WEBVTT 00:02.400 --> 00:05.570 J. MICHAEL MCBRIDE: So as you know, we're getting on to ionic 00:05.567 --> 00:09.067 reactions, and started by talking about how important 00:09.067 --> 00:11.327 the solvent is. 00:11.333 --> 00:14.533 We started last time looking at the example of the 00:14.533 --> 00:18.673 disassociation of water into ions to give H+ and O-H-, 00:18.667 --> 00:21.397 both, of course, solvated. 00:21.400 --> 00:23.470 We're interested in the important role that the 00:23.467 --> 00:25.027 solvent plays. 00:25.033 --> 00:27.933 We saw last time that we could talk about 00:27.933 --> 00:30.833 water in the gas phase. 00:30.833 --> 00:33.333 Dissociating into radicals, we know the bond 00:33.333 --> 00:35.173 dissociation energy. 00:35.167 --> 00:37.427 Then transferring an electron. 00:37.433 --> 00:40.373 And most importantly, then getting the two ions apart 00:40.367 --> 00:45.627 from one another, which is going to cost 332 kilocalories 00:45.633 --> 00:48.733 per mole just to get them apart from being like one 00:48.733 --> 00:51.773 Å to infinitely apart. 00:51.767 --> 00:55.367 Altogether those processes cost 392 00:55.367 --> 00:57.227 kilocalories per mole. 00:57.233 --> 01:00.903 So that would be absolutely out of the question. 01:00.900 --> 01:05.470 In fact, even once you start in the gas phase it's 386, so 01:05.467 --> 01:09.027 that would be 10^-290. 01:09.033 --> 01:10.233 Impossible. 01:10.233 --> 01:13.573 But the solvent makes it possible-- you know that water 01:13.567 --> 01:16.367 dissociates. 01:16.367 --> 01:21.467 So when you put another water molecule, which is a dipole, 01:21.467 --> 01:25.227 next to the O-H-, it makes it more stable. 01:25.233 --> 01:29.533 We talked about that last time or two times ago how you get 01:29.533 --> 01:33.533 hydrogen bonding between a hydroxide anion and a water. 01:33.533 --> 01:37.233 So it's more, in that case, more than just a dipole. 01:37.233 --> 01:40.433 Remember it was that double minimum that, in fact, the 01:40.433 --> 01:43.973 lowest energy level had the hydrogen in the middle. 01:43.967 --> 01:47.467 Anyhow, that's not fabulously strong; it's not like a 01:47.467 --> 01:50.567 covalent bond, but it's 28 kilocalories per mole, which 01:50.567 --> 01:52.427 is nothing to sneeze at. 01:52.433 --> 01:55.573 If you put another water on that you get another 18 01:55.567 --> 01:57.167 kilocalories per mole. 01:57.167 --> 01:59.267 And if you put another and another and another and 01:59.267 --> 02:04.067 another and they line up, you get stability by 106 02:04.067 --> 02:09.567 kilocalories per mole for solvating the hydroxide ion, 02:09.567 --> 02:10.727 to put it in water. 02:10.733 --> 02:15.273 So that's worth more than most covalent bonds. 02:15.267 --> 02:18.797 Now you also have the proton that could be solvated. 02:18.800 --> 02:20.800 That one actually forms a bond-- 02:20.800 --> 02:23.770 you can form a bond between the unshared pair on the water 02:23.767 --> 02:26.567 that's coming up and the H+. 02:26.567 --> 02:28.997 That bond is, in fact, a very strong bond. 02:29.000 --> 02:33.030 It's 164 kilocalories per mole-- about twice as strong 02:33.033 --> 02:35.233 as most covalent bond. 02:35.233 --> 02:39.073 Because it's not only a bond, it also gets the positive 02:39.067 --> 02:42.727 charge in close proximity to a bunch of other electrons. 02:42.733 --> 02:44.803 So it polarizes them. 02:44.800 --> 02:49.000 That's a little bit like solvation within the molecule. 02:49.000 --> 02:54.700 So you get 164 just for the first water onto a proton. 02:54.700 --> 02:57.670 Then, of course, that looks rather-- it's charged and it's 02:57.667 --> 03:00.227 not very much bigger than the O-H-. 03:00.233 --> 03:02.633 So it's not going to surprise you that you can put more 03:02.633 --> 03:04.533 waters onto that. 03:04.533 --> 03:09.073 And from doing a whole bunch of waters to put it into 03:09.067 --> 03:12.827 liquid water, you get another 100 kilocalories per mole on 03:12.833 --> 03:16.133 top of what you got forming H3O+. 03:16.133 --> 03:21.903 So if we sum all those together, 164, 106 and 100-- 03:21.900 --> 03:23.970 notice that those are similar to one another-- 03:23.967 --> 03:27.997 we get 370 kilocalories per mole. 03:28.000 --> 03:31.570 That means we get the energy of forming the proton and the 03:31.567 --> 03:36.467 hydroxide if they're solvated down to within only 21 and a 03:36.467 --> 03:40.227 half kilocalories of the water in water. 03:43.133 --> 03:47.803 So that means the pKa is 15.8, you know. 03:47.800 --> 03:51.600 But it has enormously to do with solvation, 03:51.600 --> 03:53.300 as you can see here. 03:53.300 --> 03:56.270 It's, in fact, very delicately balanced. 03:56.267 --> 04:01.267 It's a small difference, this 22 kilocalories per mole, of 04:01.267 --> 04:04.627 very large numbers, things that total 392 04:04.633 --> 04:06.203 kilocalories per mole. 04:06.200 --> 04:10.800 So if any of these steps had been off by a few percent, the 04:10.800 --> 04:14.600 dissociation of water would be very different. 04:14.600 --> 04:18.670 So this is a sign that you have to be careful, because 04:18.667 --> 04:22.667 whenever you're dealing with small differences that come 04:22.667 --> 04:26.897 from very large effects in the first place, it 04:26.900 --> 04:27.970 could go any place. 04:27.967 --> 04:31.227 In the case of water it happens to be that water will 04:31.233 --> 04:34.033 dissociate with a dissociation 04:34.033 --> 04:36.003 constant of [correction: 10^16] 16. 04:36.000 --> 04:41.330 But it has to be regarded mostly as an accident because 04:41.333 --> 04:45.473 of this important role of solvation. 04:45.467 --> 04:48.967 Now we're going to generalize into Brønsted acidity-- 04:48.967 --> 04:51.197 other things giving up protons. 04:51.200 --> 04:54.770 Or you could call it substitution at hydrogen. 04:54.767 --> 04:55.727 Here's HF-- 04:55.733 --> 04:59.373 and we talked about this last semester ad infinitum, of how 04:59.367 --> 05:02.727 we could make and break a bond at the same time by bringing 05:02.733 --> 05:06.703 up, say, water, and get H3O+ and F-. 05:06.700 --> 05:11.170 That is, HF acting as an acid, hydrofluoric acid. 05:11.167 --> 05:12.997 So that's Brønsted acidity, 05:13.000 --> 05:17.170 giving up a proton, but it could be thought of as 05:17.167 --> 05:18.797 substitution at hydrogen-- 05:18.800 --> 05:20.970 something new comes in, the old thing leaves, 05:20.967 --> 05:24.767 fluoride in this case. 05:24.767 --> 05:27.697 Now this happens, of course, in a solvent. 05:27.700 --> 05:31.900 Just as in the case of water, HF isn't going to disassociate 05:31.900 --> 05:34.700 to H+ and F- in the gas phase. 05:34.700 --> 05:38.430 It's the stabilization of those ions by water that make 05:38.433 --> 05:40.073 this accessible. 