Introduction to Organic Chemistry PDF

ORGANIC CHEMISTRY Suat Sarı Hacettepe University Faculty of Pharmacy [email protected] Introduction to Organic Chemistry Suat Sarı [email protected] 2 Introduction to Organic Chemistry Chemistry is the scientific study of the prop...

ORGANIC CHEMISTRY Suat Sarı Hacettepe University Faculty of Pharmacy [email protected] Introduction to Organic Chemistry Suat Sarı [email protected] 2 Introduction to Organic Chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and compounds made of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they undergo during reactions with other substances (Wikipedia). Chemistry is a central science (basic → applied) How plants grow → Botany How rocks form → Geology how atmospheric ozone is formed → Ecology the properties of the soil on the Moon → Cosmochemistry How drugs work → Pharmacology How DNA evidence in crime scene is identified → Forensics [email protected] 3 Introduction to Organic Chemistry Chemistry → derived from the word “alchemy” → derived from the word al-kīmīā (‫)الكیمیاء‬ Eras and mile stones: Early people: fire, paint, ores, metallurgy (ancient Chinese covered weapons with chromium oxide) Antient world and atomism (why different matters have different properties, what are they made of?): “Matter is composed of indivisible and indestructible particles called "atomos" (Democritus, around 380 BC) Alchemy (medieval): Alchemists were not only interested in turning metals to gold (philosopher’s stone), but also medicine, astrology, metallurgy, astrology, astronomy, etc. Early chemistry: Chemistry gets its name. Sir Francis Bacon describes (sort of) the scientific method (1605). Robert Boyle (The Sceptical Chymist) separates chemistry from alchemy. Boyle’s law (1662) → pressure and volume of gases PV = k Modern Chemistry: John Dalton’s atomic theory (1803), Avogadro (the number), Markovnikov (the addition rule), Mendeleev (periodic table), Fischer (synthesis), Ramsay (noble gases), Curie (radioactivity)… [email protected] 4 Introduction to Organic Chemistry There are many subdisciplines under chemistry Analytical chemistry Biochemistry Inorganic chemistry Nuclear chemistry Physical chemistry Theoretical chemistry … [email protected] 5  Introduction to Organic Chemistry Chemistry is the scientific study of the properties and behavior of matter (Wikipedia). Organic chemistry is the chemistry of compounds that contain the element carbon. If a compound does not contain the element carbon, it is said to be inorganic. Carbon compounds are central to the structure of living organisms and therefore to the existence of life on Earth. We exist because of carbon compounds. But, why? 1. Carbon atoms can form strong bonds to other carbon atoms to form rings and chains of carbon atoms 2. Carbon atoms can also form strong bonds to elements such as H, N, O, and S, thus carbon can be the basis for the huge diversity of compounds necessary for the emergence of living organisms. [email protected] 6 Introduction to Organic Chemistry Any place to support a life form based on, say, silicon? Nah, probably not. The bonds that silicon atoms form to each other are not nearly as strong as those formed by carbon, and therefore it is very unlikely that silicon could be the basis for anything equivalent to life as we know it. [email protected] 7 Introduction to Organic Chemistry Life on earth? A meteorite that fell near Murchison, Victoria, Australia, in 1969 was found to contain over 90 different amino acids, 19 of which are found in living organisms on Earth. Stanley Miller and Harold Urey (Miller-Urey experiment, University of Chicago, 1952) showed that five amino acids (essential constituents of proteins) were synthesized when an electric spark (think of lightning) passes through a flask containing a mixture of methane, hydrogen, water, and ammonia (think of the early atmosphere): primordial soup of the compounds In 2008 the experiment was repeated: 22 amino acids were formed. Bottom line: “Life on Earth may have developed through the gradual evolution of carbon- based molecules in a “primordial soup” of the compounds that were thought to exist on a prebiotic Earth.” [email protected] 8 Introduction to Organic Chemistry Development of Organic