KIMIA ORGANIK LANJUT (ADVANCED ORGANIC CHEMISTRY) Referensi : March, J ; Advanced Organic Chemistry : reactions,mechanisms, and structure, 3 rd, Jhon Wiley @ Sons, NY 2004Dosen : Dr. H. Djaswir Darwis, MSc, DEA Dr. Mai Efdi, MS Prof .Dr. YunazarManjang Dr. Afrizal. 1DEDE KIM-UA 2DEDE KIM-UA 3DEDE KIM-UA 4DEDE KIM-UA 5DEDE KIM-UA

IKATAN KIMIA TERLOKALISASI (LOCALIZED CHEMICAL BONDING) 6DEDE KIM-UA DEDE KIM-UA7 PENDAHULUAN PEMBENTUKAN IKATAN ANTAR ATOM KIMIA ORGANIK The Atom 8DEDE KIM-UA Periodic Table Li: solid,Cs: liquid,Ar: gas,Tc:synthetic Number of protons 9DEDE KIM-UA 10DEDE KIM-UA Kearomatisan : Huckel4n + 2elektron n= 0 atau pos integer 11DEDE KIM-UA 12DEDE KIM-UA 13DEDE KIM-UA Ikatan kovalen Molekul terjadi adalah berupa ikatan atom dengan atom yang berasal dari penggabungan elektron dari masing-masing atom. Ikatan kovalen hampir mirip dengan ikatan metalik yang merupakan penggabungan elektron.Pada senyawa organik maka ikatan kovalen adalah ikatan yang terbentuk dari 2 elektron dari masing-masing atom. 14DEDE KIM-UA A more detailed model of covalent bonding requires a consideration of valence shell atomic orbitals. For second period elements such as carbon, nitrogen and oxygen, these orbitals have been designated 2s, 2px, 2py & 2pz.The spatial distribution of electrons occupying each of these orbitals is shown in the diagram below. The valence shell electron configuration of carbon is 2s2, 2px1, 2py1 & 2pz0.If this were the configuration used in covalent bonding, carbon would only beable to form two bonds.Molecular Orbital 15DEDE KIM-UA In order to explain the structure of methane (CH4), the 2s and three 2p orbitals must be converted to four equivalent hybrid atomic orbitals,each having 25% s and 75% p character, and designated sp3.These hybrid orbitals have a specific orientation, and the four are naturally oriented in a tetrahedral fashion. Hybrid Orbitals 16DEDE KIM-UA s-orbitals have a spherical symmetry surrounding a single nucleus,-orbitals have a cylindrical symmetry and encompass two (or more) nuclei. In the case of bonds between second period elements, p-orbitals or hybrid atomic orbitals having p-orbital character are used toform molecular orbitals.For example, the sigma molecular orbital that serves to bond two fluorine atoms together is generatedytheoverlapofp-orbitals(partAbelow),andtwosp3hybridorbitalsofcarbon may combine to give a similar sigma orbital. When these bonding orbitals are occupied by a pair of electrons a covalent bond, the sigma bond17DEDE KIM-UA . The hydrogen molecule provides a simple example of MO formation. In the following diagram, two 1s atomic orbitals combine to give a sigma () bonding (low energy) molecular orbital and a second higher energy MO referred to as an antibonding orbital. The bonding MO is occupied by two electrons of opposite spin, the result being a covalent bond. 18DEDE KIM-UA the orbital may be formed from two p-orbitals by a lateral overlap, as shown in part A of the following diagram.Since bonds consisting of occupied -orbitals (pi-bonds) are weaker than sigma bonds, pi-bonding between two atoms occurs only when a sigma bond has already been established.Thus, pi-bonding is generally found only as a component of double and triple covalent bonds.Since carbon atoms involved in double bonds have only three bonding partners, theyrequire only three hybrid orbitalsto contribute to three sigma bonds. A mixing of the 2s-orbital with two of the 2p orbitals givesthree sp2 hybrid orbitals, leaving one of the p-orbitals unused. Two sp2 hybridized carbon atoms are then joined together bysigma and pi-bonds (a double bond), as shown in part B.19DEDE KIM-UA A Chime model of the p and orbitals of a double bond may be examined by . The p-orbitals in this model are represented by red and blue colored spheres, which represent different phases, defined by the mathematical wave equationsfor such orbitals. Finally, in the case of carbon atoms with only two bonding partners only two hybrid orbitals are needed for the sigma bonds, and these sp hybrid orbitalsare directed 180 from each other. Two p-orbitals remain unused on each sp hybridized atom, and these overlap to give two pi-bonds following the formation of a sigma bond (a triple bond), as shown below. 20DEDE KIM-UA The Shape of Molecules MethaneAmmoniaWater Configuration Bonding Partners Bond Angles Example Tetrahedral4109.5 Trigonal3120 Linear2180 21DEDE KIM-UA H 2.20 ElectronegativityElements Li 0.98 Be 1.57 B 2.04 C 2.55 N 3.04 O 3.44 F 3.98 Na 0.90 Mg 1.31 Al 1.61 Si 1.90 P 2.19 S 2.58 Cl 3.16 K 0.82 Ca 1.00 Ga 1.81 Ge 2.01 As 2.18 Se 2.55 Br 2.96 Electronegativity differences may be transmitted through connecting covalent bonds by an inductive effect. Replacing one of the hydrogens of water by a more electronegative atom increases the acidity of the remaining OH bond. Thus hydrogen peroxide, HOOH, is ten thousand times more acidic than water, and hypochlorous acid, ClOH is one hundred million times more acidic. This inductive transfer of polarity tapers off as the number of transmitting bonds increases, and the presence of more than one highly electronegative atom has a cumulative effect. For example, trifluoro ethanol, CF3CH222DEDE KIM-UA 1A2A3A4A5A6A7A8A 1 H 1s1

2 He 1s2 3 Li 1s2 2s1 4 Be 1s2 2s2 5 B 1s2 2s22p1 6 C 1s2 2s22p2 7 N 1s2 2s22p3 8 O 1s2 2s22p4 9 F 1s2 2s22p5 10 Ne 1s2 2s22p6 11 Na [Ne] 3s1 12 Mg [Ne] 3s2 13 Al [Ne] 3s23p1 14 Si [Ne] 3s23p2 15 P [Ne] 3s23p3 16 S [Ne] 3s23p4 17 Cl [Ne] 3s23p5 18 Ar [Ne] 3s23p6 23DEDE KIM-UA DEDE KIM-UA24 Replacingoneofthehydrogensofwaterbyamore electronegativeatomincreasestheacidityoftheremaining OH bond. Thushydrogenperoxide,HOOH,istenthousandtimes more acidic than water, and hypochlorous acid, ClOH is one hundred million times more acidic.Thisinductivetransferofpolaritytapersoffasthenumberof transmittingbondsincreases,andthepresenceofmorethan one highly electronegative atom has a cumulative effect. Forexample,trifluoroethanol,CF3CH2OHisaboutten thousand times more acidic than ethanol, CH3CH2OH.DEDE KIM-UA25 Bond Energy Sincereactionsoforganiccompoundsinvolvethemaking and breaking of bonds, the strengthofbonds,ortheirresistancetobreaking,becomesan important consideration. For example, the chlorination of methane, discussed previously, was induced by breaking a relatively weak Cl-Clcovalentbond. Bondenergyistheenergyrequiredtobreakacovalent bond homolytically (into neutral fragments). Bondenergiesarecommonlygiveninunitsofkcal/molor kJ/mol, and are generally called bond dissociationenergieswhengivenforspecificbonds,or average bond energies when summarizedfor a given type of bond over many kinds of compoundsThe Shape of Molecules MethaneAmmoniaWater ConfigurationBonding PartnersBond AnglesExample Tetrahedral4109.5 Trigonal3120 Linear2180 26DEDE KIM-UA Standard Bond Energies Single BondsH *

Single BondsH *

Multiple BondsH * HH104.2BF154C=C146 CC83BO123N=N109 NN38.4CN73O=O119 OO35NCO86C=N147 FF36.6CO85.5C=O (CO2)192 SiSi52OCO110C=O (aldehyde)177 PP51CS65C=O (ketone)178 SS54CF116C=O (ester)179 ClCl58CCl81C=O (amide)179 BrBr46CBr68C=O (halide)177 II36.CI51C=S (CS2)138 HC99CB94N=O (HONO2)143 HN93CSi83P=O (POCl3)110 HO111CP73P=S (PSCl3)70 HF135NO55S=O (SO2)128 HCl103SO87S=O (DMSO)93 HBr87.5SiF132P=P84 HI71SiCl86PP117 HB90SiO110CO258 HS81PCl79CC200 HSi70PBr65NN226 HP77PO96CN213 27DEDE KIM-UA How to show the formation Its like a jigsaw puzzle. You put the pieces together to end up with the right formula. Carbon is a special example - can it really share 4 electrons: 1s22s22p2? Yes, due to electron promotion! Another example: lets show how water is formed with covalent bonds, by using an electron dot diagram 28DEDE KIM-UA Water H O Each hydrogen has 1 valence electron - Each hydrogen wants 1 more The oxygen has 6 valence electrons - The oxygen wants 2 more They share to make each other complete 29DEDE KIM-UA Water Put the pieces together The first hydrogen is happy The oxygen still needs one more H O 30DEDE KIM-UA Water So, a second hydrogen attaches Every atom has full energy levels H O H Note the two unshared pairs of electrons 31DEDE KIM-UA Multiple Bonds Sometimes atoms share more than one pair of valence electrons. A double bond is when atoms share two pairs of electrons (4 total) A triple bond is when atoms share three pairs of electrons (6 total) Know these 7 elements as diatomic:Br2I2N2Cl2H2O2F2

32DEDE KIM-UA Dot diagram for Carbon dioxide CO2 - Carbon is central atom ( more metallic ) Carbon has4 valence electrons Wants 4 more Oxygen has 6 valence electrons Wants 2 more O C 33DEDE KIM-UA Carbon dioxide Attaching 1 oxygen leaves the oxygen 1 short, and the carbon 3 short O C 34DEDE KIM-UA Carbon dioxide Attaching the second oxygen leaves both of the oxygen 1 short, and the carbon 2 short O C O 35DEDE KIM-UA Carbon dioxide The only solution is to share more O CO 36DEDE KIM-UA Carbon dioxide The only solution is to share more O CO 37DEDE KIM-UA Carbon dioxide The only solution is to share more O CO 38DEDE KIM-UA Carbon dioxide The only solution is to share more O CO 39DEDE KIM-UA Carbon dioxide The only solution is to share more O CO 40DEDE KIM-UA Carbon dioxide The only solution is to share more O CO 41DEDE KIM-UA Carbon dioxide The only solution is to share more Requires two double bonds Each atom can count all the electrons in the bond O CO 42DEDE KIM-UA Carbon dioxide The only solution is to share more Requires two double bonds Each atom can count all the electrons in the bond O CO 8 valence electrons 43DEDE KIM-UA Carbon dioxide The only solution is to share more Requires two double bonds Each atom can count all the electrons in the bond O CO 8 valence electrons 44DEDE KIM-UA Carbon dioxide The only solution is to share more Requires two double bonds Each atom can count all the electrons in the bond O CO 8 valence electrons 45DEDE KIM-UA How to draw them? Use the handout guidelines: 1) Add up all the valence electrons. 2) Count up the total number of electrons to make all atoms happy. 3) Subtract; then Divide by 2 4) Tells you how many bonds to draw 5) Fill in the rest of the valence electrons to fill atoms up. 46DEDE KIM-UA Example NH3, which is ammonia N central atom; has 5 valence electrons, wants 8 H - has 1 (x3) valence electrons, wants 2 (x3) NH3has 5+3 = 8 NH3wants 8+6 = 14 (14-8)/2= 3 bonds 4 atoms with 3 bonds N H 47DEDE KIM-UA N HH H Examples Draw in the bonds; start with singles All8 electrons are accounted for Everything is full done with this one. 48DEDE KIM-UA Example: HCN HCN:C is central atom N - has 5 valence electrons, wants 8 C - has 4 valence electrons, wants 8 H - has 1 valence electron, wants 2 HCN has 5+4+1 = 10 HCN wants 8+8+2 = 18 (18-10)/2= 4 bonds 3 atoms with 4 bonds this will require multiple bonds - not to H however 49DEDE KIM-UA HCN Put single bond between each atom Need to add 2 more bonds Must go between C and N (Hydrogen is full) NH C 50DEDE KIM-UA HCN Put in single bonds Needs 2 more bonds Must go between C and N, not the H Uses 8 electrons need 2 more to equal the 10 it has NH C 51DEDE KIM-UA HCN Put in single bonds Need 2 more bonds Must go between C and N Uses 8 electrons - 2 more to add Must go on the N to fill its octet NH C 52DEDE KIM-UA Another way of indicating bonds Often use a line to indicate a bond Called a structural formula Each line is 2 valence electrons HHO = HHO 53DEDE KIM-UA Bond Dissociation Energies... The total energy required to break the bond between 2 covalently bonded atoms High dissociation energy usually means the chemical is relatively unreactive, because it takes a lot of energy to break it down. 54DEDE KIM-UA Standard Bond Energies Single BondsH *

