phenol và tổng hợp phenol

Hydrogen bonding in phenols i Intermolecular hydrogen bonding: Like other compounds having —OH groups phenols either solids or liquids, exhibit intermolecular hydrogen bonding.. i Acidic

chemical to be used as an antiseptic as early as 1867 (Lister) It is being used as an important raw

material in the manufacture of synthetic polymers (plastics).

A number of phenols and phenolic ethers occur in nature Salicylic acid, for example, occurs in

willow tree Some other important salicylic acid derivatives are methyl salicylate or oil of wintergreen

—a common ingradient of liniments, and acetylsalicylic acid (aspirin)—a time honoured analgesic

and antipyretic drug Thymol is a typical flavouring ingredient of thyme and is widely used in thepreparation of mouthwash because of its flavour and antiseptic property Clove oil, used by dentists

as an antiseptic, also contains a phenol, eugenol In addition, certain phenolic compounds are known

for their specific physiological actions For instance, poison ivy (irritants) are 1,2-dihydroxybenzene derivatives having a long side-chain at 3-position A complex phenolic compound, tetrahydrocannabinol,

is one of the active principles of the intoxicant marijuana.

OH

Phenol (Carbolic acid)

OH COOH

Salicylic acid (a phenol and an acid)

Methyl salicylate (a phenolic ester)

OH COOH3

OCOCH3COOH

Acetylsalicylic acid

(Aspirin)

CH3

CH(CH )3 2OH

Eugenol

CH CH 2 CH2

Thymol

OH OCH3

146

OH OH

C side chain15

Poison ivy irritants

OH OCH3

CHO

Vanillin

CH3OH

(–)-Tetrahydrocannabinol

We have mentioned above that phenols are hydroxy derivatives of aromatic (benzenoid) compounds

They are represented by the general formula Ar—OH Depending upon the number of hydroxy groups, they are classified as monohydric (one—OH group), dihydric (two—OH groups), trihydric (three—OH groups) and polyhydric (more than three—OH groups) phenols Following two systems

are in use for naming these compounds:

(i) Common system: A number of phenols are assigned special names, while others are named as

derivatives of these substances Compounds having only one additional substituent are named as the

derivatives of phenol, the position of this substituent is indicated by letters o-, m-, or p- Some

examples are given below:

OH OH OH

OH

(ii) IUPAC system: In this system the simplest phenol is called benzenol But all substituted

phenols are named as derivatives of phenol The carbon atoms of the aromatic ring are numberedcommencing with the carbon atom bearing the root functionality (the —OH groups), the ring carbonsare numbered successively so that the sum of numbers used to designate the position of substituents

is minimum Following examples are illustrative (common names in parentheses)

Dihydric, trihydric and polyhydric phenols are named as benzenediols, benzenetriols andbenzenepolyols, respectively These names are also written as hydroxy derivatives of benzene However,they are better known by their trivial names parentheses For instance,

OH OH

3 4 5 6

3

1

2 3

4

HO OH

Phenols with other substituents

3 4 5 6

Cl

OH

1 2

3 4 5 6

However, when a functional group such as carboxylic group, ester or carbonyl group is present

in addition to phenolic group, the phenols are named as hydroxy derivatives of these compounds Thecommon names of these compounds are retained as root names The ring is numbered commencingwith the designated functional group and going round successively as above Thus,

4-Hydroxy-2-nitrobenzaldehyde 5-Chloro-2,

4-dihydroxybenzaldehyde

NO2

CHO

1 2

3 4 5 6

OH

CHO

1 2

3 4 5 6

Cl

2, 4-Dihydroxybenzoic acid ( -Resorcylic acid) β Ethyl 2-chloro-4-hydroxybenzoate

Cl

COOC H2 5

1 2

3 4 5 6

OH

COOH

1 2

3 4 5 6

In phenols, the C—O bond is formed by the overlap of sp2-orbital of carbon of benzene ring with

a sp3-orbital of oxygen atom while the O—H bond is formed by the overlap of second

sp3-orbital of oxygen with 1s orbital of hydrogen (Fig 4.1) The remaining two non-bonding

sp3-orbitals of oxygen atom contain lone-pairs of electrons

H 109°

136 pm

sp –sp 2 3

1s H

Fig 4.1: Structure of phenol

Due to higher electronegativity of oxygen atom, phenol molecule is dipolar in nature with the oxygen carrying partial negative charge Due to this dipolar nature phenols form hydrogen bonds.