Chemistry Before: Organic compounds are only those that came from living organisms, and only living things could synthesize organic compounds through intervention of a vital force (vitalism, 19th century). Then: Friedrich Wöhler discovered in 1828 that an organic compound called urea (a constituent of urine) could be made by evaporating an aqueous solution of the inorganic compound ammonium cyanate. The synthesis of an organic compound, began the evolution of organic chemistry as a scientific discipline. [email protected] 9 Introduction to Organic Chemistry Atomic structure compound → elements → atoms → nucleus (protons an neutrons) + electrons Protons (+) charge, electrons (-) charge The elements commonly found in organic molecules are carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur, as well as the halogens: fluorine, chlorine, bromine, and iodine. Each element is distinguished by its atomic number (Z) = the number of protons in its nucleus = the number of electrons surrounding the nucleus (if neutral). Isotopes: atoms of the same element that have different masses. Nuclei of all atoms of the same element will have the same number of protons, some atoms of the same element may have different masses because they have different numbers of neutrons. Eg., 13C (1% of C is 13C, so mass number of C is 12.011) [email protected] 10 Basic concepts: Chemical bonds Suat Sarı [email protected] 11 Octet Rule Lewis and Kössel (1916): Atoms without the electronic configuration of a noble gas generally react to produce such a configuration because these configurations are known to be highly stable. For all of the noble gases except helium, this means achieving an octet of electrons in the valence shell. The valence shell is the outermost shell of electrons in an atom. The tendency for an atom to achieve a configuration where its valence shell contains eight electrons is called the octet rule. Two major types of chemical bonds were proposed: 1. Ionic (or electrovalent) bonds are formed by the transfer of one or more electrons from one atom to another to create ions. 2. Covalent bonds result when atoms share electrons. [email protected] 12  LiF Ionic bonds Atoms may gain or lose electrons and form charged particles called ions. An ionic bond is an attractive force between oppositely charged ions. Electronegativity is a measure of the ability of an atom to attract electrons. Electronegativity increases as we go across a horizontal row of the periodic table from left to right and it increases as we go up a vertical column. Ions form because atoms can achieve the electronic configuration of a noble gas by gaining or losing electrons. LiF crystal is much more stable than Li and F. Ionic substances, because of their strong internal electrostatic forces, usually have very high melting points (above 1000 °C.) In polar solvents, such as water, the ions are solvated, and such solutions usually conduct an electric current. Ionic compounds, often called salts, form only when atoms of very different electronegativities transfer electrons to become ions. [email protected] 13 Covalent bonds When two or more atoms of the same or similar electronegativities react, a complete transfer of electrons does not occur. Such atoms achieve noble gas configurations by sharing electrons. Covalent bonds form by sharing of electrons between atoms of similar electronegativities to achieve the configuration of a noble gas. Molecules are composed of atoms joined exclusively or predominantly by covalent bonds. How to write a molecule: Lewis structures H+ [email protected] 14 Covalent bonds: multiple covalent bonds Atoms can share two or more pairs of electrons Ions, themselves, may contain covalent bonds. [email protected] 15 ammonium ion Covalent bonds: Exceptions to the Octet Rule Atoms share electrons, not just to obtain the configuration of an inert gas, but because sharing electrons produces increased electron density between the positive nuclei. The resulting attractive forces of nuclei for electrons is the “glue” that holds the atoms together. Elements of the 2nd period of the periodic table can have a maximum of four bonds (i.e., have eight electrons around them) because these elements have only one 2s and three 2p