cid/base stuff Beauchamp 1 Problems You should be able to match a pk a value with its acid in each group below and explain the differences. You should be able to draw an arrow-pushing mechanism with general base, B: - for any of the acids, -. Include structures whenever appropriate. If there was a reaction shown between any two conjugate acids and bases, you should be able to qualitatively and quantitatively indicate which side of the equilibrium is favored, and what an approximate G is for the reaction. This is a big deal! You are learning the logic of organic, right here. 1 acidic proton varies (on,, or F) pk a = 35 pk a = 16 F pk a = 3 trongest acid has the lowest pk a. The negative charge in the conjugate base is on the most electronegative atom, because they are all about the same size. What is K eq and G for the following reactions? equilibrium lies completely to the left weaker acid K a1 = 10-50 pk a1 = 50 weaker base K eq = K a1 10-50 = = 10-13 K a2 10-37 stronger base G = (pk a1 - pk a2 ) x 1.4 = (50-37) x 1.4 = (13) x 1.4 = +18 kcal/mole stronger acid K a2 = 10-16 pk a2 = 16 stronger acid K a1 = 10-16 pk a1 = 16 stronger base equilibrium lies completely to the right weaker base K a1 10-16 K eq = = = 10 +21 K a2 10-37 G = (pk a1 - pk a2 ) x 1.4 = (16-37) x 1.4 = (-21) x 1.4 = -29 kcal/mole weaker acid K a2 = 10-37 pk a2 = 37 2 3 3 2 acidic proton varies (on,, or, in this problem F is not attached to a proton) trongest acid is ethanol, negative 2 charge is on the most electronegative 2 2 atom. Fluorine only makes one bond 3 and that is with carbon, not with a 3 3 F proton, though the presence of the pk pk F probably makes the - bonds more a = 37 a = 16 pk a =? acidic. acidic proton is always on oxygen I Br l F not stable pk a = 11 pk a = 8.7 pk a = 7.5 pk a = The acid is hypochlorous acid. ll conjugate bases have the negative charge on the oxygen, but the inductive withdrawing effect of the chlorine is greatest because it is the most electronegative. 4 pk a 's = 16 l acidic proton is always on oxygen l pk a 's = 14.3 l pk a 's = 12.8 l l l pk a 's = 12.2 More chlorines = more inductive withdrawal, which better helps stabilize the anion conjugate base. y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 2 5 acidic proton is always on carbon l l 6 3 pk a 's = 15.5 pk a 40* l l l pk a 32* pk a = 25 l acidic proton is always on oxygen 2 3 pk a 's = 15.8 3 3 3 3 3 pk a 's = 17 pk a 's = 19 similar explanation to previous problem. * = my estimate ll conjugate bases have a minus on oxygen. groups are inductively donating which destabilizes the conjugate base. 8 9 10 acidic proton varies (on F, l, Br or I) F pk a = 3 pk a = 16 l Br pk a = -7 pk a = 7 pk a = -9 e I pk a = -10 acidic proton varies (on,, e or Te) acidic proton is always on oxygen pk a = 16 pk a = 10 pk a = 4 Fluorine is most electronegative, but minus charge is more delocalized on the larger iodide. Delocalization of the minus charge is more important in this example. ll of the halogens have a Z eff = +7. Te pk a = 4 pk a = 3 similar explanation to previous problem, though all Z eff = +6. ll have minus on oxygen (good). The first conjugate base has no structures, the second has four (one on oxygen + three on carbon), the third has two structures with minus on oxygen = best of this group. y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 3 11 acidic proton is always on oxygen and another atom ( or or a second ) 3 3 3 pk a = 20 pk pk a = 15 a = 5 12 acidic proton is always on two oxygen atoms ll three conjugate bases have minus on oxygen (good), but the other structure is carbon (poorest), nitrogen (middle) or another oxygen (best) for stabilizing negative charge. 2 2 2 2 2 2 ef. pk a = 4.7 I F pk a 's = 2.59 l pk a 's = 3.2 pk a 's = 2.85 alogen atoms are electron withdrawing (F>l>Br>I) and inductively help stabilize minus in conjugate base. groups are inductively electron donating, which destabilizes minus charge (less stable = higher pk a ). 