Barbituric acid or malonylurea or 6-hydroxyuracil is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...

based on a pyrimidine

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 chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of barbiturate 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 and developed a nomenclature for cyclic compounds (that was subsequently extended and adopted as part of the IUPAC org ...

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 communications. 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 represente ...

of a key), because Baeyer had regarded barbituric acid as central (or "key") to understanding uric acid 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 ( grc, Ἁγία Βαρβάρα; cop, Ϯⲁⲅⲓⲁ Ⲃⲁⲣⲃⲁⲣⲁ; ; ), known in the Eastern Orthodox Church as the Great Martyr Barbara, was an early Christian Lebanese and Greek saint and martyr. Accounts place her in t ...

, 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 hydrate'', is the name of the organic compound with the formula OC(N(H)CO)2C(OH)2. It is classified as a derivative of pyrimidine. The anhydrous derivative OC(N(H)CO)2CO is also known, as well as a di ...

dibromide, now: 5,5-dibromobarbituric acid) with

hydrocyanic acid Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on an in ...

, and later by reducing dibromobarbituric acid with a combination of

sodium amalgam Sodium amalgam, commonly denoted 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. Sodium am ...

and hydrogen iodide. In 1879, the French chemist Édouard Grimaux synthesized barbituric acid from

malonic acid Malonic acid (IUPAC systematic name: propanedioic acid) is a dicarboxylic acid with structure CH2(COOH)2. The ionized form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic acid' ...

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...

, 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 pho ...

(POCl₃). Malonic acid has since been replaced by

diethyl malonate Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds su ...

, because using the ester avoids the problem of having to deal with the acidity of the carboxylic acid and its unreactive

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

. :

Properties

The α-carbon has a reactive hydrogen atom and is quite acidic (pKa = 4.01) even for a

diketone In organic chemistry, a dicarbonyl is a molecule containing two carbonyl () groups. Although this term could refer to any organic compound containing two carbonyl groups, it is used more specifically to describe molecules in which both carbonyls ...

species (cf.

dimedone Dimedone is a cyclic diketone used in organic chemistry to determine whether a compound contains an aldehyde group. Cyclohexanediones in general can be used as catalysts in the formation of transition-metal complexes. Other uses include applicatio ...

with pKa 5.23 and acetylacetone with pKa 8.95) because of the additional aromatic stabilization of the carbanion. : Barbituric acid, acid reaction

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 barbiturate drugs that behave as

central nervous system depressant A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the l ...

s. 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 Barbital (or barbitone), marketed under the brand names Veronal for the pure acid and Medinal for the sodium salt, was the first commercially available barbiturate. It was used as a sleeping aid (hypnotic) from 1903 until the mid-1950s. The chemic ...

(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 ep ...

was first marketed in 1912. Barbituric acid is a chemical building block in the laboratory synthesis of riboflavin (vitamin B₂) and in a method of producing the pharmaceutical drug

minoxidil Minoxidil, sold under the brand name Rogaine among others, is a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive vasodilator. It is available as a generic medication by prescription in or ...

. 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. According to Taber's Cyclopedic Medical Dictionary, overdoses cause respiratory depression, cyanosis, circulatory collapse, stupor, coma, and possibly death.

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