00:00:00 I told you he wouldn't get very far.

00:00:30 Now, Bob, about that cigarette, I feel I'd like to make a comment.

00:00:56 The people in the jazz world have an expression for it.

00:01:01 So long, Bob.

00:01:02 It's been brief but intense.

00:01:26 So long, Bob.

00:01:27 So long, Bob.

00:01:56 So long, Bob.

00:01:57 So long, Bob.

00:02:26 Those amongst you who are refugees from the world outside, that is to say our guests, will observe that in some respects our department has not changed.

00:02:44 We still work hard, sometimes very hard, but we still believe that life without fun, rather like life in a state of nature, is mean, beastly, vile, brutal, likely to be relatively short, and above all, uninspired.

00:03:09 So, as I say, we still have fun here in this way as with our chemistry.

00:03:19 The first thing I should like to do is add my personal words of welcome to all of our guests and let you know how much pleasure it gives me to see you all here.

00:03:36 I'm reminded of the occasion on which Prince Philip and I opened the then new Churchill College in the other Cambridge.

00:03:46 He had been escorted thither and yon throughout the precincts of the college during the entire day before sitting down to a well-earned dinner.

00:04:00 When the repast had followed its preordained course, or perhaps I should say courses, by which time the group was largely summoned, a brisant stroke on a gong startled the assembly.

00:04:24 The Duke jumped to his feet at once and cried,

00:04:30 He then revealed that he'd agreed with pleasure to visit Cambridge and to open Churchill.

00:04:37 But, he averred, he'd spent several hours exploring every nook and cranny of the place, and to him it looked bloody well open already.

00:04:46 Ah well, he then said, I suppose I can declare it more open than it has been until now.

00:04:53 In a similar vein, it's my hope and belief that my colleagues who've already made all of you feel most welcome and express their appreciation of your presence here.

00:05:05 And I can say, ah well, perhaps my few words of personal welcome will make you feel even a bit more welcome than you have until now.

00:05:16 Now, a few words about this paraphernalia.

00:05:22 That thing is rather simple.

00:05:25 Thinking back over 41 years of incarceration here at Harvard in connection with this occasion,

00:05:35 I encountered with no little nostalgia the thoughts of the days when Harvard was Harvard, Radcliffe was Radcliffe.

00:05:47 And for several years, I gave lectures to the Radcliffe girls on general and inorganic chemistry with demonstrations.

00:05:57 And so I could not resist the temptation to recreate just one brief moment redolent of those days of long ago.

00:06:05 This was the kind of demonstration, of course, we did.

00:06:09 As someone put it earlier today, to take one's mind off the substance of the lectures.

00:06:16 Now, the gong and the sedan chair require just a bit more education.

00:06:24 There are societies, perhaps I should say, in which one is wise to be very careful about one's casual remarks.

00:06:36 In such a context, for example, one might say, I do admire your wife.

00:06:42 Only to receive the host's reply, really, I'm highly honored. By all means, take her.

00:06:48 Some hosts in such societies go even further.

00:06:51 They'll make a present of a valuable painting of which a guest has expressed approbation.

00:06:58 Now, our research group is a bit like that.

00:07:02 In an unguarded moment, I expressed the sentiment that I rather fancied the idea of having a Chinese gong.

00:07:14 Lo, a Chinese gong appeared.

00:07:19 On another occasion, I was so careless as to indicate my prejudice in favor of the sedan chair as a means of locomotion.

00:07:28 And again, mirably dictu, that beautiful sedan chair materialized.

00:07:35 Now, it will come as no surprise to you that sedan chairs are, these days, in rather short supply.

00:07:44 Perhaps more especially so in this part of the world.

00:07:48 How, then, this miracle?

00:07:51 And here's the nub of the matter. The members made it themselves.

00:07:56 What a fine job they made of it, thus demonstrating, perhaps in a slightly unusual way,

00:08:02 one of the great and, seriously speaking, very important traditions of the group.

00:08:07 That is, the skillful use of finely developed manipulative abilities.

00:08:14 Not to mention another, the exercise so important to all good experimentalists of the capacity for improvisation.

00:08:24 And I should, of course, not fail to mention that they had one hell of a lot of fun doing it.