05:40.067 --> 05:42.967 So is it going to be like water where you have these 05:42.967 --> 05:45.597 enormous things and there's no predicting what will happen, 05:45.600 --> 05:48.370 as to how strong the acid will be? 05:48.367 --> 05:50.697 To a certain extent that's true. 05:50.700 --> 05:54.900 But fortunately, the solvation energies of analogous 05:54.900 --> 05:58.770 compounds are similar enough that we can often make 05:58.767 --> 06:01.067 reasonably accurate predictions-- 06:01.067 --> 06:03.967 or at least if not predict, at least once we've seen the 06:03.967 --> 06:07.267 results we could rationalize them reasonably-- 06:07.267 --> 06:10.927 of the relative acidities in terms of molecular structures. 06:10.933 --> 06:14.703 That is, if we can cancel out, because they're very similar, 06:14.700 --> 06:17.530 all these solvation things, then we can look at the 06:17.533 --> 06:21.773 molecules themselves and try to understand why one is more 06:21.767 --> 06:22.897 acidic than another. 06:22.900 --> 06:25.270 That's what we'd like to be able to do because it's much 06:25.267 --> 06:27.967 simpler to think about just the molecule than to think 06:27.967 --> 06:30.967 about how all the solvents would be arranged around any 06:30.967 --> 06:33.867 particular molecule or ion. 06:33.867 --> 06:35.827 So let's try that. 06:35.833 --> 06:40.533 Now as background for talking about acid you've, in your AP 06:40.533 --> 06:45.603 chemistry, looked at pH and pKa, and there's the question 06:45.600 --> 06:49.530 why should organic chemists bother about pH and pKa, which 06:49.533 --> 06:53.533 you've already done in your AP. 06:53.533 --> 06:55.173 It seems like a topic for general 06:55.167 --> 06:57.467 chemistry, not organic chemistry. 06:57.467 --> 07:00.267 But there are several reasons why it's important in organic 07:00.267 --> 07:02.797 chemistry, and I'm sure that all those various textbooks 07:02.800 --> 07:05.470 you have have a chapter, a section, 07:05.467 --> 07:08.727 about Brønsted acidity. 07:08.733 --> 07:12.803 Because in the first place, whether a molecule is ionized 07:12.800 --> 07:16.000 or not is important for predicting reactivity-- 07:16.000 --> 07:19.000 that is, the availability of HOMOs and LUMOs-- 07:19.000 --> 07:21.130 how high, how low they'll be depends on 07:21.133 --> 07:22.833 whether it's an ion. 07:22.833 --> 07:26.973 Also things like conformation, the color, the proximity to 07:26.967 --> 07:29.667 other species, mobility, particularly if you're an 07:29.667 --> 07:33.297 electric field, is a big function of 07:33.300 --> 07:34.130 whether there's a charge. 07:34.133 --> 07:37.273 So you want to know whether molecules are ionized or not. 07:37.267 --> 07:39.527 One of the simplest ways of making ions is 07:39.533 --> 07:42.473 dissociating a proton. 07:42.467 --> 07:46.067 And because the ease with which a species reacts with a 07:46.067 --> 07:49.497 proton might predict how readily it 07:49.500 --> 07:52.200 reacts with other LUMOs. 07:52.200 --> 07:56.770 So often we're not specifically interested in how 07:56.767 --> 08:00.927 easily a proton would react with some high HOMO, but we 08:00.933 --> 08:03.933 are interested in how someone else would react. 08:03.933 --> 08:06.873 And if we're comparing two high HOMOs to see which one's 08:06.867 --> 08:10.027 more reactive, it wouldn't be surprising if the one that's 08:10.033 --> 08:13.773 more reactive with a proton is also more reactive with the 08:13.767 --> 08:16.397 molecule we're interested in. 08:16.400 --> 08:21.000 So if we can easily measure reactivity with a proton, the 08:21.000 --> 08:25.430 reverse of which is acidity, if we can easily measure that 08:25.433 --> 08:29.503 equilibrium, then we have a scale to talk about how low 08:29.500 --> 08:32.670 LUMOs are, how reactive LUMOs might be. 08:32.667 --> 08:35.927 So that's why acidity is particularly important in 08:35.933 --> 08:37.373 organic chemistry, because it could 08:37.367 --> 08:39.067 predict organic reactions. 08:39.067 --> 08:43.767 That is, reaction with the LUMO sigma* CX or pi* 08:43.767 --> 08:49.397 CO might parallel the reactivity with a proton. 08:49.400 --> 08:52.730 Now we know that the acid dissociation constant is the 08:52.733 --> 08:56.773 product of [H+] and [B-] over [HB] where B is some base 08:56.767 --> 08:59.667 or HB an acid. 08:59.667 --> 09:03.627 And if we take the logs of both sides and rearrange a 09:03.633 --> 09:08.273 little bit, we see that the pH is the pKa minus the log of 09:08.267 --> 09:09.367 the ratio-- 09:09.367 --> 09:12.367 how much of the stuff is ionized and how much of the 09:12.367 --> 09:15.097 stuff is in the acidic form. 09:15.100 --> 09:21.230 If that ratio is 1, if it's half ionized, then the log of 09:21.233 --> 09:23.833 1 is zero so we forget that. 09:23.833 --> 09:26.803 And then pH is equal to pKa. 09:26.800 --> 09:29.930 So we have an acid with a certain pKa. 09:29.933 --> 09:34.303 If the pH is that value, then you have 50:50 ionized and 09:34.300 --> 09:37.970 unionized form. 09:37.967 --> 09:41.427 Now you often use things like that as indicators. 09:41.433 --> 09:45.003 It might be that the ionic form is colored or has a 09:45.000 --> 09:48.470 different color from the protonated form. 09:48.467 --> 09:51.527 Then if you see that color or not and can measure its 09:51.533 --> 09:54.373 intensity, you can tell how much is ionized. 09:54.367 --> 09:57.597 So you could measure that ratio. 09:57.600 --> 10:02.830 But you can't measure it over a really wide range, because 10:02.833 --> 10:06.833 suppose you could measure it when there's 5% of the colored 10:06.833 --> 10:11.373 species or up to 95%, but beyond that the colors aren't 10:11.367 --> 10:13.267 distinguishable. 10:13.267 --> 10:15.097 That would be fairly reasonable. 10:15.100 --> 10:21.070 So if you go from 95:5 to 5:95 that covers just this ratio, 10:21.067 --> 10:24.027 that covers just 2 and a half pH units. 10:24.033 --> 10:28.133 So if you want to use an indicator to measure the pH of 10:28.133 --> 10:31.003 something, you can only measure it with that indicator 10:31.000 --> 10:35.300 over a very narrow range by measuring the ratio of how 10:35.300 --> 10:38.530 much colored to uncolored stuff there is. 10:38.533 --> 10:41.803 Beyond that you have to get some other indicator and then 10:41.800 --> 10:44.270 some other indicator and some other indicator. 10:44.267 --> 10:47.467 So you could have a ladder of indicators that allows you to 10:47.467 --> 10:50.567 cover a wide range of pH. 10:50.567 --> 10:54.927 And then you could bootstrap that way with overlapping 10:54.933 --> 10:57.373 indicators to get a wide coverage. 11:00.667 --> 11:04.567 So with a known pKa, you measure the pH by measuring 11:04.567 --> 11:09.027 the ratio of the ions-- ionized to the unionized form. 11:09.033 --> 11:13.503 Now let's look at factors that influence the acidity, because 11:13.500 --> 11:16.730 they may also be the ones that influence reactivity and other 11:16.733 --> 11:19.673 organic reactions. 11:19.667 --> 11:22.567 Now pKa normally is defined in water. 