Single BondsH *

Multiple BondsH * HH104.2BF154C=C146 CC83BO123N=N109 NN38.4CN73O=O119 OO35NCO86C=N147 FF36.6CO85.5C=O (CO2)192 SiSi52OCO110C=O (aldehyde)177 PP51CS65C=O (ketone)178 SS54CF116C=O (ester)179 ClCl58CCl81C=O (amide)179 BrBr46CBr68C=O (halide)177 II36.CI51C=S (CS2)138 HC99CB94N=O (HONO2)143 HN93CSi83P=O (POCl3)110 HO111CP73P=S (PSCl3)70 HF135NO55S=O (SO2)128 HCl103SO87S=O (DMSO)93 HBr87.5SiF132P=P84 HI71SiCl86PP117 HB90SiO110CO258 HS81PCl79CC200 HSi70PBr65NN226 HP77PO96CN213 55DEDE KIM-UA Molecular Orbitals are... The model for covalent bonding assumes the orbitals are those of the individual atoms = atomic orbital Orbitals that apply to the overall molecule, due to atomic orbital overlap are the molecular orbitals A bonding orbital is a molecular orbital that can be occupied by two electrons of a covalent bond 56DEDE KIM-UA Molecular Orbitals - definitions Sigmabond-whentwoatomic orbitalscombinetoformthe molecularorbitalthatis symmetricalalongtheaxis connecting the nuclei Pibond-thebondingelectronsare likelytobefoundaboveandbelow the bond axis (weaker than sigma) Note pictures on the next slide 57DEDE KIM-UA - Pages 230 and 231 Sigma bond is symmetrical along the axis between the two nuclei. Pi bond is above and below the bond axis, and is weaker than sigma 58DEDE KIM-UA Bond Dissociation Energies Bond dissociation energy is the total energy required to break the bond between two covalently bonded atoms. A typical carbon-carbon single bond has a bond dissociation energy of 347 kJ.The ability of carbon to form strong bonds helps to explain its stability. They are unreactive partly because the dissociation energy of these bonds is high. 59DEDE KIM-UA Resonance is... When more than one valid dot diagram is possible. Consider the two ways to draw ozone (O3) Which one is it?Does it go back and forth? It is a hybrid of both, like a mule; and shown by a double-headed arrow found in double-bond structures! 60DEDE KIM-UA Resonance in Ozone Neither structure is correct, it is actually a hybrid of the two.To show it, draw all varieties possible, and join them with a double-headed arrow. Note the different location of the double bond 61DEDE KIM-UA Resonance Occurs when more than one valid Lewis structure can be written for a particular molecule (due to position of double bond) These are resonance structures of benzene. The actual structure is an average (or hybrid) of these structures. 62DEDE KIM-UA Resonance in a carbonate ion (CO32-): Resonance in an acetate ion (C2H3O21-): Polyatomic ions note the different positions of the double bond. 63DEDE KIM-UA Resonance structures are structures that occur when it is possible to write 2 or more valid electron dot formulas that have the sameof electron pairs for a molecule or ion. Electrons do NOT change position Bond lengths are an average of possible bond lengths. Bonds become a hybrid of all the possible bonds. Increases stability within the atom64DEDE KIM-UA 65DEDE KIM-UA DEDE KIM-UA66 V S E P R Valence Shell Electron Pair Repulsion (DAYA DORONG DARI PASANGAN ELEKTRON VALENSIYANG TIDAK BERIKATAN PADA ORBITAL IKATAN) Predicts the three dimensional shape of molecules. The name tells you the theory: Valence shell = outside electrons. Electron Pair repulsion = electron pairs try to get as far away as possible from each other. Can determine the angles of bonds. 67DEDE KIM-UA Exceptions to the Octet Some molecules exist with an oddof e- NO2 has 7 valence e- Paramagnetic containing 1 or more unpaired e- Appear heavier in magnetic fields Diamagnetic contain only paired e- O2

Recently discovered its paramagnetic Suggesting unpaired e- but double bonds make senseResonance is suggestedVSEPR Theory (Valence Shell Electron Pair Repulsion Theory) Because electrons repel, molecules adjust shape so the electron pairs are as far apart as possible. Unshared pairs of e- are also important when trying to predict shape. Methane forms a tetrahedron with angles of 109.5O (tetrahedral angle). 69DEDE KIM-UA Some common shapes:linear triatomic, trigonal planar, bent triatomic, pyramidal, tetrahedral, trigonal bipyramidal Linear triatomic Trigonal planar Formaldehyde 71DEDE KIM-UA Water 105o 72DEDE KIM-UA Ammonia 107o 73DEDE KIM-UA Tetrahedral Methane 74DEDE KIM-UA Trigonal bipyramidal 75DEDE KIM-UA 76DEDE KIM-UA VSEPR Based on the number of pairs of valence electrons, both bonded and unbonded. Unbonded pair also called lone pair. CH4 - draw thestructural formula Has 4 + 4(1) = 8( 4 from C and 4x1 from H) wants 8 + 4(2) = 16(see structure 8 of C and 4x2 of H) (16-8)/2 = 4 bonds ( bond formation ofstructure) 77DEDE KIM-UA VSEPR for methane (a gas): Single bonds fill all atoms. There are 4 pairs of electrons pushing away. The furthest they can get away is 109.5 CHH H H This 2-dimensional drawing does not show a true representation of the chemical arrangement. 78DEDE KIM-UA Angle of 4 atoms bonded Basic shape is tetrahedral. A pyramid with a triangular base. Same shape for everything with 4 pairs. C HH H H 109.5 79DEDE KIM-UA Ammonia (NH3) = 107o Water (H2O) = 105o Carbon dioxide (CO2) = 180o 80DEDE KIM-UA Methane has an angle of 109.5o, called tetrahedral Ammonia has an angle of 107o, called pyramidal Note the unshared pair that is repulsion for other electrons. 81 DEDE KIM-UA DEDE KIM-UA82 Polar Bonds and Molecules -keelektronegatifan -vsepr -Konstanta dielektrikum -sudut ikatan -- polaritas OBJECTIVES: Describe how electronegativity values determine the distribution of charge in a polar molecule. 83DEDE KIM-UA Electronegativity? The ability of an atom in a molecule to attract shared electrons to itself. Linus Pauling 1901 - 1994 84DEDE KIM-UA Table of Electronegativities 85DEDE KIM-UA H 2.20 ElectronegativityElements Li 0.98 Be 1.57 B 2.04 C 2.55 N 3.04 O 3.44 F 3.98 Na 0.90 Mg 1.31 Al 1.61 Si 1.90 P 2.19 S 2.58 Cl 3.16 K 0.82 Ca 1.00 Ga 1.81 Ge 2.01 As 2.18 Se 2.55 Br 2.96 Electronegativity differences may be transmitted through connecting covalent bonds by an inductive effect 86DEDE KIM-UA DEDE KIM-UA 87 Replacing one of the hydrogens of water by a more electronegativeatomincreasestheacidityofthe remaining OH bond. Thus hydrogen peroxide,HOOH,istenthousandtimesmoreacidicthan water,hypochlorous acid, ClOH is one hundred million times more acidic.Thisinductivetransferofpolaritytapersoffasthe numberoftransmittingbondsincreases,andthe presenceofmorethanonehighlyelectronegative atom has a cumulative effect.For example, trifluoro ethanol, CF3CH2- O-H OBJECTIVES: Describe what happens to polar molecules when they are placed between oppositely charged metal plates. Evaluate the strength of intermolecular attractions comparedwith the strength of ionic and covalentbonds. Identify the reason why network solids have high melting points. 88DEDE KIM-UA Bond Polarity Covalent bonding means shared electrons but, do they share equally? Electrons are pulled, as in a tug-of-war, between the atoms nuclei In equal sharing (such as diatomic molecules), the bond that results is called a nonpolar covalent bond 89DEDE KIM-UA When two different atoms bond covalently, there is an unequal sharing the more electronegative atom will have a stronger attraction, and will acquire a slightly negative charge called a polar covalent bond, or simply polar bond. 90DEDE KIM-UA Bond Polarity Consider HCl H = electronegativity of 2.1 Cl = electronegativity of 3.0 the bond is polar the chlorine acquires a slight negative charge, and the hydrogen a slight positive charge 91DEDE KIM-UA Only partial charges, much less than a true 1+ or 1- as in ionic bond Written as: HCl the positive and minus signs (with the lower case delta: ) denote partial charges. o+o + and 92DEDE KIM-UA Can also be shown: the arrow points to the more electronegative atom. how the electronegativity can also indicate the type of bond that tends to form HCl 93DEDE KIM-UA A polar bond tends to make the entire molecule polar areas of difference HCl has polar bonds, thus is a polar molecule. A molecule that has two poles is called dipole, like HCl 94DEDE KIM-UA The effect of polar bonds on the polarity of the entire molecule depends on the molecule shape carbon dioxide has two polar bonds, and is linear = nonpolar molecule! 95DEDE KIM-UA How Polar molecules The effect of polar bonds on the polarity of the entire molecule depends on the molecule shape water has two polar bonds and a bent shape; the highly electronegative oxygen pulls the e- away from H = very polar! 96DEDE KIM-UA When polar molecules are placed between oppositely charged plates, they tend to become oriented with respect to the positive and negative plates. 97DEDE KIM-UA Attractions between molecules They are what make solid and liquid molecular compounds possible. The weakest are called van der Waals forces - there are two kinds: 1. Dispersion forces weakest of all, caused by motion of e- increases as e- increases halogens start as gases; bromine is liquid; iodine is solid all in Group 7A 98DEDE KIM-UA Dipole interactions Occurs when polar molecules are attracted to each other. 2.Dipole interaction happens in water positive region of one molecule attracts the negative region of another molecule. 99DEDE KIM-UA Occur when polar molecules are attracted to each other. Slightly stronger than dispersion forces. Opposites attract, but not completely hooked like in ionic solids. HF o+o HF o+o 100DEDE KIM-UA Single Covalent Bonds A single covalent bond is one in which two atoms share a pair of electrons. Structural formulas are chemical formulas that show the arrangement of atoms in molecules and polyatomic ions. Chemical FormulaStructural Formula H2H-H H2O NH3 CH4 101DEDE KIM-UA Unshared pairs (lone pairs) are pairs of valence electrons that are not shared between atoms. When carbon forms bonds with other atoms, it usually forms four bonds. CH4 C2H6 102DEDE KIM-UA 103DEDE KIM-UA Double & Triple Covalent Bonds Double covalent bonds share two pairs of electrons. CO2O=C=O Triple covalent bonds share three pairs of electrons. N2:N=N: 104DEDE KIM-UA Coordinate Covalent Bonds Two nuclei are attracted to a lone pair of electrons (e-) A bond in which one atom shares an entire pair of electrons (lone pair) with another atom. Typically forms polyatomic ions In structural formulas, you can show coordinate covalent bonds as arrows that point from the atom donating the pair of electrons to the atom receiving them. 105DEDE KIM-UA 106DEDE KIM-UA KEPOLARAN DEDE KIM-UA107 When e- pairs are not shared equally between atoms Due to differences in electronegativity Polar covalent bond an uneven sharing of e- between 2 nonmetals Non-polar covalent bond an even sharing of e- between 2 nonmetals 108DEDE KIM-UA 109DEDE KIM-UA The lower case Greek letter delta shows that atoms involved in the covalent bond acquire only partial charges, much less than 1+ or 1- The polarity of a bond may also be represented with an arrow pointing to the more electronegative atom 110DEDE KIM-UA DEDE KIM-UA111 IKATAN LEBIH LEMAH DARI IKATAN KOVALEN DEDE KIM-UA112 For examplein : Hydrogen bonding the attractive force caused by hydrogen bonded to N, O, F, or Cl N, O, F, and Cl are very electronegative, so this is a very strong dipole. And, the hydrogen shares with the lone pair in the molecule. This is the strongest of the intermolecular forces. 113DEDE KIM-UA Hydrogen bonding defined: When a hydrogen atom is:

