

H2C

CH > CH3

Special case of stability of cyclopropylmethyl carbocation It is a special case in stability of carbocation. It is found that cyclopropylmethyl (CPM) carbocation is even more stable than benzyl carbocation. This stability is also increased when H of cyclopropylmethyl carbocation is replaced by another cyclopropyl group. This can be explained by the result of conjugation between bent orbitals of cyclopropyl ring and vacant p orbital of cationic carbon. This can be proved by NMR spectroscopy which tells that vacant p-orbital lies parallel to the bent orbitals of cyclopropyl ring.

Special property of carbocation Carbocations have a special property to rearrange itself for better stability. If a carbocation is less stable by electronic effects such as resonance, hyperconjugation, inductive effect or by ring strain than it will rearrange to more stable carbocation for better stability. This rearrangement can occur via following four methods: 1. By hydride shift If single bonded carbon having hydrogen along with alkyl or aryl group is directly attach with primary carbocation, hydrogen with its bonding electrons in the form of hydride migrates from that carbon to carbocation. This type of shifting is called as Hydride shifting.

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H2C

CH3 CH3
H3C

CH3 C
+

CH3

2. Methyl shift If single bonded carbon having methyl group along with alkyl or aryl group is directly attach with primary carbocation, methyl group with its bonding electrons in the form of CH3- migrates from that carbon to carbocation. This type of shifting is called as methyl shifting.
CH3 CH3
CH3 H3C C
+

H2C

CH3

H3C

3. By phenyl shift If single bonded carbon having phenyl group along with alkyl or aryl group is directly attach with primary carbocation, phenyl group with its bonding electrons in the form of Ph- migrates from that carbon to carbocation. This type of shifting is called as phenyl shifting.
H2C
+

CH3 CH3

CH3 Ph C
+

CH3

Ph

4. By bond shift If strained cyclic system is directly attached with primary or secondary carbocation then bonding electrons of cyclic system moves from one place to carbocation to reduce its strain in cycle and provide better stability than previous carbocation.
CH2
+

These rearrangements have been well applied as evidences for intermediate formation of carbocations in variety of reactions such as Pinacol-Pinacolone, Friedel-Craft alkylation etc.

Capsule of rearrangement
Less stable C+ Most stable C+

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Classification of carbocation
Carbocations are mainly classified as 2 types on the basis of making bonds with nearby atoms. 1. Classical carbocations In this carbocatons, the positive charge is localized on one carbon atom or delocalized by resonance involving an unshared paired of electrons or a double or triple bond in the allylic position. CH3+, CH3CH2+, CH2=CH-CH2+ etc. 2. Non-classical carbocations In this carbocations the positive charge is delocalized by a double or triple bond that is not in the allylic position or by a single bond.
+

(7-norbonenyl cation)

+ +

(Norbornyl cation) In such type of non-classical carbocation, neighbouring group participation of and bonds like C=C bond, C-C bonds and C-H bonds are considered. It is obvious that if in a carbocation the cationic carbon is not conjugated with bonds, then resonating structures cannot be written in a normal way, but in such cases neighbouring group participation may take place. In such cases bridged carbocations are formed which are called as non-classical carbocation. Ex.

+
CH2
+

Br ,

Hg-OCOCH3

Application of carbocations As carbocation is formed by heterolytic cleavage when carbon is bonded with more electronegative atom such as X, O, N etc. In organic chemistry majority of compounds have polarity either permanent or temporary so carbocation is formed as an intermediate in majority of the reaction such as in a. Electrophilic addition reaction of alkene and alkynes. b. Nucleophilic substitution reaction of alkyl halides, alcohol & ether. c. Elimination reaction of alkyl halide, alcohol & ether. d. Electrophilic substitution reaction of aromatic compounds. e. Acid catalysed nucleophilic addition of carbonyl compounds. f. Acid catalysed nucleophilic substitution of carboxylic acid, acid halide, amide, anhydride etc.

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2. Carbanion
Carbanion is defined as an organic anion with a pair of available electrons and a negative charge on trivalent carbon atom. Suppose in a bond C-X of organic molecule if carbon has greater electronegativity than that of X, then carbon takes away the bonding pair of electron and acquires negative charge during heterolytic cleavage of C-X bond and X+ is produced.
R1 R2 R3 X Heterolytic Fission C
-

R1 R2

R3

Electronegativity of C > X

Carbanion

Similar to carbocations, carbanion may also be primary, secondary, or tertiary depending upon the nature of carbon (Primary, Secondary or tertiary) which bears negative charge. CH3-, CH3CH2- (Primary), (CH3)2CH- (Secondary), (CH3)3C- (Tertiary) Through carbanions are electron rich species with complete octet, even then they are very reactive species due to negative charge and behaves as Lewis base. They usually attack on electron deficient centre of the substrate.

