Lecture 2 2024 Cairo.pdf

Lecture 2 Hydrocarbons. Classification of hydrocarbon radicals (R). Saturated & unsaturated hydrocarbons. General concepts of cyclic and heterocyclic compounds. Hydrocarbon-based medicines. Alan Akhmedov, PhD,...

Lecture 2 Hydrocarbons. Classification of hydrocarbon radicals (R). Saturated & unsaturated hydrocarbons. General concepts of cyclic and heterocyclic compounds. Hydrocarbon-based medicines. Alan Akhmedov, PhD, Senior lecturer of the Department of Organic and Medicinal Chemistry, Butlerov’s Chemical Institute, KFU  R- Acyclic hydrocarbons Alkanes (СnH2n+2) 801-1000 601-800 14-16 9 322 370 13 5  Methods for Obtaining Alkanes gases 1. The distillation of oil leads to Raw materials for the production of a number of fine chemicals products, mainly alkanes petrol kerosene diesel fuel oils, waxes 801-1000 601-800 14-16 9 fuel 322 370 tar 13 5  2. Methane is produced by the reaction of carbon monoxide (II) and hydrogen: 3. Catalytic hydrogenation of unsaturated hydrocarbons: 4. Reaction of halogenalkanes with metallic sodium (Wurtz reaction). 5. Electrolysis of solutions of carboxylic acid salts (Kolbe reaction) 801-1000 601-800 14-16 9 6. Hydrolysis of aluminium carbide: 322 370 13 5  Features of the Wurtz reaction: Modification of the Wurtz reaction (Wurtz-Fittig reaction) 801-1000 601-800 14-16 9 322 370 13 5  Chemical Properties of Alkanes Saturated hydrocarbons or paraffins (from the Latin parum affinis – "unrelated") are chemically inert substances under normal conditions. Reason: in alkanes, there are only simple high-energy C-C and C-H σ-bonds. Alkanes are most characterized by radical substitution reactions that happened by a radical mechanism. However, at high temperatures, alkanes can oxidize and decompose. 801-1000 601-800 14-16 9 322 370 13 5 Paraffin baths Cosmetic paraffin wax  1. Halogenation of alkanes. Alkanes react with halogens (except I2). Chlorination – chlorine reacts with methane when exposed to ultraviolet light or at high (400 °C) temperatures. Heat or light CH4 + Cl2 CH3Cl + HCl Chloromethane Heat or light Dichloromethane CH3Cl+ Cl2 CH2Cl2 + HCl Heat or light CH2Cl2+ Cl2 CHCl3 + HCl Trichloromethane Heat or light CHCl3+ Cl2 CCl4 + HCl Tetrachloromethane The reactivity of the halogens decreases in the following order: F2 > Cl2 > Br2 > I2. 801-1000 601-800 14-16 9 322 370 13 5  1. Halogenation of alkanes. What hydrogen will be replaced by We can describe three ways: halogene in a radical substitution reaction? (green, blue or red?) Hydrogen will be replaced first of all at the tertiary carbon atom, because the tertiary radical is the most stable. 801-1000 601-800 14-16 9 The stability of radicals increases in the series by this arrow This means that the tertiary radical is more stable than the secondary radical, the secondary is more stable than the 322 370 13 5 primary, and so on.  Stability of radicals, carbocations, carboanions R = Any alkyl fragment The stability of radicals increases in the series by this arrow The stability of radicals increases in the series by this arrow 801-1000 601-800 14-16 9 The stability of radicals increases in the series by this arrow 322 370 13 5  Stability of radicals, carbocations, carboanions X = F, Cl, Br, I X = NO2, OR X = COOR, C≡N The stability of radicals increases in the series by this arrow The stability of radicals increases in the series by this arrow 801-1000 601-800 14-16 9 The stability of radicals increases in the series by this arrow 322 370 13 5  2. Isomerization reaction. 