a) covalently bonded to a highly electronegative atom,b) is also weakly bonded to an unshared electron pair of a nearby highly electronegative atom. The hydrogen is left very electron deficient (it only had 1 to start with!) thus it shares with something nearby Hydrogen is also the ONLY element with no shielding for its nucleus when involved in a covalent bond! 114DEDE KIM-UA Hydrogen Bonding (Shown in water) H H O o+ o- o+ This hydrogen is bonded covalently to: 1) the highly negative oxygen, and 2) a nearby unshared pair. 115DEDE KIM-UA Hydrogen bonding allows H2O to be a liquid at room conditions. H H O 116DEDE KIM-UA Dipole Interactions o+o o+o 117DEDE KIM-UA Hydrogen Bonding 118DEDE KIM-UA Attractions Between Molecules There are several kinds of molecular attractions. The weakest attractions are collectively called van der Waals forces, which are named after the chemist who discovered them, Johannes van der Waals. Van der Waals forces consist of two types: dispersion forces and dipole interactions. 119DEDE KIM-UA Van der Waals Forces Dispersion forces are the weakest of all molecular interactions and they are caused by the motion of electrons. The strength of dispersion forces increases as theof electrons increases Dipole interactions occur when polar molecules are attracted to one another. The slightly negative region of a polar molecule is attracted to the slightly positive region of another polar molecule. Similar but much weaker than ionic bonds 120DEDE KIM-UA Hydrogen Bonds Hydrogen bonds are attractive forces in which a hydrogen covalently bonded to a very electronegative atom is also weakly bonded to an unshared electron pair of another electronegative atom. 121DEDE KIM-UA Hydrogen Bonds Usually the electronegative atom is oxygen, nitrogen, or fluorine, which has a partial negative charge. The hydrogen then has the partial positive charge. Hydrogen bonding is usually stronger than normal dipole forces between molecules. Because oxygen has two lone pairs, two different hydrogen bonds can be made to each oxygen. 122DEDE KIM-UA http://www.northland.cc.mn.us/biology/Biology1111/animations/hydrogenbonds.html 123DEDE KIM-UA Hydrogen Bonds in DNA 124DEDE KIM-UA Order of Intermolecular attraction strengths 1) Dispersion forces are the weakest 2) A little stronger are the dipole interactions 3) The strongest is the hydrogen bonding 4) All of these are weaker than ionic bonds 125DEDE KIM-UA Polar Molecules In a polar molecule, one end of the molecule is slightly negative and the other end is slightly positive. The electrically charged regions are called poles. A molecule that has two poles is called a dipolar molecule or dipole. The effect of polar bonds on the polarity of a molecule depends on its shape. CO2 H2O 126DEDE KIM-UA Polar or Non-Polar Molecule? 127DEDE KIM-UA AtomHCNOFClBrI Valence14321111 Moment dipole and Charges A large local charge separation usually results when a shared electron pair is donated unilaterally. The three Kekul formulas shown here illustrate this condition. 128DEDE KIM-UA Despite having two polar covalent bonds, carbon dioxide is non-polar. The reason for this is the molecule's linear geometry: The electrons are pulled in equal but opposite directions, causing them to cancel one another.129DEDE KIM-UA Water has two polar covalent bonds, but the polar covalent bonds pull electrons to the oxygen's region of the molecule, to make the molecule polar. The reason for this is the molecule's bent geometry: The electrons are not pulled in equal and opposite directions, despite the bonds being identical.130DEDE KIM-UA 131DEDE KIM-UA DEDE KIM-UA132 DEDE KIM-UA133 DEDE KIM-UA134 DEDE KIM-UA135 DEDE KIM-UA136 DEDE KIM-UA137 Hyperconjugation Hyperconjugation in organic chemistry is the stabilizing interaction that results from the interaction of the electrons in a sigma bond (usually C-H or C-C) with an adjacent empty (or partially filled) non-bonding p-orbital or antibonding orbital or filled orbital to give an extended molecular orbital that increases the stability of the system. Only electrons in bonds that are to the positively charged carbon can stabilize a carbocation by hyperconjugation 138DEDE KIM-UA The stabilisation arises because the orbital interaction leads to the electrons being in a lower energy orbital Let's consider how a methyl group is involved in hyperconjugation with a carbocation centre.First we need to draw it to show the C-H o-bonds.Note that the empty p orbital associated with the positive charge at the carbocation centre is in the same plane (i.e. coplanar) with one of the C-H o-bonds(shown in blue.) This geometry means the electrons in the o-bond can be stabilised by an interaction with the empty p-orbital of the carbocation centre.(this diagram shows the similarity with resonance and the structure on the right has the "double bond - no bond" character) 139DEDE KIM-UA Hyperconjugation has an effect on several chemical properties . Bond length: Hyperconjugation is suggested as a key factor in shortening of sigma bonds ( bonds) in such systems. For example, the single C-C bonds in 1,3-butadiene and methylacetylene are approximately 1.46 angstrom in length, much less than the value (1.54 angstrom) found in saturated hydrocarbons. This is due mainly to hyperconjugation that gives partial double-bond character of the bond. Dipole moments: The large increase in dipole moment of 1,1,1-trichloroethane as compared with chloroform can be attributed to hyperconjugated structures. 140DEDE KIM-UA 1.Theheatofformationofsuchmoleculesare greaterthansumoftheirbondenergies;andthe heatsofhydrogenationperdoublebondareless than the heat of hydrogenation of ethylene. 1.Stability of carbocations:(CH3)3C+ > (CH3)2CH+ > (CH3)CH2+ > CH3+TheC-Cbondadjacenttothecationisfreeto rotate, and as it does so, the three C-H bondsof the methyl group in turn undergoes the stabilization interaction.ThemoreadjacentC-Hbondsare,the larger hyperconjugation stabilization is.141DEDE KIM-UA 142DEDE KIM-UA STEREOCHEMISTRY (stereokimia) 143DEDE KIM-UA 144DEDE KIM-UA * isomers ADALAH BERBEDA SENYAWA TETAPI SAMA RUMUS MOLEKUL For example, in the case of the C4H8 hydrocarbons, most of the isomers are constitutional.145DEDE KIM-UA OPTISAKTIF DAN KHIRALITAS OPTIS AKTIF :MOLEKUL YANG DAPAT MEMUTAR BIDANG SINAR YANG TERPOLARI SASI TIDAK BERIMPITDENGAN BAYANGAN CERMINSENYAWA KHIRAL.:MOL. ORG YANG KE 4 IKATAN PD ATM C TERIKAT DENGAN ATOM ATAU MOL. YANGBERBEDA-BEDA. NCH3CHHNH3CCH2CH3HHOHCOOHHCHOHCOOHH3C::sp3sp3 sp3sp3N - simetrisC - simetrisC - asimetrisN - asimetrisKhiralKhiralAkhiralAkhiralContoh : atom N dan C tetrahedral146DEDE KIM-UA enantiomer* are stereoisomers that are mirror images of each other. Much as a left and right hand are differentbutoneisthemirrorimageofthe other arestereoisomerswhosemoleculesare nonsuperimposablemirrorimagesofeach other. Enantiomers have- when present in a symmetric environment-identicalchemicalandphysicalproperties exceptfortheirabilitytorotateplane-polarizedlightbyequalamountsbutin opposite directions. Asolutionofequalpartsofanoptically-active isomer and its enantiomer is known as aracemicsolutionandhasanetrotationof plane-polarized light of zero. 147DEDE KIM-UA Enantiomers are stereoisomers whose molecules are nonsuperimposable mirror images of one another Objects that are superimposable on their mirror images are said to be achiral CH3CH2CH HOCH3CH2CHCH3CH3OHInterchanging any two groups at a chiral centre (stereocentre) that bears four different groups converts one enantiomer into another Involves a tetrahedral sp3 atom CH3COHCH2CH32-ButanolHChiral Centre148DEDE KIM-UA One structure can be superimposed on another If any of the groups attached to the tetrahedral atom are the same, the centre is achiral. The ultimate way to test for molecular chirality is to construct models of the molecule and its mirror image and then determine whether they are superimposable A molecule will not be chiral if it possess a centre or plane of Symmetry2-PropanolCH3COH HCH3CCH3H HOCH3Screwdriver is achiral Socks are achiral Golf club is chiral Gloves are chiral 149DEDE KIM-UA 150DEDE KIM-UA 151DEDE KIM-UA Properties of Enantiomers Enantiomers have identical melting points and boiling points Enantiomers have identical solubilities in solvents Enantiomers have identical spectra and refractive index Enantiomers interact, and react with achiral molecules in the same manner Enantiomers interact and react with other chiral molecules at different rates Enantiomers rotate plane-polarised light by equal amounts but in opposite directions Plane-polarised lightOscillation of electrical field of ordinary lightoccurs in all possible directionsPolarimeter is a devise used to measure the effect of plane-polarised light on an optically active compound Chiral molecules are optically active 152DEDE KIM-UA 153DEDE KIM-UA No Correlation between the direction of rotation of plane polarised light and the absolute configuration of a molecule Clockwise Rotation (+) dextrorotatory Anti-Clockwise Rotation (-) levorotatory CCH2CH3H2CCH3HHOCCH2CH3H2CCH3HCl(R)-(+)-2-Methyl-1-butanol(R)-(-)-1-Chloro-2-methylbutanolSame ConfigurationAn equimolar mixture of two enantiomers is called a Racemic MixtureIt is Optically Inactive 154DEDE KIM-UA 155DEDE KIM-UA 156DEDE KIM-UA 157DEDE KIM-UA 158DEDE KIM-UA 159DEDE KIM-UA 160DEDE KIM-UA 161DEDE KIM-UA 162DEDE KIM-UA 163DEDE KIM-UA 164DEDE KIM-UA 165DEDE KIM-UA In chemistry (particularly organic chemistry and biochemistry), a Fischer projection is a two-dimensional representation of a three-dimensional organic molecule by projection. All bonds are depicted as horizontal or vertical lines. The carbon chain is depicted vertically, with carbon atoms represented by the center of crossing lines. The orientation of the carbon chain is so that the C1 carbon is at the topFischer projection of D-glucose 166DEDE KIM-UA The structure must not be flipped over or rotated 90 degree 167DEDE KIM-UA . 168DEDE KIM-UA Some physical properties of the isomers of tartaric acid are given in the following table. (+)-tartaric acid: []D = +13 m.p. 172 C ()-tartaric acid: []D = 13 m.p. 172 C meso-tartaric acid: []D = 0 m.p. 140 C Fischerprojectionformulasprovideahelpfulviewoftheconfigurationalrelationships withinthestructuresoftheseisomers.Inthefollowingillustrationamirrorlineisdrawn betweenformulasthathaveamirror-imagerelationship.Indemonstratingtheidentityof thetwomeso-compoundformulas,rememberthataFischerprojectionformulamaybe rotated 180 in the plane.169DEDE KIM-UA 170DEDE KIM-UA 171DEDE KIM-UA 172DEDE KIM-UA 173DEDE KIM-UA 174DEDE KIM-UA 175DEDE KIM-UA (natural) tartaric acid L-(+)-tartaric acid dextrotartaric acid D-(-)-tartaric acid levotartaric acid (1:1) DL-tartaric acid "racemic acid" mesotartaric acid 176DEDE KIM-UA 177DEDE KIM-UA 178DEDE KIM-UA 179DEDE KIM-UA 180DEDE KIM-UA 181DEDE KIM-UA ISOMER STRUKTURAL 182DEDE KIM-UA 183DEDE KIM-UA 184DEDE KIM-UA * isomers ADALAH BERBEDA SENYAWA TETAPI SAMA RUMUS MOLEKUL For example, in the case of the C4H8 hydrocarbons, most of the isomers are constitutional.C4H8 C4H8 C4H8 C4H8 185DEDE KIM-UA Selasa. Kamis, 22-10-09Jumat, 23-10-09 Configurational Stereoisomers of Alkenesalkynes are linear, there is no stereoisomerism associated with the carbon-carbon triple bond.186DEDE KIM-UA Assignment of a cis or trans prefix to any of these isomers can only be done in an arbitrary manner, so a more rigorous method is needed. * based on a set of group priority rules,assigns a Z (German, zusammen for together) is equivalent to cis or E (German, entgegen for opposite) is equivalent to transto designate the stereoisomersZ and E. The Sequence Rule for Assignment of Alkene Configurations Assign priorities to double bond substituents by looking at the atoms attached directly to the double bond carbons. The higher the atomic number of the immediate substituent atom, the higher the priority.For example, H T1 345DEDE KIM-UA The equilibrium vapor pressure is the vapor pressure measured when a dynamic equilibrium exists between condensation and evaporation H2O (l)H2O (g) Rate of condensation Rate of evaporation = Dynamic Equilibrium 11.8 346DEDE KIM-UA Molar heat of vaporization (AHvap) is the energy required to vaporize 1 mole of a liquid. ln P = - AHvap RT + C Clausius-Clapeyron Equation P = (equilibrium) vapor pressure T = temperature (K) R = gas constant (8.314 J/Kmol) 11.8 C = constant (depends on P & T) 347DEDE KIM-UA The boiling point is the temperature at which the (equilibrium) vapor pressure of a liquid is equal to the external pressure. The normal boiling point is the temperature at which a liquid boils when the external pressure is 1 atm. 11.8 348DEDE KIM-UA The critical temperature (Tc) is the temperature above which the gas cannot be made to liquefy, no matter how great the applied pressure. The critical pressure (Pc) is the minimum pressure that must be applied to bring about liquefaction at the critical temperature. 11.8 349DEDE KIM-UA Melting 11.8 Freezing H2O (s)H2O (l) The melting point of a solid or the freezing point of a liquid is the temperature at which the solid and liquid phases coexist in equilibrium 350DEDE KIM-UA Molar heat of fusion (AHfus) is the energy required to melt 1 mole of a solid substance. 11.8 351DEDE KIM-UA 11.8 352DEDE KIM-UA Sublimation 11.8 Deposition H2O (s)H2O (g) Molar heat of sublimation (AHsub) is the energy required to sublime 1 mole of a solid. AHsub = AHfus + AHvap ( Hesss Law) 353DEDE KIM-UA A phase diagram summarizes the conditions at which a substance exists as a solid, liquid, or gas. The triple point is where all 3 phases meet. Phase Diagram of Water 11.9 354DEDE KIM-UA 11.9 355DEDE KIM-UA Wheres Waldo? Can you find The Triple Point? Critical pressure? Critical temperature? Where fusion occurs? Where vaporization occurs? Melting point (at 1 atm)? Boiling point (at 6 atm)? Carbon Dioxide 356DEDE KIM-UA 11.9 357DEDE KIM-UA Chemistry In Action: Liquid Crystals 358DEDE KIM-UA ALDEHYDES AND KETONES 359DEDE KIM-UA Aldehydes and Ketones O 1s2, 2s2 2p2 2p1 2p1 3 sp2 orbitals CHRO CRROAldehydeKetoneCHHOlone Pairstbond - two overlapping 2p orbitalsobondobond- overlapping 1s H-orbital and sp2 C-orbital360DEDE KIM-UA C OH3CH118o121oC CHHHH118o121oo o+ C OH3CHC OH3CHResonanceStructuresMost Reactive Group telectrons + polarisation Useful in Synthesis al aldehydes, one - ketonesC OHHC OH3CHC OCH3CH2HC OCH3CH2CH2CH2HMethanal (formaldehyde) Ethanal (acetaldehyde) Propanal Pentanal 361DEDE KIM-UA OHH OHHBenzaldehyde trans-Cinnamaldehyde Formalin, 35-40% formadehyde in water Preservative that reacts withproteins causing them to resist decay Coelacanth, prehistoric fish OHAcrolein(2-propenal)SHThiopropionaldehyde (propanethiol)- lachrymator from chopped onion- lachrymator and pleasant "odour" from barbacuing meat362DEDE KIM-UA Propanone (ACETONE) Butanone Acetophenone Benzophenone OH3CCHCH2CH3CH33-Methyl-2-pentanone OHOCH3OHVanillinCH3OCarvone(spearmint flavour)O OH3C CH3Butadione(butter flavour)OH3C CH3OCH3OOH3C CH2CH3363DEDE KIM-UA Carbonyls readily undergo Nucleophilic Attack ANHYDROUS Conditions are required for imine formation OCRNH2oo+OCN HHROCN H RHOCN H RHCNR- H2OImineReaction between an amine and a carbonyl compound 364DEDE KIM-UA Condensation Reaction Elimination of water C OC H3C H3N NHH HHC NC H3C H3NHH+hydrazineacetonehydrazone of acetone Emil Fischer, Nobel Prize 1902 C OC H3C H3N NH HHO2NO2NC NC H3C H3NHNO2NO2+2,4-diphenylhydrazineacetonehydrazone of acetone DNP test for aldehydes & ketones gives crystalline hydrazones - H2O - H2O 365DEDE KIM-UA Professor Victor Grignard (1912 Nobel Prize) Developed this chemistry with Professor P. A. Barbier C R OHProtonationHH2OAlcoholC RXHHX = I or Bro+oCHHMgX Roo+RCH2MgXGrignard ReagentMgEtherC RXHHX = I or Bro+oCHHLi Roo+RCH2LiOrganolithium ReagentLiEtherC OR Lio+ooo+C R OLiADDITION366DEDE KIM-UA MgBrC OHHEtherCHHO MgBrH3O+CHHO HBenzylalcoholC OMgBr+EtherC OHTriphenylmethanolBenzyl GroupPhenyl, Ph GroupPh2. H3O+ Organometallics add to carbonyls to give alcohols 367DEDE KIM-UA OCH HOCR HOCR RMgI Ph MgI Ph MgI PhOC H HHPhOC R HHPhOC R RHPh+++Primary alcoholsSecondary alcohols tertiary alcoholsKetoneAldehydesFormaldehydeNucleophilic Addition Reactions your adding Ph _ 368DEDE KIM-UA MgBrOCH2CH3CH3CH2OCH2CH3 CH3CH2.. .... ..Ethers (Lewis base) stabilize the Grignard Reagent making it more reactive Organometallic Reactions must always be done under anhydrous conditions Mg BrHOHH+ooOH_+Grignards are powerful bases and will deprotonate water 369DEDE KIM-UA CARBOXYLIC ACIDS and ESTERS370DEDE KIM-UA Carboxylic Acids OCO H H2O +OCOH3O +pKa = 4 - 5 , water= 16We can distinguish a water-insoluble carboxylic acid and phenol from an alcoholOCO H NaOH +OCOH2ONaBenzoic acidSodium Benzoate371DEDE KIM-UA Highly Polar Low molecular weight acids show Appreciable Solubility in Water High Bpt Extensive H-bonds to themselves and water Carboxylic Acids Methanoic acid Ethanoic acid Propanoic acid 4-Bromo-2-ethylpentanoic acid OH OHOCH3OHOCH3CH2OHOOHBrOCC OHHOOEthanedioic acid (oxalic acid) rhubarb OOHOHO ()nn=1 = malonic acidn=2= succinic acidn=3= glutaric acidHO2C CO2HCO2HCO2HTerephthalic acid Phthalic acid 372DEDE KIM-UA Esterification condensation reaction, where H2O is lostAlcohol part appears first in the name OCH3OHCH3CH2OH +HCl or H2SO4 H+(catalyst)OCH3O CH2CH3Acetic acid(ethanoic acid)Ethyl acetateOPh OHH3C OH+ H+(catalyst)OPh O CH3Benzoic acidMethyl benzoateOOOOEthyl propanoatevinyl acetateOH OMethyl formate373DEDE KIM-UA Ester molecules cannot H-bond to each other, because they do not have an OH Consequently, B.pt is much lower than that of alcohols and acids of comparable mass H-bonding to water is possible -low mw esters are soluble in water Solubility rapidly decreases with carbon chain length.