Formation of carbanion
Carbanion can be formed by many ways but the most importants are 1. By removal of H of aldehyde or ketones by base Carbanion can be generated by loss of proton from adjacent position of C=O, -CN, -NO2 group by presence of base. This reaction is an example of acid-base reaction.
O NaOEt H3C H Acetone R CH NaNH2 liq NH3 H3C O CH2
-

EtOH

Carbanion
-

2. By reaction of alkynes with sodamide

R C

+ + +

NH3
+

3. By heterolytic cleavage of C-Metal bond in organometallic compounds

H3C Mg-Br CH3
-

Mg Br

Methyl magnesium bromide (Grignard reagent) H3C Na CH3 Na

+

Methyl sodium

4. By decarboxylation of salt of carboxylic acid in presence of soda lime When strong electron withdrawing group is attached to the position of carboxylic acid then loss of CO2 occur just on heating.

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Greater will be the stability of carbanion faster will be the rate of decarboxylation.
O R OH NaOH/CaO R-

CO2

5. By attack of nucleophile to double bonded carbon which is in conjugation with strong electron withdrawing group
O H2C NuR Nu O R

Stability of carbanions
Charged species are generally less stable than neutral one so carbanions are generally less stable than neutral molecule. Since the reactions proceed through most stable intermediate, it become essential to study the factors which affects the stability of intermediate.

Factors influencing stability of carbanionThose factors which disperse the negative charge from carbon atom will increase the stability of carbanion. If the negative charge is localized then the carbanion is less stable but if negative charge is delocalized then it is more stable. Delocalization of charge leads to decrease in charge density which is charge per unit area, so stability increases. These are some important factors which influence the stability of carbanion. 1. Aromaticity If negative charge of carbanion is present in aromaticity then stability of the carbanion is very high.

Aromatic

2. Resonance or M- Effect +M group such as OH, -NH2, -OR etc always decreases the stability of carbanion while M group such as NO2, -CN, C=O, C=C etc increases the stability of carbanion.
(- charge is dispersed through resonance thereby increasing the stability of carbanion)

If compound have equivalent resonating structures then stability of carbanion will also increases.
H2C
-

H2C CH2 CH2

-

(Equivalent resonating structures)

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3. Inductive effect + I effect of alkyl group destabilizes the carbanion while I effect of any group stabilizes the carbanion.
CH3 H3C O N O
CH2

CH3 < H3C C

-

H < H3C C
-

H < H C
-

CH3 O N

H O >
CH2

H O > O N
-

H(Decrease in stability)

CH2

(Increase in stability)

4. Stabilization by increase in s character

As the s-character increases for the atom having negative charge electron become more and more closer to the nucleus and hence of lower energy and consequently become more stable.
H3C H3C C
-

>

H3C

CH

>

CH2

5. Stabilization by d- p overlapping
When anionic carbon is directly attached to sulphur, phosphorus, chlorine etc which have vacant d- orbital then unshared pair of electron gets conjugated with this vacant d- orbital leading to the stability for carbanion.
O S R O CH2
-

O R

S O CH2

CCl3- > Ph-CH2-

6. Anti-Aromatic compound
If negative charge of carbanion is in anti-aromaticity then its stability will be least among all the carbanions known because anti-aromaticity is simply a theoretical concept and its existence in not known.

Anti-Aromatic compound

Applications of carbanions
They are electron rich species so acts as a nucleophile and can attack over electron deficient centre to give substitution as well as addition reaction. Many name reactions also proceeds via formation of carbanion such as aldol, perkins, Claisen, Reimer- Tiemann, Haloform etc.

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Main points of carbanion 1. Carbanion have 8 electrons in its octet 2. Shape of carbanion is tetrahedral. 3. If carbanion is present in resonance then shape changes from tetrahedral to planner. 4. Hybridization of carbanion is Sp 3 5. Hybridization of carbanion is Sp 2 if it is involved in resonance 6. Formed by heterolytic cleavage of C-M bond where electronegativity of M is less than C 7. It may be primary, secondary or tertiary depending on nature of carbon 8. they are named by prefixing the name of alkyl group followed by word carbanion 9. They are also very reactive similar to carbocation far neutrality 10. They are consider as nucleophiles 11. They are consider as lewis base 12. They generally do not rearrange themself for better stability 13 It is very hepfull for making more number of carbon conaining compound from less number of cabon. 14. They are seen in many name reactions such as aldol 15. EWG attach to it stabilize them while EDG destabilize them. 16. Carbanion present at bridze head is alwawys tetrahedral no matter double bond is present adjacent to it.