11:26.367 --> 11:28.867 We just saw that the dissociation constant for 11:28.867 --> 11:31.167 water in water, that is, losing the red 11:31.167 --> 11:35.127 proton there, is 15.7. 11:35.133 --> 11:38.503 Now if you tried to get the pH higher than 11:38.500 --> 11:41.870 that, what would happen? 11:41.867 --> 11:47.627 If you had water and you made its pH 20, let's say, or 18 11:47.633 --> 11:52.033 instead of some place in this range, what would happen? 11:52.033 --> 11:54.073 You'd have the strong base in there. 11:54.067 --> 11:57.467 That base would pull protons off the water, and you 11:57.467 --> 11:59.697 wouldn't have any water anymore. 11:59.700 --> 12:03.230 So it wouldn't be anything like the same solvent if you 12:03.233 --> 12:07.133 tried to get higher pH than that. 12:07.133 --> 12:10.873 And the same thing is true if you look at the dissociation 12:10.867 --> 12:13.467 constant of H3O+. 12:13.467 --> 12:20.027 At a pH of -1.7 it would be 50% protonated. 12:20.033 --> 12:25.373 But if water is 50% protonated it's not water anymore. 12:25.367 --> 12:30.227 So if you're within this range between, say, zero and 15 or 12:30.233 --> 12:34.103 something like that, then you have water and you can talk 12:34.100 --> 12:35.170 about things. 12:35.167 --> 12:38.027 But if you tried to get out of that, you can't use water 12:38.033 --> 12:40.803 anymore because all you're doing is making all 12:40.800 --> 12:43.330 the water into ions. 12:43.333 --> 12:45.373 But in that range you can work. 12:45.367 --> 12:48.197 So in that range there are a number of interesting things, 12:48.200 --> 12:50.700 like ammonia can be protonated. 12:50.700 --> 12:54.100 The ammonium ion has a pKa of 9.2. 12:54.100 --> 12:58.000 So at pH 9.2 half of ammonia is protonated, the ammonium 12:58.000 --> 12:59.570 ion, half of it is NH3. 13:02.100 --> 13:04.200 Does it surprise you-- 13:04.200 --> 13:05.870 now let's get this straight. 13:05.867 --> 13:13.567 So NH4 acting as an acid, in NH4+ is 9.2. 13:13.567 --> 13:17.167 H3O+ is -1.7. 13:17.167 --> 13:20.067 Which one gives up its proton more easily? 13:22.900 --> 13:28.030 H3O+ or NH4+? 13:28.033 --> 13:29.303 Which is a stronger acid? 13:34.767 --> 13:38.727 Which one would take the proton from the other one? 13:38.733 --> 13:40.533 Debbie, do you have an idea? 13:40.533 --> 13:41.973 STUDENT: I guess H3O+ is a stronger acid. 13:44.933 --> 13:45.373 PROFESSOR: Right. 13:45.367 --> 13:48.627 So it would protonate NH3. 13:48.633 --> 13:54.733 So if you had H3O+ and NH3, it would be downhill in energy to 13:54.733 --> 13:57.303 transfer the proton to the NH3. 13:57.300 --> 13:58.800 Why? 13:58.800 --> 14:05.130 Why is it better to put the proton onto NH3 than onto H2O? 14:05.133 --> 14:06.373 What is it about NH3? 14:11.733 --> 14:13.073 That makes that a stronger bond. 14:18.067 --> 14:20.967 So you have a proton plus something that has an unshared 14:20.967 --> 14:24.767 pair, they come together in the form of a bond. 14:24.767 --> 14:26.827 How much energy are you going to get out of that bond? 14:29.833 --> 14:32.133 The proton is the same in all cases. 14:32.133 --> 14:34.973 What difference is there in the unshared pair between 14:34.967 --> 14:37.997 nitrogen and oxygen that means that nitrogen will hold the 14:38.000 --> 14:38.900 proton more strongly. 14:38.900 --> 14:39.330 Sebastian? 14:39.333 --> 14:40.733 STUDENT: It's a higher HOMO because nitrogen has a lower 14:40.733 --> 14:42.273 nuclear charge. 14:42.267 --> 14:42.767 PROFESSOR: Right. 14:42.767 --> 14:47.027 Lower nuclear charge, higher HOMO, stronger bond. 14:47.033 --> 14:49.933 Better energy match. 14:49.933 --> 14:51.933 So we understand that difference here 14:51.933 --> 15:01.233 of about 11 pH units. 15:01.233 --> 15:06.203 Here's FH, 3.2, hydrofluoric acid. 15:06.200 --> 15:08.130 Not nearly as good an acid as H3O+. 15:10.733 --> 15:19.373 But it's a lot better acid than H-O-H, than water, by 12 15:19.367 --> 15:22.497 and a half powers of 10. 15:22.500 --> 15:25.830 The reason is the same. 15:25.833 --> 15:29.373 That oxygen has a higher HOMO and holds 15:29.367 --> 15:30.867 the proton more strongly. 15:30.867 --> 15:34.527 So we can understand that. 15:34.533 --> 15:39.073 H2S is 7.0. 15:39.067 --> 15:47.167 ‘So now that seems a little funny compared with water. 15:47.167 --> 15:51.697 But notice the bond association energies. 15:51.700 --> 15:55.070 Actually, it's reasonable-- 15:55.067 --> 15:57.497 sulfur is not as electronegative as oxygen. 15:59.967 --> 16:05.797 Its HOMO is lower. 16:05.800 --> 16:08.200 Pardon me, let me get this straight. 16:08.200 --> 16:09.970 You always have to think these things through. 16:09.967 --> 16:13.527 I realize I'm rattling it off quite fast, and it'll take a 16:13.533 --> 16:16.373 little while looking this over in your own room to get it 16:16.367 --> 16:17.897 straight in your head. 16:17.900 --> 16:21.770 But it's interesting that if you look at the bond 16:21.767 --> 16:24.367 dissociation energies, sulfur is 16:24.367 --> 16:27.597 between oxygen and fluorine. 16:27.600 --> 16:32.070 So it's more than just how strong the bond is that 16:32.067 --> 16:34.467 determined sulfur to be in the middle. 16:34.467 --> 16:36.597 So we're going to talk a little bit about that. 16:36.600 --> 16:40.830 So here are hydrogen attached to various elements, and we're 16:40.833 --> 16:43.803 going to look at the pKa's. 16:43.800 --> 16:48.170 Now if we go across the top row you see that the ease of 16:48.167 --> 16:50.867 heterolysis, how strong an acid it is, 16:50.867 --> 16:52.697 increases to the right. 16:52.700 --> 16:55.970 So it gets easier to break the bond into ions as 16:55.967 --> 16:57.567 you go to the right. 16:57.567 --> 17:01.097 But if you look at the bond strength, the bonds get 17:01.100 --> 17:03.100 stronger as you go to the right. 17:03.100 --> 17:08.400 So that ease of homolysis goes the other way. 17:08.400 --> 17:12.200 But this is exactly what we talked about a time or two ago 17:12.200 --> 17:15.530 when we looked at the energies of two things and said that 17:15.533 --> 17:20.073 homolysis and heterolysis are opposite one another, whether 17:20.067 --> 17:22.927 you take the two electrons or whether you put them both here 17:22.933 --> 17:26.633 in heterolysis, or whether you put one here and one up there 17:26.633 --> 17:28.133 in homolysis. 17:28.133 --> 17:31.733 So that's the same thing we talked about before. 17:31.733 --> 17:35.333 So the energy mismatch, the electronegativity difference 17:35.333 --> 17:42.803 makes it easier to do heterolysis, but 17:42.800 --> 17:44.930 harder to do homolysis. 17:44.933 --> 17:47.103 But notice it's not the same when you go down 17:47.100 --> 17:49.300 the periodic table. 17:49.300 --> 17:51.370 Now the red and the black arrows are in 17:51.367 --> 17:53.027 the opposite direction. 17:53.033 --> 17:57.903 Fluoride is the most electronegative, but it's the 17:57.900 --> 18:01.500 weakest acid among the hydrogen halides. 18:01.500 --> 18:04.700 And in that case, it is the bond strength that's making 18:04.700 --> 18:05.930 the difference. 