Hippuric acid
Encyclopedia
Hippuric acid is a carboxylic acid
found in the urine
of horse
s and other herbivores. Hippuric acid crystallizes in rhombic
prisms which are readily soluble in hot water, melt at 187 °C and decompose at about 240 °C. High concentrations of hippuric acid may also indicate a toluene intoxication
, however, scientists have called this correlation into question because there are other variables that influence levels of hippuric acid. When many aromatic compounds such as benzoic acid
and toluene
are taken internally, they are converted to hippuric acid by reaction with the amino acid
, glycine
.
of glycine
with benzoyl chloride
:
s to benzoic acid
and glycine. Nitrous acid
converts it into benzoyl glycolic acid, C6H5C(=O)OCH2CO2H. Its ethyl ester
reacts with hydrazine
to form hippuryl hydrazine, C6H5CONHCH2CONHNH2, which was used by Theodor Curtius
for the preparation of azoimide.
showed in 1829 that hippuric acid differed from benzoic acid, and in 1839 determined its constitution, while in 1873 Victor Dessaignes synthesized it by the action of benzoyl chloride
on the zinc salt of glycine. It was also formed by heating benzoic anhydride with glycine, and by heating benzamide
with monochloroacetic acid.
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
found in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
of horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s and other herbivores. Hippuric acid crystallizes in rhombic
Rhombus
In Euclidean geometry, a rhombus or rhomb is a convex quadrilateral whose four sides all have the same length. The rhombus is often called a diamond, after the diamonds suit in playing cards, or a lozenge, though the latter sometimes refers specifically to a rhombus with a 45° angle.Every...
prisms which are readily soluble in hot water, melt at 187 °C and decompose at about 240 °C. High concentrations of hippuric acid may also indicate a toluene intoxication
Toluene (toxicology)
-Metabolism in humans:While a significant amount of toluene, 25%-40%, is exhaled unchanged via the lungs, a greater proportion is metabolised and excreted via other pathways. The primary route of toluene metabolism is by hydroxylation to benzyl alcohol by members of the cytochrome P450 superfamily...
, however, scientists have called this correlation into question because there are other variables that influence levels of hippuric acid. When many aromatic compounds such as benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...
and toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
are taken internally, they are converted to hippuric acid by reaction with the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
, glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
.
Synthesis
A modern synthesis of hippuric acid involves the acylationAcylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
of glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
with benzoyl chloride
Benzoyl chloride
Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula C6H5COCl. It is a colourless, fuming liquid with an irritating odour...
:
Reactions
Hippuric acid is readily hydrolysed by hot caustic alkaliAlkali
In chemistry, an alkali is a basic, ionic salt of an alkali metal or alkaline earth metal element. Some authors also define an alkali as a base that dissolves in water. A solution of a soluble base has a pH greater than 7. The adjective alkaline is commonly used in English as a synonym for base,...
s to benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...
and glycine. Nitrous acid
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
converts it into benzoyl glycolic acid, C6H5C(=O)OCH2CO2H. Its ethyl ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
reacts with hydrazine
Hydrazine
Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...
to form hippuryl hydrazine, C6H5CONHCH2CONHNH2, which was used by Theodor Curtius
Theodor Curtius
- External links :* * * *...
for the preparation of azoimide.
History
Justus von LiebigJustus von Liebig
Justus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
showed in 1829 that hippuric acid differed from benzoic acid, and in 1839 determined its constitution, while in 1873 Victor Dessaignes synthesized it by the action of benzoyl chloride
Benzoyl chloride
Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula C6H5COCl. It is a colourless, fuming liquid with an irritating odour...
on the zinc salt of glycine. It was also formed by heating benzoic anhydride with glycine, and by heating benzamide
Benzamide
Benzamide is an off-white solid with the chemical formula of C6H5CONH2. It is a derivative of benzoic acid. It is slightly soluble in water, and soluble in many organic solvents.- External links :* *...
with monochloroacetic acid.