Special Synthesis

Carlo Joseph M. Moskito

BS Chemistry
Chemistry 44.1 – 1L
 Synthesis Experiment:
OVERVIEW

Synthesis of N- acetylanthranilic
acid, a triboluminescent material

Dates Performed:
February 21 & 28, 2011
INTRODUCTION

 a known compound to
exhibit triboluminescene
INTRODUCTION

 is the emission of light after

has been
applied to the crystal.
 light produced
INTRODUCTION

 named in 1895 but reported in

1605 by
 from the Greek word and
Latin which means
and respectively

Triboluminescene Spectroscopy of Common Candies

Angelos, Zink and Hardy . J. Chem. Educ. 56, 413 (1979)
INTRODUCTION

Triboluminescene Spectroscopy of Common Candies

Angelos, Zink and Hardy . J. Chem. Educ. 56, 413 (1979)
INTRODUCTION

 Emission occurs due to the

by
between the
surfaces of the fractured crystals
and subsequent flourescene.
 instantaneous charge polarization
INTRODUCTION Example:
Sugar (Sucrose)
INTRODUCTION Example:
Diamond

Triboluminescene of Diamonds.
J R Hird, A Chakravarty and A J Walton
J. Phys. D: Appl. Phys. 40 (2007) 1464–1472
INTRODUCTION Example:
Granite

Activities of Triboluminescence at Sample Failure of Granite

Itaru Maeda Hokkaido University, Sapporo 060, Japan.
Jour. Fac. Sci .. Hokkaido Univ., Ser. VII (Geophysics), Vol. 8, No.1, 65-81, 1986.
INTRODUCTION
H2N

o-toluidine

H2N
HO

O
Methalqualone
O O
A quinazolone
derivative which
O
acts as
barbiturates

Production of Methalqualone, a barbiturate.

INTRODUCTION

O OH HO O
O O

H
NH2 1. O N O
2. H2O
∆ / Heat, reflux
OH

and
O

General Reaction for the synthesis of N-acetylanthranilic acid.

INTRODUCTION
Mechanism


on Acetic Anhydride; or
 on Anthranilic Acid

Synthesis of Heterocycles from Anthranilic Acid and its Derivatives

Per Wiklund. Karolinksa University Press. Sweden.
INTRODUCTION Mechanism tetrahedral intermediate
COOH
O
O O
H
CH3
OH N
O
O
H
NH2
O CH3
At neutral conditions

O
COOH

H O
+
N
CH3 O CH3
H

O
INTRODUCTION Mechanism
Continuation

COOH O

H
O CH3
N
CH3 HO O
H

O OH H
N O
and
O
 O OH
INTRODUCTION O O

NH2
O
A CYCLIC INTERMEDIATE
∆

HO O

OH H
N O

and
O

N-Acetylanthranilic Acid as A Highly Triboluminescent Material.

John Erikson. J. Chem. Educ. 49, 688 (1972)
INTRODUCTION Mechanism
I. Formation of the cyclic intermediate
O OH O OH
H H

N CH3 N CH3

O O

OH
O O CH3

N
H
INTRODUCTION Mechanism
I. Formation of the cyclic intermediate, continuation
OH
O O CH3
O O CH3

N
N
H
H

O H

N CH3
INTRODUCTION Mechanism
II. Hydrolysis of the cyclic intermediate

O H

O O
H
O
+ O
H H O

N CH3 or -OH
N CH3
INTRODUCTION Mechanism
II. Hydrolysis of the cyclic intermediate, continuation

H
O
O O H
H

O O
H

N CH3 N

H3C O

N-acetylanthranilic acid
 O
O OH
INTRODUCTION O O
O
NH2
O

∆ N CH3
2-methylbenzisoxazinone

HO O

OH H
N O

and
O

N-Acetylanthranilic Acid as A Highly Triboluminescent Material.

John Erikson. J. Chem. Educ. 49, 688 (1972)
INTRODUCTION Formation of
2-methylbenzisoxazinone

a since
formation of six-membered rings are
favorable.
INTRODUCTION Formation of
2-methylbenzisoxazinone

 since it will be
hydrolyzed to form the product
 water is produced in the
reaction
 completely hydrolyzed thru
the addition of water in the
second reflux.
INTRODUCTION Conversion of
2-methylbenzisoxazinone

 provides a scheme
in the hydrolysis of the intermediate
to produce the product

N-Acetylanthranilic Acid as A Highly Triboluminescent Material.

