Barbital Synthesis Essay

Clinical data
AHFS/Drugs.comInternational Drug Names
MedlinePlusa682221
Routes of
administration
Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Biological half-life30.3 (± 3.2) hours
Identifiers

IUPAC name

  • 5,5-diethylpyrimidine-2,4,6(1H,3H,5H)-trione
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.000.301
Chemical and physical data
FormulaC8H12N2O3
Molar mass184.193 g/mol
3D model (JSmol)

InChI

  • InChI=1S/C8H12N2O3/c1-3-8(4-2)5(11)9-7(13)10-6(8)12/h3-4H2,1-2H3,(H2,9,10,11,12,13) Y
  • Key:FTOAOBMCPZCFFF-UHFFFAOYSA-N Y
  (verify)

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 chemical names for barbital are diethylmalonyl urea or diethylbarbituric acid; hence, the sodium salt (known as medinal, a genericised trademark in the United Kingdom) is known also as sodium diethylbarbiturate.

Synthesis[edit]

Barbital was first synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering, who published their discovery in 1903.[1] Barbital was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide, and then by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.

Barbital can also be synthesized in a condensation reaction from urea and diethyl-2,2-diethylmalonate, a diethyl malonate derivative:

Marketing[edit]

Barbital was marketed in 1904 by the Bayer company as “Veronal”. A soluble salt of barbital was marketed by the Schering company as “Medinal.” It was dispensed for “insomnia induced by nervous excitability”.[2][unreliable source?] It was provided in either crystal form or in cachets (capsules). The therapeutic dose was ten to fifteen grains (0.65-0.97 grams). 3.5 to 4.4 grams is the deadly dose but sleep has also been prolonged up to ten days with recovery.

Pharmacology[edit]

Barbital was considered to be a great improvement over the existing hypnotics. Its taste was slightly bitter, but better than the strong, unpleasant taste of the commonly used bromides. It had few side effects, and its therapeutic dose was far below the toxic dose. However, prolonged usage resulted in tolerance to the drug, requiring higher doses to reach the desired effect. "I'm literally saturated with it," the Russian tsarina Alexandra Feodeorovna confessed to a friend.[3] Fatal overdoses of this slow-acting hypnotic were not uncommon. Pioneering aviator Arthur Whitten Brown (of "Alcock and Brown" fame) died of an accidental overdose.[4] Japanese writer Ryūnosuke Akutagawa deliberately overdosed on the drug in 1927.

pH buffer[edit]

Solutions of sodium barbital have also been used as pH buffers for biological research, e.g., in immunoelectrophoresis or in fixative solutions.[5][6] As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances.[7]

References[edit]

Further reading[edit]

  • (in English) Dombrowski SM, Krishnan R, Witte M, Maitra S, Diesing C, et al. 1998. "Constitutive and barbital-induced expression of the CYP6A2 allele of a high producer strain of CYP6A2 in the genetic background of a low producer strain". Gene 221:69–77.

External links[edit]

Bottle for "Veronal" crystals, named after the Italian city of Verona, was the first commercially available barbiturate, manufactured by Bayer.
  1. ^Fischer, Emil; von Mering, Joseph (1903). "Ueber eine neue Klasse von Schlafmitteln". Therapie der Gegenwart. 44: 97–101. 
  2. ^Finley, Ellingwood (1919). "Veronal". The American Materia Medica, Therapeutics and Pharmacognosy. p. 115. Retrieved 25 July 2015. 
  3. ^Dehn, Lili The Real Tsaritsa, Boston, Little Brown, 1922, p138
  4. ^"Arthur Whitten Brown (1886–1948) – Find A Grave Memorial". Findagrave.com. Retrieved 19 April 2014. 
  5. ^"Wolf D. Kuhlmann, "Buffer Solutions""(PDF). 10 September 2006. Retrieved 28 July 2014. 
  6. ^Steven E. Ruzin (1999). Plant Microtechnique and Microscopy. Oxford University Press. Retrieved 28 July 2014. 
  7. ^Monthony, JF; Wallace, EG; Allen, DM (Oct 1978). "A non-barbital buffer for immunoelectrophoresis and zone electrophoresis in agarose gels". Clinical Chemistry. 24 (10): 1825–7. PMID 568042. 

IUPAC NAME OF Barbital : 5 ,5- di ethyl- 2 ,4 ,6 (1 H ,3 H ,5 H)- pyrimidine trione

Barbital MF: C8H12N2O3
Barbital LD50: 600 mg/kg (M, p.o.)

A white crystalline powder. A solution in water slowly decomposes. M.p. about 190°.

Soluble 1 in 5 of water (1 in 2.5 of boiling water) and 1 in 400 of ethanol; practically insoluble in chloroform and ether.

Dissociation Constant.

pKa8.0 (25°).

Partition Coefficient.

Log P(octanol/water), 0.7.

Colour Tests.

Koppanyi–Zwikker Test—violet; Mercurous Nitrate—black.

Thin–layer Chromatography.

System TD—Rf 41; system TE—Rf 32; system TF—Rf 61; system TH—Rf 51; system TAD—Rf 57; system TAE—Rf 84. (Mercuric chloride–diphenylcarbazone reagent, positive; mercurous nitrate spray, black; Zwikker's reagent, pink.)

Gas Chromatography.

System GA—barbital RI 1489, barbital-Me2 RI 1420, barbital-Me (metharbital) RI 1470, barbituric acid-Me3 RI 1645; system GF—RI 2230; system GAJ—RRT 0.612 (relative to methylphenobarbital).

High Performance Liquid Chromatography.

System HG—k 1.11; system HH—k 0.63; system HX—RI 308; system HY—RI 258; system HZ—retention time 2.2 min; system HAA—retention time 10.4 min; system HAL—retention time 1.4 min.

Ultraviolet Spectrum.

Borax buffer 0.05 M (pH 9.2)—239 nm (A11=549a); M sodium hydroxide (pH 13)—254 nm (A11=427b).

Reference(s):
Clarke's Analysis of Drugs and Poisons
Fischer; Dilthey: Justus Liebigs Ann. Chem. (JLACBF) 335, 338 (1904).

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