orbitals available for bonding. Each orbital can contain two electrons, and a total of eight electrons fills these orbitals. The octet rule, therefore, only applies to these elements. Elements of the 3rd period and beyond have d orbitals that can be used for bonding. These elements can accommodate more than eight electrons in their valence shells and therefore can form more than four covalent bonds. Examples are compounds such as PCl5 and SF6. [email protected] 16 [email protected] 17  Structural formulae Propanol C3H8O (Empirical) Formula Isopropanol [email protected] 18 Structural formulae: bond-line formula Let’s calculate molecular weight of 2-chlorobutane First get its empirical formula: C4H9Cl Then get the atomic mass of the elements involved: C 12, H 1, Cl 35.5 2-Chlorobutane And do the math: (12x4)+(9x1)+(35.5x1) = 92.5 g/mol Can you draw this? and find its molecular weight? [email protected] 19  Formal charges: how to calculate NH4+ First examine each atom and, using the periodic table, determine how many valence electrons it would have if it were an atom not bonded to any other atoms. This is equal to the group number of the atom in the periodic table (H: 1, C: 4, N: 5, O: 6). Next, examine the atom in the Lewis structure and assign the valence electrons in the following way: assign to each atom half of the electrons it is sharing with another atom and all of its unshared (lone) electron pairs Then do the following calculation for the atom: NO3- Formal charge = number of valence electrons - 1/2 number of shared electrons - number of unshared electrons F = Z - (1/2)S – U F is the formal charge, Z is the group number of the element, S equals the number of shared electrons, and U is the number of unshared electrons. It is important to note, too, that the arithmetic sum of all the formal charges in a molecule or ion will equal the overall charge on the molecule or ion. [email protected] 20 Formal charges: how to calculate Can you calculate these? [email protected] 21  Resonance theory Often more than one equivalent Lewis structure can be written for a molecule or ion. CO32- structures are converted into any other by changing only the positions of the electrons. ❖ Carbon–oxygen double bonds (1.20 Å) are shorter than single bonds (1.43 Å): X-ray studies However, all carbon–oxygen bonds of CO32- are of equal length (1.28 Å)!?? Resonance structures are not real structures for the actual molecule Resonance theory: If a molecule or ion can be represented by two or more Lewis or ion; they exist only on paper. structures that differ only in the positions of the electrons: 1. None of these structures, which we call resonance structures or resonance contributors, will be a realistic representation for the molecule or ion. None will be in complete accord with the physical or chemical properties of the substance. 2. The actual molecule or ion will be better represented by a hybrid (average) of these structures. [email protected] 22  Resonance theory !WARNING! None of these contributing structures exist. Thus, neither does the conversion, they are just hypothetical, help understand the resonance. Double headed arrow (⟷︎) indicates the hypothetical conversion. Do not mix it with “⇋” which indicates 𝛿- Partial negative equilibrium. Resonance is not equilibrium! In an electrostatic potential map, regions of relatively more negative charge are red, while more positive regions (i.e., less negative regions) are indicated by colors trending toward blue. Equality of the bond lengths in the carbonate anion (partial double bonds as shown in the resonance hybrid above) is also evident in this model. Electrostatic potential map of CO32- [email protected] 23  Arrows in chemistry Resonance rules: Resonance structures exist only on paper. We are only allowed to move electrons in writing resonance structures. We move only electrons of multiple bonds and nonbonding electron pairs. All of the structures must be proper Lewis structures. The energy of the resonance hybrid is lower than the energy of any contributing structure. The more stable a structure is, the greater is its contribution to the hybrid. [email protected] 24  Atomic orbitals and electron configuration Max Born (1926): the shapes of some s and p