Download 09. Heterofunctional carboxylic acids

LECTURE № 9
THEME: Heterofunctional
carboxylic acids.
associate. prof. Ye. B. Dmukhalska, assistant. I.I. Medvid
Outline
1. Physical and chemical properties of oxoacids.
Acetoacetic ester.
2. Physical and chemical properties of halogenacids
3. Physical and chemical properties of hydroxyacids.
4. Physical and chemical properties of phenolacids.
5. Physical and chemical properties of aminoacids.
6. Chloranhydrides of carbonic acid
a) Physical and chemical properties of a phosgene
7. Amides of carbonic acid
a) Physical and chemical properties of an urea
b) Physical and chemical properties of a guanidine
8. Sulfoacids: aliphatic and aromatic.
9. Aminoacids. Peptides.
1. Oxoacids
To oxoacids include aldehydo- and ketonoacids.
These compounds include in the structure of the
carboxyl group, aldehyde functional group or ketone
functional group.
glyoxylic acid,
oxoethanoic acid
acetoacetic acid,
3-oxobutanoic acid,
β-ketobutyric acid
oxalacetic acid,
oxobutanedioic acid,
ketosuccinic acid
pyroracemic acid,
2-oxopropanoic acid
γ-ketovaleric acid,
4-oxopentanoic acid,
levulinic acid
Methods of extraction of oxoacids:
1.
Oxidation of hydroxyacids:
O
H 2C
CH2
OH
[O]
C
HC
OH
lactic acid
2.
O
O
CH2
C
+ H 2O
OH
pyroracemic acid
Hydrolysis dihalogenocarboxylic acids
2,2-dichlorpropanoic acid
pyroracemic acid (pyruvic acid)
Chemical properties of oxoacids
1.
Decarboxylation of α-oxoacids
O
CH3
C
COOH
O
conc. H2SO4, t
CH3
H
acetaldehyd
pyroracemic acid
2.
C
+
CO2
Decarboxylation of β-oxoacids
O
CH3
C
CH2
COOH
acetoacetic acid
t
- CO2
CH3
C
O
acetone
CH3
Acetoacetic ester
Acetoacetic ester synthesis is a chemical reaction where
ethylacetate is alkylated at the α-carbon to both carbonyl
groups and then converted into a ketone, or more
specifically an α-substituted acetone.
O
2 CH3
C
C2H5O
-
Na +
O
CH3
+
C
CH2
OC2H5
COOC2H5
acetoacetic aster
ethylacetat
Acetoacetic ester is a tautomeric substance. He
characterized keto-enol tautomery.
O
H3C-C-CH2-C
O
O
H3C-C=CH -C
OC2H5
Acetoacetic ester
ketone form
( 92,5% )
OH
OC2H5
Acetoacetic ester
enol form
( 7,5% )
C2H5OH
Chemical properties of acetoacetic ester:
1.
Reactions of ketone form:
2. Reactions to enol form:
a)
interaction of “acetoacetic ester” with metallic
sodium
O
2 H3C-C=CH-C
OH
b)
+
2Na
2 H3C-C=CH -C
OC2H5
ONa
O
+H2
OC2H5
interaction of “acetoacetic ester” with NaOH
O
O
H3C-C=CH-C
OH
+ NaOH
OC2H5
H3C-C=CH -C
ONa
+H2O
OC2H5
Sodiumacetoacet
ic ester
c) interaction “acetoacetic ester” with PCL5
ethyl-3-chlorbutene-2-oate
d) interaction of “acetoacetic ester” with bromine water.
The discoloration of bromine water, that explained unsaturated
of "acetoacetic ester”.
Br
O
H3C-C-CH-C
OH
+
Br 2
O
H3C-C- CH -C
OC2H5
OH Br
-HBr
OC2H5
O
H3C-C-CH -C
O Br
OC2H5
Bromacetoacetic ester
e) interaction of “acetoacetic ester” with FeCl3
O
H3C-C=CH-C
OH
Fe3+
OC2H5
O
H3C-C=CH -C
O-Fe
violet
colour
OC2H5
The characteristic feature of “acetoacetic ester” is
the ability to ketone decomposition and acid
decomposition .
Ketone decomposition occurs when heated in the
presence of the dilute solutions of acids or alkalis.
H2O; t, H+
O
H3C-C-CH2 -C
O
OC2H5
H3C-C-CH3 + C H OH + CO
2 5
2
O
Acid decomposition of “acetoacetic ester”
O
CH3
C
CH2
NaOH (conc.)
COOC2H5
2 CH3COONa
+
C2H5OH
An “acetoacetic ester” used in the organic synthesis for the extraction
of difference ketones and carboxylic acids.