OHOHHOHO RR374DEDE KIM-UA OC RO HOC RO H................Two hydrogen bondsOC RO Rcannot H-bond to another ester molecule Highest Boiling points and exceedingly water soluble Hexane = 69 C Diethyl ether = 56 C Ethanol = 78 C Ethanoic acid = 118 C Ethyl acetate = 77 C Boiling points 375DEDE KIM-UA Redox Reactions Addition of Oxygen or Removal of Hydrogen is OXIDATION Removal of Oxygen or Addition of Hydrogen is REDUCTION CH4+ OCH3OH- 2HC OHHC OHOH+ O - 2HOCOC OHRHC RHOHReductionOxidationC ORRHC RROHReductionOxidationAldehydesPrimary AlcoholsSecondary Alcohols Ketones376DEDE KIM-UA Examples of Reduction Reactions OH2 , PtOHHCyclohexanone CyclohexanolCH3H3COH3-MethylbutanalH2 , Pd-CCH3H3COHHH3-MethylbutanolExamples of Oxidation Reactions OHHOK2Cr2O7, H2SO4, H2OOveroxidationOHO377DEDE KIM-UA H N HHR N HHR N HRR N RRAmmoniaPrimary (1o) AmineSecondary (2o) AmineTertiary (3o) AmineOrganic bases are amines Amines are derivatives of ammonia N 1s2, 2s2 2p1 2p1 2p1----------- lone pair occupies an sp3 orbital 378DEDE KIM-UA AMINES, AMIDES and ANILINE 379DEDE KIM-UA Ammonia 3oAmine Unshared lone pair of electrons in the fourth sp3 hybrid occupies slightly more space than the electrons in the obonds NHHHNRRR..107O..107O380DEDE KIM-UA H2NEt HNEt2NEt3H2NMeHNMe2NMe3where Et = CH2CH3ethylamine diethylaminetriethylamineprimarysecondarytertiarywhere Me = CH3methylaminedimethylaminetrimethylamineprimarysecondarytertiaryNaming amines NHmethylpropyl amine 381DEDE KIM-UA H2NNH2 Putrescine(found in decaying meat)NH2 Amphetamine(dangerous stimulant)NH PiperidineNTriethylamineNH2 Isopropylamine1,4-butanediamine Some Common Amines Both upper amines are 1o This amine is are 2o This amine is 3o This amine is 1o 382DEDE KIM-UA NH2HClNHHH ClBase + Acid= Ammonium SaltAmines are bases because of the lone pair on the nitrogen atom - red litmus paper to blue OO HOO HN(CH2CH3)3OOOOHN(CH2CH3)3+ 2+2oxalic acidtriethylaminetriethylaminium oxalate 383DEDE KIM-UA = aniline Aniline is useful in the synthesis of many other aromatic compounds NO2NO2NH2HNO3, H2SO4Sn, HClphenylamine384DEDE KIM-UA NH2N NNaNO2, HClbenzenediazonium chloride+Cl-0 CAniline can be converted into useful diazonium salt N NN NNuc+Cl-Nuc--385DEDE KIM-UA N NN NCN+Cl-CuCN-+KCNN NN NI+Cl-NaI-Benzene nitrile N NN NBr+Cl-HBr, CuBr-iodobenzene bromobenzene 386DEDE KIM-UA NC RR'ONC RR'OAmides Features of a Peptide Bond; 1. Usually inert 2. Planar to allow delocalisation 3. Restricted Rotation about the amide bond 4. Rotation of Groups (R and R) attached to the amide bond is relatively free ------------- Not acids or bases 387DEDE KIM-UA OCC H3NH2OCH NH2NH2OOCN H2NH2RC N H2HCOOHacetamidebenzamideureaAMINO ACIDSformamideAll are high melting point solids, only benzamide not soluble in water 388DEDE KIM-UA 389DEDE KIM-UA 390DEDE KIM-UA 391DEDE KIM-UA 392DEDE KIM-UA 393DEDE KIM-UA 394DEDE KIM-UA 395DEDE KIM-UA 396DEDE KIM-UA 397DEDE KIM-UA 398DEDE KIM-UA 399DEDE KIM-UA 400DEDE KIM-UA 401DEDE KIM-UA 402DEDE KIM-UA 403DEDE KIM-UA Solubility in Water Water has been referred to as the "universal solvent", and its widespread distribution on this planetand essential role in life make it the benchmark for discussions of solubility. Water dissolves manyionic salts thanks to its high dielectric constant and ability to solvate ions. The former reduces theattraction between oppositely charged ions and the latter stabilizes the ions by binding to them anddelocalizing charge density.when hexane or other nonpolar compounds are mixed with water, the strong association forces ofthe water network exclude the nonpolar molecules, which must then exist in a separate phase.This is shown in the following illustration, and since hexane is less dense than water, the hexanephase floats on the water phase. 404DEDE KIM-UA Water Solubility of Characteristic Compounds Compound Type Specific Compounds Grams/100mL Moles/Liter Specific Compounds Grams/100mL Moles/Liter Hydrocarbons & Alkyl Halides butane hexane cyclohexane 0.007 0.0009 0.006 0.0012 0.0001 0.0007 benzene methylene chloride chloroform 0.07 1.50 0.8 0.009 0.180 0.07Compounds Having One Oxygen 1-butanol tert-butanol cyclohexanol phenol 9.0 complete 3.6 8.7 1.2 complete 0.36 0.90 ethyl ether THF furan anisole 6.0 complete 1.0 1.0 0.80 complete 0.15 0.09Compounds Having Two Oxygens 1,3-propanediol 2-butoxyethanol butanoic acid benzoic acid complete complete complete complete complete complete complete complete 1,2-dimethoxyethane 1,4-dioxane ethyl acetate -butyrolactone complete complete 8.0 complete complete complete 0.91 completeNitrogen Containing Compounds 1-aminobutane cyclohexylamine aniline pyrrolidine pyrrole complete complete 3.4 complete 6.0 complete complete 0.37 complete 0.9 triethylamine pyridine propionitrile 1-nitropropane DMF 5.5 complete 10.3 1.5 complete 0.54 complete 2.0 0.17 complete405DEDE KIM-UA * Meerwein-Pondorf-Verley Reduction Redox Reactions Hydrogen Transfer The MVP reduction is also an oxidation, as evidenced by the conversion of isopropoxide to acetone. Consequently, the reaction can be converted into an oxidation of alcohols to ketones or aldehydes. This procedure is called the Oppenauer oxidation.406DEDE KIM-UA The Cannizzaro Reaction 407DEDE KIM-UA The Haloform Reaction base-catalyzed halogenation of methyl ketones is accompanied by CC bond cleavage, yieldinga carboxylate salt and haloform ( X3CH )408DEDE KIM-UA Alkane Reactions The alkanes and cycloalkanes, with the exception of cyclopropane, are probably the least chemicallyreactive class of organic compounds. Despite their relative inertness, alkanes undergo several importantreactions that are discussed in the following section. 1. Combustion The combustion of carbon compounds, especially hydrocarbons, has been the most important source of heat energy for humanEvery covalent bond in the reactants has been broken and an entirely new set of covalent bondshave formed in the productsCH3-CH2-CH3 + 5 O2 >3 CO2 + 4 H2O + heat Two points concerning this reaction are important:1. Since all the covalent bonds in the reactant molecules are broken, the quantity of heat evolvedin this reaction is related to the strength of these bonds (and, of course, the strength of the bondsformed in the products). Precise heats of combustion measurements can provide useful iinformationabout the structure of molecules. 2.The stoichiometry of the reactants is important. If insufficient oxygen is supplied some of the products will consist of carbon monoxide, a highly toxic gas. CH3-CH2-CH3 + 4 O2 >CO2 + 2 CO + 4 H2O + heat 409DEDE KIM-UA Cycloalkane(CH2)n CH2 Unitsn H25