John Erikson. J. Chem. Educ. 49, 688 (1972)
INTRODUCTION Conversion of
2-methylbenzisoxazinone:

 Dissolve mixture in hot mixture of

and
(Assumption: 10g intermediate
is formed) and allow mixture to
stand.
INTRODUCTION Another Side Product: Acylation
of N-acetylanthranilic Acid by
Acetic Anhydride
O OH O OH
O O
H

N CH3 N CH3
O

O O O
INTRODUCTION Mechanism
Alkylation of acetic anhydride to form a N-substituted
anthranilic acid
O O
O OH O OH
H H

O
N CH3 N CH3

O O

O OH
H

N CH3

O O

O O
INTRODUCTION O OH O OH
H H
O

N CH3 N CH3

O O O O

O O

O OH

O
N CH3
+
OH
O O
INTRODUCTION
 The alkylation of acetic
anhydride to the amino substituted
group can also be observed. This
alkylation is not favorable since

compared to
simple alkylation
INTRODUCTION

 :
serves as an

Theoretical
Melting Point:
INTRODUCTION

for
(RCOOH)
Positive Sign:
Evolution of Gas ( ) or
INTRODUCTION

O O

+ NaHCO3 + H2O + CO2(g)

C C
R O Na bubbling
R OH
INTRODUCTION

 for
(esters, amides,
acid halides, acid anhydrides and
nitriles)
Positive Sign:

Complex
INTRODUCTION

O O
H2NOH ROH, FeCl3
C C
R W R NHOH

O
Fe
R C
+ 3HCl
O
N
H 3
magenta complex
INTRODUCTION

1. to synthesize N-acetylanthranilic
acid from anthranilic acid and
acetic anhydride;
INTRODUCTION

2. to characterize the product and

the starting material thru
physico-chemical tests such as
MP determination, NaHCO3 test
and ferric hydroxamic acid test;
and
INTRODUCTION

3. to observe triboluminescene in
N- acetylanthranilic acid.
 Starting material
REAGENTS

O OH

NH2 Other Names: o-amino benzoic acid,

vitamin L1, anthranilite
Appearance: White to light tan crystalline
powder
Molecular Weight 137.14 g mol−1
Molecular Formula C7H7NO2
Melting Point 146–148 °C
Flash Point >150 °C
Density 1.4 g/cm3
 Starting material
REAGENTS

O O

Other Names: ethanoic anhydride,

Ethanoyl ethanoate, Acetic acid anhydride
O
Appearance: clear liquid
Molecular Weight 102.09 g mol−1
Molecular Formula C4H6O3
Melting Point −73.1 °C
Flash Point 49 °C
3
Density 1.082 g/cm , liquid
 Solvent
REAGENTS

O
Other Names: dihydrogen monoxide
H H Appearance: colorless liquid
Molecular Weight 18.02 g mol−1
Molecular Formula H2O
Melting Point 0°C
Boiling Point 100 °C
3
Density 1.00 g/cm , liquid
 Washing Solvent
REAGENTS

H C OH Other Names: carbinol, methyl alcohol,

wood alcohol
Appearance: colorless liquid
H Molecular Weight 32.04 g mol−1
Molecular Formula CH3OH
Melting Point −97°C
Boiling Point 64.7 °C
3
Density 0.7918 g/cm , liquid
 Reagent for NaHCO3 test
REAGENTS

O-
Na+
Other Names: sodium hydrogen
O OH carbonate, baking soda
Appearance: white crystals
Molecular Weight 84.01 g mol−1
Molecular Formula NaHCO3
Melting Point 50 °C
Boiling Point None
3
Density 2.713 g/cm , liquid
 Reagent for Ferric Hydroxamic Acid Test
REAGENTS

H
O
N H Cl-
Other Names: Hydroxylammonium
H chloride
H
Appearance: white crystalline solid
Molecular Weight 69.44 g mol−1
Molecular Formula HONH2·HCl
Melting Point 151- 152 °C (decomp)
Boiling Point None
3
Density 1.67 g/cm , liquid
 Reagent for Ferric Hydroxamic Acid Test
REAGENTS

H H
H C H
O C Other Names: ethyl alcohol , methyl
carbinol, absolute alcohol, drinking alcohol
H H Appearance: colorless liquid
Molecular Weight 46.07 g mol−1
Molecular Formula HONH2·HCl
Melting Point -114.3 °C
Boiling Point 78.4 °C
3
Density 0.789 g/cm , liquid
 Reagent for Ferric Hydroxamic Acid Test
REAGENTS