18:05.933 --> 18:15.073 And that's what made the sulfur more acidic than oxygen 18:15.067 --> 18:18.467 is because of the weaker bond strength. 18:18.467 --> 18:21.767 So that has to do with decrease of overlap; going 18:21.767 --> 18:26.567 across had to do with the energy match. 18:26.567 --> 18:28.727 So we understand those things. 18:28.733 --> 18:32.403 Now we can learn, by knowing pKa values, some of the things 18:32.400 --> 18:36.730 that influence the energies of these bonds. 18:36.733 --> 18:40.803 So here's an O-H bond in acetic acid. 18:40.800 --> 18:42.600 Of course, it's called acetic acid-- 18:42.600 --> 18:46.600 water is not called aqueic acid or something like that. 18:46.600 --> 18:48.170 So this is much more acidic-- 18:48.167 --> 18:50.367 4.8 versus 15.7. 18:50.367 --> 18:53.567 So it's 11 powers of 10 stronger as an acid. 18:53.567 --> 18:54.467 Why? 18:54.467 --> 18:57.427 Is it because the bond is intrinsically stronger? 18:57.433 --> 18:59.433 They're both O-H sigma bonds. 18:59.433 --> 19:01.673 The bonds are essentially the same. 19:01.667 --> 19:03.897 But the anions are different-- 19:03.900 --> 19:07.270 and we've talked about this before. 19:07.267 --> 19:09.497 What is it that makes the anion that you're going to 19:09.500 --> 19:12.270 make here unusually stable compared to H-O? 19:12.267 --> 19:13.267 STUDENT: Resonance. 19:13.267 --> 19:14.797 PROFESSOR: Right, there's going to be resonance that'll 19:14.800 --> 19:16.730 make it stable. 19:16.733 --> 19:19.833 Or HOMO-LUMO mixing, if we wanted not to use the language 19:19.833 --> 19:21.733 of resonance. 19:21.733 --> 19:26.403 So the low LUMO of pi* stabilizes the electrons we're 19:26.400 --> 19:29.030 putting on oxygen. 19:29.033 --> 19:33.833 Now if you make chloroacetic acid, then it's another 2 19:33.833 --> 19:36.103 powers of 10 stronger. 19:36.100 --> 19:37.830 Why would that be sensible? 19:37.833 --> 19:39.233 Anybody got an idea about that? 19:39.233 --> 19:39.403 Ellen? 19:39.400 --> 19:41.530 STUDENT: Electron induction by the chlorine. 19:41.533 --> 19:42.303 PROFESSOR: Right. 19:42.300 --> 19:43.470 It's an inductive effect. 19:43.467 --> 19:46.897 The chlorine is electronegative, it withdraws 19:46.900 --> 19:50.070 electrons from this carbon, which withdraws electrons from 19:50.067 --> 19:52.867 that carbon, which withdraws electrons from that oxygen, 19:52.867 --> 19:56.327 and makes that a better place to put a negative charge. 19:56.333 --> 19:58.173 So it's worth the factor of 100. 19:58.167 --> 20:00.097 So we have some measure here. 20:00.100 --> 20:04.230 Because these equilibrium constants are easy to measure 20:04.233 --> 20:09.273 for reversible acid dissociation, it gives us a 20:09.267 --> 20:12.267 scale that's easily accessible of how important something 20:12.267 --> 20:14.967 like inductive effect can be. 20:14.967 --> 20:16.567 Or if we look at this one where we're 20:16.567 --> 20:18.667 breaking a C-H bond. 20:18.667 --> 20:24.697 Now normal carbon-hydrogen bonds aren't acidic, but this 20:24.700 --> 20:26.300 one is rather acidic. 20:26.300 --> 20:29.230 It's as acidic as the ammonium ion. 20:29.233 --> 20:30.473 Why? 20:30.467 --> 20:35.897 Because there are two pi* vacant orbitals next door that 20:35.900 --> 20:39.370 can stabilize the high HOMO when you make carbon minus by 20:39.367 --> 20:40.497 losing that one. 20:40.500 --> 20:43.270 So again, we have a quantitative measure of how 20:43.267 --> 20:45.827 important this might be. 20:45.833 --> 20:50.203 Now here's an amino acid, alanine, in the form that's 20:50.200 --> 20:54.230 protonated here on nitrogen, and its pKa, it's even a 20:54.233 --> 20:57.373 little bit stronger acid than the chloroacetic acid. 20:57.367 --> 21:00.827 Why would you say so? 21:00.833 --> 21:02.073 Nitrogen is not more 21:02.067 --> 21:03.697 electronegative than chlorine-- 21:03.700 --> 21:07.570 not withdrawing more electrons than chlorine is. 21:07.567 --> 21:08.827 Or is it? 21:12.333 --> 21:12.803 Lauren? 21:12.800 --> 21:14.230 STUDENT: It's got the positive charge. 21:14.233 --> 21:15.633 PROFESSOR: Ah, the positive charge. 21:15.633 --> 21:18.603 That makes it very electronegative. 21:18.600 --> 21:21.370 Let's look at that one in a little more detail. 21:21.367 --> 21:24.967 And it also shows how you determine these pKa's. 21:24.967 --> 21:26.467 So you can titrate alanine. 21:26.467 --> 21:32.297 You start with this protonated form in acidic medium at pH 0, 21:32.300 --> 21:36.170 say, and it's got that red proton that could be lost. And 21:36.167 --> 21:40.467 then we're going to start running in hydroxide until 21:40.467 --> 21:42.567 we've put in two equivalents of hydroxide. 21:45.400 --> 21:50.100 When we add the first equivalent, we'll take off 21:50.100 --> 21:52.270 that red proton. 21:52.267 --> 21:55.567 And then we'll take the one off the nitrogen when we add a 21:55.567 --> 21:56.767 second equivalent. 21:56.767 --> 22:02.727 But let's look at how the pH changes as we add the base and 22:02.733 --> 22:05.473 pull off protons. 22:05.467 --> 22:06.797 So it looks like this. 22:06.800 --> 22:09.200 It changes very slowly in there and 22:09.200 --> 22:10.200 is said to be buffered. 22:10.200 --> 22:13.030 And then it changes rapidly again. 22:13.033 --> 22:14.003 Now why is that? 22:14.000 --> 22:17.500 Why isn't it just a straight line as you add more and more 22:17.500 --> 22:20.100 hydroxide and watch the pH change? 22:23.800 --> 22:28.000 If you want to change the ratio by 9-fold, you could 22:28.000 --> 22:33.330 change it from 3:1 to 1:3. 22:33.333 --> 22:35.833 So that's a 9-fold change in the ratio. 22:35.833 --> 22:40.773 And remember, the ratio is measuring the change in pH. 22:40.767 --> 22:44.797 So if you change the ratio by 9, say, approximately 10, the 22:44.800 --> 22:48.570 log of 10 is 1, so it would change the pH of 22:48.567 --> 22:50.067 the solution by 1. 22:50.067 --> 22:55.227 So adding half an equivalent of base, going from here to 22:55.233 --> 23:02.103 here, changes it by about 1 pKa unit, 2 to 3. 23:02.100 --> 23:06.170 Now suppose we want to change the pH from 3 to 4, how much 23:06.167 --> 23:08.327 do we have to add? 23:08.333 --> 23:11.733 If we change the ratio by a factor of 9-- again, I use 9 23:11.733 --> 23:15.633 just because it's convenient, 3 to 1 to 1 to 3. 23:15.633 --> 23:18.833 If we want to change it by a factor of 9 again and go up by 23:18.833 --> 23:25.233 another pKa unit, pH unit, logarithmic unit, then we only 23:25.233 --> 23:31.103 have to go from 1 to 3 to 3 to 100. 23:31.100 --> 23:34.570 That's another factor of 9 change. 23:34.567 --> 23:40.067 But it only takes 0.22 equivalents to do that. 23:40.067 --> 23:44.267 Then if we want to change it by another log unit, it takes 23:44.267 --> 23:47.027 only 0.03 equivalents. 