CH3
C
CH2
COOC2H5
C2H5O
-
Na +
C
CH3
CH
COOC2H5
O-
O
Na
CH3
C
CH
COOC2H5
O
CH3
CH3 C CH
sodium acetoacetic ester
COOC2H5
O
methylacetoacetic ester
H+ or OH - (H2O)
ketone decomposition
CH3
C
CH2
CH3
+
C2H5OH
+
CO2
O
butanon
NaOH (conc.)
acid decomposition
CH3COONa
sodium acetate
+
CH3 CH2 COONa
sodium propionate
+
C2H5OH
+
CH3I
- NaI
2. Halogenoacids
Halogenoacids are the derivatives of carboxyl acids
that contain halogen radical (1 or more).
3
H 3C
2
CH
1
O
C
OH
Br
α-bromopropanoic acid
2-bromopropanoic acid
COOH
Cl
o-chlorobenzoic acid
2-chlorobenzoic acid
2-bromo-3-methylbutanoic acid,
α - bromoisovaleric acid
Methods of extraction of halogenocarboxylic acid :
1.
Halogenation of saturated carboxylic acids:
O
H3C
CH2
+ Cl2
C
P
O
H3C
CH
C
OH
+ HCl
OH
Cl
2.
Hydrohalogenation of unsaturated carboxylic acids
O
H2C
CH
O
C
+ HCl
H2C
OH
CH2 C
OH
Cl
β-chloropropanoic acid
acrylic acid
3.
Halogenation of aromatic carboxylic acids:
O
O
C
C
OH
OH
+ Cl2
AlCl3
+ HCl
Cl
m-chlorobenzoic acid
I. Carboxyl group can react with formation of:
a)
Salts
O
H2C
CH2 C
O
+ NaOH
H2C
OH
CH2 C
ONa
Cl
+ H 2O
Cl
chloroacetate sodium
O
2 H2C
CH2 C
O
+ 2 Na
2 H2C
OH
CH2 C
ONa
Cl
+ H2
Cl
Cl
O
H2C
CH2 C
O
O
2 H2C
CH2 C
Mg + H2O
+ MgO
O
OH
Cl
H2C
Cl
O
H2C
CH2 C
OH
Cl
CH2
+ NaHCO3
H2C
C
O
O
CH2 C
ONa
+ H2CO3
Cl
H2O
CO2
b) complex ethers:
O
H2C
CH2 C
+ HO
OH
O
CH3
H2C
CH2 C
O
Cl
Cl
CH3
+ H2O
methyl ether of β-chloropropanoic acid
c) amides:
O
H2C
CH2 C
OH
Cl
+ NH3
t=200o
O
H2C
Cl
CH2 C
NH2
+ H2O
amide β-chloropropanoic acid
II. Halogen radical can react with:
a)
ammonium:
O
H2C
CH2 C
OH
O
+ 2NH3
H2C
CH2 C
O
Cl
+
NH4 + HCl
NH2
ammonium salt of β-aminopropanoic acid
b) NaOH (water solution):
1) for α-halogenoacids
O
H3C
CH
Cl
C
O
+ NaOH
OH
H2O
H3C
CH
OH
C
+ NaCl
OH
lactic acid
2) for β-halogenoacids
O
H2C
CH2
C
OH
Cl
O
H2O
+ NaOH -NaCl H2C
CH
O
H2C
CH
C
OH
OH
OH H
β-chloropropanoic acid
C
to
β-hydroxypropanoic acid
acrylic acid
3) for γ,σ-halogenoacids
O
H2C
CH2
CH2 C
OH
Cl
CH2
CH2
H2O
+ NaOH -NaCl
H2C
C
O
O
γ-butyrolactone
Representatives of halogenocarboxylic acid :
Monochloroacetic acid
Dichloroacetic acid
O
O
CH2
Cl
Trichloroacetic acid
Cl
C
CH
C
OH
Cl
OH
Cl
Cl
C
Cl
O
C
OH
These acids are used in organic synthesis
O
H3C CH
CH3
CH
Br
C
N
H
C
O
NH2
Ureide of α-bromoisovaleric acid (bromisoval) used in medical
practice as a hypnotic.
3. Hydroxyacids
Hydroxyacids are the derivatives of carboxyl acids that
contain –OH group (1 or more).
β
3
H3C
α
2
1
CH
C
O
OH
OH
2-hydroxypropanoic acid
α-hydroxypropanoic acid
glycolic acid,
hydroxyacetic acid,
hydroxyethanoic acid
tartaric acid
lactic acid,
α- hydroxypropanoic acid,
2- hydroxypropanoic acid
α,α’-dihydroxysuccinic acid,
2,3-dihydroxybutandioic acid,
citric acid,
2-hydroxy-1,2,3-propantricarboxylic acid
malic acid,
hydroxysuccinic acid
hydroxybutanedioic acid
In a row of hydroxyacids often found the optical
isomery.
D-, or (R,R)-tartaric
acid
L-, or (S,S)-tartaric
acid
mezo-, or (R,S)-tartaric
acid
Methods of peparetion of hydroxyacids:
1.
Hydrolysis
of α-halogenoacids O
O
H3C
CH
C
H3C
C
CH
+ NaCl
OH
OH
lactic acid
Oxidations of diols and hydroxyaldehydes
H3C
3.