orbitals. pure, unhybridized p orbitals are almost touching spheres. the p orbitals in hybridized atoms are lobe- shaped The square of a wave function (𝜓2) for a particular x, y, z location expresses the probability of finding an electron at that location in space: electron probability density (0-1) The volumes that we show are those that An orbital is a region of space where the probability of finding would contain the electron 90–95% of the an electron is high. time. There is a finite, but very small, Atomic orbitals are plots of 𝜓2 in three dimensions. These probability of finding an electron at greater plots generate the familiar s, p, and d orbital shapes. distance from the nucleus than shown in the [email protected] plots. 25 Electron configurations Electrons in 1s orbitals have the lowest energy because they are closest to the positive nucleus. Electrons in 2s orbitals are next lowest in energy. Electrons of the three 2p orbitals have equal but higher energy than the 2s orbital. Orbitals of equal energy (such as the three 2p orbitals) are called degenerate orbitals. Orbitals are filled so that those of lowest energy are filled first. A maximum of two electrons may be placed in each orbital but only when the spins of the electrons are paired. An electron spins about its own axis. An electron is permitted only one or the other of just two possible spin orientations. We usually show these orientations by arrows, either ↿ or ⇂. Thus two spin-paired electrons would be designated ↿⇂. For degenerate orbitals, (e.g., the three p orbitals), we add one electron to each with their spins unpaired until each of the degenerate orbitals contains one electron. (This allows the electrons, which repel each other, to be farther apart.) Then we begin adding a second electron to each degenerate orbital so that the spins are paired. [email protected] 26  II: Nonbonded interactions (hydrogen bond, Molecular orbitals halogen bond, van der Waals forces, etc.) An atomic orbital represents the region of space where one or two electrons of an isolated atom are likely to be found. As the two H atoms approach each other their 1s orbitals begin to overlap until their atomic orbitals combine to form molecular orbitals. A molecular orbital represents the region of space where one or two electrons of a molecule are likely to be found. An orbital (atomic or molecular) can contain a maximum of two spin- paired electrons. When atomic orbitals combine to form molecular orbitals, the number of molecular orbitals that result always equals the number of atomic orbitals that combine so H-H → two orbitals: 1. Bonding molecular orbital (𝜓molec) results when two orbitals of the same phase overlap. The bonding molecular orbital of a hydrogen molecule in its lowest energy (ground) state contains both electrons from the individual hydrogen atoms. 2. Antibonding molecular orbital (𝜓*molec) results when two orbitals of opposite phase overlap. The antibonding molecular orbital contains [email protected] 27 no electrons in the ground state of a hydrogen molecule.  sp3 hybridization Ground state electron configuration of carbon That’s why ah ed ro n! n e i s t et r r, me th a Howeve This applies all the single bonds that carbons make: we call them sp3 hybridized carbons. These single bonds are called sigma (𝜎) bonds [email protected] 28 sp2 hybridization Carbon–carbon double bonds are comprised of sp2-hybridized carbon atoms. Many important organic compounds exist in which carbon atoms share more than two electrons with another atom. When two carbon atoms share two pairs of electrons, for example, the result is a carbon–carbon double bond. Such Carbon-carbon double bond: compounds are called alkenes. one of them sigma (𝜎) the other pi (π) other single bonds sigma (𝜎) [email protected] 29 sp hybridization Carbon–carbon triple bonds are comprised of sp-hybridized carbon atoms. Hydrocarbons in which two carbon atoms share three pairs of electrons between them, and are thus bonded by a triple bond, are called alkynes. Carbon-carbon triple bond: one of them sigma (𝜎) the other two are pi (π) [email protected] 30 Hybridization…more Bond lengths: sp3 C-C (1.54 Å) > sp2 C=C (1.34 Å) > sp C≡C (1.20 Å) Hybridization applies to atoms other than carbon: sp3 