It is noteworthy that the dipole moment of phenol (1.54D) is smaller than that of methanol

(1.71D), because the C—O bond in phenol is less polar due to electron-withdrawing effect of the benzene ring while in methanol, C—O bond is more polar due to electron-donating effect of methyl group.

The phenol molecule cannot be depicted by any single valence bond structure In fact, it isconsidered as a hybrid of the following contributing forms:

–

– +

Resonating structures of phenol

H O

II

H O

H O

H

A perusal of the contributing forms II, III and IV clearly shows that the oxygen atom acquires

a positive charge due to resonance This polarity facilitates release of proton and formation ofphenoxide ion which is also stabilized by resonance

Hydrogen bonding in phenols

(i) Intermolecular hydrogen bonding: Like other compounds having —OH groups phenols

either solids or liquids, exhibit intermolecular hydrogen bonding Due to these hydrogen bonds theyexist as polymeric aggregates held together These aggregates break up on dilution with a non-polarsolvent first into trimers or dimers and finally into the monomers on large dilution

H O

H O

H O

H O

H O

It has been observed that the boiling point of phenol is higher as compared to toluene (having comparable mol weight) This is due to the formation of intermolecular hydrogen bonding which

results in the formation of polymeric aggregate where molecular mass increases many fold, therebyraising its boiling point The reason for the high boiling point may be due to the fact that additionalenergy is required to break the hydrogen bonds Toluene, on the other hand, does not form hydrogenbonds

Phenol is somewhat soluble in water because it forms cross-intermolecular hydrogen bonding with water molecules, as shown below:

H O

H O

H O

H O

H O

H O

(ii) Intramolecular hydrogen bonding: A phenol, in which a carbonyl or a nitro group is attached

at the ortho position, usually forms intramolecular hydrogen bonding as shown below:

CH 3

N

O

O H

O

– +

Intramolecular hydrogen bonding in o-Hydroxyacetophenone and o-Nitrophenol

This type of hydrogen bonding also alters the physical and chemical properties of these molecules

(i) From coal-tar: The middle oil fraction (443–513K) of coal-tar consists of phenol and cresols in

addition to other compounds This fraction is collected and treated with alkali The alkaline layer isseparated and carbon dioxide gas is bubbled through it The phenolic mixture that separates out issubjected to fractional distillation in order to isolate individual phenols

(ii) From halobenzenes (Dow process): Chlorine in chlorobenzene is inert to nucleophilic

displacement under usual conditions However, when chlorobenzene is heated with sodium hydroxide

at 613K under pressure it forms phenol This method is used for commercial production of phenoland was first developed by Dow chemicals, USA in 1928

Cl

OH, 613K Pressure (320atm) –

OH

Mechanism: This transformation takes place via benzyne mechanism as shown below:

–H O 2

NaOH 8%NaOH

However, if halobenzene has a strong electron-withdrawing substituent at ortho- or para-position,

the hydrolysis of these compounds becomes easier Thus, 2,4-dinitrophenol and 2,4,6-trinitrophenol(picric acid) are obtained from the corresponding aryl halides using milder conditions

NO 2

O N2

NO2HO

O N 2

H O2333K

2,4,6-Trinitrophenol (Picric acid)

(iii) From isopropylbenzene (cumene): This procedure is essentially used for the preparation of the parent compound, phenol Cumene (A) on catalytic aerial oxidation gives phenol via cumene

This reaction, which is an example of autooxidation, is carried out at 423K in presence of

hydrogen bromide as a catalyst It takes place by a free radical chain mechanism and is initiated

by the abstraction of hydrogen from hydrocarbon by a bromine radical, which is produced by aerial

oxidation of H—Br The free hydrocarbon radical thus produced picks up a molecule of oxygen forming peroxy radical which in turn abstracts hydrogen atom from H—Br in the propagation step

to give cumyl hydroperoxide

O2

H Br +

Hydroperoxide radical

The cumyl hydroperoxide so obtained is treated with acid to form phenol The reaction is called

cumyl hydroperoxide rearrangement.