H2O
OH
Cl
2.
+ NaOH
CH
CH2
OH
OH
O
[O]
H3C
[O]
C
CH
H3C
CH
H
OH
C
OH
OH
Hydration of α,β-unsaturated carboxylic acids
O
CH2
CH
C
OH
O
+
+ H2O
H
H2C
OH
4.
O
CH2
C
OH
Hydrolysis of hydroxynitriles (cyanohydrins)
β-hydroxypropanoic acid
Physical and chemical properties of
hydroxycarboxylic acid
For physical properties of hydroxycarboxylic acids are
colorless liquids or crystalline substance, soluble in water.
Chemical properties: in the molecule of hydroxyacids ether –
OH group or carboxyl group can react.
Carboxyl group can react forming:
a) salts:
O
H2C
CH2 C
+ NaOH
OH
O
H2C
CH2 C
ONa
OH
+ H 2O
OH
sodium β-hydroxypropanoic acid
O
2 H2C
CH2 C
+ 2 Na
OH
OH
O
2 H2C
CH2 C
ONa
OH
+ H2
OH
O
H2C
CH2 C
O
O
2 H2C
CH2 C
Mg + H2O
+ MgO
O
OH
OH
H2C
CH2
C
O
OH
O
H2C
O
CH2 C
OH
+ NaHCO3
H2C
CH2 C
ONa
OH
+ H2CO3
OH
H2O
CO2
b) complex ethers:
O
H2C
CH2 C
+ HO
OH
OH
CH3
O
H2C
CH2 C
O
OH
CH3
+ H2O
methyl ether of β-hydroxypropanoic acid
c) amides:
O
H2C
CH2 C
OH
+ NH3
t=200o
O
H2C
OH
CH2 C
NH2
OH
+ H2O
amide of β-hydroxypropanoic acid
II. –OH group can react with:
a) hydrohalogens (HCl, HBr, HI, HF)
O
H2C
CH2
C
+ HCl
O
H2C
OH
OH
CH2 C
OH
+ H2O
Cl
b) can oxidize
O
H 2C
OH
CH2
[O]
C
O
HC
OH
O
CH2
C
+ H 2O
OH
β-oxopropanoic acid
Related to heat of:
1. α-hydroxyacids
lactic acid
lactide
2. β-hydroxyacids
heating
3-hydroxybutanoic
acid
butene-2-onic (crotonic)
acid
3. γ-hydroxyacids
heating
4-hydroxybutanic
acid
γ-butyrolacton
Decomposition of α-hydroxyacids
O H O
СH3 С
C
H
O
к.H2SO4
O
CH3 C
t
+
H
OH
OH
acetic acid
к. Н2SO4, t
HCOOH
OH
HOOCH2 C
С
H C
С H2 COOH
formic acid
CO + H 2O
к. H2SO4
t
COOH
CO
H C
O
OH
H2O
O
+
HOOCH2 C C CH2 COOH
acetidicarbonic acid
2 CO2
H3 C C CH3
O
Phenolacids.
Phenolacids are the derivatives of aromatic carboxyl acids that
contain –OH group (1 or more).
o-hydroxycinnamic acid
salicylic acid,
2-hydroxybenzoic acid
4-hydroxybenzoic acid
3,4,5-trihydroxybenzoic acid,
gallic acid
Methods of phenolacids extraction:
1.
Carboxylation of phenols by carbon oxide (IV):
In the Kolbe synthesis, also known as the Kolbe–Schmitt reaction,
sodium phenoxide is heated with carbon dioxide under pressure, and
the reaction mixture is subsequently acidified to yield salicylic acid:
2. Hydroxylation of arenecarboxylic acids
O
C
O
O-Na+
Cu(OH)2
- NaOH
C
t
O
Cu
OH
COOH
- Cu
OH
3. Alloying of sulphobenzoic acid with alkalis
COO- K +
COOH
+ 3 KOH
SO3H
m-sulphobenzoic acid
alloying
+
K2SO3
+ 2 H2O
OH
potassium salt of
3-hydroxybenzoic acid
Chemical properties of phenoloacids:
Chemical properties of phenoloacids due to the presence
in their structure of carboxyl group, phenolic hydroxyl and the
aromatic nucleus.
COOH
COONa
+ NaHCO3
OH
+ CO2
+ H2O
OH
salicylic acid
COOH
+ FeCl3
OH
COO
O..
