Lecture 1 2024 Cairo.pdf

Organic Chemistry  Lecture 1 (Subject of organic chemistry. Classification of organic compounds according to the R-X formula. Valence states of the carbon atom. Concepts of isomerism and homology. Geometric parameters of organic molecules. Methods of drawing the structure of org...

Organic Chemistry  Lecture 1 (Subject of organic chemistry. Classification of organic compounds according to the R-X formula. Valence states of the carbon atom. Concepts of isomerism and homology. Geometric parameters of organic molecules. Methods of drawing the structure of organic molecules) Alan Akhmedov, PhD, Senior lecturer of the Department of Organic and Medicinal Chemistry, Butlerov’s Chemical Institute, KFU  Semester plan 8 leсtures: 1 lecture – subject and general issues of organic chemistry 2-5 lectures – classes of organic compounds 6-8 lectures – basics of bioorganic chemistry 11 Practical classes: Seminars on lecture topics or labs. 801-1000 601-800 14-16 9 322 370 513  Literature for mastering the course: 1. John McMurry – Organic Chemistry with Biological Applications 2e 801-1000 601-800 14-16 9 322 370 513 801-1000 601-800 14-16 9 322 370 513  Organic chemistry The main objective of the organic chemistry course: «To teach how to obtain, apply and disseminate acquired knowledge in the field of organic chemistry to all areas of professional activity» After completing this course you will be able to: 1. Establish the pattern “the structure of an organic compound is its property” 2. "Read chemical hieroglyphs" 801-1000 601-800 14-16 9 3. Make your own expert opinion about the properties of a particular drug, by looking at its chemical name or its structural formula. 322 370 513  Organic chemistry Organic chemistry is the chemistry of carbon compounds. The name "organic" may cause confusion; it has been preserved from the days when chemical compounds were divided into two classes - inorganic and organic (depending on the source of their production). Inorganic compounds included substances obtained from minerals, and organic compounds included compounds of plant and animal origin, i.e. substances formed in living organisms. Modern organic chemistry is a scientific discipline that comprehensively studies carbon compounds: Structure 801-1000 601-800 Physical and chemical properties 14-16 9 Preparation methods, synthesis 322 370 Practical uses 513  What is organic compounds? Organic compounds are compounds of carbon with other elements (hydrogen, oxygen, nitrogen, sulfur, phosphorus, halogens), which contain C-C and C-H bonds. Moreover, the presence of the C-C and C-H bonds is obligatorily. There are currently more than 16 million organic compounds. 801-1000 601-800 Why are there such a large number of organic compounds 14-16 9 that are resistant to the physical and chemical conditions of 322 370 our planet? 513  Properties of the carbon atom 1) The presence of four electrons in the outermost energy level (2s and 2p): С 2s22p2 Therefore, the carbon atom is not inclined to either lose or gain free electrons to form ions 2) Small atomic size (compared to other group IV elements): Element Atomic Element Atomic Element Atomic radius, radius, radius, nm nm nm 801-1000 601-800 14-16 9 С 0.077 Ge 0.139 Pb 0.175 Si 0.133 Sn 0.158 322 370 513  Electronic structure of the carbon atom Ground state Excited state The carbon atom goes into an excited state during bond formation. One of the two s- 801-1000 601-800 electrons moves to the free 2p orbital. The carbon atom get the electronic 14-16 9 configuration 1s22s12p3. A carbon atom in excited state has four unpaired electrons: 322 370 one s electron and three p electrons. 513  The basis of organic chemistry is the theory of structure. The creation of the theory of the structure of organic compounds is associated with the names of three great chemists of the second half of the 19th century: Archibald Scott Couper, August Kekulé & Alexander Butlerov. The key role in the creation of this theory belongs to Alexander Mikhailovich Butlerov (1861). He introduced the concept of chemical structure (he meant the order of bonds of atoms in a molecule), established that the chemical structure of a substance determines its chemical and physical properties, i.e., he explained the 801-1000 601-800 14-16 9 phenomenon of isomerism and proved the predictive power of his theory. 