H3C

CH3

CH3

General carbanion in decreasing order of stabilityH3C C H3C F 3C C F 3C R

H 2C
-

H3C < CH3 F H3C H C F H3C >

> H 2C
-

CH

<

H3C

CH2

<

CH3

> CF3

> F
-

C H H3C >
H 2C
-

H
-

CH
CHO >

CH2

NO 2

Ph

CH HC C
-

>

CH 2

>

CH 3 CH
-

>

CH 2

>

CH

>

>

CH

>

CH 3

F H 2C
-

> CH 3 C
-

H 2C

F CH 3 C
-

>

H 2C

F
-

C > Cl

C >

>

NO 2

Br

CH 3

CCl3-

>

CF3-

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H 2C

H 2C

H 2C

H 2C

>

>

>

NO 2

CH3

OCH

O H2C
-

O O CH3 > H2C

-

O > H H2C
-

O > CH3 H2C C >

-

O O CH3 > H2C

-

NH2

O CH
-

CH2 > CH
-

CH

>

OHC C
-

CHO > OHC CHO

CH

> CHO

CH3CO

CH

>

OHC

CH2

COCH 3

3. Carbon free radicals

Carbon free radicals or simply carbon radicals are those in which the carbon carries one unpaired electron. They are generally form by homolysis of either C-C, C-H sigma bond in presence of light, at high temperature in gaseous phase or in nor polar solvents or by addition of some other radical such as benzoyl peroxide.
H3C CH3 Light H3C CH2

Carbon radicals are neutral organic reaction intermediate with 7 electrons in its octet but are extremely reactive due to unpaired electron. Carbon radicals are also electron deficient similar to carbocation so those factors which generally stabilize cacrbocation i.e. (Electron donating group of any form) also stabilize carbon free radical and those factors which destabilize carbocation (Electron withdrawing group of any form) will destabilize free radicals.

General carbon radicals in decreasing order of stabilityPh C Ph Ph > C Ph Ph H2C Ph CH2 > H2C > H3C > CH3 Ph CH3 C > CH3 H CH3 C > CH3 Ph CH3 C > CH3 H H3C C > H Ph H C > CH3 H2C CH > CH3 H C H > Ph CH2

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4. Carbenes
Carbenes are very reactive species with lifetimes under one second and are defined as neutral, divalent carbon intermediate in which carbon is covalent bonded to two atoms. The simplest and the most common carbines are methylene (CH2) and dichlorocarbene (CCl2)

Formation of carbene
1. By decomposition of diazomethane Diazomethane (CH2N2) on heating produce carbene.
CH2N2 or H2C N
+ -

Heat

CH2

N2

2. By treatment of base over haloform such as Chloroform When chloroform is treated with any base a molecule of HCl is released by elimination leading to the formation of carbene.
CHCl3 Chloroform Base -H
+

CCl3-

- Cl-

CCl2: Dichlorocarbene

This reaction is of very much importance because two most important name reactions involve this dichlorocarbene formation i.e. Reimer- Tiemann reaction & Carbyl amine reaction

Configuration of carbene and their stability

A carbene may exist in its ground state as a singlet or a triplet depending upon whether the two non- bonded electrons are either in same molecular orbital with paired spin or in two orbitals of similar energy with parallel spins.
R1 C R2 Singlet carbene sp 2 hybridized Triplet carbene sp hybridized R1 C R2

The quantitative picture of bonding in singlet assumes sp2 hybridization in which one of the hybrid orbitals contains two electrons with opposite spines while the remaining two orbitals forms two bonds with two groups and one unhybridized p-orbital is empty. This singlet carbenes appears analogous to carbocations. It is important to note that R1-C-R2 bond angle is nearly 103 in singlet structure and 136 in triplet structure because of interorbital repulsion (Provided R1 & R2 are very small as H) The triplet carbene is sp hybridized with linear structure and the two unpaired electrons are present in two orthogonal p-orbitals with parallel spines. The unpaired electron in singlet carbene is in sp2 hybridized orbital and thus singlet carbene has lower energy than triplet carbene, but if electron repulsion

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energy that must be overcome to pair two electron in singlet orbital is taken into the consideration then singlet carbene will have more energy than the triplet. Therefore triplet carbine would be more stable than singlet carbene. Electron spin resonance (ESR) study has confirmed this by study of aryl and diaryl carbenes and has suggested that ground state of these carbenes have triplet structure.