3. Nitration reaction (first carried out by Mikhail Konovalov at the end of the 19th century). Alkane is heated with dilute nitric acid at 130–140 °C under pressure 801-1000 601-800 14-16 9 322 370 13 5  4. Sulfochlorination of alkanes. The reaction of a mixture of sulfur dioxide and chlorine with alkanes containing 10-18 carbon atoms (under ultraviolet) produces chloroanhydrides of alkanesulfonic acids (sulfochlorides): Liquid detergents are then obtained from them 801-1000 601-800 14-16 9 322 370 13 5  5. Dehydrogenation reaction. 601-800 801-1000 9 14-16 370 322 13 5  6. Oxidation. At room temperature, even strong oxidizing agents KMnO4, K2Cr2O7 do not react with alkanes. a) At high temperatures, in the presence of excess oxygen, the alkanes are completely oxidized: b) Oxidation of alkanes with a lack of oxidizer proceeds with the splitting of carbon- carbon bonds, with the formation of a mixture of carboxylic acids: atm. 801-1000 601-800 14-16 9 322 370 13 5  Biological oxidation of alkanes The enzyme systems of methanotrophs, bacteria capable of using methane as the only source of energy and carbon for the construction of their cells, activate oxygen chemically. An oxygen molecule is split at the expense of two electrons, which are supplied by molecules of the reduced form of nicotine adenine dicleotide (NADH) 801-1000 601-800 14-16 9 Composition of communities of methanotrophic bacteria 322 370 inhabiting bottom sediments and the water column of Lake 13 5 Baikal(https://scfh.ru/papers/est-takaya-professiya-metan-  Cycloalkanes Cyclopropane Cyclobutane Cyclopentane Cyclohexane Small Cycles Large Cycles 801-1000 601-800 14-16 9 322 370 13 5 “chair” “boat” “twist boat”  a) b) bent bond a bent bond, also known as a banana bond c) г d) 601-800 801-1000 9 14-16 370 322 13 5 “envelope” “half-chair” “envelope”  Methods for the obtaining of cycloalkanes 1. Wurtz's reaction 2. Dehydrogenation of alkanes: 3. Hydrogenation of benzene 801-1000 601-800 14-16 9 322 370 13 5  Chemical Properties of Cycloalkanes Their chemical properties are similar to alkanes, only the addition reactions for small unstable cycles (C = 3-4) occur with a cycle break; In large cycles (C = 56) there is a substitution reaction in the cycle. Hydrogenation propane cyclopropane Halogenation cyclopropane 1,3-dibromopropane 801-1000 601-800 Hydrohalogenation 1-bromobutane 14-16 9 cyclobutane 322 370 13 5  Chemical Properties of Cycloalkanes Hydrohalogenation cyclohexane chlorocyclohexane Nitration cyclohexane nitrocyclohexane Aromatization is dehydrogenation to form aromatic hydrocarbons. This is typical for cyclohexane and its homologues. Aromatization 801-1000 601-800 14-16 9 cyclohexane benzene 322 370 13 5  Naturally occurring condensed cycloalkanes Steroid Ring Designation and Numbering 601-800 801-1000 9 14-16 370 322 13 5  Natural cycloalkanes Important bioregulators, hormones, neurotransmitters. Examples: Chrysanthemic acid, prostaglandins, steroids 801-1000 601-800 14-16 9 322 370 13 5  R- Acyclic hydrocarbons Alkenes (СnH2n) 601-800 801-1000 9 14-16 370 322 13 5  Methods of obtaining of Alkenes 1. Acid dehydration of alcohol The effectiveness of dehydration increases in the following ways: Primary Alcohols → Secondary Alcohols → Tertiary Alcohols 2. Dehydrohalogenation of alkyl halides by base action ethanol Regioselectivity is determined by Zaitsev's rule. According to Zaitsev’s rule, base-induced elimination reactions generally (although not always) give the more stable alkene 801-1000 601-800 14-16 9 product—that is, the alkene with more alkyl substituents on the double-bond carbons (major products). In the following two cases, for example, the more highly substituted 322 370 13 5 alkene product predominates.  