kcal/mole H25

per CH2 Unit Ring Strainkcal/mole Cyclopropane n = 3468.7156.227.6 Cyclobutane n = 4614.3153.626.4 Cyclopentane n = 5741.5148.36.5 Cyclohexane n = 6882.1147.00.0 Cycloheptane n = 71035.4147.96.3 Cyclooctane n = 81186.0148.29.6 Cyclononane n = 91335.0148.311.7 Cyclodecane n = 101481148.111.0 CH3(CH2)mCH3m = large147.00.0 Heat of Combustion The chief source of ring strain in smaller rings is angle strain and eclipsing strain. As noted elsewhere, cyclopropane and cyclobutane have large contributions of both strains, with angle strain being especially severe.410DEDE KIM-UA 2. Halogenation Halogenation is the replacement of one or more hydrogen atoms in an organic compound by a halogen(fluorine, chlorine, bromine or iodine). Simple substitution reaction in which a C-H bond is broken and a new C-X bond is formedCH4 + Cl2 + energy >CH3Cl + HClonly two covalent bonds are broken (C-H & Cl-Cl) and two covalent bonds are formed (C-Cl & H-Cl), this reaction seems to be an ideal case for mechanistic investigation and speculationThe relative amounts of the various products depend on the proportion of the two reactants used. In the case ofmethane, a large excess of the hydrocarbon favors formation of methyl chloride as the chief product; whereas, anexcess of chlorine favors formation of chloroform and carbon tetrachloride. CH4 + Cl2 + energy >CH3Cl + CH2Cl2 + CHCl3 + CCl4 + HCl The following facts must be accomodated by any reasonable mechanism for the halogenation reaction. 1. The reactivity of the halogens decreases in the following order: F2 > Cl2 > Br2 > I2. 2. We shall confine our attention to chlorine and bromine, since fluorine is so explosively reactive it is difficult to control, and iodine is generally unreactive. 3. Chlorinations and brominations are normally exothermic. 4. Energy input in the form of heat or light is necessary to initiate these halogenations. 5. If light is used to initiate halogenation, thousands of molecules react for each photon of light absorbed. 6. Halogenation reactions may be conducted in either the gaseous or liquid phase. 7. In gas phase chlorinations the presence of oxygen (a radical trap) inhibits the reaction. 8. In liquid phase halogenations radical initiators such as peroxides facilitate the reaction.411DEDE KIM-UA The most plausible mechanism for halogenation is a chain reaction involving neutral intermediates such as free radicalsor atoms. The weakest covalent bond in the reactants is the halogen-halogen bond(Cl-Cl = 58 kcal/mole;Br-Br = 46 kcal/mole)so the initiating step is the homolytic cleavage of this bond by heat or light, note that chlorine andbromine both absorbvisible light (they are colored).. All the hydrogens in a complex alkane do not exhibit equal reactivity. For example, propane has eight hydrogens,six of them being structurally equivalent primary, and the other two being secondary. If all these hydrogen atoms wereequally reactive, halogenation should give a 3:1 ratio of 1-halopropane to 2-halopropane mono-halogenated products,reflecting the primary/secondary numbers. This is not what we observe. Light-induced gas phase chlorination at 25 C gives 45% 1-chloropropane and 55% 2-chloropropane.CH3-CH2-CH3 + Cl2 >45% CH3-CH2-CH2Cl + 55% CH3-CHCl-CH3 The results of bromination ( light-induced at 25 C ) are even more suprising, with 2-bromopropane accounting for 97% of the mono-bromo product.CH3-CH2-CH3 + Br2>3% CH3-CH2-CH2Br + 97% CH3-CHBr-CH3 412DEDE KIM-UA These results suggest strongly that 2-hydrogens are inherently more reactive than 1-hydrogens, by a factor of about 3:1.Further experiments showed that 3-hydrogens are even more reactive toward halogen atoms. Thus, light-induced chlorination of 2-methylpropane gave predominantly (65%) 2-chloro-2-methylpropane, the substitution product of the sole 3-hydrogen, despite the presence of nine 1-hydrogens in the molecule. (CH3)3CH + Cl2 >65% (CH3)3CCl + 35% (CH3)2CHCH2Cl Producing radical First Step: R3CH + X >R3C + H-X Second Step: R3C + X2 >R3CX + X . In the case of carbon-hydrogen bonds, there are significant differences, and the specific dissociation energies (energy required to break a bond homolytically) for various kinds of C-H bonds have been measuredR (in RH)methylethyli-propylt-butylphenylbenzylallylvinyl Bond Dissociation Energy (kcal/mole) 1039895931108588112 The difference in C-H bond dissociation energy reported for primary (1), secondary (2) and tertiary (3) sites agrees with the halogenation observations reported above, in that we would expect weaker bonds to be broken more easily than are strong bonds. By this reasoning we would expect benzylic and allylic sites to be exceptionally reactive in free radical halogenation, as experiments have shown. The methyl group of toluene, C6H5CH3, is readily chlorinated or brominated in the presence of free radical initiators (usually peroxides), and ethylbenzene is similarly chlorinated at the benzylic location exclusively. The hydrogens bonded to the aromatic ring (referred to as phenyl hydrogens above) have relatively high bond dissociation energies and are not substituted.413DEDE KIM-UA Free Radical Reactions of Alkenes 1. Addition of Radicals to Alkenes Protons and other electrophiles are not the only reactive species that initiate addition reactions to carbon-carbon double bondsFurther study showed that an alternative radical chain-reaction, initiated by peroxides, was responsible for theanti-Markovnikov product. This is shown by the following equations.The weak OO bond of a peroxide initiator is broken homolytically by thermal or hight energy414DEDE KIM-UA Other radical addition reactions to alkenes have been observed, one example being the peroxide induced addition of carbon tetrachloride shown in the following equation RCH=CH2 + CCl4 (peroxide initiator) > RCHClCH2CCl3 Since the addition of carbon radicals to double bonds is energetically favorable, concentrated solutions of alkenes are prone to radical-initiated polymerization, as illustrated for propene by the following equation. The blue colored R-group represents an initiating radical species or a growing polymer chain; the propene monomers are colored maroon. The addition always occurs so that the more stable radical intermediate is formed.RCH2(CH3)CH + CH3CH=CH2 > RCH2(CH3)CH-CH2(CH3)CH + CH3CH=CH2 > RCH2(CH3)CHCH2(CH3)CH-CH2(CH3)CH > etc. 415DEDE KIM-UA C6H5CH2CH3 + Cl2 >C6H5CHClCH3 + HClSince carbon-carbon double bonds add chlorine and bromine rapidly in liquid phase solutions, free radical substitution reactions of alkenes by these halogens must be carried out in the gas phase, or by other halogenating reagents. One such reagent is N-bromosuccinimide (NBS), shown in the second equation below. By using NBS as a brominating agent, allylic brominationsare readily achieved in the liquid phase. The covalent bond homolyses that define the bond dissociation energies listed above may are described by the general equation: R3C-H + energy >R3C + H 416DEDE KIM-UA that alkyl radical stability increases in the order:phenyl < primary (1) < secondary (2) < tertiary (3) < allyl benzyl.Because alkyl radicals are important intermediates in many reactions, this stability relationship will prove to be very useful infuture discussions. The enhanced stability of allyl and benzyl radicals may be attributed to resonance stabilizationThe poor stability of phenyl radicals, C6H5, may in turn be attributed to the different hybridization state of the carbonbearing the unpaired electron (sp2 vs. sp3).3. Addition Reactions Involving Other Cyclic Onium Intermediates Hydroboration417DEDE KIM-UA 4. Hydrogenation Addition of hydrogen to a carbon-carbon double bond is called hydrogenation.hydrogenation reaction is exothermic, a high activation energy prevents it from taking place under normal conditions.This restriction may be circumvented by the use of a catalyst, as shown in the following diagram. Catalysts act by lowering the activation energy of reactions, but they do not change the relative potential energy of the reactants and products. Finely divided metals, such as platinum, palladium and nickel, are among the most widely used hydrogenation catalysts. Catalytic hydrogenation takes place in at least two stages, as depicted in the diagram. First, the alkene must be adsorbed on the surface of the catalyst along with some of the hydrogen. Next, two hydrogens shift from the metal surface to the carbons of the double bond, and the resulting saturatedhydrocarbon, which is more weakly adsorbed, leaves the catalyst surface. The exact nature and timing of the last events is not well understood418DEDE KIM-UA Alkene Isomer(CH3)2CHCH=CH2 3-methyl-1-butene CH2=C(CH3)CH2CH3 2-methyl-1-butene (CH3)2C=CHCH3 2-methyl-2-butene Heat of Reaction ( H ) 30.3 kcal/mole28.5 kcal/mole26.9 kcal/mole From the mechanism shown here we would expect the addition of hydrogen to occur with syn-stereoselectivity. This is often true, but the hydrogenation catalysts may also cause isomerization of the double bond prior to hydrogen addition, in which case stereoselectivity may be uncertain.A non-catalytic procedure for the syn-addition of hydrogen makes use of the unstable compound diimide, N2H2. This reagent mustbe freshly generated in the reaction system, usually by oxidation of hydrazine, and the strongly exothermic reaction is favored by the elimination of nitrogen gas (a very stable compound). Diimide may exist as cis-trans isomers; only the cis-isomer serves as a reducing agent. Examples of alkene reductions by both procedures are shown on the right. 419DEDE KIM-UA 5. Oxidations (i) Hydroxylation Dihydroxylated products (glycols) are obtained by reaction with aqueous potassium permanganate (pH > 8) the metallocyclic intermediate may be isolated in the osmium reaction.420DEDE KIM-UA (ii) Epoxidation oxidation reactions of alkenes give cyclic ethers in which both carbons of a double bond become bonded to the sameoxygen atom. These products are called epoxides or oxiranes. An important method for preparing epoxides is by reaction with peracids, RCO