13 3 pk a = 5 acidic proton is always on two oxygen atoms l l 2 pk a = 2.8 l 14 acidic proton is always on two oxygen atoms l pk a = 4.8 l pk a = 4.5 pk a = 4.0 15 pk a 's = 10 pk a 's = 28 pk a = 1.3 l l pk a 's = 41 l l Br pk a 's =2.90 pk a = 0.7 pk a = 2.8 3 pk a 's = 4.8 More chlorines = more inductive withdrawal, which better helps stabilize the anion conjugate base. nly one chlorine atom in each conjugate base. It has the effect when it is closest to the negative charge of the conjugate base. acidic proton varies (on,, or ) More electronegative atoms stabilizes the negative charge best (>>) and more delocalization stabilizes the minus better than no delocalization. pk pk a 's = 18 pk a 's = 37 a 's = 50 16 acidic proton is always on two oxygen atoms 3 F 2 pk pk ef. pk a = 4.2 a = 4.3 a = 3.9 pk a = 3.6 pk a = 3.5 ll conjugate bases have negative charge spread over two oxygen atoms. tronger electron withdrawal stabilizes minus better and donation destabilizes it. y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 4 17 pk a = 23.6 minus delocalizes onto nitrogen (good) pk a = 24.8 inductive withdrawal by nitrile group pk a = 28 The acidic proton is always on nitrogen and in all cases delocalized into the ring. In the first example it is also delocalized (by ) onto the second nitrogen (good), which is not in the second example. 19 acidic proton is always on carbon and sometimes on one or two oxygen atoms F 3 F 3 pk a = 5 pk a = 20 on two oxygen on one atoms, plus inductive effect oxygen atom of fluorine atoms pk a = 9 on two oxygen atoms 20 21 l 22 23 acidic proton is always on oxygen and has in the ring pk a 's = 10.2 inductive donation pk a 's = 9.4 2 pk a 's = 10.0 reference acidic proton is always on oxygen and has in the ring pk a 's = 10.0 reference l pk a 's = 8.4 inductive withdrawal pk a 's = 9.0 acidic proton is always on two oxygen atoms pk a = 2.85 3 pk a = 4.7 reference acidic proton is always on carbon 2 pk a = 42 two structures 2 pk a 's = 7.1 inductive withdrawal, plus extra with minus charge on second oxygen of the 2 group. l pk a 's = 85 inductive withdrawal, closest pk a = 5.70 nly one chlorine atom in each conjugate base. It has the effect when it is closest to the negative charge of the conjugate base. The neutral diacid is more electron withdrawing (stronger acid than reference), while the anion conjugate base is more electron donating (weaker acid than reference). The first negative charge makes it harder to form the second negative charge. pk a = 15* * also aromatic five structures y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 5 24 pk a = 44 acidic proton is always on carbon pk a = 25 The electronegativity of hybrid orbitals is: sp (50% s) > sp 2 (33% s) > sp 3 (25% s). Greater electronegativity is better able to stabilize the negative charge in the conjugate base, so sp - bonds are the most acidic of these hydrocarbons, then sp 2 - and lastly sp 3 - (lowest acidity of any acid in our course). emember pk a units are approximately exponents. 25 acidic proton is always on nitrogen pk a = 5 pk a = -10 pk a = 9 similar explanation to previous problem. Bascity Use full headed arrows to show two electron movement. Water is the reference acid in usual K b tables. We won't use pk b values. Instead, we will compare pk a values and judge bases to be stronger when their acids are weaker (larger pk a ) and bases to be weaker when their acids are stronger (lower pk a ). In the examples that follow pair up each base with the pk a value of its conjugate acid. B B judge the strength of the base from the weakness of the acid use this acid's pk a value to judge the electron donating power of B: to the reference acid, 2. ere are a few qualitative examples. Where is the most basic site in each molecule below? an an order of basicity be explained for some or for all of the bases (approximate pk a s of the conjugate acids are provided)? 3 3 3 3 3 3 pk a -7 pk a -7 pk a -6 pk a -0.5 Use the lone pair of the =X: as the most basic site. pk a 0.2 pk a 5 (my guess) pk a 7 pk a 13.6 The double bond lone pair is the most basic site. In the ketone it is the only lone pair. In the other bases there will be structures if you use the double bond lone pair and nitrogen is a better donor than oxygen and 2x nitrogen is better than 1x nitrogen. carbon is positive too y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 6 Problem W at is the order of basicity among the following molecules of each group (1 = most basic)? Explain your reasoning. Match the given pk a values with the conjugate acids of the indicated bases. Write arrow-pushing mechanisms with general acid, - to illustrate the reactions. Include structures whenever appropriate. Where is the most basic site in each molecule? Explain your reasoning using arguments of inductive effects (electronegativity), effects (electron delocalization) or both. For any reaction between two conjugate acids and bases, you should be able to qualitatively and quantitatively indicate which side of the equilibrium is favored, and what is an approximate G is for the reaction. 