Reactions of indole
Electrophilic aromatic substitution Electrophilic aromatic substitution of indole occurs on the five-membered pyrrole ring, because it is more reactive towards such reaction than a benzene ring. As an electron-rich heterocycle, indole undergoes electrophilic aromatic substitution primarily at C-3, for example bromination of indole. The Mannich reaction is another example of electrophilic aromatic substitution where indole can produce an aminomethyl derivative. Similarly, using the Vilsmeier...
Pharmaceutical importance of aromatic compounds some examples
There are numerous examples of aromatic compounds that are pharmaceu-tically important as drugs or pharmaceutical additives. Just a few examples of pharmaceutically important aromatic compounds are cited here. Aspirin, a well known non-narcotic analgesic and antipyretic drug, is a classic example of a pharmaceutically important benzene derivative. Morphine, an aromatic alkaloid, is a narcotic habit-forming analgesic that is used extensively for the management of post-operative pain. Aromatic...
Significance of stereoisomerism in determining drug action and toxicity
Pharmacy is a discipline of science that deals with various aspects of drugs. All drugs are chemical entities, and a great majority 30-50 per cent of them contain stereocentres, show stereoisomerism and exist as enantiomers. Moreover, the current trend in drug markets is a rapid increase of the sales of chiral drugs at the expense of the achiral ones. In the next few years, chiral drugs, whether enantiomerically pure or sold as a racemic mixture, will dominate drug markets. It is therefore...
I 1
While dehydration of 2 and 3 alcohols is an E1 reaction, dehydration of 1 alcohols is an E2 reaction. Dehydration of 2 and 3 alcohols involves the formation of a carbocation intermediate, but formation of a primary carbocation is rather difficult and unstable. For example, dehydration of propanol gives propene via E2. ch3ch2ch2oh h-oso3h CH3CHjCH2 Ch3C Ch2 An E2 reaction occurs in one step first the acid protonates the oxygen of the alcohol a proton is removed by a base HSO4 and simultaneously...
Preparation of isoxazole pyrazole and isothiazole
Isoxazole and pyrazole synthesis While 1,3-diketones undergo condensation with hydroxylamine to produce isoxazoles, with hydrazine they yield corresponding pyrazoles. Isothiazole synthesis Isothiazole can be prepared from thioamide in the following way. Reactions of isoxazole, pyrazole and isothiazole Like 1,3-azoles, due to the presence of a pyridine-like nitrogen atom in the ring, 1,2-azoles are also much less reactive towards electrophilic substitutions than furan, pyrrole or thiophene....
Acidity of terminal alkynes
Terminal alkynes are acidic, and the end hydrogen can be removed as a proton by strong bases e.g. organolithiums, Grignard reagents and NaNH2 to form metal acetylides and alkynides. They are strong nucleophiles and bases, and are protonated in the presence of water and acids. Therefore, metal acetylides and alkynides must be protected from water and acids. CH3CH2Li _ - - RC C Li CH3CH3
Importance of functional groups in determining drug actions and toxicity
In Chapter 2, you have already learned that most drugs bind to the appropriate receptor molecules to exhibit their pharmacological actions, and also toxicity, which in fact is the adverse pharmacological action. A drug's pharmacological activity is inherently related to its chemical structure. Various functional groups present in the drug molecules are involved in the drug-receptor binding or interaction. For example, drugs containing hydroxyl or amino groups tend to be involved in hydrogen...
Reactions of monosaccharides as alcohols
Monosaccharides contain a number of alcoholic hydroxyl groups, and thus can react with acid anhydrides to yield corresponding esters. For example, when glucose is treated with acetic anhydride and pyridine, it forms a pentaacetate. The ester functions in glucopyranose pentaacetate undergo the typical ester reactions. pentaacetate Monosaccharides also form phosphate esters with phosphoric acid. Mono-saccharide phosphate esters are important molecules in biological system. For example, in the DNA...