Reactions of carbene
Carbenes are very reactive reaction intermediate which show many important reactions such as 1. Cycloaddition reaction with alkenes and alkynes
H3C H cis H3C H cis CH3 H CH2: triplet CH3 H CH2: singlet H3C H cis H3C H cis CH3 H H3C H CH3 H

+
H CH3 trans

When carbene reacts with alkene cyclopropane derivatives are obtained. Singlet carbenes adds to alkenes stereospecifically i.e. the stereochemistry of alkene is retained in the product while reaction of triplet carbene is not stereospecific and produce mixture of product. 2. Insertion reaction Carbenes when reacts with alkane shows insertion reaction in between C-H bond.
H 3C CH 3 Propane CH 2 : H 3C CH 3 Butane H 3C

CH 3 H 3C Isobutane

3. Carbylamine reaction
When primary amine is heated with CHCl3 & KOH then a bad smelling liquid of isocyanide is formed. Such reaction is called as carbylamine reaction.
R NH2 CHCl3/KOH R NC

3 KCl

3 H2O

Primary amine

Alkylisocyanide

4. Reimer- Tiemann reaction

When phenol is treated with CHCl3 & KOH then salicylaldehyde is formed as a major product. Such reaction is called as Reimer- Tiemann reaction.
OH CHCl3/KOH Salicylaldehyde OH CHO

Phenol

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5. Nitrenes
Similar to carbenes, nitrenes are its nitrogen analogues and are defined as monovalent, neutral nitrogen organic reaction intermediate with electron deficiency at nitrogen with six electrons in its octet. Nitrenes are too reactive for isolation but alkyl nitrenes has been isolated by trapping at 4K, whereas aryl nitrenes being less reactive can be trapped at 77K. The simplest nitrene is H N which is also known as imidogen, azene or imene. It is not usually formed because it has tendency to polymerise as soon as it is formed (NH)n

Formation of nitrene
Following are some methods by which nitrene intermediates can be formed. 1. By photolysis of hydrazoic acid (HN3)
H N N
+ -

Light

HN:

N2

Hydrazoic acid

2. By photolysis of acylazides and isocyanates

O N N
+

O N
-

Light

N R Acyl nitrene

+ +

N2

R Acyl azide R N C O Light

CO

Alkyl isocyanate

Configuration of nitrenes and their stability

Similar to carbine, nitrenes may also exist in its ground state as a singlet or a triplet depending upon whether the non- bonded electrons are either in same molecular orbital with paired spin or in orbitals of similar energy with parallel spins.

N H Singlet nitrene sp2 hybridized

Triplet nitrene sp hybridized

Reactions of nitrene
Similar to carbenes, nitrenes are very reactive reaction intermediate and behaves as an electrophile and show many important reactions such as

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1. Cycloaddition reaction with alkenes and alkynes

H3C H cis H3C H cis CH3 H N3COOC2H5 triplet H3C H N CH3 H H3C N3COOC2H5 singlet H N H CH3 H CH3 cis

COOC2H5 H3C H N

+
H CH3 COOC2H5 trans

COOC2H5 cis

Similar to carbine, nitrene reacts with alkene to form N- substituted dimethylaziridine. Singlet nitrene adds to alkenes stereospecifically i.e. the stereochemistry of alkene is retained in the product while reaction of triplet nitrene is not stereospecific and produce mixture of product.

2. Insertion reaction
The main importance of nitrenes involves the insertion of nitrogen atom into the variety of molecules such as when isopentane and ethylazidoformate is heated at 120C for 4 H, then insertion of nitrogen takes place at all types of carbon i.e. primary, secondary, tertiary and mixture of products are obtained.
H3C CH3 H3C Isopentane O 120* N3 C 2 H 5O 4H NH H3C CH3 H3C H3C CH3 NH

+
H3C H5C2OOC

CH3 NH

H3C H5C2OOC

Ethylazidoformate H5C2OOC

This reaction is also the evidence for triplet nitrene.

