77-21-4 Usage
Chemical Properties
White, crystalline powder.Saturated solution is slightly acid.
Freely soluble in acetone, ethyl acetate, and chloroform; soluble in ethanol and methanol; practically
insoluble in water.
Originator
Doriden,U.S.V.,US,1955
Uses
Sedative-hypnotic.
Manufacturing Process
The 2-phenyl-2-ethyl-pentane-1,5-diacid-mononitrile-(1) of melting point 72°
to 76°C, used as starting material in this process, can be produced for
example from α-phenyl-butyric acid nitrile by condensation with acrylic acid
methyl ester and subsequent hydrolysis of the thus-obtained 2-phenyl-2-
ethyl-pentane-1,5-diacid-monomethyl ester-mononitrile-(1) of boiling point
176° to 185°C under 12 mm pressure.
140 parts by weight of 2-phenyl-2-ethyl-pentane-1,5-diacid-mononitrile-(1)
are dissolved in 200 parts by volume of glacial acetic acid and, at an initial
temperature of 60°C, 100 parts by volume of concentrated sulfuric acid added
in portions. In this operation the temperature of the reaction mixture rises to
100°C. The whole is finally maintained for a short time on the boiling water
bath, then cooled and poured on ice and neutralized with alkali to a pH of 6.
Extraction with chloroform is then effected and the chloroform extract washed with dilute caustic soda solution, dried over calcium chloride, the chloroform
evaporated and the residue crystallized from ethyl acetate with addition of
ligroin. The obtained 3-phenyl-3-ethyl-2,6-dioxo-piperidine melts at 78° to
81°C.
Brand name
C "5";Doridene;Doriden-sed;Doridine;Dorimide;Elrodorm;Gludorm;Sarodormin;Somid;Tardyl.
World Health Organization (WHO)
Glutethimide, a piperidine derivative, was introduced in 1955 for
use as a sedative-hypnotic drug. Its addiction liability and severity of withdrawal
symptoms are equal to those of the barbiturates and it is controlled under
Schedule III of the 1971 Convention on Psychotropic Substances.
(Reference: (UNCPS3) United Nations Convention on Psychotropic Substances (III),
, , 1971)
General Description
Glutethimide, 2-ethyl-2-phenylglutarimide(Doriden), is one of the most active nonbarbituratehypnotics that is structurally similar to the barbiturates,especially phenobarbital. Because of glutethimide’s lowaqueous solubility, its dissolution and absorption from theGI track is somewhat erratic. Consistent with its highlipophilicity, it undergoes extensive oxidative metabolismin the liver with a half-life of approximately 10 hours.Glutethimide is used as a racemic mixture with the (+)enantiomer being primarily metabolized on the glutarimidering and the (—) enantiomer on the phenyl ring. The productof metabolic detoxification is excreted after conjugationwith glucuronic acid at the hydroxyl group. The drug is anenzyme inducer. In the therapeutic dosage range, adverse effectstend to be infrequent. Toxic effects in overdose are assevere as, and possibly more troublesome than, those of thebarbiturates.
Hazard
Manufacture and use controlled by law.
Safety Profile
Poison by ingestion and
intraperitoneal routes. Human systemic effects by
ingestion: pupillary dilation, ataxia, somnolence,
coma, and blood pressure depression. An
experimental teratogen. Other experimental
reproductive effects. When heated to
decomposition it emits toxic fumes of NOx.
Caution: May be habit forming. This is a controlled
substance (depressant) listed in the US. Code of
Federal Regulations, Title 21 Part 1308.13 (1985)
Purification Methods
Crystallise glutethimide from diethyl ether or ethyl acetate/pet ether. It has m 91-92o (from aqueous EtOH), 87-87.5o (from Et2O/pet ether), 84-87o (from isopropanol), and 83-84o (from Et2O). [Penprase & Biles J Am Pharm Assoc 47 523 1958, Hofmann et al. Helv Chim Acta 40 387, 393 1957, Beilstein 21 III/IV 5493.] The R(+)-enantomer crystallises from EtOAc/pet ether with m 103-104o, and [ ] 20+184o (c 1,
Check Digit Verification of cas no
The CAS Registry Mumber 77-21-4 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 7 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 77-21:
(4*7)+(3*7)+(2*2)+(1*1)=54
54 % 10 = 4
So 77-21-4 is a valid CAS Registry Number.
InChI:InChI=1/C13H15NO2/c1-2-13(10-6-4-3-5-7-10)9-8-11(15)14-12(13)16/h3-7H,2,8-9H2,1H3,(H,14,15,16)
77-21-4Relevant articles and documents
Direct Deamination of Primary Amines via Isodiazene Intermediates
Berger, Kathleen J.,Driscoll, Julia L.,Yuan, Mingbin,Dherange, Balu D.,Gutierrez, Osvaldo,Levin, Mark D.
supporting information, p. 17366 - 17373 (2021/11/04)
We report here a reaction that selectively deaminates primary amines and anilines under mild conditions and with remarkable functional group tolerance including a range of pharmaceutical compounds, amino acids, amino sugars, and natural products. An anomeric amide reagent is uniquely capable of facilitating the reaction through the intermediacy of an unprecedented monosubstituted isodiazene intermediate. In addition to dramatically simplifying deamination compared to existing protocols, our approach enables strategic applications of iminium and amine-directed chemistries as traceless methods. Mechanistic and computational studies support the intermedicacy of a primary isodiazene which exhibits an unexpected divergence from previously studied secondary isodiazenes, leading to cage-escaping, free radical species that engage in a chain, hydrogen-atom transfer process involving aliphatic and diazenyl radical intermediates.
Tert-Butoxide-Mediated Arylation of 2-Substituted Cyanoacetates with Diaryliodonium Salts
Qian, Xiaofei,Han, Jianwei,Wang, Limin
, p. 940 - 946 (2016/04/05)
A transition metal-free direct arylation of 2-substituted cyanoacetates with diaryliodonium salts was developed. With this approach, a wide range of α-tolunitrile derivatives has been synthesized in good to excellent yields of 45-92%. Furthermore, the practicability of this approach is further manifested in the synthesis of a related bioactive agent of glutarimide.
An efficient synthesis of N-benzyl-3-sulfonyl glutarimides. Formal synthesis of the aromatase inhibitor AG-1
Chang, Meng-Yang,Chang, Bo-Rui,Tai, Huo-Mu,Chang, Nein-Chen
, p. 10273 - 10276 (2007/10/03)
A formal [3+3] cycloaddition strategy to substituted glutarimides was studied. N-Benzyl α-sulfonylacetamides and various α,β-unsaturated esters were used as starting materials. (C) 2000 Elsevier Science Ltd.
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