The mechanistic path of this rearrangement involves initial protonation of the —OH group of

hydroperoxide The resulting oxonium ion loses water to form a species with electron-deficientoxygen A carbocation, generated by phenyl migration, is stabilized by resonance Nucleophilic attack

of water on this carbocation gives a hemilketal which undergoes acid-catalysed split to form theproducts

(iv) From diazonium salts: Addition of diazonium salt solution to a large excess of warm 50%

sulphuric acid at 323K results in the formation of phenol

(v) From sulphonic acids: Fusion of the alkali metal salt of an aromatic sulphonic acid with

sodium or potassium hydroxide (solid) affords the corresponding phenol

Phenoxide –Na SO2 3

Various physical parameters such as boiling points, melting points, water solubilities and Ka values

of some phenols listed in Table 4.1, are discussed below:

(i) Physical state: A look at the Table reveals that most of the simpler monohydric phenols are

either liquids or low melting solids Pure phenols are colourless but they usually turn reddish browndue to atmospheric oxidation

(ii) Melting and boiling points: Nitrophenols, aminophenols and phenols having more than one

hydroxyl group have relatively higher melting and boiling points This is probably due to the increased

polar character resulting in higher degree of association involving intermolecular hydrogen bonding.

In general phenols are more polar than cycloalkanols having similar carbon skeletons Thisdifference in polarities is reflected in higher melting and boiling points of phenol (m.p 316K;b.p 454K) as compared to those of cyclohexanol (m.p 298K; b.p 434K)

Table 4.1: Physical Properties of Some Phenols

Further, among the isomeric fluoro- and nitrophenols, the ortho isomers have lower melting points, boiling points and water solubilities and are weaker acids than the corresponding meta and para-isomers This is due to intramolecular hydrogen bonding in the case of ortho isomers and intermolecular hydrogen bonding in the case of meta- and para-isomers.

(Intramolecular hydrogen bonding) o-Nitrophenol

–

(i) Infrared spectra: Like alcohols the infrared spectra of phenols are characterized by the typical

band in the 3600–3200 cm–1 region due to O—H stretching vibrations This band, however, shifts to

3610 cm–1 on dilution, due to the ‘free’ O—H group Further, the O—H stretching vibrations of thosephenols which are capable of forming intramolecular hydrogen bonding appear in the 3200–2500

cm–1 region The phenols are distinguished from alcohols because of different frequencies ofC—O stretching vibrations which show up at 1230 cm–1 in the former (Fig 4.2) The other

characteristics of the infrared spectra are the typical absorption bands as expected from benzenederivatives

OH

3040 3340

1465 1492 1580

(ii) Ultraviolet spectra: The ultraviolet spectra of phenols are characterized by the typical E and

B bands of aromatics which appear at relatively longer wavelength compared to benzene (bathochromic shift) This is probably due to the extended conjugation involving —OH group The λmax of phenol,for instance, appears at 215 nm, 270 nm and 275 nm Additional bathochromic shift appears inalkaline solution because of resonance involving phenoxide ion (dispersal of charge)

(i) Acidic character: Both alcohols and phenols contain an —OH group and due to difference in

electrongativities of oxygen and hydrogen, both types of compounds are expected to be acidic in

nature Though both exhibit acidic properties (react with electropositive metals), phenols areconsiderably more acidic than alcohols This difference in acid strength is reflected in the formation

of phenoxide salts when phenols are treated with aqueous alkali whereas alcohols do not react underthese conditions

Explanation for greater acid strength of phenols than alcohols.

Alcohols neither react with NaOH nor turn blue litmus red This could be explained by considering

the fact that due to resonance involving benzene rings, phenols and phenoxides are more stable thanalcohols and alkoxides, respectively Further, as shown in Fig 4.3, the phenoxide ions are much morestable than alkoxides ions due to dispersal of negative charge in the former, whereas the difference

in stability of phenols (involving separation of charge) and alcohols is not much pronounced

H

O

Resonance stabilization of phenol separation of charge, less stable( )

Resonance stabilization of phenoxide ion dispersal of charge, more stable( )

Thus acid strength of phenol becomes evident from the fact that phenoxide ion is resonancestabilized to a larger extent due to dispersal of charge, compared to phenol where resonance involvesseparation of charge

