CHEM 31.1 MIDTERMS REVIEWER EXPERIMENT 1: SOLUBILITY OF ORGANIC COMPOUNDS • Solubility of a compound depends on its structure • solubility class of an unknown compound can help in determination of its main functional group • solubility in certain solvents often leads to more specific information about the functional group • if a compound is soluble in solvent to the extent of approximately 3-5% weight/volume or volume/volume • do not depend solely on intermolecular forces between the solute and solvent • can arise from the reaction between solute and solvent • Soluble in water & diethyl ether - ration of the polar groups to the number of carbon atom is 1:4 —> soluble in water - number of carbon atom per group is greater than 5 —> insoluble or sparingly soluble in water Water Soluble (S1 & S2) • Functional groups that can form H-bond with water - Amines, Carboxylic acids, aldehyde, ketones • Organic salts are soluble in water • Carbon chain length: # of C must be less than 5 for every electronegative atom • Carbon Chain Length & Solubility - ex: alcohols - Polyhydroxy alcohols are more soluble than monohydroxy alcohols - For monohydroxy alcohols, increasing chain length = decreasing water solubility - Branching of alkyl group = decrease in intermolecular forces of attraction = increase solubility in water (only for low MW monohydroxy alcohols) • smaller surface area exposed • only for low mw monohydroxy alcohols • S1 (WEAKLY POLAR) - soluble in water and in diethyl ether - Non ionic - contains 4 or less carbon atoms - contains only one strong polar group - In water: H-bond - In ether: LDF - Members: • low MW aldehydes • ketones • monohydroxy alcohols • aliphatic acids • S2 (STRONGLY POLAR) - soluble in water, insoluble in diethyl ether - Ionic - contains 2 or more polar groups with no more than 4 carbon atoms per each polar group - Members: • ionic salts of carboxylic acids • amines • polyhydroxylated compounds • carbohydrates Acidic Compounds (A1 & A2)
• soluble in 5% NaOH = acidic —> involves acid-base • •
•
neutralisation reaction NaHCO3 (weaker base than NaOH): used to determine whether the compound is a strong or weak acid A1 (STRONG ACID) - soluble in 5% NaOH and 5% NaHCO3 - Members: • carboxylic acids • phenols with electron withdrawing groups (ex: NO2) - Note: carbon chain length of carboxylic acids - low pKa = stronger acid A2 (WEAK ACID) - soluble in 5% NaOH and insoluble in 5% NaHCO3 - Members: • phenols • amino acids - Note: Reaction between weak acid and weak base is not favourable - do not react significantly with weak base
Basic Compounds (B)
• Compounds which are soluble in 5% HCL • dissolution process mainly due to the acid-base •
neutralisation reaction that produces soluble organic salts Members: - primary, primary, secondary & tertiary amines
Miscellaneous Compounds (M)
• insoluble in 5% HCl and contain nitrogen or sulfur atom • Members: - Nitrogen-containing but not basic (ex: Amides) - Sulfur-containing but not acidic (ex: thioethers) Inert Compounds (I) • insoluble in 5% HCl • insoluble in concentrated sulfuric acid • Members: - aliphatic (saturated) hydrocarbons - aromatic hydrocarbons - alkyl halides - aryl halides Neutral Compounds (N) • insoluble in 5% HCl • soluble in concentrated sulfuric acid - almost all compounds containing oxygen, nitrogen or sulfur atom are easily protonated by concentrated sulphuric acid • reacts via forced protonation • Members: - high MW alcohols - aldehydes - ketones - nitriles - esters & ethers (more than 4 carbon atom) - unsaturated hydrocarbons EXPERIMENT 2: RECRYSTALLIZATION AND MELTING POINT DETERMINATION OF BENZOIC ACID • Purification of Organic Compounds:
- Solids: Recrystallization - Liquids: Solvent Extraction - Solids and Liquids: Gas or liquid chromatography
• fluted filter paper: maximizes surfaces area =
• Recrystallization in the Industry - used to manufacture the correct crystal size and
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•