1 electron pair donation varies (on,, or F) 2 base 3 2 base 3 2 pk a = 35 pk a = 16 electron pair donation varies (on,, or F) 2 2 3 3 3 2 pk a = 37 2 3 pk a = 16 F base F pk a = 3 3 base 3 trongest base has the negative charge is on the least electronegative atom (smallest Z eff ), so it is best able to donate (share) its electron density (because they are all about the same size). The most electronegative atom (F) is best able to carry the negative charge and least basic. 2 F pk a = pk a =? (very negative) trongest base has the negative charge is on the least electronegative atom (), so it is best able to donate (share) its electron density (because all the atoms are about the same size). Fluorine is neutral in this example and not expected to be basic. 2 F 3 3 best base = 2x nitrogen donating 3 pk a = 7 3 2nd best base = 1x nitrogen & 1x oxygen donating 3 pk a = 0 3 3 base = 2x oxygen donating pk a = -7 emember, pk a is of conjugate acid (with the proton on). emember, pk a is of conjugate acid (with the proton on). The largest pk a is the acid, having the most basic conjugate base. y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 7 4 5 best base = 3x nitrogen donating pk a = 5 pk a = 13 base pk a = -10 2nd best base = 2x nitrogen donating pka = 7 base pk a = 9 3rd best base = 1x nitrogen donating sp 3 obitals are less electronegative and better able to share electron density (more basic) because they are only 25% s. sp orbitals are more electronegative and less able to share electron density (50% s). pk a = 5 Donating nitrogen atoms are all sp 2. but more delocalization with full octets is better for conjugate acid (= weaker acid and stronger base) 6 2nd best base pk a = 10 best base pk a = 16 3rd base pk a = 5 The most stable anion (3rd structure) is the least basic and the least stable anion (middle structure) is sthe most basic. tability based on number of structures and the electronegativity of the atoms (2x oxygen > 1x oxygen + 3x carbon > 1x oxygen). 7 F 3 F 3 pk a = 9 least basic pk a = 5 most basic pk a = 20 These are the conjugate bases of the acids in example 19 above. The most stable one ( + inductive withdrawal) is the least basic. The least stable one is the most basic 6 3 3 3 2 Less electronegative atoms are less stable with negative charge and more basic. least basic most basic pk a = 5 pk a = 15 pk a = 20 These are the conjugate bases of the acids in example 11 above. The most stable one ( = 2x oxygen) is the least basic. The least stable one is the most basic y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 8 9 least basic most basic pk a = 25 pk a = 44 These are the conjugate bases of the acids in example 24 above. The most stable one is sp (most electronegative hybrid orbital) and the least basic. sp 3 orbital is least electronegative orbital and the worst for carrying the negative charge, thus most basic. 10 least basic most basic pk a = 15 pk a = 42 These are the conjugate bases of the acids in example 23 above. The most stable one ( = 5x carbon) is the least basic. The least stable one (1x carbon) is the most basic cid/base arrow pushing worksheet 1. These proton transfer reactions are the first step in multistep mechanisms to be studied later in the course. upply the necessary curved arrows, lone pairs of electrons and/or formal charge to show how the first step each reaction proceeds. tarting at e are simple proton transfer reactions generating a carbanions (very important for organic ). Generally, there is some stabilizing feature that allows a carbanion to form via acid/base, such as inductive and/or effects, but this is not always the case. In working the problem below, show any important structures or identify the inductive effect that makes the reaction. Estimate a K eq for each reaction using the K a s. a. b. c. a sodium hydride - alcohols a K K a = 10-16 a = 10-37 K eq = 10-16 = 10 +21 10-37 Equilibrium lies completely to the right. thiols K a = 10-9 carboxylic acids K a = 10-5 a sodium hydroxide K eq = 10-9 10-16 = 10 +7 Equilibrium lies completely to the right. a sodium hydroxide K eq = 10-5 +11 = 10 Equilibrium lies completely to the right. 