00:08:33 Now, after that short preamble, I should raise a question.

00:08:41 Why am I standing here?

00:08:50 In the course of preparing this occasion, our chairman, Dudley Hirschberg, kindly invited me to be one of the speakers.

00:09:03 I indicated that circumstances were such that I must decline,

00:09:09 reminded Dudley that there was no dearth of talent at his command,

00:09:13 and, of course, today's events have shown the correctness of that to surmise.

00:09:21 But Bobby said, Won't you say anything?

00:09:24 Well, Dudley, I replied, As it happens, you have chosen the date upon which I shall be in Cambridge.

00:09:33 Consequently, of course, I shall attend the symposium or meeting or whatever we call it.

00:09:41 I am, on occasion, capable of congeniality, perhaps even conviviality.

00:09:50 So it would violate no natural law were it to turn out that I might say any number of things to any number of people.

00:09:58 But, I said to Dudley, I must ask you not to include me in any way in the formal program.

00:10:05 Now, everything seemed very clear at that point.

00:10:12 But now it turns out that Dudley, in fact, has either a less subtle or perhaps a more subtle mind than I had supposed.

00:10:22 I'm not just sure which.

00:10:25 What was the next development in this mini-saga?

00:10:28 This was it. I, along with all the other members of the Association of Harvard Chemists, received an invitation with a program

00:10:38 on which I aspired to my horrified astonishment.

00:10:43 Writ large, letter-spelling remarks, R. B. Woodward.

00:10:49 In short, I've been sandbagged.

00:10:58 Now, to make matters worse, in the week since then, I've been unable to appear anywhere among humankind.

00:11:09 In our parking lot on the streets in Basel, sitting on the plane next to a girl bound for Singapore,

00:11:16 all sorts of places, without being exposed to the dreaded refrain,

00:11:22 I or we are looking forward very much to your remarks at the symposium.

00:11:29 Or, slightly less alarming, I'm so sorry I won't be able to be at the symposium to hear your remarks.

00:11:39 Well, and it doesn't end there.

00:11:42 Nearly every letter that I've received in the last few weeks, nearly every telephone call,

00:11:46 contained an illusion which was another dagger plunged into my helpless flesh.

00:11:52 Now, having no remarks in mind, and well aware that such things can only be taken seriously,

00:12:01 all of this placed me very much in a class of one,

00:12:05 since I certainly have not been looking forward to my remarks at this symposium.

00:12:14 Well, so be it.

00:12:17 I'm not accustomed to the, unaccustomed to the uses of adversity,

00:12:23 and mercifully for all of you as well as myself, it will soon, well, soon,

00:12:35 it'll be over in due course.

00:12:40 So, all right, here are some remarks.

00:12:54 This is a great department.

00:13:04 And we all wanted to do so.

00:13:10 I'd like first to single out a particular facet of our life here, which has meant a great deal to me.

00:13:20 Throughout all those 41 years I've spent here, I've felt, literally felt strongly,

00:13:27 the active help and support and encouragement of my colleagues in the department,

00:13:32 given unfailingly, I'm sure sometimes not without difficulty, if you consider two things my nature.

00:13:42 Some of them must have had to battle attitudinal imperatives with which they had been imbued

00:13:47 by their variously conservative upbringings.

00:13:52 Would you like me to repeat that?

00:14:00 So, the support, sometimes even the approval of my colleagues has been an important factor

00:14:05 in making my life here a happy one.

00:14:08 Indeed, just offhand, I can think of only two occasions on which a colleague has done anything

00:14:15 which must be regarded as not the act of a friend.

00:14:18 Now, when I prepared these unprepared remarks, that's what I prepared, you see.

00:14:24 I said I could think of only two occasions on which a colleague had done anything

00:14:28 which must be regarded as not the act of a friend.

00:14:32 Now, since these unprepared remarks were prepared, it turns out there are three occasions.

00:14:43 Now, as originally prepared, the unprepared remark went as follows,

00:14:48 and as luck would have it, the malfactor in both cases was Dudley Hirschbart.

00:15:00 Now, I don't have to make much of a modification because it now turns out that in all three cases

00:15:08 the malfactor was Dudley Hirschbart.