3. Hofmann bromamide reaction

When amide is treated with bromine in presence of KOH then amines are forms. Such reaction is called as Hofmann- Bromamide reaction
O R Br2/KOH NH2 R NH2

K2CO3

KBr

H2O

4. Curtius rearrangement reaction

When acyl azides are decomposed in inert solvent followed by treatment of water then amines are obtained. Such reaction is called as Curtius reaction.
O N3 R Acyl azide Heat R N C O Alkyl isocyanate H2O R-NH2 Amine

CO2

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6. Benzyne (1,2-Dehydrobenzene or Aryne)

There are some aromatic substitution reactions which are entirely different from SNAr reaction. This type of different reaction is observed in aryl halide having no activating groups when treated with some strong base such as NaNH2 or some metal oxides such as potassium tertiary butoxide. The most important and interesting point which is noted is that, incoming substituent does not always take the same position from where leaving group halide is eliminated. This can be experimentally seen by labeling 1-14CChlorobenzene with KNH2.
Cl 14 NaNH
2

NH2 14 14 NH2

+
50 % 50 %

Mechanism
Cl 14 H NaNH2 - NH3 1- 14C- Chlorobenzene Benzyne 50% 50% Normal substitution Cine substitution Cl 14 14 NH3 -H
+

NH2 14

14

NH2

Since benzyne is symmetrical therefore equal amount of both products are obtained.

Evivence in support of Benzyne mechanism

1. If aryl halide contains two ortho substituents are present then the reaction will not be observed. 2. When o-Bromoanisol is treated with KNH2 then m-aminoanisol is obtained because here the intermediate benzyne is not symmetrical. 3. These benzynes are not isolated under ordinary conditions but these can be isolated by some reaction such as Diel- Alder reaction and can also be observed by IR- spectroscopy.

Structure of Benzyne
It is important to note that the extra pair of electrons do not affects its aromaticity and original aromatic sextet still function as a closed ring of 6 electrons. Here the two additional electrons are located in orbitals that cover only two electrons.

or

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In benzyne, the triple bond is not like triple bond of ethyne because of hexagonal geometry of benzene ring. This new bond of benzyne is formed just by sidewise overlapping of sp2 orbital outside the hexagon in the plane of pi system of the ring. Since this sidewise overlapping is not very good so this new bond of benzyne is a weak bond and thus benzynes are highly reactive organic reaction intermediate. Benzyne has two unpaired electrons present in two available orbitals, thus it is similar to carbene and are observed as singlet and triplet structures.

Singlet Benzyne

Triplet benzyne

Reaction of benzyne
1. When an equimolar mixture of bromobenzene and o-deuterobromobenzene reacts with limited amount of sodamide then the recovered starting material contains more o-deuterobromobenzene than bromobenzene. This reaction indicates, amination of bromobenzene is faster than o-deuterobromobenzene.
Br NaNH2 Fast H Bromobenzene NH3 NH2 NaNH2 Slow D o-Deuterobromobenzene Br

Aniline

2. Benzyne are very unstable so they combine with any nucleophiles present in the reaction container. But if no nucleophile is available then they may dimerise and trimerise to form biphenylene and triphenylenes respectively.
Ph PhLi Li Benzyne CO2 H
+

Ph

COOH Diphenyl-2-carboxylic acid

Organometalic compound

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+
Diphenylene Benzyne Triphenylene

Knowledge of reaction intermediate is very much important for deciding many chemical reactions such as of substitution, elimination, addition or rearrangement reaction etc. Many rules are also based on stability of intermediates such as Markownikoff rule, Anti- Markownikoff rule, zaitsev rule, Hoffmann rule and even stability of intermediates explains the exceptions to these rules.
So it is very much importance in terms of solving problems in organic reactions in competition such as IIT-JEE, AIEEE & AIPMT etc and also in prediction of any reaction product in drug designing, natural product analysis etc. I have also proposed a rule Ajnish rule which is based on stability of intermediate which can help you to decide nearly all organic reaction and even it include nearly all these rules with explanation of their exception.

During any organic reaction if an intermediate is formed in the rate determining step then stability of intermediate will decide the formation of major product. Greater is the stability of intermediate, major is the corresponding product and the stability of intermediate is generally decided by Resonance, Hyperconjugation & Inductive effect.

Ajnish Rule:

Always yours

Ajnish Kumar Gupta (AKG) M.Sc. & CSIR-NET-2006 Lecturer of Organic Chemistry Resonance Eduventures Pvt. Ltd. For more notes, Hints, Solutions of various competitive exam, Videos of organic reactions etc Visit our website

www.OrganicChemistry.co.in
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