Structural elucidation

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Nidhi jadhav Structural elucidationIntroduction nicotine Introduction Nicotine was isolated from tobacco leaves (Nicotiana tabacum) in 1828, but the powerful effects of nicotine were already well recognizedThe tobacco plant is native to the Americas and its use as a medicine and stimulant goes back at least 2000 years and most likely many millennia before that.Tobacco appears to part of the healing arts and sacred rituals of many of the native peoples of the Americas. Codex, 16th century.)Nicotine is a potent parasympathomimetic alkaloid found in the nightshade family of plants (Solanaceae) and a stimulant drugIt is a nicotinic acetylcholine agonist receptor. It constitutes approximately 0.63.0% of the dry weight of tobacco and is present in the range of 27g/kg of various edible plants.It functions as an antiherbivore chemical; consequently, nicotine was widely used as an insecticide in the past and nicotine analogs such as imidacloprid are currently widely used.

NomenclatureChemical names:- Nicotinamide :- Pyridine-3-crboxamide; nicotinic acid amide; 3-pyridine carboxylic acid amide; 3- pyridine carboxamideNicotinic acid:- pyridine -3- crboxamide;3-pyridine crboxamide; pyridine-- carboxylic acid.Generic name :- nicotinamide; niacinamide; nicotylamide; nicotinamidum; vitamin PP; vitamine B3 ; aminocotin; dipegyl; pilonin amide; amide PP.Trade name:- nicotinamide: nicamina; nicobion; nicosedine; nicovel; nicovit; nicamindon; nicotamide; nicofort; niozymin;pelmine; benicot; vinietyl; amisyl; farmabion

colour:- Nicotinamide exists as colourless crystal or white crystalline powder. odor :- faint characteristic Taste: salty and better.while nicotinic acid appears as needle or white to creamy- white crystals or crystalline powderOptical activity:- both the drug substance are optically inactive because of the absences of chemical asymmetry.

Solubility:- Nicotinamideis highly soluble in water and alcohol 1g dissolves in about 1ml of water in about 1.5ml alcohol and in 10 ml glycerol. it is slightly soluble in ether and chloroform , while it is soluble in solution of alkali. nicotinic acid 1g is soluble in 55 to 60 ml of water and 100 ml of ethanol, very slightly in chloroform. practically insoluble in ether. soluble in alkaline solution of hydroxides and carbonates.

Moisture content and hygroscopity:-Nicotinamide absorbs insignificant amount of moisture at 250 c at relative humidities up to about 90%Stability:-nicotinamide is stable in air, light, and at certain PH-changes Storage:- both drug substances should be stored in air-tight container

Identification :-Color test:- to 2ml 0.1% solution of nicotinamide or nicotinic acid add 6ml of cyanogen bromide solution and 1 ml of a 2.5% v/v solution of aniline golden yellow i.e konigs reaction. Nicotinamide gives brown- orange color with nessler reagent.Microcrystal test:Nicotinamide yield with gold chloride solution dense rosettes and with platinic iodide solution a mass of hair like needles

Nicotinamide Nicotinic acid

Spectral propertiesUltraviolet spectrum:-

The Ultraviolet scanning of ethanolic solution of nicotinamide.

Ultraviolet spectrum: The Ultraviolet spectrum of nicotinamide in ethanol . The spectrum of the drug exhibits a maximum at 261nm . The UV-running of methnolic maximum at about 263nm.

Infrared spectrum The Infrared spectrum of nicotinamide in KBr disc, is presented . the frequencies had nicotinic acid are shown in table

Frequency (cm-1) assignment1600-1630C=C (stretch ,amide and acid)1700C=O (amide)1710C=O ( acid)3200N-H (stretch ,amide)3100O-H (stretch ,acid)Proton nuclear spectrum (1H-NMR)The 1H-NMR running were undertaken for each drug substances . the 1H-NMR spectrum of nicotinamide.Each drug substances was dissolved in deuterium oxides and its spectrum determined on a varian T6A NMR spectrometer using DSS ( sodium-2,2-dimethyl-2-silapentane-5-sulfonate) as the internal standard . the structural assignments are

Chemical shift (,ppm) MultiplicityProton assignment7.69MultiplicityH(3)8.25MultiplicityH(2)8.72MultiplicityH(4)8.93DoubletH(1)9.16 singletH(5) ) (amide)9.14SingletH(6) (acid)

Carbon-13 NMR SPECTRUM ( 13C-NMR)The ( 13C-NMR) spectrum of nicotinamide in deuterium oxide using DSS as the internal reference were obtained using jeo1 FX 100 MHZ spectrometer at an ambient temperature . Represents the 1H- decoupled spectrum of nicotinamide

Chemical shift (,ppm)MultiplicityCarbon assignmentAcid amide150.3 150.2 DoubletC(1)133.5 131.3 singletC(2)138.6 138.7 DoubletC(3)124.6 126.8DoubletC(4)151.5 154.3DoubletC(5)173.8 172.0 singletC(6)PilocarpineDried leaves of pilocarpus jaborandi ; Fam: rutaceae.Origin of the Drug-South American Shrub - Pilocarpus jaborandi -Isolated in 1875Pilocarpine binds to muscarinic receptorActivates receptor binds G-protein Removal of GDP and addition of GTP to G-protein Dissociation of G-protein from muscarinic receptor Separation of G-protein into alpha and beta-gamma subunits