322 370 513  Excursion into history It was in the chemical laboratory of Kazan University that a scientific school arose in the mid-19th century, which gave the world a whole galaxy of wonderful scientists, whose works constitute the golden fund of world chemical science! Karl Ernst Claus, Nikolay Zinin, Alexander Butlerov, Vladimir Markovnikov, Alexander Popov, Konstantin Flavitsky, Alexander Zaytsev, Yegor Wagner, Alexey Albitsky, Sergey Reformatsky, Alexander Reformatsky, Aleksandr Arbuzov, Alexander Razumov, Gilm 801-1000 601-800 Kamay, Boris Arbuzov, Arkady Pudovik, Vasily Abramov, Alexander Konovalov – here is a 14-16 9 list of outstanding names that make up the “main line” of the school. 322 370 “The cradle of Russian organic chemistry” – this is how historians of chemistry defined 513 Kazan, the chemical laboratory of Kazan University.  Museum of the Kazan Chemical School Nikolay Zinin Alexander Butlerov Butlerov’s audience 801-1000 601-800 14-16 9 322 370 513 Alexander Zaytsev Vladimir Markovnikov  Butlerov’s Theory (1861) "Every organic compound has a single chemical formula that reflects the order in which atoms bind in a molecule and determines its properties." Key points: 1. The strict sequence of bonding of atoms to each other in a molecule. This is called structure. 2. The chemical properties of a substance are determined by the nature of its elementary components, their quantity and chemical structure. 3. If compounds with the same composition and molecular weight have different structures, this is called isomerism. 4. In some reactions, only some parts of the molecule change; studying the structure of the reaction product helps determine the structure of the initial molecule. 5. The chemical nature (reactivity) of individual atoms of a molecule may different depending on the environment, that is, on which atoms of other elements they are 801-1000 601-800 bonded with. 14-16 9 322 370 513 801-1000 601-800 14-16 9 322 370 513  Structural isomerism Chain isomerism – a sequence of chemically bonded carbon atoms. 801-1000 601-800 Hexane isomers. 14-16 9 322 370 513  Functional group isomerism: multiply bond 801-1000 601-800 14-16 9 322 370 513  Functional group isomerism: mutual position in the aromatic ring Metamerism is a case of isomerism associated with the position of a heteroatom in the chain of aliphatic compounds. 801-1000 601-800 14-16 9 322 370 513  Position isomerism Functional group – an atom or group of atoms that determines whether a compound belongs to a particular class and is responsible for its chemical properties Stereoisomerism: geometrical isomerism Compounds with the same order of atoms, but different in the arrangement of the same atoms in space. 801-1000 601-800 14-16 9 322 370 513  Stereoisomerism: optical isomerism Chirality (from Ancient Greek. χειρ — hand) — the property of a molecule not to be combined in space with its mirror image. The term is based on the ancient Greek name for the most recognizable chiral object, the hand. Thus, the left and right hands are mirror images, but cannot be combined with each other in space. For example, molecules with 4 different substituents around the sp3-carbon are chiral. This carbon atom itself is called a stereocenter, or asymmetric atom. 801-1000 601-800 14-16 9 322 370 513  Stereoisomerism: optical isomerism mirror 801-1000 601-800 14-16 9 322 370 513  Features E,Z-nomenclatures E,Z descriptors are assigned by using a system for ranking priority of the groups attached to each double bonds. 1) Compare the atomic mass (or number) of the atoms directly attached to the double bond; the group having the atom of higher atomic number receives higher priority. 2) If there is a tie, we must consider the atoms at distance 2 from the stereocenter—as a list is made for each group of the atoms bonded to the one directly attached to the stereocenter. Each list is arranged in order of decreasing atomic number. Then the lists are compared atom by atom; at the earliest difference, the group containing the atom of higher atomic number receives higher priority. 