Introduction to natural product drug discovery process
Natural products are products from various natural sources, plants, microbes and animals. Natural products can be an entire organism e.g. a plant, an animal or a micro-organism , a part of an organism e.g. leaves or flowers of a plant, an isolated animal organ , an extract of an organism or part of an organism and an exudate, or pure compound e.g. alkaloids, coumarins, flavonoids, lignans, steroids and terpenoids isolated from plants, animals or micro-organisms. However, in practice, the term...
Cascarosides
Cascara bark Rhamnus purshianus contains various anthraquinone O-glycosides, but the main components are the C-glycosides, which are known as cascarosides. Rhubarb Rheum palmatum also contains several different O-glycosides and cascarosides. Aloe vera mainly produces anthra-quinone C-glycosides, e.g. aloin. Cascaroside A R OH Cascaroside B R OH Cascaroside C R H Cascaroside D R H Cascaroside A R OH Cascaroside B R OH Cascaroside C R H Cascaroside D R H
Why the CF group is meta directing
All meta-directing groups have either a partial positive charge or a full positive charge on the atom directly linked to the benzene ring. In the trifluoromethyl group CF3 , there are three electronegative fluorine atoms, which make this group strongly electron withdrawing. As a result CF3 deactivates the benzene -CF3 Is an electron-withdrawing group -CF3 Is an electron-withdrawing group ring, and directs further substitutions to meta positions. The ortho and para electrophilic attacks in...
Nomenclature of heterocyclic compounds
Most of the heterocycles are known by their trivial names, e.g. pyridine, indole, quinoline, thiophene and so on. However, there are some general rules to be followed in a heterocycle, especially in the use of suffixes to indicate the ring size, saturation or unsaturation as shown in the following table. For example, from the name, pyridine, where the suffix is -ine, one can understand that this heterocyclic compound contains nitrogen, has a six-membered ring system and is unsaturated. Ring...
Pyridine and piperidine alkaloids
Alkaloids, e.g. piperine, coniine, trigonelline, pilocarpine, nicotine and sparteine, possess a pyridine or modified pyridine heterocyclic ring system e.g. piperidine ring . Piperine Piperine, molecular formula C17H19NO3, a component of black pepper Piper nigrum , has been used in various traditional medicine preparations, and also as an insecticide. Piperine has various effects on human drug metabolizing enzymes, and is marketed under the brand name, Bioperine , as an adjunct for increasing...
2r 3r -2-bromo-3-phenylpentane In Its Lowest Energy Conformation About The
After completing this chapter the student should be able to outline different types of isomerism distinguish between conformational isomers and configurational isomers discuss conformational isomerism in alkanes explain the terms torsional energy, torsional strain, angle strain, enan-tiomers, chirality, specific rotation, optical activity, diastereomers, meso compounds and racemic mixture designate the configuration of enantiomers using the D and L system and the R and S system explain...
Heavy metal acetylides test for terminal alkynes
The position of the triple bond can alter the reactivity of the alkynes. Acidic alkynes react with certain heavy metal ions, e.g. Ag and Cu , to form precipitation. Addition of an alkyne to a solution of AgNO3 in alcohol forms a precipitate, which is an indication of hydrogen attached to the triple bonded carbon. Thus, this reaction can be used to differentiate terminal alkynes from internal alkynes.
Conversion of alkyl tosylates
Tosylates are excellent leaving groups, and can undergo a variety of SN2 reactions. The reaction is stereospecific, and it occurs with inversion of configuration. For example, S -2-butanol reacts with TsCl in pyridine to produce S -2-butane tosylate, which reacts readily with Nal to give R -2-iodobutane via SN2 reaction. i. TsCl, pyridine H'C-OH - Similarly, alkyl tosylate reacts with other nucleophiles, e.g. H , X , HO , R'O, R' , NH2 or NH3, CN_, N3 and R'CO2 following the SN2 reaction...