Alpha subunit interacts with and activates Phospholipase C - Phosphatidyl inositol biphosphate (PIP) complex Phospholipase breaks down PIP into inositol 1,4,5-triphosphate (IP3)and diacylglycerol (both 2o) IP3 interacts with ER membrane which releases Ca2Chemical Structure:-

Chemical name:- 2-ethyl1-3-(1-methyl1-5-imidazolyl)methyl) -4 butanolide.(3s-cis-3-ethyldihydro-4-(methyl-1H-imidazole-5-yl)-2-(3H)-furanone.Generic name:-PipocarpinePilocarpine hydrochloride; pilocarpine muriate;almocarpine.Pilocarpine nitrate; licarpin .Trade nameFor base: OCUSERT pilo.For nitrate : PV cerpine

Formula :-C11 H16 N2O2 (base)C11 H17Cl N2O2 (hcl.salt)C11 H17 N3O5 (nitrate salt)Molecular weight:- 208.25 (base)244.72 (HCl salt) 271.30 ( nitrate salt)

Appearance, color, odor:- Pilocarpine base : Colorless oil or crystal.Pilocarpine hydrochloride: colorless crystal or white , crystalline powder; odorless. Hydroscopic.Pilocarpine nitrate: colorless crystal or a white ,crystalline powder; odorless.Physical properties: Melting point: Pilocarpine base: 340Pilocarpine hydrochloride 195-198oPilocarpine nitrate 173.5-1740

Pka value:-Pilocarpine base shows two ionization costants, pk1=7.15 and pk2 =12.57 at 200Specific rotation :- The specific rotation for Pilocarpine and its official salts are shows on the following table and this constant is used to differentiate and identify Pilocarpine, the cis- isomer and the pharmacologically active one, from its tran-isomer, isoPilocarpine.Moisture content and hygroscopicity: 8.7-14.1%,crude piperine:- 2.8-9.0%,crude fibre:-8.7-18.1% Storage: Store in a cool, dry place,

IdentificationColor test :- Pilocarpine hydroclorid: dissolve 10 mg into 5 ml of water add 0.1 ml of M sulphuric acid 0.1 ml of H2O2 solution, 1 ml toluene and 0.5 ml of potassium chromate solution. Shake well and allow to separate; the touene layer is colored bluish violet and the aqueous laye remains yellowPilocarpine nitrate: dissolve 10 mg into 2 ml h2o, add 0.1 ml of 5%w/v solution and 2ml of chloroform and shake ; the chloroform layer turns violet.Crystal test:- Pilocarpine can be identified by forming characteristic crystals, with the following reagents: 1) gold bromide solution; feathering rosettes. 2) platonic chloride solution plates in cluster.

Degradation test : the following tests were cited by the WHO in the international pharmacopeia . if the substances does not pass this test, this indicates that gross ,Degradation of both Pilocarpine hydrochloride and Pilocarpine nitrate had occurred.Stability:- Pilocarpine possessesseveral pharmacological properties, e.g., it possesses amotic action and lowers the intraocular pressure. Its chief clinical application in opthomology has been for the treatment of glaucoma in buffered iisotonic silution renging from 0.5 to 6% as Pilocarpine nitrate or hydrocholoride . however, pilocarpine in aq. Solution decomposes through two major pathways which are both base catalysed .

Spectral properties: Ultraviolet spectrum: Pilocarpine HCl in H2O exhibits maximum at 215 nm as shown in figure clarke reported the UV absorption spectrum of Pilocarpine in 0.2N H2SO4 to show a maximum at 215nmBen bassat and lavis reported the ultraviolet spectroscopic propirties of V and the eefect of quaternization of this drug among other characteristic changes in the NMR and IR properties

Infrared spectrum

The IR spectrum of pilocarpine HCl in KBr disc. The major assignments areFrequency cm-1Assignments3080,3020N-CH3 quaternary and aromatic CH stretch1770C=O(five membered -lactone ring)1620C=C aromatic stretchProton magnetic resonance spectrumA typical PMR spectrum of pilocarine HCl is shown in figure . The spectrum was determined on varian T60A spectrometer. The smple was dissolve in D2O with 3-(trimethylsilyl)-propionic acid) sodium salt as an internal standard.The following structural assignments have been made for figure .

Chemical shift () Assignment Triplet at 1.1CH3 CH2Quartet at 1.7CH3 CH2Complex multiplet centered at 3.00 -CH2 at C8 and CH at C4Singlet 3.9Complex multiplet Between 4 and 4.6CH2 at C5 and CH at C3 Singlet at 7.4Aromatic proton at c4Singlet at 9.4Aromatic proton at c2

Mass spectrum The mass spectrum of pilocarpine hydrochloride obtained by electron ionization is shown in figure


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