been classified as reductions or oxidations, depending on the change in oxidation state of the functional carbons. It is important to remember that whenever an atom or group is reduced, some other atom or group is oxidized, and a balanced equation must balance the electron gain in the reduced species with the electron loss in the oxidizedmoiety, as well as numbers and kinds of atoms421DEDE KIM-UA The previous few reactions have been classified as reductions or oxidations, depending on the change in oxidation state of the functional carbons422DEDE KIM-UA The Variables of Organic Reactions In an effort to understand how and why reactions of functional groups take place in the way they do, chemists try to discoverjust how different molecules and ions interact with each other as they come together. To this end, it is important to consider the various properties and characteristics of a reaction that may be observed and/or measured as the reaction proceeds .1. Reactants and ReagentsA. Reactant Structure:Variations in the structure of the reactant may have a marked influence on the course of a reaction, even though the functional group is unchanged. Thus, reaction of 1-bromopropane with sodium cyanide proceeds smoothly to yield butanenitrile, whereas 1-bromo-2,2-dimethylpropane fails to give any product and is recovered unchanged. In contrast, both alkyl bromides form Grignard reagents (RMgBr) on reaction with magnesium. B. Reagent Characteristics: Apparently minor changes in a reagent may lead to a significant change in the course of a reaction. For example, 2-bromopropane gives a substitution reaction with sodium methylthiolate but undergoes predominant elimination on treatment with sodium methoxide. 423DEDE KIM-UA 2. Product Selectivity A. Regioselectivity: It is often the case that addition and elimination reactions may, in principle, proceed to more than one product. Thus 1-butene might add HBr to give either 1-bromobutane or 2-bromobutane, depending on which carbon of the double bond receives the hydrogen and which the bromine. If one possible product out of two or more is formed preferentially, the reaction is said to be regioselective. B. Stereoselectivity: If the reaction products are such that stereoisomers may be formed, a reaction that yields one stereoisomer preferentially is said to be stereoselective. In the addition of bromine to cyclohexene, for example, cis and trans-1,2-dibromocyclohexane are both possible products of the addition. Since the trans-isomer is the only isolated product, this reaction is stereoselectiveC. Stereospecificity: This term is applied to cases in which stereoisomeric reactants behave differently in a given reaction.424DEDE KIM-UA (i) Formation of different stereoisomeric products, as in the reaction of enantiomeric 2-bromobutane isomers with sodium methylthiolate, shown in the following diagram. Here, the (R)-reactant gives the configurationally inverted (S)-product, and (S)-reactant produces (R)-product.(ii) Different rates of reaction, as in the base-induced eleimination of cis & trans-4-tert-butylcyclohexyl bromide

425DEDE KIM-UA Chemical reactions involve breaking and making some (or even all) of the bonds that hold together the atoms of reactant and product molecules. Energy is required to break bonds, and since the strengths of different kinds of bonds differ, there is often a significant overall energy change in the course of a reaction. In thecombustion of methane, for example, all six bonds in the reactant molecules are broken, and six new bondsare formed in the product molecules (equation 1). Reaction Energetics The sum of the product bond strengths in this case is greater than the sum of reactant bond strengths;Reactants Products 426DEDE KIM-UA the products are energetically (or thermodynamically) more stable than the reactants, and energy is released in the form of heat. Such reactions are called exothermic It is helpful to think of exothermic reactions as proceeding from a higher energy (less stable) reactant state to a lower energy (more stable) product statePhotosynthesis (equation 2) is an important example of an endothermic process. Energy in the form of photons (sunlight) drives the reaction, which requires chlorophyll as a catalystReactantsProducts427DEDE KIM-UA 428DEDE KIM-UA Atomic Structure & Chemistry Anyone who is not shocked about quantum theory has not understood it. - Niels Bohr 429DEDE KIM-UA The Atom 430DEDE KIM-UA Nomenclature Carbon-14 has: 6 Protons 8 Neutrons 14 Nucleons 431DEDE KIM-UA The Bohr Hydrogen Atom What is it about an atom that allows it to absorb or emit radiation at only specific wavelengths?Do the wavelengths tell us anything about the structure of the atoms? Niels Bohr suggested that emitted or absorbed radiation corresponds to changes in the orbits of electrons about the nucleus.Moreover, the electrons can not orbit at any distance from the nucleus, but exist only in specific allowed orbits. To explain the allowed orbits, Bohr postulated that electrons had both wave and particle properties.The allowed orbits were those for which a wavelength fit perfectly inside the orbit, just as only certain wavelengths are allowed on a vibrating string. Niels Bohr (1885-1962) was a Danish Physicist.His model for the hydrogen atom was the beginning of quantum theory. Atomic Structure 432DEDE KIM-UA Atomic Structure According to Bohr, an atom arranges its electrons into discrete orbits.These orbits have discrete energy levels that are specific to the element. For hydrogen, the energy of level n is:En =-10.97 h c /(n2) When a transition is made between two levels, a photon is emitted with an energy equal to the change in the energy of the two levels: E = h c/The atom loses energy and that energy goes into the emitted photon. Energy is conserved.lower energy orbit higher energy orbit 433DEDE KIM-UA Quantum Leaps and Photons 434DEDE KIM-UA Spectroscopy Gases emit and absorb light at only specific wavelengths, called spectral lines.For example, in the visible region of the spectrum, hydrogen will absorb or emit only at 0.656, 0.481, 0.434, and 0.410 microns.Chemicals can be easily identified by measuring the wavelength of absorbed or emitted light. The spectrum of atomic hydrogenSpectral Lines 435DEDE KIM-UA Solar Spectrum Absorption lines appear as hydrogen atoms in the Suns atmosphere capture photons and jump to more excited atomic levels.436DEDE KIM-UA The Riddle of the Hydrogen Spectrum microns1 197 . 1012 2|.|

\| =m n Spectroscopists discovered some simple formulas relating the wavelengths of the spectral lines of atomic hydrogen. Where is the wavelength of the emitted light and n and m are integers. Pick any two integers n and m (n must be less than m), calculate the wavelength and hydrogen will have a spectral line at that wavelength. There are no spectral lines at any wavelengths not given by this equation. 437DEDE KIM-UA First 4 shells of aHydrogen atom. 438DEDE KIM-UA Atomic Shells The discrete electron levels are arranged in shells.Each shell has a maximum occupancy.The first electronic shell can have at most 2 electrons, the second shell has room for 8 electrons and so on.The 1st shell has the lowest energy.Thus, elements, in their lowest energy state fill the 1st level first, and then fill the 2nd level next. These elements are listed in the 1st and 2nd rows of the periodic table. Atoms are most stable if their outer shell is full. The electrons in outer shells are shielded by the inner shells from the full attraction of the nucleus.These electrons participate most readily in chemical reactions. 439DEDE KIM-UA The Periodic Table 440DEDE KIM-UA Molecular Sizes 441DEDE KIM-UA Periodic Table Li: solid,Cs: liquid,Ar: gas,Tc:synthetic # protons 1 e- in outer shell (Alkali Metals) Full outer shell (Noble Gases) 1 e- missing to fill shell (Halogens) 442DEDE KIM-UA Ionic Bonds Atoms with one electron in the outer shell, and atoms with one electron missing are, on the other hand, highly reactive.These atoms form ionic bonds. The alkali gives up an electron.The halogen takes the electron.Elements are bonded by the electric force between theions.443DEDE KIM-UA Example of ionic bonds Ruby Sapphire Aluminum oxide,Al2O3 444DEDE KIM-UA Metallic Bonds Atoms in a metals also give up electrons, however the electrons are not transferred to the other atom.Instead, the electrons are shared by all the atoms.The sea of electrons allow current to flow through metal.Metals thus make good conductors.