3) If there is still a tie, each atom in each of the two lists is replaced with a sublist of the other atoms bonded to it (at distance 3 from the double bond), the sublists are arranged in decreasing order of atomic number, and the entire structure is again compared atom by atom. This process is repeated recursively, each time with atoms one bond farther from the double bond, until the tie is broken. 801-1000 601-800 14-16 9 322 370 513  Valence states of the carbon atom. Tetragonal state (sp3-state) 801-1000 601-800 14-16 9 322 370 513  Trigonal state (sp2-state) Ethylene molecule 801-1000 601-800 14-16 9 322 370 513  Digonal state (sp-state) Acetylene (C2H2) – linear molecule 801-1000 601-800 14-16 9 322 370 513  Classification of Organic Compounds Organic compounds Acyclic (aliphatic) Functional derivatives Cyclic Heterocyclic Saturated Unsaturated Carbocyclic N N H Alkanes Alkenes Alkynes Alicyclic Aromatic СnH2n+2 (Cycloalkanes) (Arenes) 801-1000 601-800 СnH2n СnH2n-2 14-16 9 >C=C< -CΞC- 322 370 513  Classification of Organic Compounds R-X R- -X Acyclic hydrocarbons Functional derivatives of Cyclic & Aromatic hydrocarbons hydrocarbons R – Hydrocarbon Radical: Х – Functional group: -Hal Alkanes, Alkenes, Alkynes, Cyclic (-F, -Cl, -Br, -I), -OH, -O-, -NH2, -SH, - hydrocarbons, Arenes etc. NO, -NO2, >С=О, -СООН etc. 801-1000 601-800 14-16 9 To denote radicals, the suffix -yl is used For example: methyl, ethyl etc. 322 370 513  Acyclic hydrocarbons Acyclic (aliphatic) Saturated Unsaturated Alkanes Alkenes Alkadienes Alkynes СnH2n+2 СnH2n СnH2n-2 СnH2n-2 801-1000 601-800 14-16 9 >C=C< >C=C-C=C< -CΞC- 322 370 513  Cyclic hydrocarbons Carbocyclic Alicyclic Aromatic (Cycloalkanes) (Arenes) Carbocyclic – may be saturated Aromatic – contain conjugate and unsaturated cyclic double bonds hydrocarbons 801-1000 601-800 14-16 9 322 370 513 Cyclopentane Cyclohexane Naphthalene Fullerene С-60  Heterocyclic compounds In addition to carbon atoms, they contain one or more heteroatoms (N, S, O) in the cyclic skeleton Heteroaromatic compounds: Pyridine Pyrimidine Triazine Pyrazine 801-1000 601-800 14-16 9 Furan Thiofen Imidazole 322 370 513 Favipiravir  Main Functional Groups Functional group Organic Compound Class Formula Name Class Name General Class Formula -Hal (-F, -Cl, -Br, -I) Halogens Halogen-derivatives R-Hal -OH Hydroxyl Alcohols, phenols R-OH, Ar-OH -O- Oxy Ethers R-O-R' Etheric Oxygen -NH2 Amino Primary amines R-NH2 >NH Secondary amines R2NH >N- Tertiary amines R3 N -SH Mercapto Thiols (Mercaptans) R-SH 801-1000 601-800 14-16 9 322 370 513  Main Functional Groups Functional group Organic Compound Class Formula Name Class Name General Class Formula -NO Nitroso group Nitroso compounds R-NO -NO2 Nitro group Nitro compounds R-NO2 >С=О Carbonyl Aldehydes R-CH=O Ketones R-CO-R' Carboxyl Carboxylic acids R-COOH Ester group Esters R-COOR Amide group Amides R-CONH2 R-CONHR R-CONR2 801-1000 601-800 14-16 9 -CN Cyano group Nitriles R-CN 322 370 513  Ways to drawing of Organic Molecules 1) Structural formulas 4) Bond line structure butane Dash structure Condensed structure 5) 3D-structure 2) Lewis structure or dot structure methane ethane 801-1000 601-800 3) Molecular (gross) formula 14-16 9 322 370 CH4, C2H6 513  Ways to drawing of Organic Molecules There are other ways of representing chemical structures, mainly for computer applications. SMILES: C1(=C(C(=C(C(=C1OC(C([H])([H])[H])=O)[H ])[H])[H])C)C(=O)O[H] SMART: c1(c(c(c(c(c1-[#8]-[#6](-[#6](-[#1])(-[#1])- [#1])=[#8])-[#1])-[#1])-[#1])-[#1])- [#6](=[#8])-[#8]-[#1] 801-1000 601-800 InChI: 14-16 9 Acetylsalicylic acid (aspirin) InChI=1S/C9H8O4/c1-6(10)13-8-5-3-2-4- 7(8)9(11)12/h2-5H,1H3,(H,11,12) 322 370 513  Nomenclature of organic compounds Nomenclature is a system of terms that denote the structure of substances and the spatial arrangement of atoms in their molecules 1) Rational: A complex substance is considered to be a derivative of a simpler one, obtained by replacing hydrogen with other atoms or atomic groups (outdated). 2) Trivial: Traditional Compound Names. 