Sodium ethylate Thiopental

Thiopental Sodium, USP. Thiopental. sodium, sodium S-ethyl-S-(l-methylbutyl)-2-lhiobarbilurale (Pentothal Sodium). is the mo.st widely u.sed ultra-short-acting anc.sthctic barbiturate. Additionally, the compound is the prototype for the ultra-short-acting barbiturates. Most discussions of how structure influences duration of action in this group of agents relate specifically to it. The compound s onset of action is about equal to the time required for it to travel to the brain from the site of administration. Consciousness is regained within 30 minutes. 

Thiopental Thiopental, 5-ethyl-5-(l-methylbutyl)2-thiobarbituric acid (1.2.10), is synthesized by the alkylation of ethyhnalonic ester with 2-bromopentane in the presence of sodium ethoxide. The product ethyl-(l-methylbutyl)malonic ester (1.2.9) undergoes hete-rocyclization with thiourea, using sodium ethoxide as a base [16,17]. 

Thiopental Sodium, 5.Ethyldihydro-5 ( I-methyl-butyl)-2-thioxo-4,6(lH,SH)-pyrimidinedione monosodium salt 5-ethyl-5-iI-methy(butyl)-2-thiobarbituric acid sodium salt thiomebumal sodium penthiobarbital sodium thiopen -tone sodium thionembutal Pentothal Sodium Nesdonal Sodium Intraval Sodium Trapanal Thiothal Sodium. C,.-Hl7N2Na02S mol wt 264.33. C 49.98%, H 6,48%, N 10.60%, Na 8,70%, O 12-11%, S 12.13%. Prepn U.S. pats. 2,153,729 (1939) 2,876,225 (1959). Prepn of nonhygrosopic crystals Hartop, U.S. pat. 3,109,001 (1963 to Abbott). Acute toxicity Christensen, Lee, Toxicol. Appl. Pharmacol. 26, 495 (1973). 

Sodium 5-ethyl-5 (1-methyl butyl)-2-thiobarbiturate 4, 6 (IH, 5H)-Pyrimidinedione, 5-ethyldihydro-5-(l-methyl butyl)-2 thioxo-, monosodium salt Thiopental sodium U.S.P., Thiopentone sodium B.P., Eur. R, Ind. R, Int. P. 

Diethyl malonate on reaction with sodium metal gives rise to sodium malonic ester which on treatment with ethyl bromide results into the formation of diethyl ester of ethyl malonic acid with the elimination of hydrobromic acid. The resulting ester on further reaction with 2-bromopentane gives the desired eompound, i.e., diethyl ester of ethyl (1-methyl butyl) malonic acid which on subsequent treatment with thiourea forms thiopental with the elimination of two moles of ethanol. Ultimately, the enol-iorm of thiopental when reaeted with a ealeulated amoimt of sodium hydroxide, it gives thiopental sodium. 

In method A, ethyl (1-methylbutyl) malonate (I) was condensed with thiourea (II) in the presence of sodium ethoxide in absolute alcohol. After heating at reflux for several hours the solvent was removed and the residue dissolved in cold water. Thiopental (III) was precipitated by the addition of dilute hydrochloric acid. Further purification could be accomplished by dissolving m in dilute sodium hydroxide and precipitating with carbon dioxide [6]. 

Thiopentone sodium, although soluble in water, in acid solutitm is converted to the free acid (thiopental) which is water insoluble. The assay of thiopental sodium in both biological fluids and proprietaty preparations takes advantage of these acid-base diaracteristics. Extraction is accomplished by acidifrcation followed by shaking with organic solvents. Solvents commonly employed include chloroform [25-27], methylene chloride [28-31] and diethyl or petroleum ether [32-36]. Less frequently used are benzene [37], toluene [38,39], ethyl acetate [40,41], n-hexane [15,28] and n-butyl chloride [42]. Additional selectivity and sensitivity was obtained by back-extraction into sodium hydroxide [25,28,35,36,42,43]. 

The sodium salt of 5-ethyl-5(l-methylbutyl)-thiobarbituric acid Pentothal, Thiopental) was determinedwith silver nitrate as titrant and either a dropping mercury or rotating platinum electrode. 

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