In sodium, for example, 1 out of the 11 electrons is released so that Na has two filled shells.The extra electrons move around the metal in a sea of negative charge.This negatively charged sea moves around a regular structure of positive Na ions. 445DEDE KIM-UA Covalent Bonds Certain molecules are formed by sharing electrons.The covalent bond that forms resembles metallic bonds in that electrons are shared. Yet, like ionic bonds the electrons are shared in discrete shells of the atoms and dont run willy nilly throughout the material.The main constituents of our atmosphere are covalently bonded molecules. 446DEDE KIM-UA Multiple Covalent Bonds N2 78% O221% H2O0-4% Ar0.9% CO20.035% Ne0.0018% He0.0005% CH40.0001% H20.00005% O30.000004% Earths Atmosphere Gases in Earths atmosphere are mainly covalently bonded molecules or noble gases.447DEDE KIM-UA Bonding There are three major ways that elements bond to form molecules. 448DEDE KIM-UA Molecular attractions Polar molecules are more positively charged on one side and more negative on the other.This provides a cohesion.449DEDE KIM-UA 450DEDE KIM-UA 451DEDE KIM-UA TAUTOMERI Greek tauto, meaning the same, and meros, meaning part 452DEDE KIM-UA Keto-Enol Tautomerism Carbonyl compounds with o-hydrogens rapidly equilibrate with corresponding enol (ene + alcohol) Interconversion known as keto-enol tautomerism Individual isomers called tautomers Keto-Enol Tautomerism Tautomers are constitutional isomers Isomers are different compounds with different structures Atoms arranged differently Different from resonance structures that differ only in the position of their electrons Most carbonyl compounds exist almost exclusively in the keto form at equilibrium Keto-Enol Tautomerism Mechanism of acid-catalyzed enol formation Protonated intermediate can lose H+, either from theoxygen atom to regeneratethe keto tautomer or from the o carbon atom to yield an enol tautomer Mechanism of base-catalyzed enol formation The intermediate enolate ion, a resonance hybridof two forms, can beprotonated either on carbon to generate the starting keto tautomeror on oxygen to give an enol tautomer Only o-hydrogens are acidic o-Hydrogens are acidic because the enolate ion that results from deprotonation is resonance stabilized with the electronegative oxygen of the carbonyl |-, -, o-Hydrogens (and so on) are not acidic because the ion that results from deprotonation is not resonance stabilized457DEDE KIM-UA o-Substitution and Carbonyl Condensation Reactions Alpha-substitution reactions occur at the carbon next to the carbonyl carbon the o position Involve substitution of o-hydrogen by electrophile Proceed through enol or enolate ion intermediate Carbonyl condensation reactions occur between two carbonyl partners Combination of o-substitution and nucleophilic addition steps Gives |-hydroxy carbonyl compound 458DEDE KIM-UA Reactivity of Enols:o-Substitution Reactions Enols are nucleophiles that react with electrophiles There is a substantial build-up of electron density on the o carbon of the enol Mechanism of carbonyl o-substitution reaction on an enol Enol is formed with acid catalysis Electron pair from C=Cbond of enol attacks anelectrophile (E+), formingnew C-E bond and aresonance stabilizedintermediate Loss of H+ from oxygen yields the neutral alpha- substitution product andrestores the C=O bondAcid-catalyzed o-halogenation (Cl2, Br2, and I2) of aldehydes and ketones is a common laboratory reaction o-Halogenation occurs in biological systems o-Halogenation of ketones in marine alga Mechanism of acid-catalyzed bromination of acetone Isotopic labeling experiments support reaction mechanism of acid-catalyzed halogenation For a given ketone, the rate of deuterium exchange is identical to the rate of halogenation Enol intermediate involved in both processes Reactivity of Enols: o-Substitution Reactions o-Bromoketones are dehydrobrominated by base to yield o,|-unsaturated ketones E2 reaction mechanism 2-Methylcyclohexanone gives 2-methylcyclohex-2-enone on heating in pyridine Acidity of o Hydrogen Atoms: Enolate Ion Formation Presence of neighboring carbonylgroup increases the acidity of theketone over the alkane by a factorof 1040 Proton abstraction from carbonyl occurs when the o C-H bond is oriented parallel to the p orbitals of the carbonyl group A carbon of the enolate ion has a p orbital that overlaps neighboring p orbitals of the carbonyl group Negative charge shared with oxygen atom by resonance 465DEDE KIM-UA Acidity of o Hydrogen Atoms: Enolate Ion Formation Strong base required for enolate formation If NaOCH2CH3 is used the extent of enolate formation is only about 0.1% If sodium hydride, NaH, or lithium diisopropylamide (LDA), [LiN(i-C3H7)2], is used the carbonyl is completely converted to its enolate conjugate base LDA is prepared by reaction of butyllithium with diisopropylamine Acidity of o Hydrogen Atoms: Enolate Ion Formation A C-H bond flanked by two carbonyl groups is even more acidic Enolate ion is stabilized by delocalization of negative charge over both carbonyl groups Pentane-2,4-dione has three resonance forms Acidity of o Hydrogen Atoms: Enolate Ion Formation 468DEDE KIM-UA Acidity of o Hydrogen Atoms: Enolate Ion Formation 469DEDE KIM-UA Identifying Acidic Hydrogens in a Compound Identify the most acidic hydrogens in each of the following compounds, and rank the compounds in order of increasing acidity: Identifying Acidic Hydrogens in a Compound Strategy Hydrogens on carbon next to a carbonyl group are acidic. In general, a |-dicarbonyl compound is most acidic, a ketone or aldehyde is next most acidic, and a carboxylic acid derivative is least acidic. Remember that alcohols, phenols, and carboxylic acids are also acidic because of their OH hydrogens 471DEDE KIM-UA Identifying Acidic Hydrogens in a Compound Solution The acidity order is (a) > (c) > (b).Acidic hydrogens are shown in red: Alkylation of Enolate Ions Enolate ions are resonance hybrides of two nonequivalent contributors Enolate ions are vinylic alkoxides (C=CO-) Reaction on the oxygen yields an enol derivative Enolate ions are a-keto carbanions (-CC=O) Reaction on the carbon yields an a-substituted carbonyl compound Enolate ions undergo alkylation by treatment with an alkyl halide or tosylate Nucleophilic enolate ion reacts with the electrophilic alkyl halide in an SN2 reaction Leaving group displaced by backside attack Alkylations are subject to all constraints that affect all SN2 reactions Alkyl group R should be primary or methyl and preferably allylic or benzylic Secondary alkyl halides react poorly and tertiary are unreactive due to competing E2 reaction The Malonic Ester Synthesis Preparation of carboxylic acids from alkyl halides while lengthening the carbon chain by two atoms Diethyl propanedioate, commonly known as diethyl malonate, or malonic ester is more acidic than monocarbonyl compounds (pKa = 13) because its o hydrogens are flanked by two carbonyl groups Easily converted to enolate ion by sodium ethoxide in ethanol Et is used as an abbreviation for CH2CH3 Malonic ester contains two a hydrogens Product of o-alkylation can itself undergo alkylation Alkylated of dialkylated malonic ester undergoes hydrolysis to yield the diacid followed by decarboxylation (loss of CO2) to yield the monoacid Decarboxylation is unique to carboxylic acids with a second carbonyl group located at the | position Decarboxylation occurs via a cyclic mechanism Involves initial formation of an enol