Miscellaneous carbohydrates Sugar phosphates
These sugars are formed by phosphorylation with ATP, e.g. glucose 6-phosphate. They are extremely important in carbohydrate metabolism. We have already seen that nucleotides contain sugar phosphates. Glycosylamines In these sugars, the anomeric -OH group of common sugars is replaced by an amino -NH2 group for example, adenosine. Amino sugars In amino sugars, a non-anomeric -OH group of common sugars is replaced by an amino -NH2 group for example, glucosamine, which is found in exoskeletons of...
Oxidation
Aldoses are easily oxidized to produce aldonic acid. Aldoses react with Tollens' Ag in aqueous NH3 , Fehling's Cu2 in aqueous sodium tartrate and Benedict's reagents Cu2 in aqueous sodium citrate , and produce characteristic colour changes. All these reactions produce oxidized sugar and a reduced metallic species. These reactions are simple chemical tests for reducing sugars sugars that can reduce an oxidizing agent . Reaction with Fehling's and Benedict's reagent, aldehydes and ketones i.e....
Structure of benzene Kekule structure of benzene
In 1865, August Kekule proposed the structure of benzene C6H6 . According to his proposals, in benzene a all six carbon atoms are in a ring b all carbon atoms are bonded to each other by alternating single and double bonds c one hydrogen atom is attached to each carbon atom d all hydrogen atoms are equivalent. Limitations of Kekule structure The Kekul structure predicts that there should be two different 1,2-dibromobenzenes. In practice, only one 1,2-dibromobenzene has ever been found. Kekule...
Isoquinoline alkaloids
Isoquinoline is in fact an isomer of quinoline, and chemically known as benzo c pyridine or 2-benzanine. Any alkaloids that possess an isoquinoline skeleton are known as isoquinoline alkaloids, e.g. papaverine and morphine. The isoquinoline backbone is biosynthesized from the aromatic amino acid tyrosine. Isoquinoline itself is a colourless hygroscopic liquid at room temperature. It has an unpleasant odour. It is slightly soluble in water but well soluble in ethanol, acetone, ether and other...
Separation of stereoisomers resolution of racemic mixtures
A number of compounds exist as racemic mixtures , i.e. a mixture of equal amounts of two enantiomers, and . Often, one enantiomer shows medicinal properties. Therefore, it is important to purify the racemic mixture so that active enantiomer can be obtained. The separation of a mixture of enantiomers is called the resolution of a racemic mixture. Through luck, in 1848, Louis Pasteur was able to separate or resolve racemic tartaric acid into its and forms by crystallization. Two enantiomers of...
Reactions of pyrrole furan and thiophene
Pyrrole, furan and thiophene undergo electrophilic substitution reactions. However, the reactivity of this reaction varies significantly among these heterocycles. The ease of electrophilic substitution is usually fur-an gt pyrrole gt thiophene gt benzene. Clearly, all three heterocycles are more reactive than benzene towards electrophilic substitution. Electrophilic substitution generally occurs at C-2, i.e. the position next to the hetero-atom. Vilsmeier reaction Formylation of pyrrole, furan...
Sennosides
The most important anthraquinone glycosides are sennosides, found in the senna leaves and fruits Cassia senna or Cassia angustifolia . These are, in fact, dimeric anthraquinone glycosides. However, monomeric anthraquinone glycosides are also present in this plant.
Structural types
Sesquiterpenes can be of various structural types, some of which are presented with specific examples in the following table. Simple farnesane-type acyclic sesquiterpenes frans- 3-Farnesene A potent aphid-repellant found in hops and sweet potatoes frans- 3-Farnesene A potent aphid-repellant found in hops and sweet potatoes Cyclobutane and cyclopentane sesquiterpenes Abscisic acid A plant-growth regulatory agent Abscisic acid A plant-growth regulatory agent Lepidozanes and bicyclogermacrane...