shape of a material. These factors can have a very significant impact on how a medicine acts when taken by a patient Benzoic Acid - usually additive in food & drinks - acts as preservatives —> anti bacterial - insoluble in water: reacts with base - sodium benzoic acid —> soluble Recrystallization - separate soluble solutes from a mixture of them in solution - can be single solvent or mixed solvent process - a crystal is highly ordered assembly of molecules, extending in 3 spatial dimensions - one of the most important method for purification of solids
General Steps in the Recrystallization of a compound 1. Find a suitable solvent for the recrystallisation —> Solvent Selection • most critical part • Properties: - soluble in hot solvent, insoluble in cold solvent - impurities insoluble at all temperature with the solvent - boiling point = low and lower than the melting point - no reaction between solute and solvent - cheap, non-flammable & non-toxic • Single Solvent (Water) • Mixed Solvent - solvent pair: • 1st solvent - dissolves the crystals • 2nd solvent - poorly dissolves - two solvents must be miscible with each other - ethanol reacts with water —> benzoic acids appear (white powder/crystals) 2. Dissolve the impure solid in a minimum volume of hot solvent —> Dissolving in Hot Solvent (Single & Mixed) • Heat saturated solution with stirring • excessive solvent = decreases % percent recovery • excess solvent will dissolve the benzoic acid —> no recrystallisation may happen • small amount of charcoal = absorbed coloured impurities • Types of Impurities - soluble - insoluble - partially soluble - can be coloured 3. Remove any insoluble impurities by filtration —> Hot Filtration • removes insoluble impurities and prevents premature recrystallization
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faster filtration • Short-stemmed funnel: lessen contact areas • pre-heated receiving flask with minimum amount of hot solvent Slowly cool the hot solution to crystallise the desired compound from the solution —> Crystallization Process • rate of cooling and crystallisation affects the crystal size and purity of the resulting cr ystals • slow cooling = larger crystal = more pure - more time = more time to organize & remove impurities = bigger crystals • rapid cooling = smaller crystals = less pure - impurities may be trapped inside • What do to if recrystallisation is a failure: - make the solution supersaturated by seeding (a small crystal of the pure substance is added) - boiling off excess solvent - scratching the sides of the beaker Filter the solution to isolate the purified solid compound —> Obtaining the Crystal • filtration • wash with cold solvent • dry
Assessing the Purity: Melting Point Determination • a pure substance has a fixed melting point while an impure substance melts over a wide range of temperatures and at a lower temperature than the pure substance • narrow range = high purity • broad range = impure Consequence of Impurities • The presence of impurities normally lowers the melting point of a crystal as impurities “defect” the crystal lattice and therefore reduce the energy (in the form of heat) required to break the lattice bonds EXPERIMENT 3: EXTRACTION AND PURIFICATION OF CAFFEINE • Caffeine - Systematic Name: 1,3,7-trimethyl-1H-purine-2,6(3H, 7H)-dione - C5H10N4O2 - Melting point: 238C - Sublimation point: 178C - belongs to a large class of organic compounds called alkaloid - 1 nitrogen is basic —> not part of another group - binds with adenacine that’s why we do not feel sleepy after drinking coffee - uses: • treats migraine • increases the potency of analgesics • relives asthma attacks • Caffeine Sources - coffee, coffee decaf - tea - cocoa, milk chocolate
- baking chocolate - coca-cola • Other Components of Coffee - lignin: gives the coffee its dark color - many acids: nicotinic acid, Quinic acid &
• maintains basic pH = minimizes the caffeine lost • washing with water: removes the remaining tannin 4.