3) IUPAC*, (Systematic): the name of the compound is constructed as a compound word consisting of a root (ancestral name), prefixes and a suffix that characterize the number and nature of substituents, the degree of saturation; If necessary, locants (the numbers of carbon atoms at which the substituents are located) are indicated. 801-1000 601-800 14-16 9 322 370 513 * International Union of Pure and Applied Chemistry, Geneva, 1892  Trivial names 2,3-Dihydroxybutanedioic Acid – Acetylsalicylic Acid – Aspirin Tartaric Acid 801-1000 601-800 14-16 9 β-carotene – 2,2'-((1E,3E,5E,7E,9E,11E,13E,15E,17E)-3,7,12,16- tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaene-1,18-diyl)bis(1,3,3- 322 370 513 trimethylcyclohex-1-ene)  Rational nomenclature Rational names of hydrocarbons are based on the names of the founder of the homologous series, for example, "methane". The substituents are then listed in order of increasing complexity of the names of the radicals associated with the central carbon atom. If there are several identical radicals in a molecule, a prefix formed from Greek numerals (di-two, three-three, tetra-four, penta- five, hexa-six) is placed before their name. methane dimethylmethane diethylmethylpropylmethane Unsaturated hydrocarbons with a double (triple) bond are considered as substituted for ethylene (acetylene) with an indication of the C atoms at which the substituents (α, 801-1000 601-800 β) are located: 14-16 9 322 Unsym. methyl ethylene 370 513 Iso-butylacetylene Methyl-iso-propylacetylene α-methyl-α-ethylethylene  IUPAC Nomenclature Principles 1. Find the largest C-C chain in the molecule. Number the atoms in the chain starting from the highest functional group or the branching closest to the edge. 2. The name is based on the root of the word, denoting a saturated hydrocarbon with the same number of atoms as the main chain (meth-, eth-, prop-, but-, pent-, etc.). 3. A suffix is added to the root to characterize the degree of saturation: -an (saturated, no multiple bonds); -en (presence of double bond); -yn (presence of triple bond). If there are several multiple bonds, then the suffix indicates the number of such bonds (-diene, triene, etc.). Don’t forget to indicate the position of the multiple bond after the suffix, for 801-1000 601-800 example: 14-16 9 СН3–СН2–СН=СН2 but-1-ene 322 370 СН3–СН=СН–СН3 but-2-ene 513 СН =СН–СН=СН buta-1,3-diene  IUPAC Nomenclature Principles 3. Next, the suffix contains the name of the highest priority functional group in the molecule, indicating its position with a number. 4. Other substituents are designated using prefixes in alphabetical order. The position of the substituents is indicated by the number before the prefix, for example: 3-Methyl, 2-Chloro. If there are several same substituents in the molecule, then their number is indicated before the name of this group (For example, Dimethyl- , Trichloro- etc.). 5. All numbers in the names of molecules are separated from words by hyphens and from each other by commas. 801-1000 601-800 14-16 9 322 370 513  Transformation of an organic molecule 801-1000 601-800 14-16 9 322 370 513  A chemical bond is a set of interactions between electrons and nuclei that lead to the union of atoms into a molecule Main Types of C h e m i c a l B o n d s Ionic bond Covalent bond Dative bond Δχ > 2 Δχ < 2 Polar Covalent Nonpolar Semi-polar bond Bond Covalent Bond 2 > Δχ > 0.5 0.4 > Δχ = 0 Increase in differences in electronegativity (Δχ) of bonded atoms 801-1000 601-800 Relative electronegativity of elements according to L. Pauling 14-16 9 Element K Li Na Mg H Se C S Br N Cl O F  0.8 0.95 1.0 1.2 2.1 2.4 2.5 2.58 2.8 3.05 3.16 3.5 3.98 322 370 13 5 Increase in electronegativity  Properties of Covalent Bond 1) Directivity: the bonding of the atoms is carried out in the direction in which the maximum overlap of the orbitals is ensured. 2) Saturability: the ability of atoms to form a limited number of covalent bonds. 3) Polarity: the result of an uneven distribution of electron density. 4) Dipole bond moment (μ): A vector quantity that characterizes the polarity of a bond. μ [D, C·m] 1D = 3,4·10-30 C·m 801-1000 601-800 5) Polarizability: electron density displacement under the influence of an 14-16 9 external field, environment, reagents, catalysts. 