NH3 H2 O acetonitrile [email protected] 31 Reaction Types Suat Sarı [email protected] 32  Organic reactions Chemical reaction: process that leads to the Reagent(s) (reactant(s)): initial substance(s) (A and B) chemical transformation of one set of chemical Product(s): C and D substances to another. Intermediate(s): temporary product(s) that yield the Atoms rearrange/chemical bonds break final product(s) and/or form Reaction conditions: solvent, catalysts, reaction temp. Energy change and duration, etc. Catalyst: interacts with reagents or intermediates, New products increases reaction rate/yield or lowers required energy, emerges unchanged Reaction rate: at given conditions, slow or fast? Energy: endothermic or exothermic? Yield: how much product obtained Stoichiometry: how the reactants and products are related in terms of weight methane oxygen carbon dioxide water Step: Reactions usually take place in multiple steps Rate-limiting step: slowest step in a reaction CH4 16 g/mol, O2 32 g/mol, CO2 44 g/mol, H2O 18 g/mol [email protected] 33  It’s alw ays el ectron s that Reaction types move /attac k in a reac Substitution reactions tion Elimination reactions Addition reactions Rearrangement reactions Oxidation-reduction (Redox) reactions Radical reactions [email protected] 34  Nucleophile: reagent that seeks a positive center. Any negative ion or uncharged molecule with an unshared electron pair is a potential nucleophile. Substitution reactions E.g., HO-, R-OH, H2O, NH3, RNH2, X-, R3C-, etc. Electrophile: reagent that seeks electrons so as to achieve a stable shell of electrons like that of a noble gas. E.g., H+ or H3O+, R3C+, CO2, SO3, AlCl3, BF3, X+ (from X2), etc. Nucleophilic substitution (SN) reactions Electrophilic substitution (SE) reactions [email protected] 35 Elimination reactions the fragments of some molecule (YZ) are removed (eliminated) from adjacent atoms of the reactant, leading to the creation of a multiple bond: [email protected] 36 Addition reactions An addition reaction results in the conversion of one π bond and one 𝝈 bond into two 𝝈 bonds [email protected] 37 Addition reactions Nucleophilic addition reactions (A N): nucleophile attacks the electron-deficient end of multiple bond Electrophilic addition reactions (AE): the π bond electrons of multiple bond attack electrophile [email protected] 38  Rearrangement reactions the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule Beckmann Fries Claisen 1,2 rearrangement [email protected] 39 Redox reactions Transfer of electrons between two species is involved, oxidation states of the species change. Oxidation: reaction with oxygen, loss of electrons, increase of bond order Reduction: gaining electrons, losing oxygen, decrease of bond order [email protected] 40 Radical reactions Radicals possess an unpaired electron, they are unstable, thus short-lived. They react with other molecules to form new radicals. [email protected] 41  Intro O Carboxylic acids Nomenclature O OH ? COOH CO2H OH Common names: Formic acid, acetic acid, butyric acid O O O Na O Na sodium propanoate sodium hexanoate Acidity O H O [email protected] 42  Can you name these? (E)-5-chloro-2-hexenoic acid 5-phenylpentanoic acid Sodium 4-bromobutanoate [email protected] 43 What is the acidity order? [email protected] 44  Dicarboxylic acids Nomenclature for carb. derivatives IUPAC: alkanedioic acid Carboxylic anhydrides Esters O O O ? Amides Acyl chlorides Nitriles O NH 2 ? IUPAC: [email protected] Common: 45 How do you name this insect repellent? N,N-Diethyl-3-methylbenzamide [email protected] 46  Carboxylic acids: synthesis 1. Oxidation of alkenes 3. Benzylic oxidation of alkylbenzenes 4. Oxidation of the benzene ring 5. Hydrolysis of cyanohydrins and other nitriles 2. Oxidation of primary alcohols 6. Carbonation of Grignard reagents [email protected] 47 How to synthesize benzoic acid from the following? 