hydroxycinnamic acid
- water soluble —> water cannot be used alone for extraction
• Other components of Tea - chlorophyll, cellelose, common flavanoids, tannic acid Solvent Extraction • the method of separating a substance from a mixture by dissolving one or more of the components in a solvent • use 2 solvents - 2nd solvent: to get the compound that you need • Solvents: - Non-toxic - Easily removed - Desired constituent is soluble - Non-reactive General Procedure 1. Solid-Liquid Extraction • Solvent: water • Cellulose, caffeine, chlorophyll, tannins, flavonoids extraction with H2O (100C) - H20 insoluble —> extracted leaves = cellulose - H2O soluble —> Aqueous tea solution = caffeine, chlorophyll, tannins, flavonoids • Basic nature of caffeine - N: more soluble if protonated - caffeine bound to tannic acid —> we remove tannic acid by reacting this with a strong acid so that only the caffeine will remain - more soluble in nonpolar solvent - more soluble in water • Removing Tannins - another way: add Ca(OH)2 or CaCO3 - basic form of caffeine predominates - Ca(OH)2 reacts with tannic acid 2. Liquid-Liquid Extraction • Solvent: Dichloromethane • used for separation of complex mixtures by selective partitioning between two phases, between two immiscible liquids • Aqueous solution of caffeine, tannins, chlorophyll, flavanoids PLUS 20mL dichloromethane - Organic Layer: Caffeine, impurities of chlorophyll & tannins - Aqueous Layer: Hydrolyzable and nonhydrolyzable tannins, chlorophyll, flavanoids • organic layer not always on top —> it depends on the density of the solutions • drop test: adding of water —> which layer adds, that’s the aqueous layer • how to remove pressure: shake, tilt & remove the pressure quickly 3. Liquid Washings • NaOH and Water • washing with NaOH: removes remaining impurities
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salts and water soluble impurities Drying • Crude Caffeine • drying the organic layer = removing traces of water • by adding an insoluble inorganic solid to the solution which will absorb the water, this “drying” it • drying agents, should not be dissolved in the solvent they are “drying” and easy to recover • to decant easily • drying agent —> calcium chlorite Purification by Sublimation • can be used if the vapor pressure of the impurities in a solid are significantly lower than that of a solid sample • the compound’s sublimation point must be far away from its melting point • caffeine’s sublimation point: 178C • Melting Point: 238C • not all organic compounds can be purified by sublimation • sublimation: easy to do —> not solvents used = pure crystals - draw back: few crystals • impurities should not sublime • sublimation point must be lower than the melting point
Recrystallization vs Sublimation Recrystallization • Procedure - tedious - involves many steps • Applicability - wide array of compounds • Percent Yield - high • Percent Purity - low Sublimation • Procedure - simple and easy - involves only 1 step - doesn’t require solvents • Applicability - limited compounds (only with sublimation point) • Percent Yield - low • Percent Purity - high (almost 100% purity) EXPERIMENT 4: PAPER CHROMATOGRAPHY Chromatography • a technique for separating mixtures into their components in order to analyse, identify, purify an/or quantify the mixture of components • separates the components of a mixture by their distinctive attraction to the mobile phase and the stationary phase
Paper Chromatography Components • Stationary Phase - water bound to the cellulose structure of the paper fibers - where the solute is initially deposited - other stationary phase: • silica (SiO2) • Alumina (Al2O3) • cellulos - in the experiment, paper is polar thus when the solvent does not move it is in the stationary phase • Mobile phase/Developing Solvent/ Eluent - usually a mixture of 2 or more solvents - carries the individual components a certain distance through the stationary phase, depending on their attraction to both of the phases - moderately volatile, cheap & relatively less toxic • Developing Chamber • Solute/Extract/Mixture Types of Chromatography • Normal Phase - stationary phase is more polar than the mobile phase - what was used in the experiment • Reverse Phase - stationary phase is less polar than the mobile phase Preparing the Chromatography Paper • use pencil in marking the origin line & solvent font - no ink —> it may join with the solvent • spot should be small & concentrated • for multiple spots, make sure each spot has enough distance from other spot Developing Chromatogram • the developing chamber must be pre-saturated with solvent before putting the paper and closed during the elution - saturated chamber = faster movement of the spots: more efficient movement of the spots • ensure that the spots are not soak with solvent Visualization of Spots • UV light - aromatics • Iodine Chamber - reacts with double bonds • Reacting Reagent Rf: solvent dependent - Rf = distance traveled/distance of solvent Applications of Chromatography • Isolation of Compounds • Reaction Monitorung • Mixture of biphenyl, benzoic acid, benzyl alcohol EXPERIMENT 5: ISOMERISM & STEREOCHEMISTRY Isomerism • same molecular formula, different structure • Isomers = isos & meros —> “made of the same parts” Isomers • Constitutional/structural isomers: different connectivity of atoms • Stereoisomers: different spatial orientation of atoms - conformational isomers - geometric isomers
- optical isomers Constitutional Isomerism • different connectivity of atoms • different names • different physical properties • avoid drawing the same isomer twice Stereoisomerism • different spatial orientation of atoms 1. Conformational isomerism 2. Geometric Isomerism 3. Optical Isomerism Conformational Isomerism • free rotation about C-C single bonds —> adopt variety of 3D shapes —> conformations • Conformations with higher potential energy —> less stable • Conformations with lower potential energy —> more stable • Same physical properties • Wedge & dashes • Seahorse • Newman Projection - Staggered conformation - has steric strain due to electron cloud repulsion - Eclipsed conformation EXPERIMENT 6: PREPARATION & PURIFICATION OF AN ALKYL HALIDE Synthesis of Alkyl Halide • often carried out by nucleophilic substitution of alcohols due to the following advantages: - often inexpensive and readily available - “Targeted” placement of the halide group where the OH group was - usually produces only the desired major product • Steps: - Separatory funnel: 10ml tertbutyl alcohol + 20 ml cold concentrated HCL - Stand for 20 mins. Add 3-5 ml 6M NaCL - Note the aqueous and organic layer - Get the organic layer + solid NaHCO3 until bubble formation stops - Get the organic layer + anhydrous CaCl2 - Simple Distillation • Reagents: Cold Concentrated HCl - Cold = to prevent the volatilization of product, to reduce the possibility of side reactions (E1 and condensation) - Excess = drives the reaction forward - Concentrated = small amount of HCl needed, ensures HCl is in excess
EXPERIMENT 7: ALCOHOL, PHENOLS & EHTERS Alcohols • no gaseous alcohols are known • alcohols higher than C12 are solids & are insoluble in water • Branched vs Straight Chain —> Boiling point • Numerous uses
Reactions of Alcohols • Alcohol + Na metal —> alkoxide + H2 (g) • Williamson Ether Synthesis • Substitution & Elimination • Oxidation • Combustion • Condensation Lucas Test • used to distinguish among primary, secondary & tertiary water-soluble alcohols - secondary & tertiary alcohols react via SN1 mechanism with the Lucan reagent - primary alcohols react in a similar fashion except the free cation is not generated, the substitution of SN2 type • Reagent: concentrated hydrochloric acid & zinc chloride • positive result: cloudiness, two immiscible layers Complications • often observe competing elimination with heating • carbocations can lead to rearranged products • volatility of formed alkyl halide • “fresh: Lucas reagent • Insolubility of alcohol in Lucan reagent —> false positive • “The reaction time is lower if the proportion of reagent to alcohol is smaller, or it the temperature is lower” Experimental Results (Test solutions + Lucas Reagent) • Ethanol = almost an hour = no • Isopropyl Alcohol = 5-10 minutes, layers form • Tert-butyl Alcohol = Layers form immediately • Benzyl Alcohol = Layers form immediately • Diethyl ether = No visible reaction Oxidation • Primary and secondary alcohols give positive results — > formation of brown precipitate Experimental Results (Test Solutions + neutral KMnO4) • Ethanol = Decolorization —> brown precipitate • Isopropyl Alcohol = Decolorization —> brown precipitate • Tert-butyl Alcohol = Purple Solution • Benzyl Alcohol = Decolorization —> brown precipitate • Diethyl Ether = Purple solution Phenols • Physical Properties • Acidity of Phenols - more acidic (pKa>>10) than alcohols (pKa>>16-20) - less acidic than carboxylic acids (pKa>>5) - conjugation exists between an unshared electron pair on the oxygen and the aromatic ring Effect of Substituent Groups on Phenols Acidity • - Electron withdrawing groups enhance the acidity - Electron donating substituents decrease the acidity - More favored if EWGs are located ortho & para with regards to OH group Experimental Results (Test solutions & pH) • Phenol = 5 • Para-nitrophenol = 3 • Picric Acid = 1 • naphthol = • Para-bromophenol = • trend (increasing acidity): Phenol < para-nitrophenol < picric acid Complexation with FeCl3
• Phenol - orange to purple • P-nitrophenol - Orange to wine red • P-bromophenol - Orange to dark yellow • n - Orange to apple green solution Bromination of Phenol • Occurs via EArS mechanism Oxidation of Phenols • Positive result: decolorization of solution + brown precipitate • most fruits contain polyphenolic compounds that are enzymatically oxidised to form qionones Ethers • diethyl ether did not decolonize the neutral permanganate and bromine = inert —> very useful as solvent • medical use: diethyl ether anesthetic EXPERIMENT 8: ALIPHATIC AND AROMATIC HYDROCARBONS Physical Properties • Saturated - C-C bond - inert towards most chemical reagents - Solubility class: I - Boiling & Melting point increases with increasing molecular weight - Can either be solid, liquid or gas - Insoluble in water - Less dense than water • Unsaturated - C=C or C=C bond - Presence of pi elections —> more reactive - Solubility class: N - react with strong acids —> conc. HCl, H2SO4 - Almost same physical properties with saturated HCs (ex: MP, BP) - More volatile, can exhibit different colours Experimental Results • Hexane - liquid - colorless - insoluble - less dense than water • Limonene - liquid - yellow - insoluble - less dense than water • Benzene - liquid - colorless - insoluble - less dense than water Free-Radical halogenation
Halogenated Products
Combustion • exothermic react —> source of heat and energy • complete combustion • incomplete combustion: produces carbon monoxide (toxic for our body) • Saturated hydrocarbon - blue or orange flame - clean • Orange crystals = reacted Experimental Result • Hexane - t-BuCl/AlCl3 = white to yellow crystals - Br2, light = light yellow to colourless - Br2 dark = Red-orange - KMnO4 = purple solution - Combustion = blue, non-smokey flame
• Unsaturated Hydrocarbons - Halogenation • occurs via electrophilic addition • Br & Limonene exposed in light —> no reaction — > electrophilic cannot happen
• Limonene: free radical
- Oxidation • Baeyer’s test for unsaturation • Alkenes to cis-diols (oxidation: syn-hydroxylation)
EXPERIMENT 9: RELATIVE RATES OF ELECTROPHILIC AROMATIC SUBSTITUTION Aromatic Hydrocarbons • Physical Properties - some are liquids at room temperature while others are crystalline solids - most are non-polar (insoluble in water) - volatile - they have a characteristic odor - Solubility class: I • Chemical Properties - Unsaturated, presence of ring structure - Chemically stable - Carcinogenic —> planar • Friedel-Crafts Reaction (Alkylation)
• Combustion Experimental Results • Benzene - t-BuCl/AlCl3 = white to orange crystals - Br2, light = smoky yellow - Br2, dark = red-orange - KMnO4 = Purple solution - Combustion = yellow, smokey or sooty Benzene and Aromatic Compounds • a compound is considered aromatic if it has cycles and conjugated double bonds with 4n+2 pi elections (where n = 0,1,2…)
Electrophilic Aromatic Substitution • in order to enhance the rate of reaction and the reactivity of aromatic compounds, strong electrophiles & Lewis catalysts are used
- Combustion • most often, incomplete combustion of unsaturated compounds occurs
• Carbon atom consumes more oxygen atoms than hydrogen does
Substituent Effects • Electron Donating Groups - activates the ring, ortho & para directors
• Electron Withdrawing Groups (EWG) - deactivates the ring, meta directors (except Halogens)
Experiment: EA Bromination • Theoretical Result - aniline > phenol > acetanilide > para-nitrophenol > benzene > chlorobenzene Bromination of Acetanilide: Role of Solvent
Role of Solvent • acetic acid polarises Br-Br bond —> increases the rate of reaction • cyclohexane - non-polarizing solvent —> decreases the rate of reaction