23:47.033 --> 23:50.933 So during this region when the ratio is some place close to 23:50.933 --> 23:55.173 50:50, it takes a lot of conversion in order to change 23:55.167 --> 23:56.927 the ratio very much. 23:56.933 --> 24:00.173 But when you're out at the end and you only have 1% or a 24:00.167 --> 24:02.467 couple percent of something, then it doesn't take much 24:02.467 --> 24:06.097 change to change the ratio enormously. 24:06.100 --> 24:09.500 So that's why you get this behavior as a buffer, where if 24:09.500 --> 24:12.670 you put a lot of that stuff in, and you have roughly 50:50 of 24:12.667 --> 24:16.727 the ionized and unionized form, you can do a lot of 24:16.733 --> 24:19.573 adding acid or base and it doesn't change the pH 24:19.567 --> 24:20.567 significantly. 24:20.567 --> 24:22.797 But if you're out in this region where you only have a 24:22.800 --> 24:25.470 few percent of one or the other, then it changes 24:25.467 --> 24:26.997 drastically. 24:27.000 --> 24:30.930 Now if we keep going, we take off this proton, and again 24:30.933 --> 24:34.733 it's slow and buffered and then it goes up again. 24:34.733 --> 24:43.703 Now, how can you find the pKa of the compound, having done 24:43.700 --> 24:47.530 one of these titrations where you run in and measure the pH 24:47.533 --> 24:50.633 as you're going along? 24:50.633 --> 24:56.533 Remember, the pKa is the same as the pH when what? 24:56.533 --> 25:00.333 When the ratio is 50:50. 25:00.333 --> 25:04.133 So that means if we take it where the ratio is 50:50, 25:04.133 --> 25:06.973 that's the first pKa, the pKa for this 25:06.967 --> 25:10.097 proton, the red one here. 25:10.100 --> 25:14.070 So the pK1 is 2.35. 25:14.067 --> 25:19.167 Now it's reasonable that the proximity of the positive 25:19.167 --> 25:23.127 charge to the carboxyl group that's going to be losing a 25:23.133 --> 25:26.203 proton, having the plus charge here-- what Lauren 25:26.200 --> 25:27.730 was telling us about-- 25:27.733 --> 25:32.773 is going to make it, here it is, 300 times easier to remove 25:32.767 --> 25:37.727 the H+ from this cation rather than acetic acid, which was 25:37.733 --> 25:39.603 4.5 in its pKa. 25:39.600 --> 25:42.500 So we went from 4.5 to about 2.5. 25:42.500 --> 25:44.570 Well, a little bit more than 2.5. 25:44.567 --> 25:47.727 We went 300 times better because of that positive 25:47.733 --> 25:52.433 charge, stabilizing the anion we're going to get here by 25:52.433 --> 25:54.873 having these two charges near one another. 25:54.867 --> 25:57.697 So that's reasonable. 25:57.700 --> 26:01.300 Now we take off the second proton, and we find that 26:01.300 --> 26:04.270 that's pKa 9.87. 26:04.267 --> 26:08.197 Now how would you expect that to compare with taking a 26:08.200 --> 26:12.130 proton away from a normal amine? 26:12.133 --> 26:15.833 Here we're taking the proton away from an ammonium ion to 26:15.833 --> 26:19.373 generate an amine, but now we have a negative charge that's 26:19.367 --> 26:24.367 making this more stable, be harder to pull away. 26:24.367 --> 26:27.367 So at first glance you'd say it would be at about the same. 26:27.367 --> 26:33.827 If this was easier by a factor of 300 because this is so 26:33.833 --> 26:38.503 stable, then this one, taking that second proton off, should 26:38.500 --> 26:44.530 be harder than 300 compared to a normal amine because this 26:44.533 --> 26:47.333 thing is so stable. 26:47.333 --> 26:50.373 So with a proximity to the negative charge should make it 26:50.367 --> 26:53.397 about 300 times harder to remove proton from this 26:53.400 --> 26:54.730 so-called zwitterion-- 26:54.733 --> 26:57.673 the thing that has both positive and negative charge-- 26:57.667 --> 27:01.527 than from a normal amine, like say ethylamine. 27:01.533 --> 27:05.403 Now ethylamine is pKa 10.6. 27:05.400 --> 27:08.300 It's actually 5 times easier to take the 27:08.300 --> 27:13.730 proton away from alanine. 27:13.733 --> 27:16.903 From the zwitterion of alanine it's easier to take it away. 27:16.900 --> 27:20.400 The same way this one was easier as compared to a normal 27:20.400 --> 27:21.970 ammonium ion. 27:21.967 --> 27:23.597 That seems absolutely backwards- 27:23.600 --> 27:25.270 that it should be 300 times easier. 27:25.267 --> 27:26.997 Why? 27:27.000 --> 27:32.730 Why is it easier rather than harder to take it away from 27:32.733 --> 27:36.703 here rather than here? 27:36.700 --> 27:41.100 So you'll notice that it's a question of compared to what. 27:41.100 --> 27:46.370 Is this a good model for this when it has a proton on it and 27:46.367 --> 27:48.727 isn't charged? 27:48.733 --> 27:51.903 Not really, because this has this carbon with a bunch of 27:51.900 --> 27:53.730 oxygens in it. 27:53.733 --> 27:57.403 And this one, the ethylamine doesn't. 27:57.400 --> 28:00.330 So maybe the electron withdrawing effect of those 28:00.333 --> 28:08.173 oxygens is making it easier to give up a proton here, 28:08.167 --> 28:09.927 stabilizing the anion. 28:09.933 --> 28:12.003 The same way chlorine did. 28:12.000 --> 28:14.530 Remember, in chloroacetic acid, it was withdrawing 28:14.533 --> 28:16.503 electrons and making it easier. 28:16.500 --> 28:22.900 So maybe we should compare this, not with ethylamine, but 28:22.900 --> 28:24.700 with something that has the oxygens but 28:24.700 --> 28:27.830 doesn't have the charge. 28:27.833 --> 28:33.303 So we can do that by making it an ester instead of an acid so 28:33.300 --> 28:34.970 it doesn't have the charge on it. 28:34.967 --> 28:38.297 Its pKa is 7.3. 28:38.300 --> 28:42.200 So now, in fact, it is harder to take it away, and it's 28:42.200 --> 28:46.970 about 400 times, about what we expected if we have the right 28:46.967 --> 28:49.097 comparison. 28:49.100 --> 28:53.930 So having these charges changes the pKa in a 28:53.933 --> 28:56.503 reasonable way. 28:56.500 --> 29:00.270 So apparently the CO2 group, lacking charge, is 29:00.267 --> 29:03.167 sufficiently electron withdrawing to destabilize 29:03.167 --> 29:06.897 that cation more than the negative charge stabilizes it. 29:09.567 --> 29:13.297 Now notice here we've changed the scale-- now we're going 29:13.300 --> 29:14.570 from 10 to 50. 29:14.567 --> 29:19.597 We're going to very, very weak acids. 29:19.600 --> 29:23.130 And, of course, we can't do that in water because water 29:23.133 --> 29:30.373 has a pKa of 16, and if we try to get more basic than that we 29:30.367 --> 29:33.467 just convert water into hydroxide-- 29:33.467 --> 29:35.997 it's not water anymore. 29:36.000 --> 29:39.630 So we're going to have to use other solvents to do that. 29:39.633 --> 29:42.673 But if we use these other solvents, and again, use 29:42.667 --> 29:51.127 indicators with boot straps to go on up. Then we get that a 29:51.133 --> 29:52.903 hydrogen attached to nitrogen. 29:52.900 --> 29:55.900 Now we're not talking about an ammonium ion. 29:55.900 --> 29:57.970 That's what we were just talking about, taking a proton 29:57.967 --> 30:01.267 away from RNH3+. 30:01.267 --> 30:02.667 It's not that anymore. 30:02.667 --> 30:04.797 it's taking the hydrogen right away from 30:04.800 --> 30:07.100 nitrogen without the charge. 