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1. LACTAM
ORGANIC CHEMISTRY
11/19/2017
RABIA AZIZ, BS-III, VI SEMESTER, CHEMISTRY
SUBMITTED TO MISS RUBINA

2. RABIA AZIZ
CONTENTS:
1.Introduction
2.Nomenclature
3.Synthesis
4.Beta Lactam Antibiotics
5.Conclusion
6.References

3. RABIA AZIZ
LACTAM
ABSTRACT:
In chemistry, lactam is a cyclic amide. Lactams are named according to the size of the cyclic ring
in the lactam: -lactams, -lactams, -lactams and -lactams contain rings made of three,
four, five or six atoms, respectively. -lactams are also called aziridinones. Many widely used
antibiotic drugs, including the penicillins and cephalosporins, owe their activity to the presence
of a -lactam structure. Beta-lactams are four-membered cyclic amides, best known for the
penicillins based on a bicyclo-thiazolidine, as well as the cephalosporins based on a bicyclo-
thiazine, and including monocyclic monobactams. The beta-lactamases hydrolyze the beta
lactam ring, accounting for beta-lactam resistance of infective bacteria.The lactams may have
substitutions added to the nitrogen atom or any of the non-carbonyl carbon atoms in the base
structure.
INTRODCTION:
Lactam is a cyclic amide formed from aminocarboxylic acids by elimination of water; lactams
are isomeric with lactims, which are enol
forms of lactams. The name is derived from
two chemical terms, lactone, referring to a
cyclic ketone, and amide, a compound
containing a nitrogen atom next to a carbonyl
group. The lactams may have substitutions
added to the nitrogen atom or any of the non-
carbonyl carbon atoms in the base structure.
Nomenclature:
Greek prefixes in alphabetical order indicate
ring size:
 α-Lactam (3 ring atoms)
 β-Lactam (4 ring atoms)
 γ-Lactam (5 ring atoms)
 δ-Lactam (6 ring atoms)
 ε-Lactam (7 ring atoms)
-lactams, -lactams, -lactams and -lactams contain rings made of three, four, five or six
atoms, respectively. -lactams are also called aziridinones.

4. RABIA AZIZ
This ring-size nomenclature stems from the fact that a hydrolyzed α-Lactam leads to an α-amino
acid and a β-Lactam to a β-amino acid, etc.
Synthesis of lactams
General synthetic methods exist for the organic synthesis of lactams.
 Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann
rearrangement.
 Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction.
 Lactams form from cyclisation of amino acids.
 Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic
abstraction reaction.
 In iodolactamization an iminium ion reacts with an halonium ion formed in situ by
reaction of an alkene with iodine.
 Lactams form by copper catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the
Kinugasa reaction
 Diels-Alder reaction between cyclopentadiene and chlorosulfonyl isocyanate (CSI) can be
utilized to obtain both β- as well as γ-lactam. At lower temp (−78 °C) β-lactam is the preferred
product. At optimum temperatures, a highly useful γ-lactam known as Vince Lactam is obtained
What is an iminium ion?
R2C=(NR2)+ Note:Nitrogenhasapositive charge. It can be generated
by treatinganaldehyde orketone withaprimaryor secondaryamine.

5. RABIA AZIZ
• Synthesis of alpha-lactams
The cyclization reaction of an alpha-haloamide precuror in the presence of sodium
hydride and 15-crown-5 ether at room temperature in dichloromethane (CH2Cl2) is a
high-yielding, general route to alpha-lactam (aziridinone) products. The hydrogen gas
and sodium halide by-products are readily removed.
• Beta-lactam Synthesis
The Breckpot synthesis
 The synthesis of substituted β-lactams from the cyclization of beta amino acid esters
using the Grignard reagent
Staudinger Synthesis

6. RABIA AZIZ
The reaction was discovered in 1907 by the German chemist Hermann Staudinger. The
Staudinger Synthesis, also called the Staudinger Ketene-Imine Cycloaddition, is a chemical
synthesis in which an imine reacts with a ketene through a non-photochemical 2+2 cycloaddition
to produce a β-lactam. The reaction carries particular importance in the synthesis of β-Lactam
antibiotics.
Mechanism