1. KMNO 4, HO - O D OH + CHOOH 2. H 3O+ [email protected] 48 How do you obtain this via Grignard method? Mg 1. CO2 Et 2O 2. H 3O+ OH Cl MgCl O [email protected] 49 Acyl substitution: nucleophilic addition-elimination at the acyl carbon Less reactive acyl compounds can be synthesized from more reactive ones, but the reverse is usually difficult and, when possible, requires special reagents. [email protected] 50  Acyl chlorides Synthesis Reactions [email protected] 51  Carboxylic acid anhydrides Synthesis Reactions [email protected] 52  Esters Synthesis Acid-catalyzed esterification: Fisher esterification Where does the OH of H2O come from? E.g. [email protected] 53  Esters Synthesis Reactions from acyl chloride Transesterification Acidic hydrolysis from carboxylic anhydrides Basic hydrolysis: Saponification [email protected] 54  What is the order of stability for these? CH3 OH OCH3 O CH3 O [email protected] 55  Lactones Synthesis Hydrolysis [email protected] 56  Amides Synthesis from esters from acyl chlorides from carboxylic anhydrides Reactions [email protected] 57  Lactams IUPAC: Aziridine-2-one Pyrrolidin-2-one Piperidin-2-one [email protected] 58 What are A, B, and C? [email protected] 59  Nitriles Synthesis Reactions [email protected] 60  Other carbonic acid derivatives O H H Alkyl chloroformates and carbamates CO2 + H 2O O O Carbonic acid phosgene Unstable derivatives [email protected] 61  Decarboxylation of carboxylic acid slow fast [email protected] 62  Amines Suat Sarı Hacettepe University Faculty of Pharmacy [email protected] [email protected] 64  NH3 Nomenclature ammonia Amine as substituent Aromatic amines [email protected] 65 Nomenclature [email protected] 66  Can you name these? 2-phenyl-1-ethanamine (R)-1-phenylpropan-2-amine 4-(2-aminoethyl)imidazole or 2-(imidazole-4-yl)ethanamine 4-(2-aminoethyl)benzene-1,2-diol or 2-(3,4-dihydroxyphenyl)-1-ethanamine or 4-(2-aminoethyl)catechol [email protected] 67 Physical properties and structure Lone pair Tetrahedron when lone pair is considered [email protected] 68  Basicity Aromatic amines are less basic than aliphatic amines Cyclic amines are similar to aliphatic amines [email protected] 69  Basicity Amides are far less basic than amines! [email protected] 70 Which is the least basic? [email protected] 71 Aminium (ammonium) salts and quaternary ammonium salts N + Br [email protected] 72  Synthesis Nucleophilic substitution Alkylation of ammonia Alkylation of azide ion and reduction Not convenient, multiple alkylation occurs (using a large excess of ammonia may help): Azides are explosive and hard to handle Gabriel synthesis But it’s OK with tertiary amines [email protected] 73  Synthesis Aromatic amines through nitro reduction Reductive amination [email protected] 74  Synthesis Reduction of nitriles, oximes, and amides A convenient way for monoalkylation [email protected] 75  Synthesis Hofmann and Curtis rearrangements Hofmann Curtis [email protected] 76  Reactions Reactions with nitrous acid HNO2 is unstable, prepared in situ: Reactions of primary aliphatic amines with nitrous acid Not of synthetic significance, too many side products Oxidation Reactions of primary aromatic amines with nitrous acid [email protected] 77  Reactions Reactions with nitrous acid Reactions of secondary amines with nitrous acid Reactions of tertiary amines with nitrous acid Yields nitrosamines [email protected] 78  Reactions Reactions with nitrous acid: Replacements using nitrous acid Sandmeyer reaction: cuprous catalysts are used Arene diazonium salts unstable over 5°C Explosive when dry Prepared in situ and proper reagent is added to yield the products above (except for ArF) [email protected] 79  Reactions Reactions with nitrous acid: Replacements using nitrous acid Replacement by iodine Replacement by H: Deamination Hypophosphorous acid is used. Why remove amine when e.g., aniline is synthesized from benzene? Replacement by fluorine HBF4 is used, diazonium fluoroborate is isolated m-Bromotoluene cannot be synthesized from toluene (o- and p- isomers are obtained instead) [email protected] 80  Reactions Coupling reactions of arenediazonium salts Arenediazonium ions are weak electrophiles, they react with phenols and tertiary arylamines to yield azo compounds: diazo coupling [email protected] 81  Reactions Reactions with sulphonyl chlorides Synthesis of sulphanilamides [email protected] 82  Reactions Eliminations The Hofmann elimination The Cope elimination Which product is preferred? Zaitsev rule: Eliminations with non-charged substrates yield mainly more substituted product H H Hofmann rule: Eliminations with charged