30:07.100 --> 30:09.830 So it's much harder to take it away than it is to take it 30:09.833 --> 30:16.903 away from water, which is what you expect because the energy 30:16.900 --> 30:20.530 match was better here. 30:20.533 --> 30:26.133 And if we go to carbon then it's way, way up there, 52. 30:26.133 --> 30:28.703 Now in your various books you'll have 30:28.700 --> 30:30.100 different values of that. 30:30.100 --> 30:34.800 It might vary by as much as 3 or even 4 pKa units, because 30:34.800 --> 30:37.600 you have to go from one solvent to another here and 30:37.600 --> 30:40.330 use these indicators to know what the 30:40.333 --> 30:43.373 equivalent of pH would be. 30:43.367 --> 30:46.967 And it depends on which ones you use to do that. 30:46.967 --> 30:49.967 But anyhow, it's way up there. 30:49.967 --> 30:53.367 So these values are approximate because the 30:53.367 --> 30:56.327 equilibrium for bases stronger than hydroxide can't be 30:56.333 --> 30:59.573 measured in water-- you have to bootstrap by comparing 30:59.567 --> 31:03.767 these acid base pairs in other solvents. 31:03.767 --> 31:07.197 So that one's a bad E match for O-H, a better E match for 31:07.200 --> 31:11.530 N-H, and a great E match for C-H, so it's holding the bonds 31:11.533 --> 31:16.433 stronger together and making it harder to form the anions. 31:16.433 --> 31:18.903 Now here's another C-H bond, but it's 31:18.900 --> 31:20.230 significantly more acidic. 31:24.133 --> 31:28.403 The hydrogen attached to a double bonded carbon. 31:28.400 --> 31:34.270 Anybody got any ideas why that would be easier to break? 31:34.267 --> 31:37.067 Can anybody think of an idea why it might be harder to 31:37.067 --> 31:40.627 break a proton away, to break a bond to hydrogen when it's 31:40.633 --> 31:42.603 attached to a double-bonded carbon? 31:42.600 --> 31:43.000 Ellen? 31:43.000 --> 31:43.870 STUDENT: sp2? 31:43.867 --> 31:46.267 PROFESSOR: Ah, it's sp2 hybridized, so the bond's 31:46.267 --> 31:48.767 going to be stronger that you're going to be breaking. 31:48.767 --> 31:51.797 But, in fact, it's easier to ionize it. 31:51.800 --> 31:55.070 So it's not because of the bond strength-- 31:55.067 --> 31:56.397 that would go the other direction. 31:56.400 --> 32:00.270 It must be the ion that's unusually stable. 32:00.267 --> 32:05.267 Can anybody think about why the ion might be stable in 32:05.267 --> 32:07.727 this double-bonded carbon, the unshared pair? 32:07.733 --> 32:08.273 Anurag? 32:08.267 --> 32:10.897 STUDENT: The pi* of the ion will stabilize the charge. 32:10.900 --> 32:13.130 PROFESSOR: Ah, you could get resonance. 32:13.133 --> 32:18.503 The pi* stabilizes it, but thanks for biting on that, 32:18.500 --> 32:20.030 because it doesn't work. 32:20.033 --> 32:21.503 Do you see why? 32:21.500 --> 32:26.830 So here's the two hydrogens on the carbon, double bond here 32:26.833 --> 32:27.873 on that carbon. 32:27.867 --> 32:31.027 Why is it that when you pull this proton off and generate a 32:31.033 --> 32:34.133 pair of electrons here, why isn't it 32:34.133 --> 32:36.633 stabilized by the pi*? 32:36.633 --> 32:37.603 STUDENT: They're orthogonal. 32:37.600 --> 32:38.830 PROFESSOR: They're orthogonal. 32:38.833 --> 32:40.773 So you're not going to get it that way. 32:40.767 --> 32:48.127 But this orbital is sp2, not sp3, as it is in the other 32:48.133 --> 32:49.603 one, the one that's 52. 32:49.600 --> 32:53.000 So it's a lower energy orbital for the electrons to be in, so 32:53.000 --> 32:55.230 it's a more stable anion. 32:55.233 --> 32:56.103 That's good. 32:56.100 --> 33:02.870 Now here's an acetylene that loses its proton, and it's 20 33:02.867 --> 33:05.597 powers of 10 better at losing the proton. 33:05.600 --> 33:06.470 Why? 33:06.467 --> 33:08.197 Anurag, let's come back to you on that one. 33:08.200 --> 33:10.600 STUDENT: The resonance on the ion? 33:10.600 --> 33:12.770 PROFESSOR: No, it's still not resonance because-- 33:12.767 --> 33:15.397 so here's the carbon, here's the hydrogen 33:15.400 --> 33:17.000 coming out at you. 33:17.000 --> 33:20.230 There's a pi ‘orbital that's this way, and a pi orbital 33:20.233 --> 33:24.003 that's this way in the acetylene, but both of them 33:24.000 --> 33:27.100 are orthogonal to that. 33:27.100 --> 33:28.400 What's good about it? 33:28.400 --> 33:29.200 STUDENT: It sp hybridized. 33:29.200 --> 33:31.170 PROFESSOR: It's sp hybridized. 33:31.167 --> 33:36.527 So here we go from sp3 to sp2 to sp, and it 33:36.533 --> 33:39.473 gets more and more-- 33:39.467 --> 33:43.697 so sp3 anion, sp anion-- 33:43.700 --> 33:47.530 no pi overlap, and an sp2 anion-- 33:47.533 --> 33:49.003 no pi overlap. 33:49.000 --> 33:51.770 And Anurag, I'm going to do you one more because you're 33:51.767 --> 33:53.297 being so good to me here. 33:53.300 --> 33:57.030 So we're going to take it away from this hydrogen, which is 33:57.033 --> 33:59.533 not on the triple bond-- 33:59.533 --> 34:02.203 this one the hydrogen was on the triple bond. 34:02.200 --> 34:04.770 Now we're taking it away from a carbon next 34:04.767 --> 34:06.797 to the triple bond. 34:06.800 --> 34:09.870 Or here we're taking it away from a carbon that's on a 34:09.867 --> 34:11.197 double bond. 34:11.200 --> 34:13.500 But it's also next to a double bond. 34:18.533 --> 34:20.433 Now why do you say it's good? 34:20.433 --> 34:21.733 STUDENT: Resonance. 34:21.733 --> 34:23.503 PROFESSOR: Resonance-- now you got it right. 34:23.500 --> 34:26.800 Because when it's not one that's on this, either a 34:26.800 --> 34:31.000 double bond or a triple bond, but it's on the carbon next to 34:31.000 --> 34:33.930 it, now it can point this way, and be like that, and overlap 34:33.933 --> 34:34.673 and get the resonance 34:34.667 --> 34:36.097 stabilization, so you were right. 34:38.967 --> 34:43.327 So this is a HOMO-pi* overlap finally. 34:43.333 --> 34:44.603 And there we see it. 34:48.033 --> 34:52.503 Now there are fabulous tables of people who have measured 34:52.500 --> 34:53.530 these things. 34:53.533 --> 34:57.173 So, for example, this is a website from a course at 34:57.167 --> 35:01.667 Harvard, Chem 206, which has six pages-- 35:01.667 --> 35:03.427 this is the first of six pages-- 35:03.433 --> 35:07.803 so all different pKa's of many, many different compounds 35:07.800 --> 35:10.170 losing their protons. 35:10.167 --> 35:13.497 There's another compilation at another website here, which I 35:13.500 --> 35:15.700 think is even bigger. 35:15.700 --> 35:19.730 So these are interesting tables to look at to see if 35:19.733 --> 35:22.373 you can figure out-- look at molecules that are very 35:22.367 --> 35:23.797 similar to one another-- 35:23.800 --> 35:26.530 so solvation will be more or less the same and you don't 35:26.533 --> 35:27.933 have to worry about that-- 35:27.933 --> 35:30.373 and see what it is about the change from one 35:30.367 --> 35:32.067 molecule to the next. 35:32.067 --> 35:35.027 How can you explain in terms like we've been talking 35:35.033 --> 35:38.573 about-- hybridization, resonance, electronegativity. 