7. RABIA AZIZ
Beta Lactam Antibiotics:
Beta-lactam:
A beta-lactam (β-lactam) ring is a four-membered lactam. (A lactam is a cyclic amide.) It is
named as such because the nitrogen atom is attached to the β-carbon atom relative to the
carbonyl. The simplest β-lactam possible is 2-azetidinone.
History
The first synthetic β-lactam was prepared by Hermann Staudinger in 1907 by reaction of the
Schiff base of aniline and benzaldehyde with diphenylketene in a [2+2] cycloaddition (Ph
indicates a phenyl functional group):
Up to 1970, most β-lactam research was concerned with the penicillin and cephalosporin groups,
but since then, a wide variety of structures have been described.
Antibiotics:
Beta Lactam antibiotics are bactericidal drugs.
Cephalosporins
Penicillin core structure
Beta Lactam antibiotics are bactericidal drugs.

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Effectiveness:
 They inhibit building of bacterial cell wall by interference with the synthesis of
peptidoglyocan.
 The bacterial enzymes that are affected by beta lactam antibiotics are called penicillin-
binding proteins (PBPs). There are various PBPs differing in their detail function,
quantity, and affinity for beta-lactam antibiotics.
 Principally, the effect of beta-lactam antibiotics is mostly expressed against multiplying
bacteria that are building their cell wall intensively.
 On the other hand, beta-lactam antibiotics could not be effective against microbes
without the peptidoglycan-containing cell wall (chlamydiae, mycoplasmata, rickettsiae,
and mycobacteria).
Activity:
 The activity of cephalosporins, penicillins, and some other antibiotics are due to the
presence of the beta-lactam, which binds irreversibly, via acylation, to penicillin-binding
proteins, thereby inhibiting the peptidogycan layer of bacterial cell wall synthesis.
Resistance:
 The beta-lactamases hydrolyze the beta lactam ring, accounting for beta-lactam resistance
of infective bacteria.
List of Beta Lactam Antibiotics:
A) Penicillins Antibiotics
1. Natural penicillins
2. Anti-staphylococcal penicillins
3. Aminopenicillins
4. Ampicillin + sulbactam

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5. Amoxicillin + clavulanic acid
B) Cephalosporins Antibiotics
1. 1st generation
2. 2nd generation
3. 3rd.generation
4. 4th generation
C) Carbapenems Antibiotics
D) Monobactams Antibiotics
CONCLUSION:
Lactam is a cyclic amide. -lactams, -lactams, -lactams and -lactams contain rings made
of three, four, five or six atoms, respectively. There are many synthetic ways to synthesis alpha
and beta lactam. The beta-lactam forms the center structure of many antibiotic drugs, such as the
cephalosporins and the penicillins. In the penicillins, the non-lactam ring is one atom smaller
compared to the cephalosporins. The activity of cephalosporins, penicillins, and some other
antibiotics are due to the presence of the beta-lactam, which binds irreversibly, via acylation, to
penicillin-binding proteins, thereby inhibiting the peptidogycan layer of bacterial cell wall
synthesis. Cephalosporins and penicillins are often made semi-synthetically, using a core
structure obtained from a natural organism, such as a fungus, due to the difficulty and expense of
synthesizing these lactams. Beta-lactams are four-membered cyclic amides, best known for the
penicillins based on a bicyclo-thiazolidine, as well as the cephalosporins based on a bicyclo-

10. RABIA AZIZ
thiazine, and including monocyclic monobactams. Many organisms produce beta-lactamase
enzymes that can destroy these antibiotics. This is a common cause of bacterial resistance to
antibiotics. The beta-lactamases hydrolyze the beta lactam ring, accounting for beta-lactam
resistance of infective bacteria. The lactams may have substitutions added to the nitrogen atom
or any of the non-carbonyl carbon atoms in the base structure.
REFERENCE:
1. http://www.antibiotics.tips/2016/04/beta-lactam-antibiotics-list-classification-indications-
contraindications.html
2. http://vebriachemist.blogspot.com/2012/06/lactam.html
3. https://en.wikipedia.org/wiki/Staudinger_synthesis