10-16 a K a = 10-16 K a = 10-16 y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 9 d. e. f. Li LD ester K a = 10-25 -78 o 2 K a = 10-37 K eq = 10-25 = 10 +12 10-37 Equilibrium lies completely to the right. g. Li LD -78 o 2 tertiary amide K a = 10-37 K a = 10-30 h. K eq = 10-30 = 10 +7 10-37 Equilibrium lies mostly to the right. Li LD -78 o nitrile K a = 10-30 K eq = 10-30 = 10 +7 10-37 Equilibrium lies mostly to the right. 2 K a = 10-37 y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 10 i. 3-78 o 3 1,3-dicarbonyl K a = 10-9 3 3 etc. etc. - K a = 10-37 sodium hydride a K eq = 10-9 = 10 +28 Equilibrium lies completely to the right. 10-37 j. k. dithiane Li 2 2 2 3-78 o K a 10-35 n-butyl lithium 2 2 2 3 K a =10-50 l. Li 2 3 2 2 sulfur ylid n-butyl lithium = phenyl K a 10-35 K eq = 10-35 m. K eq = 10-35 =10 +15 Equilibrium lies completely to the right. 10-50 -78 o with sulfur d orbitals? 10-50 = 10 +15 Equilibrium lies completely to the right. 2 2 2 K a = 10-50 3 P Br phosphorous ylid ( = phenyl) K a 10-35 Li 2 3 2 2 n-butyl lithium K eq = 10-35 -78 o P with phosphorous P d orbitals? 10-50 = 10 +15 Equilibrium lies completely to the right. 2 2 2 K a = 10-50 3 y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 11 2. Lone pair donors to very strong acid ll of the following functional groups react with strong protic acid as the first step of a reaction studied in organic. ften subsequent occurs after that initial step and you will study most of those reactions later in the course. how how they react in the first step by including all lone pairs, curved arrows to show electron movement and formal charge. cid/base arrow pushing worksheet lone pair donors lone pair acceptor pk a 's = -3, -2 equilibrium K eq = 103 +1 = 10 Equilibrium lies to the right. 10 2 ammonia K eq =? pk a 's = -2, 9 K eq = 102 =10 11 Equilibrium lies completely to the right. 10-9 equilibrium 1 o amine pk a 's = -2, 10 K eq = 102 = 10 12 10-10 Equilibrium lies completely to the right. equilibrium 2 o amine pk a 's = -2, 10 K eq = 102 = 10 12 10-10 Equilibrium lies completely to the right. equilibrium 3 o amine pk a 's = -2, 10 K eq = 102 = 10 12 10-10 Equilibrium lies completely to the right. equilibrium y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 12 alcohol K eq = 102 pk a 's = -2, -3 10 3 = 10-1 Equilibrium is pretty even ether K eq = 102 pk a 's = -2, -3 10 3 = 10-1 Equilibrium is pretty even epoxide (ether) pk a 's = -2, -3 K eq = 102 = 10-1 10 3 Equilibrium is pretty even ketone ' pk a 's = -2, -7 K eq = 102 = 10-4 10 6 ' (2) Equilibrium lies a little to the left ' nitrile 3 sulfuric acid pk a 's = -3, -10 (2) K eq = 103 = 10-7 Equilibrium lies to the left but still generates some of the protonated nitrile that can react further. 10 10 y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 13 carboxylic acid pk a 's = -2, -6 K eq = 102 = 10-5 Equilibrium lies a little to the left 10 7 ester ' pk a 's = -2, -6 ' ' K eq = 102 = 10-4 Equilibrium lies a little to the left 10 6 ' 2 amide pk a 's = -2, 0 2 2 K eq = 102 = 10 +2 Equilibrium lies a little to the right 10 0 2 2 K eq = 102 pk a 's = -2, 12 2 2 2 10-12 = 10 +14 Equilibrium lies completely to the right y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D
cid/base stuff Beauchamp 14 arbon-carbon pi bonds as weak electron pair donors to very strong acid 3 carbocation pk 2 a 's = -3, -10 alkene sulfuric acid 2 K eq = 103-7 10 Equilibrium lies to the left but still generates some 10 10 of the protonated alkene that can react further. 2 enol ether K eq = 102 pk a 's = -2, -7 10 7 10-5 Equilibrium lies a little to the left 2 (2) 2 alkyne sulfuric acid 3 pk a 's = -3, -10 K eq = 103-7 10 Equilibrium lies to the left but still generates some 10 10 of the protonated alkyne that can react further. aromatic E E pk a 's = -10, -10 E + = electrophile (Lewis acid = electron pair acceptor) K eq = 1010 = electrophile E 10 10 1 Equilibrium is even (not really sure about pk a of electrophile, but they are very reactive) E E t this point we are mainly interested in understanding acid/base proton transfers, curved arrow pushing, formal charge, recognizing structures and using the logic arguments of inductive effects and effects to explain relative stabilities of acids and bases. If you can do these things, you are well on your way to understanding organic and bio. Tautomers - There are many worked examples in the tautomer section. Use those to practice with and then try some possibilities without worked answers. sk me if you get stuck. y:\files\classes\315\315 andouts\315 Fall 2013\1b acid-base list, 315 answers, 14p.D