H
complex helatic salt of
salicylic acid
(violet colour)
Decarboxylation
COOH
OH
salicylic acid
t
Fe + 3HCl
3
+
OH
phenol
CO2
COOH
+
OH
Br
2 Br 2
6
1
5
4
3
COOH
+ 2 HBr
OH
2
Br
3, 5-dibromsalicylic acid
white precipitate
COOH
+ Br2
OH
Br
Br
Br
+ HBr + CO2
OH
Br
Br
yellow precipitate
COOH
O
O
C
acetylsalicylic acid
HOH
CH3
t
COOH
+ CH3COOH
OH
salicylic acid
OH
C
COONa POCl 3, C 6H 5ONa
NaHCO 3
O
OH
OC 6H 5
-CO 2, -H 2O
-NaCl, -NaPO 3
Phenylsalicylate, salol
Sodium salicylate
O
OH
COOH
O
(CH 3CO) 2O
C
NH 2
CH 3
COOH
-C 6H 5OH
- CH 3COOH
Salicylic acid
Acetylsalicylic acid,
aspirin
CH 3OH
-H 2O
OH
(H 2SO 4)
OH
OH
COOCH 3
Methylsalicylate
O
OH
C
NH 3
O
C
NH 2
NH
Salicylamide
Oxaphenamide
OH
The best known aryl ester is O-acetylsalicylic acid, better
known as aspirin. It is prepared by acetylation of the phenolic
hydroxyl group of salicylic acid:
5. Aminoacids

An aminoacid is an organic compound that
contains both a amino (–NН2) group and a
carboxyl (-СООН) group. The amino acids
found in proteins are always α-amino acids.
Methods of aminoacids extraction:
1. Effects of ammonia on halogencarboxylic acids :
CH3 CH COOH +
NH4Cl
+ 2 NH3
CH3 CH COOH
NH2
Cl
α-chlorpropanoic acid
2.
α-aminopropanoic acid
Effects of ammonia and HCN on aldehydes
CH3
O
NH3
H
- H2O
C
acetalaldehyde
NH
CH3
CH
CH3
H
aldimine
NH2
CH3
C
COOH
α-aminopropanoic acid
NH2
HCN
CH
+
2 H2O; H
C
N
α-aminopropanonitrile
- NH3
3. Accession of ammonia to the α, β–unsatured acids
CH2
CH
+
COOH
CH2
: NH3
acrylic acid
CH2
COOH
NH2
β-aminopropanoic acid
4. Reduce of nitrobenzoic acid
COOH
COOH
[H]
- H2O
NO2
n-nitrobenzoic acid
NH2
n-aminobenzoic acid
Optical properties
Physical and chemical properties of aminoacids
Both an acidic group (-СООН) and а basic group (-NН2) are
present on the same carbon in an α-amino acid.
The net result is that in neutral solution, amino acid molecules
have the structure:
А zwitter-ion is а molecule that has а positive charge on one
atom and а negative charge on another atom.
Reactions on amino-group:
HCl
R
CH
COOH
+ NH Cl 3
chlorhydrolic salt
RI
R
CH
COOH
- HI
NH2
RCOCl
R
CH
COOH
NHR
N-alkilderivate
R
CH
- HCl
COOH
NHCOR
N-acylderivate
HNO2
-N2, - H2O
R
CH
COOH
OH
hydroxyacid
Reactions on carboxylic group:
NaOH
R CH COONa
- H2O
NH2
sodium salt
ROH, H +
R CH
COOH
- H2O
NH2
RNH2
- H2O
R CH
COOR
NH2
ester
R CH
CONHR
NH2
amide
PCl5
- POCl3, - HCl
R CH
COCl
NH2
chloranhydrid
Heating of:
1.
α-aminoacids
H
O
t
2 CH3
CH
NH2
CH3
α-aminopropanoic acid
CH3
CH
C
COOH
CH
N
+
C
2 H2O
O
N
H
3,6-dimethyl-2,5-diketopiperazine
2.
β-aminoacids
t
CH3
CH
CH2 COOH
CH3
CH
CH
NH2
β-aminooil acid
crotonic acid
COOH
+
NH3
3. γ-aminoacids
t
CH2
CH2
CH2 COOH
NH2
γ-aminooil acid
N
O
+
H
γ-lactam
H2O
React α-aminoacids with ninhydrin
O
O
OH
+
+ H3N-CH-COOOH
R
N-CH-COOH+H2O
R
O
O
Ninhydrin
O
O
O
H
O
N-CH-C
R
H
H2O
O
N=C-C
OH
O
O
NH2
OH
R
O
2-aminoindandion
O
O
OH
O
H
H
N
+
OH H2N
O
O
O
O
O
O
N
O
O
H+
O
Вlue - violet dye-stuff
Functional derivates of carbonic acid.
Cl
C
Cl
OH
C
HO
Cl
C
OC2H5
O
O
dichoranhydride carbonic acid , monoethyl ester of
phosgene
carbonic acid,
O
monochoranhydride carbonic acid ,
chlorcarbonic acid
monoethyl carbonate
C2H5O
C
OC2H5
O
diethyl ester of
carbonic acid,
diethyl carbonate
Cl
C
HO
C
NH2
H2N
O
monoamide carbonic acid,
carbamic acid
OC2H5
O
ethyl ester of
chlorcarbonic acid
C2H5O
C
NH2
O
diamide carbonic acid,
carbamide,
urea
NH2
O
ethyl ester of
carbamic acid,
urethane
C
6. Chloranhydrides of carbonic acid
Cl
C
Cl
OH
O
monochoranhydride carbonic acid ,
chlorcarbonic acid
C
Cl
O
dichoranhydride carbonic acid ,
phosgene
Produces phosgene by interaction of carbon oxide (II)
with chlorine on the light.