Pyrimidine
Pyrimidine is a six-membered aromatic heterocyclic compound that contains two nitrogen atoms, separated by a carbon atom, in the ring. Nucleic acids, DNA and RNA, contain substituted purines and pyrimidines. Cyto-sine, uracil, thymine and alloxan are just a few of the biologically significant modified pyrimidine compounds, the first three being the components of the nucleic acids. A number of drug molecules contain a modified pyrimidine skeleton, the best known examples being the anticancer...
Medicinal importance of heterocyclic compounds
More than 50 of all known organic compounds are heterocyclic compounds. They play important roles in medicine and biological systems. A great majority of important drugs and natural products, e.g. caffeine, nicotine, morphine, penicillins and cephalosporins, are heterocyclic compounds. The purine and pyrimidine bases, two nitrogenous heterocyclic compounds, are structural units of RNA and DNA. Serotonin, a neurotransmitter found in our body, is responsible for various bodily functions. An...
Physical properties of phenols
The simplest phenols are liquids or low-melting solids. Because of hydrogen bonding, phenols have a quite high boiling point e.g. the boiling point of m-cresol is 201 C . Phenol itself is somewhat soluble in water 9 g per 100 g of water because of hydrogen bonding with water. Most other phenols are insoluble in water. Generally, phenols themselves are colourless. However, they are easily oxidized to form coloured substances. Phenols are acidic in nature and most phenols have Ka values of 10 10....
Reactions of quinoline and isoquinoline
Electrophilic aromatic substitutions Quinoline and isoquinoline undergo electrophilic aromatic substitution on the benzene ring, because a benzene ring is more reactive than a pyridine ring towards such reaction. Substitution generally occurs at C-5 and C-8, e.g. bromination of quinoline and isoquinoline. Nucleophilic substitutions Nucleophilic substitutions in quinoline and isoquinoline occur on the pyridine ring because a pyridine ring is more reactive than a benzene ring towards such...
Separation of aniline and a neutral compound from a mixture by solvent
If a mixture contains aniline and a neutral compound, both the constituents can easily be separated and purified by the solvent extraction method. To purify these compounds, the mixture is dissolved in diethylether, HCl and water are added and the solution is shaken in a separating funnel. Once two layers, aqueous and ether layers, are formed, they are separated. The lower layer aqueous contains the salt of aniline, and the ether layer has the neutral compound. Ether is evaporated from the...
Reactions of naphthalene
Naphthalene undergoes electrophilic substitutions on the ring, resulting in its various derivatives. In addition to the usual electrophilic substitutions, naphthalene can also undergo oxidation and reduction reactions under specific conditions as outlined below. Oxidation Oxidation of naphthalene by oxygen in the presence of vanadium pentoxide V2O5 destroys one ring and yields phthalic anhydride an important industrial process . However, oxidation in the presence of CrO3 and acetic acid AcOH...
Synthesis of naphthalene from benzene Haworth synthesis
Naphthalene can be synthesized from benzene through multi-step synthesis involving, notably, Friedel-Crafts FC acylation, Clemmensen reduction and aromatization reactions as outlined in the following scheme.
Why halogens are orthopara directing
Halogens are the only deactivating substituents that are ortho-para directors. However, they are the weakest of the deactivators. Halogens withdraw electrons from the ring through the inductive effect more strongly than they donate electrons by resonance. It is the resonance-aided electron-donating effect that causes halogens to be ortho-para-directing groups. Halogens can stabilize the transition states leading to reaction at the ortho and para positions. On the other hand, the...
Benzylic bromination of toluene
Bromine selectively substitutes for a benzylic hydrogen in toluene in a radical substitution reaction to produce bromomethylbenzene or benzylbro-mide. N-bromosuccinimide is used to carry out benzylic bromination of toluene. Bromomethylbenzene or benzylbromide can be subjected to further nucleophilic reactions. Bromine can be replaced by a variety of nucleophiles by means of an SN2 and SN1 reaction, resulting in various monosubstituted benzenes.