Extent of resonance stabilization

of phenoxide compared to alkoxide

Extent of resonance stabilization

of phenol compared to alcohol

ArO RO

ArOH ROH

–

–

Fig 4.3: Comparative acidic strength of phenols and alcohols

Comparison of acid character of phenols and carboxylic acids

Though stronger than alcohols, phenols are weaker acids than carboxylic acids(Ka = 10–5) or even carbonic acid (Ka= 10–7) This is the reason why phenols fail to react with sodiumcarbonate or bicarbonate In fact the phenols are precipitated from aqueous solution of phenoxides

by bubbling carbon dioxide gas Further, the difference in acid strength of phenols and carboxylicacids provides a convenient method for their separation with aqueous sodium bicarbonate in whichthe latter are soluble leaving the former behind

Effect of substituents on the acid strength of phenols

The acid strength of phenols is effected considerably by the presence of substituents on the ring

An electron-withdrawing substituent helps in greater dispersal of negative charge on the phenoxide ion either by inductive effect (–I) or by resonance effect (–R) or both This would result in the increase in acid strength of phenol Conversely, the electron-donating groups due to +I or +R or both effects, decrease the acid strength.

(i) Effect of electron-withdrawing substituents: Phenols having electron-withdrawing groups

(–I, –R) such as —CN, —NO2, —COOH, —CHO, —COR etc., at ortho and para-positions with

respect to the phenolic group are stronger acids than phenol Here it may be mentioned that only theinductive effect is not responsible for the increase in acid strength In fact it is the resonance effect(–R in this case) which plays a major role in stabilising the corresponding phenoxide ion Since theconjugation is extended upto oxygen of the nitro group, this anion is more stable than phenoxide ion

where no such extended conjugation is possible This is evident from the fact that p-nitrophenol

(Ka = 700 × 10–10) is 700 times as strong as phenol (Ka = 1 × 10–10)

Resonance stabilization of p-nitrophenoxide ion

–

– + –

As the number of contributing forms is more and the negative charge is spread over two electronegative oxygen atoms, the resulting anion is more stabilized than phenoxide ion.

(ii) Effect of electron-donating substituents: Phenols having electron donating groups

(+I, +R) such as —CH3, —OCH3, —NH2., etc., at ortho or para position with respect to —OH group

are weaker acids.This may be attributed to the intensification of negative charge on the correspondingphenoxide ion due to resonance (+R), resulting in its destabilization

However, the groups such as —NH2, —OH, —OR etc., when present in m-position increase the

acid strength of phenols due to –I effect The order of acid strength for some typical phenols is asunder:

(iii) Effect of position of the substituent: It may be worthwhile to understand here that the

acid-weakening effect of the donating groups and acid-strengthening effect of the

electron-withdrawing groups is more pronounced at o- and p-positions with respect to the OH group than at m-position This may be explained on the basis of the fact that both inductive and resonance effects influence the stability of phenoxide ion left after the removal of a proton In some cases, both

inductive and resonance effects reinforce while in other cases they may oppose each other dependingupon the nature and position of the substituent on the benzene ring as discussed below:

(a) Resonance effects: Nitro group has a powerful –I as well as –R-effect, therefore, irrespective

of the position of nitro group, all nitrophenols are stronger acids than phenol Although –I-effect

decreases with distance, –R-effect is more pronounced at o-and p-positions than at m-position To explain this, let us compare the stabilities of o-, m- and p-nitrophenoxide ions.

–

–

+ –

–

+

– –

+ –

–

+ –

O

O

N O

O

O

N O

O O

It is clear from the above structures that both o- and p-nitrophenoxide ions are stabilized by five

resonating structures In one of the structures in each case (I or II), conjugation is extended upto

oxygen atom of the nitro group But no such conjugation is possible for m-nitrophenoxide ion due

to which m-nitrophenoxide is stabilized by only four resonating structures In other words, o-nitrophenoxide ion and p-nitrophenoxide ions are more stable than m-nitrophenoxide ion Therefore, o-nitrophenol and p-nitrophenol are stronger acids than m-nitrophenol.

Out of o-nitrophenol and p-nitrophenol, o-nitrophenol is little less acidic than p-nitrophenol This may be due to the fact that acidic hydrogen of OH group is involved in intramolecular H-bonding

or chelation which makes loss of the proton a little more difficult.

