Laboratory Synthesis Of Benazepril

Preparation of  Benazepril

IUPAC name Benazepril  [S- (R *,R *)]-3- [[1- (ethoxy carbonyl)- 3- phenyl propyl ]amino]- 2 ,3 ,4 ,5- tetra hydro- 2- oxo- 1 H- 1- benzazepine- 1- acetic acid

Benazepril Use: antihypertensive (ACE inhibitor)

Benazepril MW: 424.50

Benazepril MF: C24H28N2O5

Benazepril M.p. 148.5°.

Proprietary names. Briem; Cibace; Cibacen; Cibacene; Labopal; Lotensin; Tensanil; Zinandril.

C₂₄H₂₈N₂O₅,HCl=461.0

CAS—86541–74–4

A white to off–white crystalline powder. It is soluble in water, ethanol and methanol.

Partition Coefficient.

Log P(octanol/water), 3.50.

Gas Chromatography.

System GP—RI 3030 (benazepril-ME); RI 2985 (M (benazeprilate)-ME3).

Column: 3% OV-101 on Gaschrom Q, 80–100 mesh (Ciba-Geigy), pyrex glass (1.5 m × 2 mm i.d.). Column and injector port temperature: 275°. Carrier gas: helium, flow rate 30 mL/min. MS detection (EI, SIM). Retention times: benazepril (methyl ester derivative) 2.55 min; benazeprilat (derivative) 2.3 min. [G. Kaiser et al.,J. Chromatogr.,1987, 419, 123–133].

High Performance Liquid Chromatography.

System HAA—retention time 17.0 min.

Column: C₁₈ (RP-BDS, 5 μm packing, 250 × 3 mm i.d.). Mobile phase: sodium dihydrogen phosphate (0.025 M, pH 4.8):acetonitrile (55:45). 0.4 mL/min flow rate. UV detection (λ=250 nm). Retention time: benazepril hydrochloride, 4.95 min. [I. E. Panderi and M. Parissi-Polou,J. Pharm. Biomed. Anal.,1999, 21, 1017–1024].

Column: Hypersil ODS (5 μm, 250 × 4.5 mm). Mobile phase: sodium heptanesulfonate (20 mM, pH 2.5):acetonitrile (5% THF) (52:48 v/v), 1.0 mL/min flow rate. UV detection (λ=215 nm). Retention time: 15 min. [D. Bonazzi et al.,J. Pharm. Biomed. Anal.,1997, 16, 431–438].

Ultraviolet Spectrum.

Aqueous acid (0.2 M NH₂SO₄)—237 nm; basic—241 nm; aqueous acid (0.1 M hydrochloric acid)—237.2 nm (hydrochloride salt).

Reference(s):
Clarke's Analysis of Drugs and Poisons
Watthey, J.W.H. et al.: J. Med. Chem. (JMCMAR) 28, 1511 (1985).
US 4 410 520 (Ciba-Geigy; 18.10.1983; prior. 11.8.1981, 9.11.1981, 19.7.1982).
EP 72 352 (Ciba-Geigy; appl. 5.8.1982; USA-prior. 11.8.1981, 9.11.1981).

Laboratory Synthesis Of Benorilate/Benorylate/Benorilato

synthesis of Benorilate

IUPAC NAME Benorilate CN: 2- (acetyl oxy )benzoic acid 4- (acetyl amino )phenyl ester

Use: analgesic, antirheumatic.it is a pro drug of paracetamol

Benorilate MW: 313.31 

Benorilate MF: C17H15NO5
Benorilate LD50: 1551 mg/kg (M, p.o.);3500 mg/kg (R, p.o.)

Partition Coefficient.

Log P(octanol/water), 2.2.

Colour Tests.

Liebermann's test—black; Mandelin's test—green; Marquis test—violet.

Thin–layer Chromatography.

System TA—Rf 67; system TB—Rf 00; system TC—Rf 51; system TL—Rf 62; system TAE—Rf 86. (Marquis reagent, positive.)

Gas Chromatography.

System GA—benorilate RI 1840, aspirin RI 1309, paracetamol RI 1687.

High Performance Liquid Chromatography.

System HD—benorilate k 0.7, aspirin k 0.5, paracetamol k 0.1; system HW—benorilate k 22.4, aspirin k 2.7, paracetamol k 0.32.

Ultraviolet Spectrum.

Dehydrated alcohol—240 nm (A¹₁=740a).

Reference(s):
Clarke's Analysis of Drugs and Poisons
US 3 431 293 (Sterling Drug; 4.3.1969; GB-prior. 9.4.1964).
FR 1 436 870 (Sterwin; appl. 8.4.1965; GB-prior. 9.4.1964).

Laboratory Synthesis Of Benserazide

Preparation of Benserazide

IUPAC name Benserazide CN: DL- serine 2- [(2 ,3 ,4- tri hydroxy phenyl )methyl ]hydrazide

Benserazide Use: antiparkinsonian (in combination with levodopa), decarboxylase inhibitor

Benserazide MW: 257.25 

Benserazide MF: C10H15N3O5

Benserazide monohydrochloride

MW: 293.71 MF: C10H15N3O5 · HCl
LD50: 5 g/kg (M, p.o.);5300 mg/kg (R, p.o.)

An off–white crystalline powder. M.p. 146° to 148°.Soluble 1 in 3 of water, 1 in 118 of ethanol, 1 in 66 of acetone, 1 in 180 of chloroform and 1 in 455 of ether.

Colour Tests.

Ammoniacal silver nitrate—black; p-Dimethyl–aminobenzaldehyde—red/-; Ferric chloride—green–brown; Folin–Ciocalteu reagent—blue; Methanolic potassium hydroxide—red; Millon's reagent—red–orange; Nessler's reagent—black; Palladium chloride—orange→brown; Potassium dichromate—brown.

Thin–layer Chromatography.

System TA—Rf 01; system TB—Rf 00; system TC—Rf 01; system TL—Rf 03; system TAE—Rf 7.

High Performance Liquid Chromatography.

System HX—RI 35.

Ultraviolet Spectrum.

Aqueous acid—203, 269 nm.

Reference(s):
Clarke's Analysis of Drugs and Poison
DE 1 165 607 (Roche; appl. 8.5.1962; CH-prior. 16.6.1961).
US 3 178 476 (Roche; 13.4.1965; CH-prior. 16.6.1961).
L-form:
US 3 557 292 (Roche; 19.1.1971; appl. 16.8.1968).
DE 1 941 284 (Roche; appl. 13.8.1969; CH-prior. 16.8.1968).
DAS 1 966 821 (Roche; appl. 13.8.1969; CH-prior. 16.8.1968).

Laboratory Synthesis Of Barbital

BARBITAL SYNTHESIS

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

Use: hypnotic

Barbital MW: 184.20

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.

pK_a8.0 (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).