Organic Chemistry II (College of Pharmacy) Lecture Notes PDF 2024-2025

ORGANIC CHEMISTRY II College of Pharmacy 2nd Stage/1st semester 1st Lecture 2024-2025 Lecturer :Mohammed S.Nawrooz Pharmacognosist 1  Aromatic Hydrocarbons Introduction: An aromatic hyd...

ORGANIC CHEMISTRY II College of Pharmacy 2nd Stage/1st semester 1st Lecture 2024-2025 Lecturer :Mohammed S.Nawrooz Pharmacognosist 1  Aromatic Hydrocarbons Introduction: An aromatic hydrocarbon is an unsaturated cyclic hydrocarbon with a pattern of bonding that makes it chemically stable. Chemists have found it useful to divide all organic compounds into two broad classes: aliphatic compounds and aromatic compounds. The original meanings of the words "aliphatic" (fatty) and "aromatic" (fragrant). The word aromatic is used for historical reasons to refer to the class of compounds related structurally to benzene. 2  Importance of aromatic compounds Aromatic compounds play key roles in the biochemistry of all living things. The four aromatic amino acids histidine, phenylalanine, tryptophan, and tyrosine each serve as one of the 20 basic building-blocks of proteins. Further, all 5 nucleotides (adenine, thymine, cytosine, guanine, and uracil) that make up the sequence of the genetic code in DNA and RNA are aromatic purines or pyrimidines. Chlorophyll also has a similar aromatic system. Also, present in chemical structures of natural active constituents. 3  Properties of Aromatic Hydrocarbons 1. Some are liquids at room temperature while others are crystalline solids 2. Most are non-polar because of the symmetrical shape 3. Insoluble in water 4.Volatile 5.Carcinogenic 6.They burn with a strong sooty yellow flame because of the high carbon–hydrogen ratio. Benzene is the simplest aromatic hydrocarbon 4  Types of aromatic compounds 1.Neutral homocyclics : Benzene 2.Heterocyclics: A heterocycle is a cyclic compound that contains atoms of two or more elements in its ring, usually carbon along with nitrogen, oxygen, or sulfur. Pyridine and pyrimidine, for example, are six-membered heterocycles with nitrogen in their rings. 3. polycyclic aromatic compounds 5  BENZENE &AROMATICITY In the early days of organic chemistry, the word aromatic was used to describe such fragrant substances as benzaldehyde (from cherries, peaches, and almonds), toluene (from Tolu balsam), and benzene (from coal distillate). It was soon realized, however, that substances grouped as aromatic differed from most other organic compounds in their chemical behavior 6 - Today, the association of aromaticity with fragrance has long been lost, and we now use the word aromatic to refer to the class of compounds that contain six- membered benzene-like rings with three double bonds. - Many naturally occurring compounds are aromatic in part, including steroids such as estrone and well-known pharmaceuticals such as the cholesterol- lowering drug atorvastatin,( marketed as Lipitor). - Benzene itself causes a depressed white blood cell count (leukopenia) on prolonged exposure and should not be used as a laboratory solvent. 7  Sources of Aromatic Compounds Simple aromatic hydrocarbons come from two main sources: coal and petroleum. Coal is an enormously complex mixture made up primarily of large arrays of benzene-like rings joined together. Thermal breakdown of coal occurs when it is heated to 1000 °C in the absence of air, and a mixture of volatile products called coal tar. Fractional distillation of coal tar yields benzene, toluene, xylene (dimethylbenzene), naphthalene, and other aromatic compounds 8 9  Unlike coal, petroleum contains few aromatic compounds and consists largely of alkanes. During petroleum refining, however, aromatic molecules are formed when alkanes are passed over a catalyst at about 500 °C under high pressure. Aromatic substances, more than any other class of organic compounds, have acquired a large number of nonsystematic names. IUPAC rules discourage the use of most such names but do allow for some of the more widely used ones to be retained. Thus, methylbenzene is known commonly as toluene; hydroxybenzene, as phenol; aminobenzene, as aniline; and so on. 10  Nomenclature Sometimes you will see the greek prefixes ortho-, meta-, and para-used to represent the 1,2 position, 1,3 position, and 1,4 positions on the benzene ring respectively. 11 12 1…Mono substituted benzenes are named systematically in the same manner as other hydrocarbons, with -benzene as the parent name. Thus, C6H5Br is bromo benzene, C6H5NO2 is nitrobenzene, and C6H5CH2CH2CH3 is propyl benzene. 2…Alkyl-substituted benzenes are sometimes referred to as arenes and are named in different ways depending on the size of the alkyl group. If the alkyl substituent is smaller than the ring (six or fewer carbons),the arene is named as an alkyl-substituted benzene. 13  If the alkyl substituent is larger than the ring (seven or more carbons), the compound is named as a phenyl-substituted alkane.*Phenyl (C6H5 ) 14  3…Disubstituted benzenes are named using one of the prefixes ortho (o), meta (m), or para (p). An ortho-disubstituted benzene has its two substituents. benzenes are named as ortho (1,2 disubstituted), meta (1,3 disubstituted), or para (1,4 disubstituted) derivatives. 15  The ortho , meta, para system of nomenclature is also useful when discussing reactions. For example, we might describe the reaction of bromine with toluene by saying, “Reaction occurs at the para position”—in other words, at the position para to the methyl group already present on the ring. 16  As with cycloalkanes , benzenes with more than two substituents are named by choosing a point of attachment as carbon 1 and numbering the substituents on the ring so that the second substituent has as low a number as possible. If ambiguity still exists, number so that the third or fourth substituent has as low a number as possible, until a point of difference is found. The substituents are listed alphabetically when writing the name. 17  Benzene (C6H6) has six fewer hydrogens than the corresponding six-carbon cycloalkane (C6H12) and is clearly unsaturated, usually being represented as a six membered ring with alternating double and single bonds. Yet it has been known that benzene is much less reactive than typical alkenes and fails to undergo typical alkene addition reactions. Cyclohexene, for instance, reacts rapidly with Br2 and gives the addition product 1,2-dibromocyclohexane, but benzene reacts only slowly with Br2 and gives the substitution product C6H5Br. 18 19 20 21  Stability of the benzene ring. Reactions of benzene Benzene undergoes substitution rather than addition. Kekule's structure of benzene is one that we would call "cyclohexatriene." We would expect this cyclohexatriene, like the very similar compounds, cyclohexadiene and cyclohexene, to undergo readily the addition reactions characteristic of the alkene structure. -The types of reactions in cyclohexane are ? 22 As the examples in Table 10.1 show, this is not the case; under conditions that cause an alkene to undergo rapid addition, benzene reacts either not at all or very slowly 23  Carbon-carbon bond lengths in benzene All carbon- carbon bonds in benzene are equal and are intermediate length between single and double bonds. Carbon-carbon double bonds in a wide variety of compounds are found to be about (1.34 A) long. Carbon-carbon single bonds, in which the nuclei are held together by only one pair of electrons, are considerably Longer(1.54 angstroms). * Hence, C−C bond length in benzene is 1.39 ˚A. Benzene undergoes substitution reactions that retain the cyclic conjugation rather than electrophilic addition reactions that would destroy the conjugation. 24 25