Barbituric acid or malonylurea or 6-hydroxyuracil is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

based on a

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of

barbiturate Barbiturates are a class of depressant, depressant drugs that are chemically derived from barbituric acid. They are effective when used medication, medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological a ...

drugs, although barbituric acid itself is not pharmacologically active. The compound was first synthesised by

Adolf von Baeyer Johann Friedrich Wilhelm Adolf von Baeyer (; 31 October 1835 – 20 August 1917) was a German chemist who synthesised indigo dye, indigo and developed a Von Baeyer nomenclature, nomenclature for cyclic compounds (that was subsequently extended a ...

Naming

It remains unclear why Baeyer chose to name the compound that he discovered "barbituric acid". In his textbook ''Organic Chemistry'', the American organic chemist Louis Frederick Fieser (1899–1977) initially speculated that the name stemmed from the German word ''Schlüsselbart'' (literally, the beard (''Bart'', Latin: ''barba'') of a key (''Schlüssel''), that is, the

bit The bit is the most basic unit of information in computing and digital communication. The name is a portmanteau of binary digit. The bit represents a logical state with one of two possible values. These values are most commonly represented as ...

of a key), because Baeyer had regarded barbituric acid as central (or "key") to understanding

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the Chemical formula, formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the meta ...

and its derivatives. However, Fieser subsequently decided that Baeyer had named the compound after a young lady whom he had met and who was called "Barbara"' hence the name "barbituric acid" was a combination of the name "Barbara" and "uric acid". Other sources claim that Baeyer named the compound after

Saint Barbara Saint Barbara (; ; ; ), known in the Eastern Orthodox Church as the Great Martyr Barbara, was an Early Christianity, early Christian Greek saint and martyr. There is no reference to her in the authentic early Christian writings nor in the origin ...

, either because he discovered it on the feast day of St. Barbara (December 4) or because he sometimes lunched with artillery officers and St. Barbara is their patron saint.

Synthesis

Barbituric acid was first prepared and named in 1864 by the German chemist

, by reducing what Baeyer called ''Alloxanbromid'' (

alloxan Alloxan, sometimes referred to as alloxan monohydrate, is an organic compound with the formula . It is classified as a derivative of pyrimidine. The anhydrous derivative is also known, as well as a dimeric derivative. These are some of the earlie ...

dibromide, now: 5,5-dibromobarbituric acid) with hydrocyanic acid, and later by reducing dibromobarbituric acid with a combination of

sodium amalgam Sodium amalgam, with the common formula Na(Hg), is an alloy of mercury and sodium. The term amalgam is used for alloys, intermetallic compounds, and solutions (both solid solutions and liquid solutions) involving mercury as a major component. ...

and

hydrogen iodide Hydrogen iodide (HI) is a diatomic molecule and hydrogen halide. Aqueous solutions of HI are known as hydroiodic acid or hydriodic acid, a strong acid. Hydrogen iodide and hydroiodic acid are, however, different in that the former is a gas und ...

. In 1879, the French chemist Édouard Grimaux synthesized barbituric acid from malonic acid,

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

, and

phosphorus oxychloride Phosphoryl chloride (commonly called phosphorus oxychloride) is a colourless liquid with the formula . It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from phos ...

(POCl₃). Malonic acid has since been replaced by diethyl malonate, because using the ester avoids the problem of having to deal with the acidity of the

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

and its unreactive

carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an anion, an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,... ...

. :

Properties

The α-carbon has a reactive hydrogen atom and is quite acidic (pKa = 4.01) even for a diketone species (cf. dimedone with pKa 5.23 and

acetylacetone Acetylacetone is an organic compound with the chemical formula . It is classified as a 1,3-diketone. It exists in equilibrium with a tautomer . The mixture is a colorless liquid. These tautomers interconvert so rapidly under most conditions that ...

with pKa 8.95) because of the additional aromatic stabilization of the carbanion. :

Uses

Using the

Knoevenagel condensation In organic chemistry, the Knoevenagel condensation () reaction is a type of chemical reaction named after German chemist Emil Knoevenagel. It is a modification of the aldol condensation. A Knoevenagel condensation is a nucleophilic addition o ...

reaction, barbituric acid can form a large variety of

drugs that behave as central nervous system depressants. As of 2007, more than 2550 barbiturates and related compounds have been synthesised, with 50 to 55 in clinical use around the world at present. The first to be used in medicine was barbital (Veronal) starting in 1903, and the second,

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...

was first marketed in 1912. Barbituric acid is a chemical building block in the laboratory synthesis of

riboflavin Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in ...

(vitamin B₂) and in a method of producing the pharmaceutical drug

minoxidil Minoxidil is a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive and a vasodilator. It is available as a generic medication by prescription in oral administration, oral tablet (pharmacy), ...

. It is one of the four ingredients in the synthesis of riboflavin. Before barbituric acid was substituted in the synthesis of riboflavin, it was too expensive to synthesize riboflavin.

Health and safety

Overdose of barbiturate drugs can cause respiratory depression and death. Barbiturates are dependence-producing, and abrupt cessation of high doses can result in a very medically serious, even lethal, withdrawal syndrome. Barbituric acid derivatives are considered DEA Schedule III controlled substances.Title 21, Subchapter I, Part B §812. Schedules of controlled substances https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm

References

External links

* {{Authority control Barbiturates Pyrimidines 1864 in science Substances discovered in the 19th century