35:38.567 --> 35:41.927 That is, the HOMOs and LUMOs. 35:41.933 --> 35:44.203 How can you explain these trends seen 35:44.200 --> 35:48.000 over similar compounds? 35:48.000 --> 35:51.770 So here's the problem for Wednesday. 35:51.767 --> 35:56.997 List the factors that help determine the pKa for an acid. 35:57.000 --> 36:00.700 Then choose a set of several related acids from one of 36:00.700 --> 36:05.070 these pKa tables, or your text will have some, too, I'm sure. 36:05.067 --> 36:08.427 And explain what they teach about the relative importance 36:08.433 --> 36:10.373 of these factors-- 36:10.367 --> 36:13.497 which is more important, resonance or hybridization, as 36:13.500 --> 36:15.400 we were talking about here. 36:15.400 --> 36:18.770 So just practice yourself by choosing a set of three or 36:18.767 --> 36:22.867 four, or whatever number seems to be there, of related 36:22.867 --> 36:25.697 compounds where you see structural changes, and see if 36:25.700 --> 36:30.570 you can rationalize why they have the pKa's they have. Then 36:30.567 --> 36:33.597 once you've done that in the privacy of your own room, 36:33.600 --> 36:36.630 explain your conclusions to at least one other class member 36:36.633 --> 36:40.033 and decide together how unambiguous your lesson is. 36:40.033 --> 36:43.633 Did you think it through, or was there something you forgot 36:43.633 --> 36:46.003 or did you get something backwards? 36:46.000 --> 36:49.200 So that's your assignment for Wednesday, and feel free to 36:49.200 --> 36:52.170 consult the problems in textbook-- they'll have 36:52.167 --> 36:56.197 problems about pKa's, and the references at the end of the 36:56.200 --> 36:58.330 tables if you want to. 36:58.333 --> 37:03.073 There's a hint that that would make a good exam question for 37:03.067 --> 37:06.897 you to explain something like that. 37:06.900 --> 37:10.300 Now, nucleophilic substitution and beta-elimination. 37:10.300 --> 37:14.600 So we've been talking about this Brønsted acidity in order 37:14.600 --> 37:17.600 to understand reactivity and more 37:17.600 --> 37:19.370 typical organic reactions. 37:19.367 --> 37:22.497 So let's see if we could use these ideas in understanding 37:22.500 --> 37:25.730 nucleophilic substitution and beta-elimination. 37:25.733 --> 37:29.903 In the Jones textbook that's chapter seven, but there will 37:29.900 --> 37:32.770 be corresponding chapters in all of the books that you 37:32.767 --> 37:37.897 have. We also started talking about this in lecture 16, as 37:37.900 --> 37:40.770 you'll remember, where we talked about acid base 37:40.767 --> 37:44.697 reactions, and about SN2 substitution, and that they 37:44.700 --> 37:47.800 really were the same reaction in terms of the orbitals that 37:47.800 --> 37:49.070 were involved. 37:51.233 --> 37:56.503 In fact, the beta-elimination or E2 elimination, remember we 37:56.500 --> 38:00.600 talked about at the same time in lecture 16 where the base 38:00.600 --> 38:03.370 takes off this proton, you generate the double bond and 38:03.367 --> 38:07.327 lose the leaving group there. 38:07.333 --> 38:11.973 Now these reactions weren't discovered by people who 38:11.967 --> 38:19.797 understood mechanisms and applied them to see what they 38:19.800 --> 38:21.500 could make in the laboratory. 38:21.500 --> 38:24.730 They were discovered by people fiddling around with things 38:24.733 --> 38:26.533 and seeing what would happen. 38:26.533 --> 38:30.533 And it's only 100 years or 150 later that people began to 38:30.533 --> 38:33.033 really understand what was going on. 38:33.033 --> 38:36.973 So, for example, Alexander William Williamson in Britain 38:36.967 --> 38:40.667 in 1852 discovered that treating this alkoxide with 38:40.667 --> 38:44.597 ethyl bromide could do a double displacement reaction 38:44.600 --> 38:47.400 where you exchange partners and the ethyl goes on the 38:47.400 --> 38:51.230 oxygen and the sodium goes with the bromide. 38:51.233 --> 38:57.733 Finkelstein, who was a chemist in the Netherlands in 1910, 38:57.733 --> 39:02.133 found that sodium iodide reacting with R-Cl could give 39:02.133 --> 39:06.673 R-I, so you could exchange iodine in place of chlorine 39:06.667 --> 39:08.467 and get sodium chloride. 39:08.467 --> 39:11.367 Now all these things have their own little bit of lore 39:11.367 --> 39:12.227 about them. 39:12.233 --> 39:16.533 The reason that reaction works so well is that sodium iodide 39:16.533 --> 39:20.473 is soluble in acetone, the solvent that's used. 39:20.467 --> 39:24.627 But sodium chloride is not soluble in acetone. 39:24.633 --> 39:27.573 So when you mix the two, you could imagine either of them 39:27.567 --> 39:29.267 replacing the other one. 39:29.267 --> 39:32.067 But the equilibrium is driven toward the products by the 39:32.067 --> 39:34.367 fact that sodium chloride precipitates. 39:34.367 --> 39:37.597 So all of these reactions have their own twists about them 39:37.600 --> 39:42.200 that make them interesting and variable. 39:42.200 --> 39:44.500 But there's generality, too. 39:44.500 --> 39:48.670 For example, he could also do this trick with an alkyl 39:48.667 --> 39:52.127 bromide instead of alkyl iodide. 39:52.133 --> 39:56.303 So if you could only do something in one particular 39:56.300 --> 39:58.770 case, no one cares very much about it. 39:58.767 --> 40:01.897 But if it's general, then people can apply it to their 40:01.900 --> 40:05.900 own problems and it becomes much more interesting. 40:05.900 --> 40:08.870 So generalization is the name of the game here. 40:08.867 --> 40:11.527 And both of those reactions, the Williamson ether 40:11.533 --> 40:14.933 synthesis, and the two flavors of the Finkelstein reaction, 40:14.933 --> 40:17.333 both of them involve exchanging ions. 40:17.333 --> 40:19.703 You start with one pair of ions and you end with a 40:19.700 --> 40:21.770 different pair of ions-- it's one of these double 40:21.767 --> 40:24.627 decomposition reactions. 40:24.633 --> 40:31.373 Then in Russia, Menshutkin in 1890 discovered that you could 40:31.367 --> 40:32.267 react triethylamine with an 40:32.267 --> 40:36.197 alkyl iodide and generate the salt-- 40:36.200 --> 40:41.470 tetravalent ammonium salt as an iodide. 40:41.467 --> 40:44.267 Notice that this seems to be different from the first one, 40:44.267 --> 40:47.527 because the first one just exchanged ions; this one 40:47.533 --> 40:50.333 actually creates ions where there weren't ions in the 40:50.333 --> 40:51.833 first place. 40:51.833 --> 40:55.303 Or Hans Meerwein working right after the Second World War in 40:55.300 --> 40:59.030 Germany discovered that you could use this thing called 40:59.033 --> 41:02.973 Meerwein's reagent, which is a special kind of oxygen-- 41:02.967 --> 41:06.267 oxygen plus because it has three things attached to it. 41:06.267 --> 41:08.827 Trimethyloxonium. 