CO
+
hv
Cl2
Cl
C
Cl
O
dichoranhydride carbonic acid ,
phosgene
7. Amides of carbonic acid
HO
H2N
NH2
C
NH2
C
O
diamide carbonic acid,
carbamide,
urea
O
monoamide carbonic acid,
carbamic acid
Esters of carbamic acid are named urethanes
Cl
C
OCH3
+
NH3
C
OC2H5
O
diethyl ester of
carbonic acid,
diethyl carbonate
C
OCH3
+
HCl
O
methyl ester of
carbamic acid
O
methyl ester of
chlorcarbonic acid
C2H5O
H2N
+
NH3
C2H5O
C
NH2
O
ethyl ester of
carbamic acid,
urethane
+
C2H5OH
Meprothan used in a medicine as a medicament,
which has tranquilization and hypnotic effects.
CH3
H2N
C
O
O
CH2
C
O
CH2
CH2 CH2
O
C
NH2
CH3
meprothan (meprobamate),
dicarbamate 2-methyl-2-propylpropandiol-1,3
Urea or carbamide is an organic compound with the chemical
formula (NH2)2CO. The molecule has two amine (-NH2)
residues joined by a carbonyl (-CO-) functional group. Urea
was first discovered from urine in 1773 by the French chemist
Hilaire Rouelle.
In 1828, the German chemist Friedrich Wöhler obtained urea
by treating of silver isocyanate with ammonium chloride in a
failed attempt to prepare ammonium cyanate:
AgNCO + NH4Cl → (NH2)2CO + AgCl
In the industry urea produces by interaction of an
ammonia with carbon oxide (IV)
2 NH3
+
CO2
p, t
H2N
C
NH2
O
diamide carbonic acid,
carbamide,
urea
+
H2O
Physical and chemical properties of urea
The urea molecule is planar. Each carbonyl oxygen atom accepts four N-H-O hydrogen
bonds. This dense and energetically favourable hydrogen-bond network is probably
established at the cost of efficient molecular packing. The structure is quite open, the
ribbons forming tunnels with square cross-section. The carbon in urea is described as
sp² hybridized, the C-N bonds have significant double bond character, and the carbonyl
oxygen is basic compared to formaldehyde. Its high solubility is due to extensive
hydrogen bonding with water: up to eight hydrogen bonds may form - two from the
oxygen atom, one from each hydrogen atom and one from each nitrogen atom.
1. Interaction of an urea with strong acids
+
H2N
NH2
C
+
HNO3
H2N
C
NH2
O
OH
urea
nitrate urea
NO3
-
2. Hydrolysis of an urea during the heating
H2N
C
O
urea
NH2
+
+
H or OH
H2O
CO2
+ 2 NH3
3. Interaction of an urea with halogen alkanes (alkylation)
H2N
C
NH2
+
C2H5I
C2H5
NH
C
NH2
+
HI
O
O
ethylurea
urea
4. Interaction of an urea with halogen anhydrides of
carboxylic acids (acylation)
O
H2N
C
O
urea
NH2
+
CH3
C
CH3
Cl
C
O
NH
C
O
acetylurea
NH2
+
HCl
Dicarboxylic acids can form with an urea
cycle ureides. For example,
barbituric acid or malonylurea or 6hydroxyuracil is an organic compound
based on a pyrimidine heterocyclic
skeleton. It is an odorless powder soluble
in hot water. Barbituric acid is the parent
compound of barbiturate medicine,
although barbituric acid itself is not
pharmacologically active.
5. Interaction of an urea with HNO2
H2N
C
NH2
+
2 HNO2
CO2
+ 2 N2
+ 3 H2O
O
urea
6. Interaction of an urea with water solution of
hypobromides. This reaction as the previous can be used to
quantitative determination of an urea.
H2N
C
O
urea
NH2
+
3 NaOBr
CO2
+
N2
+ 2 H2O + 3 NaBr
5. Biuret reaction. Used for qualitative determination of an urea
and proteins, as containing in its structure of a group–СO-NH-.
By-product of a biuret reaction is the isocyanuric acid, which
forms as a result of trimerazation of cyanuric acid.
H2N
O C
H2N
H2N
+
H
NH2
C O
+
+
C
N
NH2
3NH3
NH2
O C
C O
H N
N H
+
C
O
O
isocyanuric acid
N
HO C
C OH
N
N
C
OH
cyanuric acid
Physical and chemical properties of a guanidine
H2N
NH2
C
NH
guanidine
1. Interaction a guanidine with acids
+
H2N
C
NH2
+
HCl
H2N
NH
C
NH2
Cl
NH2
guanidine
guanidinium chloride
2. Interaction a guanidine with bifunctional compounds
(diesters, diketones)
O
H2N
C
NH
guanidine
NH2
C2H5O
+
H2SO4; POCl3; H2
C
CH2
C2H5O
N
H2N
N
C
O
2-aminopyrimidine
The remain of guanidine is the structural components of
many compounds. For example:
Arginine plays an important
role in cell division, the healing of
wounds, removing ammonia from the
body, immune function, and the release
of hormones.