Methods of obtaining of Alkenes 3. Dehydrogenation and cracking of alkanes 4. Dehalogenation of vicinal dihaloalkanes 801-1000 601-800 14-16 9 322 370 13 5  Methods of obtaining of Alkenes 5. Reduction of acetylene hydrocarbons and dienes alkyne alkyne cis-alkene trans-alkene Chemical Properties of Alkenes Electrophilic addition (AdE) is an addition reaction in which the electrophile is the attacker at the rate of the limiting stage. Electrophile is a reactant or molecule having a free orbital at the outer electron layer. 801-1000 601-800 14-16 9 322 370 13 5  Chemical Properties of Alkenes Nucleophiles Electrophiles 801-1000 601-800 14-16 9 322 370 13 5  Chemical Properties of Alkenes The main type of reaction is addition to double-bond 801-1000 601-800 14-16 9 322 370 13 5  Chemical Properties of Alkenes Alkenes are characterized by electrophilic addition reactions 1. Halogenation σ-bond π-bond breaks π-bond 601-800 801-1000 914-16 370322 13 5  Chemical Properties of Alkenes 2. Hydrohalogenation Markovnikov's 3. Hydration rule 4. Addition of alcohols 801-1000 601-800 14-16 9 322 370 13 5  The addition of HX to an unsymmetrical alkenes (Markovnikov's rule) Markovnikov's rule. The rule states that with the addition of HX to an asymmetric alkene, the hydrogen (H) gets attached to the carbon with more hydrogen substituents, and the (X) group gets attached to the carbon with more alkyl substituents. The rule was first proposed by Kazan chemist Vladimir Markovnikov in 1869. Vladimir Markovnikov 601-800 801-1000 914-16 370322 13 5  Exception to Markovnikov's rule (The Kharasch Effect) HBr in Hydrogen Peroxide: Due to formation of free radicals, and the mechanism in which it reacts, the alkyl free radical forms at the middle atom, where it is most stable, and a hydrogen attaches itself here. Note here hydrogen addition is the second step, unlike in the above example. Only with HBr Peroxy compounds In this reaction, we have changed Contains -O-O- fragment the conditions (in green above the arrow). In the case of HBr, We can write it like this: using peroxy compounds as (PhCOO)2 conditions, we can obtain an 601-800 801-1000 914-16 exception product from H2O2 Markovnikov's rule. 370322 13 5  Oxidation of alkenes 601-800 801-1000 9 14-16 370 322 13 5  Oxidation of alkenes a) Epoxidation: Prilezhaev reaction b) Hydroxylation: Wagner's reaction. 601-800 801-1000 9 14-16 370 322 13 5  c) Ozonolysis We can get different products by using different conditions: Alcohols Aldehydes or ketones (ketone if one or both atoms in the double bond contain two R) Carboxyl acids 601-800 801-1000 9 14-16 370 322 13 5  Oxidation of alkenes d) oxidation cleavage of alkenes 801-1000 601-800 14-16 9 322 370 13 5  Polymerization Stage 1 – Initiation: Stage 2 – Propagation: etc. Stage 3 – Termination: etc. 601-800 801-1000 9 14-16 370 322 13 5  Alkenes with two double bonds. Alkadienes 1. General formula of alkadienes: СnH2n-2 2. There are three different types of alkadienes: a) Cumulated dienes have the double bonds sharing a common atom. The result is more specifically called an allene (A on the picture below). b) Conjugated dienes have conjugated double bonds separated by one single bond. Conjugated dienes are more stable than other dienes because of resonance(B, C on the picture below). c) Unconjugated dienes have the double bonds separated by two or more single bonds. They are usually less stable than isomeric conjugated dienes. This can also be known as an isolated diene. (D on the picture below) 601-800 801-1000 9 14-16 370 322 13 5  Chemical Properties of Alkadienes 1,2-addition In both cases, one double bond out of two remains. Note that in the case of 1,4 addition, the double bond is moved to X = Cl, Br, OH the middle. 