N O H

+

O

Thus, the acid strength of nitrophenols relative to phenol decreases in the order:

p-Nitrophenol > o-Nitrophenol > m-Nitrophenol > Phenol Further, greater the number of electron withdrawing groups at o- and p-positions, more stable is

the phenoxide ion and hence more acidic is the phenol Thus, acid strength of nitrophenols withrespect to phenol decreases in the order:

2,4,6-Trinitrophenol > 2,4-Dinitrophenol > 4-Nitrophenol or 2-Nitrophenol > Phenol

(b) Inductive and hyperconjugation effects

(i) Comparison of the acidic strength of halophenols Halogens have +R and –I-effects, but the –I-effect predominates over the +R-effect Therefore, all halophenols (except p-fluorophenol) are

more acidic than phenol itself Further, since –I-effect decreases with distances, the acidic strength

of halophenols decreases in the order:

o-Halophenol > m-Halophenol > p-Halophenol

In case of p-fluorophenol +R-effect and –I-effect of F almost balance each other due to almost identical sizes of 2 p-orbitals of C and F and hence it is almost as acidic as phenol itself.

Out of o-halophenols, o-fluorophenol is the weakest acid due to strong intramolecular H-bonding

while the acid strength of other halophenols decreases as the —I-effect of the halogen decreases

F H O

Therefore, the acid strength of all the o-halophenols decreases in the order:

o-Chorophenol > o-Bromophenol > o-Iodophenol > o-Fluorophenol (ii) Comparison of the acidic strength of cresols The alkyl groups are electron donating due to

hyperconjugation effect Therefore, all cresols (methylphenols) are less acidic than phenol itself

Futher, hyperconjugation effect cannot operate at m-position due to which m-cresol is more acidic than o- and p-cresols Due to field effects which make the loss of a proton little more difficult, p-cresol is more acidic than o-cresol Thus, the acid strength of cresols relative to phenol decreases

in the order:

phenol > m-cresol > p-cresol > o-cresol.

(iii) Comparison of acid strength of dihydric phenols i.e, catechol, resorcinol and hydroquinone.

In case of catechol due to intramolecular H-bonding the loss of a proton is little difficult compared

to that in hydroquinone Hence hydroquinone is more acidic than catechol But in case of resorcinol,

the two OH groups are situated at m-position due to which one of them can not enter into the

resonance with the other OH group Instead –I-effect of one OH groups on the other makes resorcinolmore acidic than catechol and hydroquinone Thus, the order is:

Resorcinol > Hydroquinone > Catechol (iv) Comparison of acid strength of phenol with m-methoxyphenol and m-aminophenol A group present at m-position cannot enter into resonance with the hydroxy group of phenols, but can exert

inductive effect from this position Due to –I-effect of both methoxy and amino groups,

m-methoxyphenols and m-aminophenols are more acidic than phenol Futher, due to more –I-effect

of methoxy group than of amino group, m-methoxyphenol is a stronger acid than m-aminophenol.

Therefore, their acid strength decreases in the order:

m-methoxyphenol > m-aminophenol > phenol.

(iv) Ester formation–Acylation: Phenols are converted into the corresponding esters by the

action of acid chlorides or acid anhydrides in presence of either acidic or basic catalysts

Different mechanisms operate under different conditions

(a) Base catalysed esterification (B AC 2 mechanism): Under basic conditions the reaction is

initiated by the nucleophilic addition of phenoxide anion, (produced by the action of alkali on phenol)

on the carbonyl carbon of the acid chloride or anhydride, forming a tetrahedral intermediate Loss of

XV from the intermediate gives rise to the products.

(b) Acid catalysed esterification (A AC 2 mechanism): The reaction is initiated by protonation of

the carbonyl oxygen resulting in the development of full positive charge on carbonyl carbon so that

a relatively weak nucleophile such as phenol can attack Proton exchange followed by elimination of

HX gives the product Acetylation with acidic anhydride in presence of concentrated sulphuric acidtakes place in the following steps:

O X

H C3C

+

OH C

Fries rearrangement: The phenolic esters, upon heating with anhydrous aluminium chloride, are

converted into the isomeric o- and p-hydroxy ketones or more often, into a mixture of both.