322 370 13 5  Formation of covalent σ and π bonds Bond line 801-1000 601-800 14-16 9 Nodal Plane 322 370 13 5  Comparison of - and -bonds -bond is formed as a result of the overlap of atomic orbital along a line connecting the centers of the nuclei. – -bonds have axial symmetry and atoms can rotate freely around bond. – All single bonds are -bonds. -bond is formed as a result of the overlapping of the p-orbitals above and below the line connecting the centers of the nuclei. – -bonds have regions of increased electron density above and below the -bond axis; 801-1000 601-800 Rotation around the -bond is not possible. 14-16 9 – A double bond is a -bond + a -bonds. 322 370 13 5 – A triple bond is -bond + two -bonds  Electronic Effects in Organic Chemistry Electron effects are the displacement of electron density in a molecule under the influence of substituents. Inductive Mesomeric shift of electron density in shift, delocalisation or molecules along σ-bonds redelocalisation of electron density towards a more in compounds of an unsaturated electronegative atom or group nature. of atoms. 1) π–π – Conjugated Systems (= – =). 801-1000 601-800 The inductive effect fades with distance. 2) р–π (n–π)—Conjugate systems 14-16 9 (Ä – = ). 322 370 Key 13 5 Atom  Acids-Bases theories 1. Brønsted's Proton Theory, or Brønsted's Theory of Acids and Bases (1923) кислота acid основание base сопряженное conjugated сопряженная conjugated основание base кислота acid The acid is the proton donor, and the base is the acceptor; Acids and bases exist only as conjugated pairs; The proton does not exist in solution in free form, in water it Johannes-Nikolaus forms an oxonium cation. Brønsted 801-1000 601-800 14-16 9 322 370 13 5  Acids-Bases theories The strength of an acid is determined by the stability of its conjugate base. СН3OH (Alcohols) < H2O < СН3RCOOH (Carboxylic acids) Increasing acidity Increasing stability anion (conjugated CH3OH + H2O H3C O + H3O base) In the periods of the H2O + H2O H O + H3O periodic table, acidity O O increases as it grows 801-1000 601-800 + H 3O electronegativity of the 14-16 9 H3C C + H2O H3C C element to which the OH O 322 370 proton is bound 13 5  Acids-Bases theories The basicity of organic compounds is higher the greater the electron density on the atom, which is a proton acceptor. Therefore, basicity increases in the next series of amines: NH2 -I,+M < NH3 < H3C NH2 +I 801-1000 601-800 14-16 9 322 370 13 5  Acids-Bases theories 2. The Electron Theory of Acids and Bases, or Lewis's Theory (1926) According to Lewis: Acids are substances capable of receiving a pair of electrons (electron pair acceptor), while bases are substances capable of giving a pair of electrons (electron pair donors) Gilbert AlCl3 + Cl– = [AlCl4]– Newton Lewis 801-1000 601-800 14-16 9 Acid Base 322 370 13 5 Zn2+ + 4H2O = [Zn(H2O)4]2+  Acids-Bases theories Lewis acids include not only the proton H+, but also all cations. as well as metal halides of groups 2 and 3 of the periodic table:AlX3, FeX3, BX3, SbX5, SnX4, ZnX2 (X=F, Cl, Br, I). BF3, AlCl3, NO2+, H+ Lewis bases include all anions OH-, OR-, CH3COO-, NH2- etc. and neutral compounds having lone electron pairs or π-bonds - H2O, ROH, ROR, RCH=O, RSH, NH3, R3N, RCH=CH2, R-C6H5 etc. 801-1000 601-800 14-16 9 Currently, Lewis acids are called electrophiles, and Lewis bases are called nucleophiles 322 370 13 5  Acids-Bases theories Electrophiles: H+, HNO3, H2SO4, HNO2, (i.e.+NO2, +SO3, +NO), PhN2+, BF3, AlCl3, ZnCl2, FeCl3, Br2, I*-Cl, H2O2, O3, O N S Nucleophiles: H-, H2N-, HO-, RO-, RS-, RCOO-, Hal-, HSO3-, -CN, RC≡C-, -CH(COOEt)2, O * * * *- R*MgBr, R*Li, LiAlH*4 C O C* CO2 * O 801-1000 601-800 R Cl 14-16 9 * 322 370 13 5  Acids-Bases theories n-Lewis Bases Lewis acids n-Complexes π-Lewis Bases Lewis acids π-Complexes 801-1000 601-800 14-16 9 322 370 13 5  Lecture 1 (Subject of organic chemistry. Classification of organic compounds according to the R-X formula. Valence states of the carbon atom. Concepts of isomerism and homology. Geometric parameters of organic molecules. Methods of drawing the structure of organic molecules) Thank you for your attention! Alan Akhmedov [email protected]