Guanine is one of the five main nucleobases
found in the nucleic acids DNA and RNA.
Sulfoacids called the derivatives of organic
compounds in which an atom of hydrogen
replaced by the residue of sulfuric acid –
sulfogroup – SO3H.
Aliphatic sulfoacids
СH3-SO2OH
СH3-СH2-SO2OH
methanesulfonic acid
ethanesulfonic acid
(methanesulfoacid)
(ethanesulfoacid)
Functional derivatives of sulfoacids
CH3-SO2Cl - choranhydride of methanesulfoacid (methane
sulfonylchloride)
CH3-SO2ONa – sodium salt of methanesulfoacid
(methanesulfate sodium)
CH3-SO2NH2 – amide of methanesulfoacid
(methanesulfonamide)
CH3-SO2-OC2H5 – ethyl ester of methanesulfoacid
(ethylmetanesulfonate)
1.
Extraction of aliphatic sulfoacids :
Sulfochlorination:
CH3
CH3
+
SO2
+
hv
Cl2
CH3
CH2 SO2Cl
+
HCl
ethanesulfonylchloride
Sulfooxidation:
2R-H + 2SO2 + O2 = 2R-SO2OH
alkanesulfonic acid
3. Oxidation of thiols:
2.
C2H5
SH
ethanethiol
KMnO4 or HNO3
SO2 +
ethanesulfoacid
C2H5
H2O
4. Sulfonation of alkanes by conc. H2SO4 :
CH3
H3C
CH
+
SO3
H2SO4
CH3
H3C
SO2OH
C
CH3
CH3
2-methyl-2-propanesulfoacid
isobutane
5. Accession of hydrosulfites to alkenes:
R OOR
R
CH
CH2
+
NaHSO3
R CH2
CH2 SO2ONa
alkanesulfonate sodium
Chemical properties of aliphatic sulfoacids
1. Formation salts of sulfoacids:
C2H5-SO2-OH + NaOH = C2H5-SO2-ONa + H2O
2 C2H5-SO2-OH + 2 Na = 2 C2H5-SO2-ONa + H2
C2H5
2 C2H5
SO2OH
+
Ca
C2H5
SO2
SO2
O
Ca
O
+
2. Formation of sulfonylchlorides
R-SO2-OH + PCl5 = R-SO2Cl + POCl3 + HCl
3. Formation of sulfonamides
R-SO2-Cl + 2 NH3 = R-SO2-NH2 + NH4Cl
4. Formation esters of sulfoacids
R-SO2-Cl + 2 NaO-R′ = R-SO2-O-R′ + NaCl
H2
Aromatic sulfoacids
SO3H
SO3H
CH3
benzol sulfoacid
SO3H
H3OS
p-toluol sulfoacid
SO3H
SO3H
1,3,5-benzoltrisulfoacid
SO3H
m-benzoldisulfoacid
Extraction of aromaric sulfoacids:
1. Sulfonation of aromatic ring
SO3H
+ H2SO4
+ H2O
OH
OH
OH
H2SO4
H2SO4
t=-20
t=+100
HO3S
SO3H
p-hydroxybenzylsulphoacid
o-hydroxybenzylsulphoacid
CH3
CH3
CH3
SO2OH
25 C
2
+ 2 H2SO4
+
SO2OH
p-toluol sulfoacid 65%
+
2 H2O
p-toluol sulfoacid 32%
SO3H
SO3H
210 C
+
SO3
H2SO4
SO3H
SO3, 275C
Hg
SO3H
SO3H
SO3H
Chemical properties of aromatic sulfoacids
I.
