When there are two functional groups of unequal reactivity within a molecule, the more reactive group can be made to react alone, but it may not be possible to react the less reactive functional group selectively. A group the use of which makes possible to react a less reactive functional group selectively in presence of a more reactive group is known as protecting group. A protecting group blocks the reactivity of a functional group by converting it into a different group which is inert to the conditions of some reaction(s) that is to be carried out as part of a synthetic route

2. I wish to convey my sincere regards and thanks to Dr.
Renu Gupta, Head Department of Chemistry Lucknow
Christian P.G College, Lucknow for her keen interest,
encouragement and fruitful suggestions and for providing
library facilities.
I would like to place on record my deep gratitude to Mr.
Mayank Joseph under whose guidance this project entitled
“Protecting Groups In Organic Synthesis ” is being
submitted, but for the constant support and encouragement
at every stage, it would not have been possible complete this
study.
My sincere thanks are to Dr. Stuti Gupta & Dr. Abhas
Asthana for their co-operation during the completion of the
project.
Apoorva Rastogi

4. Introduction

5.  When there are two functional groups of unequal reactivity
within a molecule, the more reactive group can be made to
react alone, but it may not be possible to react the less
reactive functional group selectively.
 A group the use of which makes possible to react a less
reactive functional group selectively in presence of a more
reactive group is known as protecting group.
 A protecting group blocks the reactivity of a functional group
by converting it into a different group which is inert to the
conditions of some reaction(s) that is to be carried out as part
of a synthetic route

6. When we choosing a suitable protecting group, the
following features must be considered :-
◦ Cheap and commercially available.
◦ Simple to put in high yield.
◦ Stable to reaction conditions.
◦ Easy to remove in high yield

7. ◦ Protection of Alcohols.
◦ Protection of Carbonyl Groups in Aldehyde And Ketones.
◦ Protection of Carboxylic acid.
◦ Protection of amines.

8. Protection of Alcohols

9.  By putting a bulky protecting group on the hydroxyl
oxygen which can sterically prevent it from
competing effectively for electrophiles.

10.  By delocalising the lone pairs of electrons by
conjugation

11.  Acetals Or Ketals As Protecting Groups For Alcohols
 Ether As Protecting Groups For Alcohals
 Ester As Protecting Groups For Alcohals

13.  Acelals or ketals not only serve as useful protecting groups
for aldehydes and ketones but they also find widespread
use in the protection of alcohols.
 Commonly used ketals include Tetrahydropyranyl (THP)
derivatives, methoxyethoxymethyl (MEM) derivative
and methoxymethyl (MOM) derivative.
 Acetals / ketals are simply removed by treatment with
aqueous acid.

17.  Alcohols may be simply converted to ethers by
nucleophilic attack on a suitable alkyl halide.
 Ethers are stable to basic and mildly acidic
conditions; they do not react with oxidizing /
reducing agents and are inert to organo-metallic
reagents. However, this stability means that many
others are not easily cleaved to their parent alcohol
under mild conditions. Therefore, only certain
ethers, which are easily cleaved under mild
conditions, are commonly used as protecting groups
for alcohols.

18.  Benzyl ether which are converted to alcohols under
neutral conditions by catalytic hydrogenolysis.

19.  t-butyl ethers which are readily hydrolyzed with
dilute acid.

20.  Tri-phenylmethyl group is the most important
for the protection of 1°-alcoholic group. Only 1°-
alcohols react at a useful rate with trityl-chloride in
pyridine so selective protection of primary hydroxyl
groups is possible.

24.  Trichloroacetate esters [Cl3CCOOR]:
 Pivoloate ester [Me3CCOOR]:-

26.  Cis 1, 2 diols and cis and trans-1,3 diols can be
protected as cyclic acetals and ketals (e.g., dioxlanes
and dioxanes) or cylic ortho esters that are cleaved
by acidic hydrolysis or as cylic esters (e.g,
carbonates) that are cleaved by basic hydrolysis.
 Cyclic ortho esters are more readily cleaved by acidc
hydrolysis than cyclic acetals or ketals.


27. Isopropylidene (acetonides):-
 1, 2 acetanoid formation is usually favored over 1, 3
acetonidess
 Cleavage:-mild aqueous acid

33.  The acetal / ketals protective group is introduced by
treating the carbonyl compounds with an alcohol, an
ortho-ester, or a diol in the presence of a Lewis acid as
catalyst.
 Acetals / ketals are stable to strong aqueous bases,
nucleophilic reducing agents, organometallic reagents,
oxidation under non-acidic conditions, Na or Li/NH3
reductions.
 Acetals / ketals are cleaved by acid-catalyzed hydrolysis

34.  General order of reactivity of various carbonyl
groups (probably due to the steric effect).
 1,3-dioxanes (six-membered ring) hydrolyze faster
than the corres-ponding 1,3-dioxolanes (five-
membered ring acetal)

35.  Acyclic acetals is prepared by the reaction of
aldehyde with monohydric alcohal in the presence
of dry HCl.

36.  Acylic ketones cannot be prepared with monohydric
alcohols under the same condition of acetals
formation because of the unfavourable entropy,
which the equillbrium towards the ketones So
acyclic ketals are prepared by the reaction of
ketones with ethylorthoformate in presence of the
NH4Cl.

38.  Thioacetals / thioketals are quite stable toward
hydrolysis; there is no special need to remove the
H2O formed during the reaction.

42.  Protecting groups for carboxylic acids are used to
avoid reaction of the acidic -COOH hydrogen with
bases and nucleophiles or to prevent nucleophilic
additions at the carbonyl carbon.

43.  Most common group for the protection of
acid is ester.

52.  The basic problem of peptide synthesis is one of
protecting the amino group. In bringing about
interaction between the carboxyl group of one
amino acid and the amino group of a different amino
acid, one must prevent interaction between the
carboxyl group and the amino group of the same
amino acid. In preparing glycylalanine, for example,
one must prevent the simultaneous formation of
glycylglycine. Reaction can be forced to take place in
the desired way by attaching to one amino acid a
group that renders the NH2 unreactive.

59.  Amides are readily prepared from an amine and an
acid chloride or anhydride. These are relatively
more stable compounds that, classically, are cleaved
by heating in strongly acidic or basic solutions.

65. [1] Singh, J ; Yadav, L.D.S; Organic Synthesis;Pragati
Publicaton; thirteenth edition- 2017; pp. 696-
721.
[2] Kar, K.R.; Application of Redox and Reagents
in Organic Synthesis; New Central Book
Agency (P) Ltd; volume-1; pp 376-385.
[3] Clayden, J; Greeves, N; Warren, S; Wothers, P;
Organic Chemistry; pp 633-637 & 657

66. [4] Hanson, J.R.; Protecting Groups in Organic
Synthesis; Sheffield Academic Press; pp 8- 80.
[5] Morrison, R.T.; Boyd R.N.; Organic Chemistry;
Prentice-Hall of India Private Limited; Sixth Edition-
2002; pp. 1147
[6] March, J; Smith, M.B.; March’s Advanced
Organic Chemistry: Reactions, Mechanisms, and
Structure; Wiley Publication; Sixth Edition; pp
1271-1279