41:08.833 --> 41:12.173 Fluoroborate is the anion that he used. 41:12.167 --> 41:16.497 This could react with RO- to give R-O methyl-- 41:16.500 --> 41:18.470 that is, it's a methylating agent, it 41:18.467 --> 41:21.167 puts methyl onto oxygen. 41:21.167 --> 41:24.297 But notice in this one you actually destroy ions. 41:24.300 --> 41:27.870 You start with four ions and you end with two ions. 41:27.867 --> 41:31.667 So at the top we have exchange of ions, then we have creating 41:31.667 --> 41:35.897 ions, now we have destroying ions. 41:35.900 --> 41:40.600 And then there's solvolysis, where the reagent actually is 41:40.600 --> 41:41.300 the solvent-- 41:41.300 --> 41:45.430 ethyl can react with the carbon 41:45.433 --> 41:49.503 displacing bromide as HBr. 41:49.500 --> 41:52.900 So that solvolysis means breaking apart, that's the 41:52.900 --> 41:55.300 "lysis" by the solvent. 41:55.300 --> 41:57.170 So all these seem to be-- 41:57.167 --> 42:00.167 if you had a list of reactions you'd have to memorize, we 42:00.167 --> 42:01.527 have all these different reactions-- 42:01.533 --> 42:03.773 the Williamson ether synthesis, the Finkelstein 42:03.767 --> 42:06.767 reaction, the Menshutkin reaction, the Meerwein 42:06.767 --> 42:08.997 reagent, solvolysis reactions and so on. 42:09.000 --> 42:13.170 But the great thing is that they're all the same. 42:13.167 --> 42:15.797 Once you understand the mechanism, they're all 42:15.800 --> 42:20.670 nucleophilic substitution, which is the subject of this 42:20.667 --> 42:22.967 part of the course, because all of them have some 42:22.967 --> 42:27.597 unusually high HOMO which reacts with an unusually low 42:27.600 --> 42:30.130 LUMO, which is the sigma* orbital. 42:30.133 --> 42:33.873 So it breaks the sigma* as the new bond is 42:33.867 --> 42:35.127 formed with the HOMO. 42:37.400 --> 42:40.730 So if we're talking about the generality of nucleophilic 42:40.733 --> 42:43.833 substitution, we should generalize over variety and 42:43.833 --> 42:46.433 all the different components of the reaction. 42:49.467 --> 42:52.497 Just to give you an example of how many different kinds of 42:52.500 --> 42:57.470 nucleophilic substitutions there are, consider adenine, 42:57.467 --> 42:59.627 which has lots of different unshared 42:59.633 --> 43:02.573 pairs on the nitrogen. 43:02.567 --> 43:06.667 And ribose, a sugar. 43:06.667 --> 43:11.497 Now here you have a HOMO on the nitrogen and a sigma* 43:11.500 --> 43:13.330 LUMO of the carbon-oxygen. 43:16.000 --> 43:19.930 And you can substitute the nitrogen for the oxygen. 43:19.933 --> 43:22.873 Actually, as we'll see shortly, it's not quite the 43:22.867 --> 43:25.927 same where you push the O-H out. 43:25.933 --> 43:28.333 But anyhow that's a substitution at carbon, which 43:28.333 --> 43:31.273 loses water then, and makes that N-H [correction: N-C] bond. 43:31.267 --> 43:33.767 And that stuff is called adenosine. 43:33.767 --> 43:38.597 So the adenine, plus the "-ose" comes from ribose, so 43:38.600 --> 43:39.870 that's adenosine. 43:41.933 --> 43:43.503 So we have adenosine. 43:43.500 --> 43:46.730 And here's methionine, an amino acid. 43:46.733 --> 43:49.473 And it has a HOMO, which is an unshared pair 43:49.467 --> 43:50.897 on the sulfur there. 43:50.900 --> 43:55.200 And it has an O-H that could be a leaving group. 43:55.200 --> 44:00.570 So you can substitute SR2 for O-H at carbon and do another 44:00.567 --> 44:02.967 nucleophilic substitution, and you get this thing that's 44:02.967 --> 44:06.367 called S-adenosylmethionine. 44:06.367 --> 44:11.427 It's methionine that has this adenosyl on it. 44:11.433 --> 44:15.073 And that is this stuff you may have heard of, SAMe, 44:15.067 --> 44:16.667 S-adenosylmethionine-- 44:16.667 --> 44:19.527 you can buy it in vitamin stores. 44:19.533 --> 44:22.633 But it's very popular with nature as well. 44:22.633 --> 44:25.373 So if you have an amino acid or something that has a 44:25.367 --> 44:28.897 nitrogen with an unshared pair, like the nitrogen in 44:28.900 --> 44:34.370 arginine, then you can do a nucleophilic substitution 44:34.367 --> 44:39.767 reaction where you substitute NHR2 for SR2. 44:39.767 --> 44:42.597 So it attacks that carbon, the leaving group leaves, so 44:42.600 --> 44:45.970 here's the third nucleophilic substitution reaction. 44:45.967 --> 44:48.927 And it ends up with a methylated amino acid. 44:48.933 --> 44:51.733 Or that arginine could've been part of a protein and you'd 44:51.733 --> 44:55.373 have a methylated protein. 44:55.367 --> 44:58.297 Then you could have another one, where a base comes along 44:58.300 --> 44:59.830 and takes the proton away. 44:59.833 --> 45:04.573 But that's nothing but a substitution at hydrogen, and 45:04.567 --> 45:06.267 leave the electron pair on nitrogen. 45:09.333 --> 45:12.873 And this is biological methylation, which I know 45:12.867 --> 45:16.727 practically nothing about, except for the fact that our 45:16.733 --> 45:20.233 daughter, who was a student in this course 20 years ago, is 45:20.233 --> 45:23.273 now a professor of biology at Bowdoin College. 45:23.267 --> 45:28.097 She works on biological methylation, on protein 45:28.100 --> 45:30.630 modification by methyltransferases. 45:30.633 --> 45:33.033 I talked to her on the phone the night before last 45:33.033 --> 45:33.903 to check this out. 45:33.900 --> 45:37.000 She says yes, indeed, this is the compound that's used in 45:37.000 --> 45:40.330 practically all biological methylation 45:40.333 --> 45:42.033 reactions of proteins. 45:42.033 --> 45:45.333 So these nucleophilic substitutions have broad 45:45.333 --> 45:47.503 generality and are very important. 45:47.500 --> 45:49.870 And what we're going to be studying then is how the 45:49.867 --> 45:53.197 different components influence the rate of these reactions. 45:53.200 --> 45:56.970 So we have the nucleophile, the high HOMO that's coming, 45:56.967 --> 45:58.797 we could vary that. 45:58.800 --> 46:01.870 We have the substrate, what various R groups we could 46:01.867 --> 46:04.827 have. Included in the substrate is, of course, 46:04.833 --> 46:06.873 whatever's going to be leaving-- the leaving group, 46:06.867 --> 46:10.467 we could vary that and see how it affects the reaction. 46:10.467 --> 46:13.127 It takes place in some solvent, that's going to make 46:13.133 --> 46:14.033 a difference. 46:14.033 --> 46:16.673 And, of course, there's some product being formed. 46:16.667 --> 46:18.567 So all of these things can vary. 46:18.567 --> 46:24.397 And now, although we looked schematically early on in the 46:24.400 --> 46:25.770 middle of the semester-- 46:25.767 --> 46:29.567 last semester we looked at this idea of the HOMO 46:29.567 --> 46:32.597 attacking the sigma* and the leaving group leave. Now 46:32.600 --> 46:35.530 we're going to look at the details of how, as you vary 46:35.533 --> 46:39.173 these things, the reaction becomes more or less easy or 46:39.167 --> 46:41.297 takes some completely different course. 46:41.300 --> 46:44.870 So that's going to be the project we begin next lecture.