Reactions of the sulfogroup:
a) formation salts of sulfoacids:
C6H5SO2OH + NaOH = C6H5SO2Na + H2O
b) formation of sulfonylchlorides:
C6H5SO2OH + PCl5 = C6H5-SO2-Cl + POCl3 + HCl
C6H5 + 2 HO-SO2Cl = C6H5-SO2Cl + H2SO4 + HCl
c) formation of sulfonamides:
C6H5SO2Cl + 2 NH3 = C6H5-SO2-NH2 + NH4Cl
d) formation esters:
C6H5SO2Cl + HO-C2H5 = C6H5-SO2-O-C2H5 + HCl
e) reduced of the sulfogroup:
6H
C6H5
SO2OH
Zn + H2SO4
C6H5
SH
+
3 H2O
f) synthesis of saccharin
CH3
CH3
+
2
HOSO2Cl
CH3
+ 2 NH3
- NH4Cl
SO2Cl
O
SO2Cl
CH3
KMnO4
SO2NH2
COOH
SO2NH2
o-toluolsulfonamide of
benzoic acid
o-toluolsulfonamide
O
+ NaOH, H2O
C
N
SO2
saccharin
Na * 2 H20
C
t
- H2O
N H
SO2
o-toluolsulfonimide of
benzoic acid
II. Reactions of SE, SN of sulfo-group:
a) desulfonation
C6H5 SO2OH
+
t
H2O
C6H6
HCl
+
H2SO4
b) a reaction of alkali floating
C6H5 SO2OH
+
C6H5 SO2ONa +2 NaOH
C6H5 ONa
+
C6H5SO2ONa
NaOH
H2CO4
C6H5 SO2ONa + NaCN
t
H+
t, Sn
C6H5ONa
C6H5OH
C6H5CN
+
+
H2O
Na2SO4
+
NaHCO3
+
Na2SO3
+
H2O
Sulphanylamidic preparations. All sulphanylamidic
medicines contain the next fragment:
O
O
O2S
N
H
NH2
NH2
NH2
O2S
C
CH3
Albucyde
Альбуцил,
сульфацил
(sulphacyl)
N
H
NH2
O
N
O2S
C
NH2
Urosulphane
Уросульфан
N
H
S
Норсульфазол
Norsulphazol
O2S
N
H
C
N
H
C4H9
Bucarbane
Букарбан
Albucyde (sulphacyl) – is an antibacterial mean, is a part of eyedrops.
Urosulphane – is an antibacterial mean by infection of urinal
canals.
Norsulphazol – is used by pneumonia, meningitis,
staphylococcal and streptococcal sepsis, infectious diseases.
Bucarbane – is a hypoglycemic mean.
According to the chemical origin of the residue
connected with α-aminoacid fragment –
CH(NH2)COOH, α-aminoacids divided on aliphatic,
aromatic and heterocyclic.
In heterocyclic α-aminoacids proline and oxyproline αaminoacid’s fragment presents in hetecyclic structure.
According to the quantity of –NH2 and –COOH groups in
molecule α-aminoacids divided on monoaminocarbonic,
monoaminodicarbonic and diaminomonocarbonic.
5). Chemical properties of α-aminoacids
A.
Reaction on amino-group
1) Formation of N-acylderivatives. This reaction use for blocking
(protection) of aminogroup at the synthesis of peptides. As
acylation agents use benzoxycarbonylchloride (a) or tretbutoxycarboxazide (b)
Blocked carbobenzoxygroup removed by catalytic hydrogenolysis or by
action of HBr in acetic acid in cold.
Tret-butoxycarbonyl group destroyed by action of
triftoracetic acid:
2) Deamination:
a)
oxidation deamination – important pathway for the
biodegradation of α-aminoacids:
b)
hydrolytic deamination – reaction with nitrous acid.
Aminoacids react with nitrous acid to give hydroxyacid
along with the evolution of nitrogen.
The nitrogen can be collected and measured. Thus
this reaction constitutes one of the methods for the
estimation of amino acids.
c) intramolecular deamination - unsaturated acids
are formed:
d) redaction deamination – saturated carboxylic
acid formation:
3) Tranceamination. Reaction goes under the
present of enzymes tranceaminases and
coenzyme pyridoxalphosphate:
4) Interaction with carbonyl compounds:
5) Reaction with phenylisothiocyanate (Edmane
reaction). Form derivatives of 3-phenyl-2thiohydantoine (derivatives of
phenylthiohydantoine):
6) Interaction with 2,4-dinitroftorbenzol (Senher’s
reagent):
B. Reaction on carboxyl group
1) Formation of helate compounds ( complex
salts with ions of heard metals)
2) Reaction with alcohols – difficult esters formation:
3) Reaction with ammonia – amides formation. The amides of
aspartic and glutamic acid acids, asparagine and glutamine, play
important role in the transport of ammonia in the body.
4) Formation of halogenanhydrides and anhydrides ( like
carbonyl acids). Before these reaction blocked
aminogroup by formation of N-acylderivatives.
5) Decarboxylation. Aminoacids may be decarboxylated by heat, acids, bases or
specific enzymes to the primary amines:
Some of the decarboxylation reaction are of great importance in the body,
decarboxylation of histidine to histamine:
In the presence of foreign protein introduced into the body, very large
quantities of histamine are produced in the body and allergic reactions
become evident. In extreme cases shock may result. The physiological
effects of histamine may be neutralized or minimized by the use of
chemical compounds known as antihistamines.
C. Formation of salts. All aminoacids can react
with some inorganic acids and bases and
form two kind of sold:
D. Peptide formation. Two aminoacids can react in а
similar way - the carboxyl group of one aminoacid
reacts with the amino group of the other aminoacid.