Overall result of malonic ester synthesis is the conversion of an alkyl halide into a carboxylic acid while lengthening the carbon chain by two carbons Malonic ester synthesis can be used to prepare cycloalkane-carboxylic acids Three-, four-, five-, and six-membered rings can all be prepared in this way Using the Malonic Ester Synthesis to Prepare a Carboxylic Acid How would you prepare heptanoic acid using a malonic ester systhesis? 483DEDE KIM-UA Using the Malonic Ester Synthesis to Prepare a Carboxylic Acid Strategy The malonic ester synthesis converts an alkyl halide into a carboxylic acid having two more carbons. Thus, a seven-carbon acid chain must be derived from the five-carbon alkyl halide 1-bromopentane 484DEDE KIM-UA Using the Malonic Ester Synthesis to Prepare a Carboxylic Acid Solution The Acetoacetic Ester Synthesis The acetoacetic ester synthesis converts an alkyl halide into a methyl ketone having three more carbons Ethyl-3-oxobutanoate, commonly called ethyl acetoacetate or acetoacetic ester, contains o hydrogens flanked by two carbonyl groups Enolate ion is readily formed and alkylated under SN2 reaction conditions A second alkylation product can be derived from monoalkylated productAlkylated or dialkylated acetoacetic ester is hydrolyzed in aqueous acid to a |-keto acid |-Keto acid undergoes decarboxylation to yield ketone product Ketone product formed in three-step sequence: 1. Enolate formation 2. Alkylation 3. Hydrolysis/decarboxylation Sequence applicable to all |-keto esters with acidic o hydrogens Cyclic |-keto esters such as ethyl 2-oxocyclohexanecarboxylate can be alkylated and decarboxylated to give 2-substituted cyclohexanones Using the Acetoacetic Ester Synthesis to Prepare a Ketone How would you prepare pentan-2-one by an acetoacetic ester synthesis? 491DEDE KIM-UA Using the Acetoacetic Ester Synthesis to Prepare a Ketone Strategy The acetoacetic ester synthesis yields a methyl ketone by adding three carbons to an alkyl halide: Thus, the acetoacetic ester synthesis of pentan-2-one must involve reaction of bromoethane Using the Acetoacetic Ester Synthesis to Prepare a Ketone Solution Alkylation of Enolate Ions Direct Alkylation of Ketones, Esters, and Nitriles A strong, sterically hindered base such as LDA converts a ketone, ester, or nitrile to its enolate ion Use of a sterically hindered base avoids nucleophilic addition A nonprotic solvent such as THF is required Aldehydes rarely give high yields of alkylation products because their enolate ions undergo carbonyl condensation reactions 494DEDE KIM-UA Alkylation of Enolate Ions Example alkylations 495DEDE KIM-UA Alkylation of Enolate Ions Example alkylations Alkylation of Enolate Ions Example alkylations Using an Alkylation Reaction to Prepare a Substituted Ester How might you use an alkylation reaction to prepare ethyl 1-methylcyclohexanecarboxylate? Using an Alkylation Reaction to Prepare a Substituted Ester Strategy An alkylation reaction is used to introduce a methyl or primary alkyl group onto the o position of a ketone, ester, or nitrile by SN2 reaction of an enolate ion with an alkyl halide. Look at the target molecule and identify any methyl or primary alkyl groups attached to an o carbon. The target has an o methyl group, which might be introduced by alkylation of an ester enolate ion with iodomethane 499DEDE KIM-UA Using an Alkylation Reaction to Prepare a Substituted Ester Solution Biological Alkylations Alkylations are not common in biological systems o-Methylation occurs in the biosynthesis of the antibiotic indolmycin from indolylpyruvate Carbonyl Condensations:The Aldol Reaction Carbonyl condensation reactions occur between an electrophilic carbonyl group of one partner and the nucleophilic enolate ion of the other partner Combination of o-substitution and nucleophilic addition steps Carbonyl Condensations:The Aldol Reaction Aldehydes and ketones with an o hydrogen atom undergo a base-catalyzed carbonyl condensation reaction called the aldol reaction Treatment of acetaldehyde with sodium ethoxide yields 3-hydroxybutanal (an aldol) Carbonyl Condensations:The Aldol Reaction Position of the aldol equilibrium depends both on reaction condition and substrate structure Equilibrium favors condensation product in the case of aldehydes with no o substituent (RCH2CHO) Carbonyl Condensations:The Aldol Reaction Equilibrium favors reactant for disubstituted aldehydes (R2CHCHO) and most ketones Carbonyl Condensations:The Aldol Reaction Aldol reactions occur by nucleophilic addition of the enolate ion of the donor molecule to the carbonyl group of the acceptor molecule Resultant tetrahedral intermediate is protonated to give an alcohol product The reverse process occurs when base abstracts the OH hydrogen from the aldol to yield a |-keto alkoxide ion, which cleaves to give one molecule of enolate ion and one molecule of neutral carbonyl compound Predicting the Product of an Aldol Reaction What is the structure of the aldol product from propanal? 507DEDE KIM-UA Worked Example 17.5 Predicting the Product of an Aldol Reaction Strategy An aldol reaction combines two molecules of reactant, forming a bond between the o carbon of one partner and the carbonyl carbon of the second partner 508DEDE KIM-UA Predicting the Product of an Aldol Reaction Solution Carbonyl Condensations:The Aldol Reaction Carbonyl Condensations versus o-Substitutions Carbonylcondensation reactions and o substitutions take place under basic conditions and involve enolate-ion intermediates Alpha-substitution reactions require a full equivalent of strong base and are carried out so that the carbonyl compound is rapidly and completely converted into its enolate ion at low temperature before addition of the electrophile Carbonyl Condensations:The Aldol Reaction Carbonyl condensation reactions require only a catalytic amount of a relatively weak base Enolate ion is generated in the presence of unreacted carbonyl compound 17.6 Dehydration of Aldol Products |-Hydroxy aldehydes or ketones formed in aldol reactions can be easily dehydrated to yield a,b-unsaturated products, or conjugated enones Aldol reactions were named condensation reactions due to the loss of water Dehydration of Aldol Products Aldol products dehydrate easily because of carbonyl group Under basic conditions, an acidic o hydrogen is removed, yielding an enolate ion that expels the OH leaving group in an E1cB reaction Under acidic conditions an enol is formed, the OH group is protonated, and water is expelled in an E1 or E2 reaction Dehydration of Aldol Products Reaction condition needed for aldol dehydration are often only slightly more vigorous than conditions for aldol formation Conjugated enones are often obtained directly from aldol reactions without isolating the intermediate |-hydroxy carbonyl compounds Conjugated enones are more stable than nonconjugated enones Interaction between t electrons of C=C bond and the t electrons of the C=O bond Dehydration of Aldol Products Removal of water from reaction mixture drives the aldol equilibrium toward product Worked Example 17.6 Predicting the Product of an Aldol Reaction What is the structure of the enone obtained from aldol condensation of acetaldehyde? 516DEDE KIM-UA Worked Example 17.6 Predicting the Product of an Aldol Reaction Strategy In the aldol reaction, H2O is eliminated and a double bond is formed by removing two hydrogens from the acidic o position of one partner and the carbonyl oxygen from the second partner. 517DEDE KIM-UA Worked Example 17.6 Predicting the Product of an Aldol Reaction Solution Intramolecular Aldol Reactions Some dicarbonyl compounds react when treated with base in an intramolecular aldol reaction Leads to formation of cyclic product Intramolecular Aldol Reactions Intramolecular aldol reactions may lead to product mixtures Most thermodynamically stable product formed selectively All reaction steps are reversible Most thermodynamically stable product predominates at equilibrium 17.8The Claisen CondensationReaction Reversible condensation reaction between two esters is called the Claisen condensation reaction Esters have weakly acidic o hydrogens When an ester with an o hydrogen is treated with 1 equivalent of a base a |-keto ester is formed The Claisen Condensation Reaction Claisen condensation mechanism proceeds through a tetrahedral intermediate The tetrahedral intermediate expels an alkoxide leaving group to yield an acyl substitution product If the product |-keto ester has another acidic o proton, 1 full equivalent of base is used for deprotonation Deprotonation of |-keto ester drives reaction to the product side giving high yields of Claisen product Worked Example 17.7 Predicting the Product of a Claisen Condensation Reaction What product would you obtain from Claisen condensation of ethyl propanoate? 523DEDE KIM-UA Worked Example 17.7 Predicting the Product of a Claisen Condensation Reaction Strategy The Claisen condensation of an ester results in loss of one molecule of alcohol and formation of a product in which an acyl group of one reactant bonds to the o carbon of the second reactant. 524DEDE KIM-UA Worked Example 17.7 Predicting the Product of a ClaisenCondensation Reaction Solution 17.9Intramolecular ClaisenCondensations Intramolecular Claisen condensations are called Deickman cyclizations Reaction works best for 1,6 and 1,7 diesters 1,6 Diester gives a five-membered cyclic |-keto ester 1,7 Diester gives a six-membered cyclic |-keto ester Intramolecular Claisen Condensations Mechanism of Dieckmann cyclization Same as Claisen reaction mechanism Intramolecular Claisen Condensations The cyclic |-keto ester produced in an intramolecular Claisen cyclization can be further alkylated and decarboxylated 2-cyclohexanones and 2-cyclopentanones are prepared by the following sequence: 1. Intramolecular Claisen cyclization 2. |-Keto ester alkylation 3. Decarboxylation 17.10 Conjugate Carbonyl Additions: The Michael Reaction The conjugate addition of a nucleophilic enolate ion to an o.|-unsaturated carbonyl compound is known as the Michael reaction Best reactions are derived from addition of a b-keto ester or other 1,3-dicarbonyl compound to an unhindered o.|-unsaturated ketone Ethyl acetoacetate reacts with but-3-en-2-one in the presence of sodium ethoxide to yield the Michael addition product Conjugate Carbonyl Additions:The Michael Reaction The Michael reaction Conjugate addition of a nucleophilic enolate ion to | carbon of an o.|-unsaturated carbonyl compound Best Michael reactions between stable enolate ions and unhindered o.|-unsaturated ketones Conjugate Carbonyl Additions: The Michael Reaction Michael reaction occurs with a variety of o.|-unsaturated carbonyl compounds Worked Example 17.8 Using the Michael Reaction How might you obtain the following compound using a Michael reaction? Worked Example 17.8 Using the Michael Reaction Strategy A Michael reaction involves the conjugate addition of a stable enolate ion donor to an o.|-unsaturated carbonyl acceptor, yielding a 1,5-dicarbonyl product Usually the stable enolate ion is derived from a |-diketone, |-keto ester, malonic ester or similar compound The C-C bond made in the conjugate addition step is the one between the o carbon of the acidic donor and the | carbon of the unsaturated acceptor 533DEDE KIM-UA Worked Example 17.8 Using the Michael Reaction Solution 17.11 Carbonyl Condensations with Enamines: The Stork Reaction Enamine nucleophiles add to o.|-unsaturated acceptors in Michael-like reactions Reactions are particularly important in biological chemistry Enamines are prepared by reaction between a ketone and a secondary amine Carbonyl Condensations with Enamines: The Stork Reaction Enamines are electronically similar to enolate ions Overlap of the nitrogen lone-pair orbital with the double-bond p orbitals leads to an increase in electron density on the o carbon atom Carbonyl Condensations with Enamines: The Stork Reaction Stork reaction Enamine adds to an o.|-unsaturated carbonyl acceptor in a Michael-like reaction Initial product is hydrolyzed by aqueous acid to yield a 1,5-dicarbonyl compound Overall reaction is a three-step sequence: 1. Enamine formation from a ketone 2. Michael addition to an o.|-unsaturated carbonyl compound 3. Enamine hydrolysis back to ketone 537DEDE KIM-UA Carbonyl Condensations with Enamines: The Stork Reaction The net effect of the Stork reaction is a Michael addition of a ketone to an a,b-unsaturated carbonyl compound Carbonyl Condensations with Enamines: The Stork Reaction Two advantages to the enamine-Michael reaction that make the pathway useful in biological systems 1. Enamine is neutral and easily prepared and handled Enolate is charged and difficult to prepare and handle 2. Enamine from a monoketone can be used in the Michael addition Only enolate ions from |-dicarbonyl compounds can be used 539DEDE KIM-UA Worked Example 17.9 Using the Stork Enamine Reaction How might you use an enamine reaction to prepare the following compound? Worked Example 17.9 Using the Stork Enamine Reaction Strategy The overall result of an enamine reaction is the Michael addition of a ketone as donor to an o.|-unsaturated carbonyl compound as acceptor, yielding a 1,5-dicarbonyl product The C-C bond made in the Michael addition step is the one between the o carbon of the ketone donor and the | carbon of the unsaturated acceptor 541DEDE KIM-UA Worked Example 17.9 Using the Stork Enamine Reaction Solution 17.12 Some Biological Carbonyl Condensation Reactions Biological Aldol Reactions Aldol reactions are particularly important in carbohydrate metabolism Enzymes called aldolases catalyze addition of a ketone enolate ion to an aldehyde Type I aldolases occur primarily in animals and higher plants Operate through an enolate ion Type II aldolases occur primarily in fungi and bacteria 543DEDE KIM-UA Some Biological Carbonyl Condensation Reactions Mechanism of Type I aldolase in glucose biosynthesis Dihydroxyacetone phosphate is first converted into an enamine by reaction with the NH2 group on a lysine amino acid in the enzyme Enamine adds to glyceraldehyde 3-phosphate Resultant iminium ion is hydrolyzed Some Biological Carbonyl Condensation Reactions Mechanism of Type II aldolase in glucose biosynthesis Aldol reaction occurs directly Ketone carbonyl group of glyceraldegyde 3-phosphate complexed to a Zn2+ ion to make it a better acceptor Some Biological Carbonyl Condensation Reactions Biological Claisen Condensations Claisen condensations occur in a large number of biological pathways In fatty acid biosynthesis an enolate ion generated by decarboxylation of malonyl ACP adds to the carbonyl group of another acyl group bonded through a thioester linkage to a synthase enzyme The tetrahedral intermediate expels the synthase, giving acetoacetyl ACP Some Biological Carbonyl Condensation Reactions Mixed Claisen consensations occur frequently in living organisms Butyryl synthase, in the fatty-acid biosynthesis pathway, reacts with malonyl ACP in a mixed Claisen condensation to give 3-ketohexanoyl ACP Functional Groups with Single Bonds to Heteroatoms Group Formula

Class Name

Specific Example

IUPAC Name

Common Name

HalideH3C-IIodomethaneMethyl iodide AlcoholCH3CH2OHEthanolEthyl alcohol EtherCH3CH2OCH2CH3Diethyl etherEther AmineH3C-NH2AminomethaneMethylamine Nitro CompoundH3C-NO2Nitromethane ThiolH3C-SHMethanethiolMethyl mercaptan SulfideH3C-S-CH3Dimethyl sulfide 548DEDE KIM-UA Functional Groups with Multiple Bonds to Heteroatoms Group Formula