substrates yield N mainly less substituted product O [email protected] 83  Isomerism Suat Sarı Hacettepe University Faculty of Pharmacy [email protected] Isomer: same atoms different combination Types of isomerism 1. Constitutional isomers 2. Stereoisomers Same molecular formula, different connectivity Same molecular formula, same connectivity, different spatial orientation 2a. Enantiomers Stereoisomers that are nonsuperposable mirror images of each other chain/ position 2b. Diastereomers Stereoisomers that are not mirror images of each other functional i. Molecules with more than one chiral center ii. Geometric isomers (E/Z isomers) tautomerism 85  Chirality Chiral objects Handedness [email protected] 86  Enantiomers Enantiomers only occur with compounds whose molecules are chiral. A chiral molecule and its mirror image are called a pair of enantiomers. The relationship between them is enantiomeric. A molecule that contains one chirality center is chiral and can exist as a pair of enantiomers. A chirality center is a tetrahedral carbon atom that is bonded to four different groups. Racemates are mixtures of equal amounts of enantiomers IUPAC: enantiomers get R or S suffix All the four groups attached to the carbon must be different These are not tetrahedral (sp3-hybridized) carbons I: (S)-2-butanol II: (R)-2-butanol [email protected] 87  Enantiomers Biological importance Dextropropoxyphene Levopropoxyphene analgesic antitussive m e r o er -dist om eut [email protected] 88  Enantiomers Symmetry operation Properties of enantiomers Non-superposable mirror images Pure enantiomers have identical physicochemical properties Presence of a chiral center Enantiomers show different behavior only when they Symmetry operation interact with other chiral substances, including their own enantiomer Enantiomers rotate planed-polarized light at equal degrees but in opposite directions (“optically active”) (+) → rotate planed-polarized light clockwise (-) → rotate planed-polarized light counterclockwise Enantiomers are different compounds [email protected] 89  Enantiomers Synthesis Reactions carried out with achiral reactants can lead to chiral products. In the absence of any chiral influence from a If a reaction produces preferentially one enantiomer catalyst, reagent, or solvent, the outcome of such a over its mirror image, the reaction is said to be an reaction is a racemic mixture. enantioselective reaction. l If a reaction leads preferentially to one diastereomer over others that are possible, the reaction is said to be a diastereoselective reaction. enantioselective → a chiral reagent, catalyst, or solvent needed Single enantiomer – enantiomerically pure – enantiomeric excess (ee) 100% [email protected] 90  Diastereomers Molecules with more than one chirality center: enantiomers vs. diastereomers Stereoisomers of 2,3-dibrompentane: Number of possible stereoisomers = 2n N: number of chirality center diastereomer diastereomer 22 = 4 stereoisomers 28 = 256 stereoisomers (only one is biosynthesized) Diastereomers have different physicochemical properties (boiling point, solubility, etc.) Stereochemistry is indicated for each chirality center in the name: (2R,3R)-2,3-dibromobutane [email protected] 91  Diastereomers Molecules with more than one chirality center: meso compounds two chirality centers + mirror images + superposable → meso compounds C and D are achiral, they are the “same” compound C and D have internal plane of symmetry Meso compounds are achiral, optically inactive dodooooooooooooodooooooooooooo [email protected] 92  Chirality Stereoisomerism of cyclic compounds Ring plane: alpha → under the plane, beta → above the plane trans cis chiral achiral Both compounds have plane of symmetry Both achiral Not meso because no chirality center They are diastereomers [email protected] 93  Stereoisomerism of cyclic compounds 1,3-dimethylcyclohexane has 2 chirality centers but 3 stereoisomers trans-1,3-dimethylcyclohexane has a pair of enantiomers cis-1,3-dimethylcyclohexane is meso, achiral [email protected] 94  Stereoisomerism Uncommon cases Chirality center: other atoms Atropisomers: stable conformational isomers 1,3-dichloroallene [email protected] 95 Diastereomers Geometric isomers [email protected] 96