In aminoacid chemistry, amide bonds that link
aminoacids together are given the specific name of peptide
bond. А peptide bond is а bond between the carboxyl
group of one aminoacid and the amino group of another
aminoacid. Under proper conditions, many aminoacids can
bond together to give chains of aminoacids containing
numerous peptide bonds. For example, four peptide bonds
are present in а chain of five aminoacids.
The structural formula for а polypeptide may be written
out in full, or the sequence of aminoacids present may be
indicated by using the standard three-letter aminoacid
abbreviations. The abbreviated formula for the tripeptide:
which contains the aminoacids glycine,
alanine, and serine, is Gly – Ala – Ser. When
we use this abbreviated notation, by
convention, the aminoacid at the N-terminal
end of the peptide is always written on the left.
The repeating chain of peptide bonds and α-carbon atoms
in а peptide is referred to as the backbone of the peptide. The
R group side chains are substituents on the backbone. Peptides
that contain the same aminoacids but in different order are
different molecules (structural isomers) with different
properties. For example, two different dipeptides can be
formed from one molecule of alanine and one molecule of
glycine.
In the first dipeptide, the alanine is the N-terminal residue,
and in the second molecule, it is the С-terminal residue. These
two compounds are isomers with different chemical and
physical properties.
Two important hormones produced by the pituitary gland are
oxytocin and vasopressin, Each hormone is а nonapeptide (nine
amino acid residues) with six of the residues hells in the form of а
loop by а disulfide bond formed from the interaction of two
cysteine residues.
Oxytocin regulates uterine contractions and lactation. Vasopressin
regulates the excretion of water by the kidneys; it also affects blood pressure.
The structure of vasopressin differs from that of oxytocin at only two
aminoacid positions: the third and eighth aminoacid residues. The result of
these variations is а significant difference in physiological action.
Xanthoprotein test. On treatment with concentrated nitric acid,
certain proteins give yellow color. This yellow color is the same that
is formed on the skin when the latter comes in contact with the
concentrated nitric acid. The test is given only by the proteins
having at least one mole of aromatic aminoacid, such as tryptophan,
phenylalanine, and tyrosine which are actually nitrated during
treatment with concentrated nitric acid. When you add after conc.
HNO3 conc. NaOH forms light orange color (hynoid structure).
The primary structure of а protein is the sequence of aminoacids present in its
peptide chain or chains. Knowledge of primary structure tells us which
aminoacids are present, the number of each, their sequence, and the length and
number of polypeptide chains.
The first protein whose primary structure was determined was insulin, the
hormone that regulates blood-glucose level; а deficiency of insulin leads to
diabetes. The sequencing of insulin, which took over 8 years, was completed
in 1953. Today, thousands of proteins have been sequenced; that is,
researchers have determined the order of amino acids within the polypeptide
chain or chains.
The secondary structure of а protein is the arrangement in
space of the atoms in the backbone of the protein. Three major
types of protein secondary structure are known; the alpha
helix, the beta pleated sheet, and the triple helix. The major
force responsible for all three types of secondary structure is
hydrogen bonding between а carbonyl oxygen atom of а
peptide linkage and the hydrogen atom of an amino group (NH) of another peptide linkage farther along the backbone.
This hydrogen-bonding interaction may be diagrammed as
follows:
The Alpha Helix The alpha helix (α-helix) structure resembles а
coiled helical spring, with the coil configuration maintained by hydrogen
bonds between N – Н and С= О groups of every fourth aminoacid, as is
shown diagrammatically in Figure.2.
Figure. Three representations of (а) the а helix protein structure.
Hydrogen bonds between amide groups (peptide linkages) are shown in (b)
and (с). (d) The top view of an а helix shows that amino acid side chains (R
groups) point away from the long axis of the helix.
Figure. Two representations of the p pleated sheet protein structure. (а) А
representation emphasizing the hydrogen bonds between protein chains. (b) А
representation emphasizing the pleats and the location of the R groups.
Proteins have varying amounts of α-helical secondary structure, ranging from
а few percent to nearly 100 %. In an α-helix, all of the aminoacid side chains
(R groups) lie outside the helix; there is not enough room for them in the
interior. Figure.3d illustrates this situation. This structural feature of the αhelix is the basis for protein tertiary structure.
Collagen, the structural protein of
connective tissue (cartilage, tendon, and skin),
has а triple-helix structure. Collagen molecules
are very long, thin, and rigid. Many such
molecules, lined up alongside each other,
combine to make collagen fibers. Crosslinking gives the fibers extra strength.
Figure. Four types of interactions between aminoacid R
groups produce thetertiary structure of а protein. (а) Disulfide
bonds. (b) Electrostatic interactions (salt bridges). (с) Hydrogen
bonds. (d) Hydrophobic interactions. Electrostatic interactions,
also called salt bridges, always involve aminoacids with charged
side chains. These aminoacids are the acidic and basic
aminoacids. The two R groups, one acidic and one basic, interact
through ion — ion attractions. Figure.b shows an electrostatic
interaction.
Table. 1 Some common fibrous and globular proteins
Table.2. Types of conjugated proteins
Thank you for attention!