+ -
Na O H
Other Names: Caustic soda, Lye
Appearance: White opaque crystals
Molecular Weight 39.99 g mol−1
Molecular Formula NaOH
Melting Point 318 °C
Boiling Point 1388 °C
3
Density 2.13 g/cm , liquid
 Reagent for Ferric Hydroxamic Acid Test
REAGENTS

H Cl Other Names: Muriatic Acid, chlorane,

hydrogen chloride, Acidum Muriaticum
Appearance: clear colorless liquid to light
yellow liquid
Molecular Weight 36.46 g mol−1
Molecular Formula HCl
Melting Point -27.32 °C
Boiling Point 110 °C
3
Density 1.18 g/cm , liquid
 Reagent for Ferric Hydroxamic Acid Test
REAGENTS

3+ -
Fe Cl Other Names: Molysite, Iron (III) chloride
Appearance: brown solution/ green black in
color
Molecular Weight 162.2 g mol−1
Molecular Formula FeCl3
Melting Point 306°C
Boiling Point 315 °C
3
Density 2.898 g/cm , liquid
PROCEDURE
O

2g
OH
(reflux set-up)
NH2

O O

10 mL
O

Bring mixture slowly to reflux

temperature and heat for 15
minutes.

A
 A
PROCEDURE Cool Mixture

O
2mL H H

Bring to soft boil and cool slowly.

Suction filtration with washings of
small amount of cold methanol

FILTRATE RESIDUE
traces of unreacted HO O
anthranilic acid, acetic
anhydride; methanol and H
N O
water

determine
melting point
PROCEDURE

 aids the complete

conversion of the product by
supplying energy to the
reaction.
PROCEDURE
PROCEDURE

 with the aid

of a Büchner Funnel; used to
obtain crystals of N-
acetylanthranilic acid.
PROCEDURE

 Melting Point Determination

 NaHCO3 Test
 Ferric Hydroxamic Acid Test
 O O O
O O

OH O OH
O H2O

NH2 N CH3 NH

Synthesis of N-acetylanthranilic acid

O CH3
DISCUSSION
O

O O
OH

NH2 O

2.0 g anthranilic acid

Limiting Reagent
6.0 mL acetic anhydride
Excess Reagent
DISCUSSION
COOH
Acetate ion, a
weak conjugate H
CH3

base is the leaving

N

O
H
group from acetic O CH3

anhydride
O
COOH

H O
+
N
CH3 O CH3
H

O
DISCUSSION
During reflux, the
nucleophile
(anthranilic acid)
attacks the acyl
carbon of acetic
anhydride
O
O O

OH
O

NH2
DISCUSSION

Second reflux,
hydrolyzes the
intermediate,
2-methylbenzisoxanone
O

O
+ O
H H
N CH3 or -OH
DISCUSSION
Percent Yield of N-acetylanthranilic acid

Parameter Mass (in g)

Theoretical Yield 2.61
Experimental Yield 2.148
Percent Yield 82.30 %
DISCUSSION
DISCUSSION
Melting Point Determination of N-acetylanthranilic acid

Parameter Temp (OC)

Theoretical MP 183 - 185
Experimental MP 174 - 180
Percent Error 2.70 - 4.91 %
DISCUSSION
O O

OH ONa
NaHCO3
+ H2O + CO2(g)
NH2 NH2

O O
NaHCO3
No Reaction

HO O Na O O

H H
N O NaHCO3 N O
+ H2O + CO2(g)
DISCUSSION
DISCUSSION
O

OH H2NOH
No Reaction
FeCl3, etOH

NH2

O O O O O
H2NOH FeCl3, etOH
+ + 3HCl
FeCl3, etOH

O OH NHOH NHOH
3 Fe
magenta/burgundy

HO O

H
N O H2NOH
No Reaction
FeCl3, etOH
DISCUSSION
DISCUSSION
DISCUSSION

 Recent theories suggest that the

emission of light is due to the
“highly charged” crystal lattice
or charge separation of the
fractured crystal for electric potential
to exist.

Triboluminescence and the potential of fracture surfaces

Avik Chakravarty and Tacye E Phillipson
J. Phys. D: Appl. Phys. 37 (2004) 2175–2180
DISCUSSION

 This in return, when crystal lattice

returns to its neutral state or charges
recombine, the electric discharge
ionizes the surrounding air,
releasing a blue green sparks.