COCH3HO

AlCl , 298K3AlCl , 438K3

o-Hydroxyacetophenone

COCH3OH

Although p-isomer is obtained more easily, the o-isomer is more stable, due to intramolecular

hydrogen bonding

O H O C

CH3

Mechanism: The reaction can take place by two alternate mechanistic pathways, i.e., by a

one-step or a two-step mechanism That this reaction takes place by a two-step mechanism in most

of the cases, has been proved by the isolation of cross products when a mixture of two identical but

differently substituted substrates is treated under the conditions of the reaction Thus, for instance,esters I and II give the ketones III and IV, respectively When a mixture of I and II is heated withaluminium chloride, apart from III and IV cross products V and VI are also obtained

+ +

OH

CH3COCH3

In the first step an acylium ion (RCO+) is formed which attacks the benzene ring at o- and

p-positions in the second step This two-step mechanism of Fries migration may be outlined asfollows:

AlCl 3

COR H

(v) Ether formation; Williamson’s synthesis: Phenols can be converted into the corresponding

alkyl ethers by treating sodium or potassium phenoxides with alkyl halides

Mechanism: The reaction does not require any catalyst and shows first order kinetics with

respect to the allyl aryl ether The Claisen rearrangement is an example of pericyclic reactions and

is known as sigmatropic rearrangement The reaction has been shown to proceed in a concerted

manner as evidenced by heating a mixture of ethers VII and VIII having two different allyl groups,whereby cross-products are not obtained

No cross-products are formed.

473 K

CH2 CH CH2OH

OH

C H6 5+

O CH2 CH CHC H6 5

O CH2 CH CH2+

VII

VIII

An interesting feature of the rearrangement is that when migration takes place to the ortho

position, the γ-carbon of the allyl group (with respect to oxygen) attaches itself to the ring carbon

In other words, ortho migration involves an inversion in the position of substituents with respect to that of the starting compound However, no such inversion takes place in the case of para migration ortho rearrangement

473 K

O CH2 CH CH

CH2 CH CH2

OH R

R

Mechanism of ortho-rearrangement: The above observations point towards the fact that the

ortho- isomerization is a concerted process and the reaction proceeds through a six-membered cyclic transition state The rupture of the allyl-oxygen bond is synchronous with the formation of allyl- carbon bond at the ortho position A cyclohexadienone intermediate IX is thus formed which undergoes prototropic change to give the o-allylphenol By doing so the ring regains the aromatic character.

CH2

CH CH3

CH O

OH

CH3

O H

IX

CH CH CH2

CH3

Mechanism of para-rearrangement: As mentioned above when both the ortho positions are

blocked the allyl group migrates to para position without any inversion in the position of substituents

on allyl group with respect to the starting compound This indicates that the overall para migration

takes place in two stages In the first stage the usual ortho migration leading to the formation of

cyclohexadienone intermediate takes place Since there is no hydrogen at this position, tautomerization

is not possible hence the ring cannot undergo aromatization The intermediate, therefore, undergoes

another isomerization involving migration of the allyl group to para position again through a membered cyclic transition state with another inversion Thus, in a para rearrangement one inversion

six-is followed by another and overall there six-is no inversion The driving force for the para migration six-is

regaining of aromatic character after allylic migration

CH2

CH CH3

CH O

Following observations further confirm the above reaction sequences:

(i) The intermediate cyclohexadienone has been trapped by Diels-Alder reaction and has also been synthesized independently It has been found to give the allyl phenol on heating.

(ii) When ortho- 14 C-labelled allyl 2,6-diallyl ortho ether was heated the 14 C label was found to

be equally distributed between ortho and para positions in the rearranged product This experiment unequivocally established the intermediacy of triallylcyclohexadienone (XII) in which either the labelled or unlabelled allyl group migrates to para position with equal ease.

In addition to aryl alkyl ethers, diaryl ethers of the type Ar—O—Ar’ are also known and they

can be obtained by the treatment of a phenoxide with aryl halide at high temperature or in presence

of a copper catalyst (Ullmann reaction) The exact role of copper catalyst is not very well understood.

It has, however, been proposed that Cu coordinates with halogen and withdraws electrons from

C—X bond thus making the displacement of halogen easy.

C H 6 5 Br + Cu C H 6 5 Br Cu+ C H O6 5 C H 6 5 O C H 6 5+ Br + Cu

–

– –

However, if a strong electron-withdrawing group such as a nitro group is present in the

ortho-or para-position with respect to the halogen atom, it can be displaced by phenoxide anion by a

bimolecular nucleophilic displacement without the use of copper catalyst

O O O

N Cl

O

– + –

+