1,4-addition By changing the reaction conditions, we can get different products In the case of halogens, this reaction looks like: 1,2-addition 601-800 801-1000 914-16 1,4-addition 370322 13 5  Chemical Properties of Alkadienes Cycloaddition (Diels-Alder reaction) Another examples: 601-800 801-1000 914-16 370322 13 5  Enzymes as Catalysts of Chemical Reactions The substrates of enzymatic reactions bind to a specific 601-800 801-1000 9 14-16 site of the enzyme protein 370 322 13 5  Active cite The active site is usually a depression, groove, or crevice on the surface of the enzyme. It must be available to the substrate. 801-1000 601-800 14-16 9 322 370 13 5  Natural alkenes 601-800 801-1000 9 14-16 370 322 13 5  Alkenes, biologically active compounds Vitamin A. Treatment of vitamin A deficiency. Acitretin. Treatment of severe psoriasis. 601-800 801-1000 9 14-16 Alitretinoin. For topical treatment of skin 370 322 Naftifine. Antifungal drug. lesions in patients with AIDS-associated 13 5 Kaposi's sarcoma.  R- Acyclic hydrocarbons Alkynes (СnH2n-2) 601-800 801-1000 9 14-16 370 322 13 5  Methods of Obtaining Alkynes 1. Hydrolysis of carbides 2. Alkane cracking 3. Berthelot Synthesis 4. Synthesis from alkenes 801-1000 601-800 5. Synthesis from dihalides 14-16 9 322 370 13 5  Chemical Properties of Alkynes 1. C-H acidity (acetylenide products) acid strength: 801-1000 601-800 14-16 9 322 370 13 5  2. Acetylenide Reactions with Carbon Skeleton Elongation 3. Electrophilic Addition Reactions Vinyl cation 801-1000 601-800 14-16 9 Reactions proceed according to Markovnikov's rule! 322 370 13 5  4. Kucherov reaction (ketone synthesis) Compounds containing a It looks like both hydrogens from hydroxyl group at the double H2O have attached to one carbon bond (they are called "enols") atom, and the oxygen has are unstable and rearrange attached to the other carbon according to this scheme atom. In this case we have to use 801-1000 601-800 Markovnikov’s rule 14-16 9 322 370 13 5  5. Reduction Reactions 801-1000 601-800 14-16 9 322 370 13 5  Oxidation a) mild oxidation b) cleavage oxidation mixture of carboxylic acids 801-1000 601-800 14-16 9 322 370 13 5  Cyclisation reactions 801-1000 601-800 Major product Minor product 14-16 9 322 370 13 5  Natural Alkynes The first naturally occurring Tariric acid is an acetylenic fatty acid that acetylene compound, the ether of can be found in the tallow tree, Ximenia dehydromatricaria, was isolated americana. from the Artemisias pecies in 1826. Falcarinol (also known as carotetoxin or 801-1000 601-800 panaxinol) is a natural pesticide and fatty 14-16 9 Cicutoxin is a naturally occurring alcohol found in carrots (Daucus carota) and poisonous diyn produced by Apiaceae red ginseng (Panax ginseng). 322 370 13 5 plants.  Alkynes in medicines Efavirenz (EFV) is an antiretroviral drug Terbinafine, marketed under the brand used for the treatment and prevention of name Lamisil, is an antifungal drug. HIV/AIDS. Calicheamicin is one of the most aggressive anticancer drugs known. Enediyns undergo rearrangement to form highly reactive 801-1000 601-800 radical intermediates that attack the DNA 14-16 9 inside the tumor. 322 370 13 5  Thank you for your attention! Alan Akhmedov [email protected]