Triboluminescence and the potential of fracture surfaces

Avik Chakravarty and Tacye E Phillipson
J. Phys. D: Appl. Phys. 37 (2004) 2175–2180
DISCUSSION
DISCUSSION
DISCUSSION

 Other Source of Mechanical

Energy:

Triboluminescene Spectroscopy of Common Candies

Angelos, Zink and Hardy . J. Chem. Educ. 56, 413 (1979)
DISCUSSION

Other ways of synthesizing N-acetylanthranilic acid includes the

conversion of anthranilic acid to sodium anthranilate in a slight
excess of NaOH in water followed by addition of acetic anhydride.
Wiklund and Bergman (2004) that basic salts of anthranilic acid and
its N---substituted derivatives undergo O-alkylation when reacting
with alkylating agents. Excess alkylating agent will cause the N-
alkylation to occur followed by hydrolysis and protonation

Alkylation and acylation of basic salts of anthranilic acid.

Wiklund, Bergman .Tetrahedron Letters 45 (2004) 969 – 972
DISCUSSION Mechanism of N-acetylanthranilic
acid biosynthesis in Aerobacter
aerogenes and Escherichia coli

Aerobacter aerogenes

Escherichia coli

Biochim. Biophys. Acta 230 (1971) 451 - 467

APPLICATIONS

Triboluminescent Materials for Smart Optical

Damage Sensors for Space Applications
M.D. Aggarwal, B.G. Penn, and J. Miller
Marshall Space Flight Center, Marshall Space Flight Center, Alabama
S. Sadate and A.K. Batra
Alabama A&M University, Normal, Alabama
May 2008
APPLICATIONS

Triboluminescence in sodiumchloride
Srinivasan Arjun Tekalur
Michigan State University
Journal of Luminescence 130 (2010) 2201–2206
APPLICATIONS
Newer N-substituted anthranilic
acid derivatives as potent
anti-inflammatory agents
Shalabh Sharma , Virendra Kishor Srivastava, Ashok Kumar

Mefenamic acid and meclofenamates:

N-phenylanthranilic acid derivatives,

Eur. J. Med. Chem. 37 (2002) 689–697

SUMMARY AND
CONCLUSION The synthesis of N-acetylanthranilic
acid from anthranilic acid and acetic
anhydride falls under the nucleophilic
acyl substitution on acetic anhydride and
acylation on anthranilic acid with the aid
of the nitrogen lone pairs together with
acetic acid as a by product. In the
mechanism, anthranilic acid in reaction with
acetic anhydride formed the intermediate,
2-methylbenzisoxanone, which is
hydrolyzed to form the desired product
 From 2.0 g anthranilic acid and 6.0
SUMMARY AND
CONCLUSION
mL acetic anhydride, 2.148 g out of the
2.61 g theoretical yield. Percent Yield for
the synthesis is 82.30%. Side products
include 2-methylbenzisoxanone and the
acylated N-acetylanthranilic acid.
Experimental melting point for the product
obtained from the Fisher Johns Melting
Point Apparatus was from 174 – 180 oC
compared to theoretical melting point of
183 - 185 oC with percent error of 2.70
to 4.91 %.
SUMMARY AND
CONCLUSION

On the characterization tests,

anthranilic acid and the product
showed positive results on NaHCO3
test as shown by bubbling and
acetic anhydride on the ferric
hydroxamic acid test as shown by
the formation of a burgundy complex.
SUMMARY AND
CONCLUSION
Triboluminescene was
observed on N-acetylanthranilic acid
as shown by a blue green light
emission. This particular emission of
light is primarily due to electric
discharge on the crystals of the
product.
 Angelos, Zink and Hardy. 1979. J. Chem. Educ. 56: 413 – 414 .
REFERENCES

Avik Chakravarty and Tacye E Phillipson. 2004. J. Phys. D: Appl.

Phys. 37:2175–2180.

Erikson, John. 1972. J. Chem. Educ. 49: 688.

Shriner, RL, Herman, CF et al. 1998. The Systematic Identification

of Organic Compounds. 7th ed. John Wiley and Sons, Inc.

United Nations Office on Drugs and Crime. 2010. Recommended

methods for the identification and analysis of
methaqualone/mecloqualone. United Nations.

Wiklund, Per and Bergman, Jan. 2004. Tetrahderon. 45: 969 – 972.