Preparation of alkenes and cycloalkenes
Alkenes are obtained by the transformation of various functional groups, e.g. dehydration of alcohols see Section 5.4.3 , dehalogenation of alkyl halides see Section 5.4.5 and dehalogenation or reduction of alkyl dihalides see Section 5.4.5 . These reactions are known as elimination reactions. An elimination reaction results when a proton and a leaving group are removed from adjacent carbon atoms, giving rise to a p bond between the two carbon atoms. Alkenes are obtained from selective hydrog...
Reactions of purine
Nucleophilic substitutions Aminopurines react with dilute nitrous acid to yield the corresponding hydroxy compounds. Deamination of aminopurines Adenine undergoes deamination to produce hypoxanthine, and guanine is deaminated to xanthine. Oxidation of xanthine and hypoxanthine Xanthine and hypoxanthine can be oxidized enzymatically with xanthine oxidase to produce uric acid.
Reactions of aniline
Aniline undergoes electrophilic substitutions. In aniline, the substitutions take place in ortho and para positions. As the -NH2 group is a strong activating group, the reaction rate is much faster than usually observed with benzene. A number of other types of reaction can also be carried out with aniline. Some of these reactions are discussed here. Salt formation As aniline is a base, it forms salt with mineral acids. N-alkylation The hydrogen atoms of the amino group in aniline can be...
Physical properties of quinoline and isoquinoline
Quinoline and isoquinoline are basic in nature. Like pyridine, the nitrogen atom of quinoline and isoquinoline is protonated under the usual acidic conditions. The conjugate acids of quinoline and isoquinoline have similar pKa values 4.85 and 5.14, respectively to that of the conjugate acid of pyridine. Quinoline, when exposed to light, forms first a yellow liquid, and slowly a brown liquid. It is only slightly soluble in water but dissolves readily in many organic solvents. Isoquinoline...
Quinoline and isoquinoline
Quinoline and isoquinoline, known as benzopyridines, are two isomeric heterocyclic compounds that have two rings, a benzene and a pyridine ring, fused together. In quinoline this fusion is at C2 C3, whereas in isoquinoline this is at C3 C4 of the pyridine ring. Like benzene and pyridine, these benzopyridines are also aromatic in nature. A number of naturally occurring pharmacologically active alkaloids possess quinoline and isoquinoline skeleton. For examples, papaverine from Papa-ver...
Physical properties of aniline
Aniline is a polar compound, and can form intermolecular hydrogen bonding between two aniline molecules. Aniline has higher b.p. 184 C than nonpolar compounds of the same molecular weight. It also forms hydrogen bonds with water. This hydrogen bonding accounts for the solubility of aniline in water 3.7 g 100 g water . Intermolecular hydrogen bonding Intermolecular hydrogen bonding in aniline of aniline with water Intermolecular hydrogen bonding Intermolecular hydrogen bonding in aniline of...
Reactions of phenols
Phenols undergo electrophilic substitutions. In phenol, the substitutions take place in ortho and para positions. As the OH group is an activating group, the reaction rate is much faster than usually observed with benzene. For example, the bromination of phenol produces ortho-bromophenol 12 and para-bromophenol 88 . A number of other reactions can also be carried out with phenols as follows. Salt formation Phenol is acidic in nature, and can form a salt with alkali, e.g. NaOH. Ether formation...
Preparation of quinoline and isoquinoline
Quinoline synthesis Skraup synthesis is used to synthesize the quinoline skeleton by heating aniline with glycerol, using sulphuric acid as a catalyst and dehydrating agent. Ferrous sulphate is often added as a moderator, as the reaction can be violently exothermic. The most likely mechanism of this synthesis is that glycerol is dehydrated to acrolein, which undergoes conjugate addition to the aniline. This intermediate is then cyclized, oxidized and dehydrated to give the quinoline system. A...