00:15:11 And I'm going to have to change the order of these unprepared remarks.

00:15:15 You know, one of these acts has already been described.

00:15:18 That is, his getting myself in this particular one.

00:15:24 And I'm going to have to describe the third before the second.

00:15:29 Having got me here, at two o'clock this afternoon, mind you, two o'clock this afternoon,

00:15:35 he said, Bob, you don't have much time. I want to speak myself.

00:15:39 Or something to that effect. Can you believe it?

00:15:53 Well, the second of these acts, not that of a friend,

00:15:58 involves a lovely niche in the converse corridor just outside my office door.

00:16:04 That niche cries out for use.

00:16:07 And our group for some time has been considering various possibilities.

00:16:12 The frontrunner at the moment involves placing in that niche a pedestal

00:16:17 on which would be placed, let us say, the bust of the week.

00:16:23 Or, as the case might be of the month, should creative imagination flag in a quantitative sense.

00:16:31 You yourselves, of course, may put your own construction

00:16:38 on which the several meanings of bust might be preferred in our group.

00:16:44 In any event, that project is at the moment only a gleam in our group eye.

00:16:48 But Dudley, too, was attracted to that obvious vacuum.

00:16:54 And he caused, some time past, to be hung in it a copy of Gainsborough's Blue Boy.

00:17:12 Now, he shouldn't be, for that, too severely faulted.

00:17:16 Certainly he had the germ of a good idea.

00:17:20 It was the execution that left much to be desired.

00:17:25 Had it been the original,

00:17:32 it could not but have been viewed with approbation.

00:17:36 But alas, it was a poor $1.99 copy,

00:17:40 and I had no choice but to order it to be removed at once.

00:17:45 Have I made any point here?

00:17:49 Certainly.

00:17:50 The tradition of this department is that in the execution of any idea,

00:17:54 however good one it might be,

00:17:57 the highest experimental standards are to be rigorously observed.

00:18:04 Now, I cannot conclude this section of my remarks without saying

00:18:09 that it is my hope that my colleagues feel, as I do,

00:18:13 that is, that they, too, have enjoyed the moral and personal support of their fellows.

00:18:19 And in their cases also, this rapport has been a factor in their achievements.

00:18:32 By the way, if you think I'm overdoing that,

00:18:34 I just direct again to your attention the fact that I've been here for 41 years,

00:18:38 and I could have been anywhere.

00:18:44 That we have been, by and large, a congenial group

00:18:48 may be further illustrated by my revealing some of the secret and sacred

00:18:53 inner workings of the department acting as a whole.

00:18:57 I cannot recall any case,

00:19:01 nor can I imagine one occurring,

00:19:04 which would be decided by, say, a 7 to 5 vote.

00:19:10 Any matter which reached such a point would be quietly dropped.

00:19:17 We act only when we achieve substantial consensus.

00:19:22 And given our fierce individualism, individual characteristics,

00:19:30 and the often wide variety of our initial positions,

00:19:35 we do so, that is, reach that consensus surprisingly often.

00:19:41 In short, we might put it that we have in this department

00:19:44 not just outstanding scientists, but men who are at the least good human beings.

00:19:50 May it ever be so.

00:19:54 Some moments ago,

00:19:57 I referred to the fact that some things here at Harvard have not changed,

00:20:03 but, of course, others have.

00:20:13 Certainly chemistry has changed.

00:20:23 And we in the department,

00:20:28 and those of you who have helped us,

00:20:31 may be gratified that we have played a prominent role

00:20:33 in bringing about many of the changes in chemistry

00:20:37 during the last generation.

00:20:42 I was a student,

00:20:45 I suppose in the interests of precise use of language,

00:20:48 I should say I was designated a student,

00:20:51 in the early 1930s.

00:20:55 Now in those days,

00:20:58 which was some time after Arrhenius,

00:21:01 many, indeed most, textbooks

00:21:07 still were wary of ions.

00:21:11 Cassium cyanide was written K-C-N,

00:21:15 or, if the author was particularly bold,

00:21:18 K-dot-C-N-stroke.

00:21:22 Now, and that was in dealing with inorganic substances.

00:21:27 Almost without exception,

00:21:30 ions in organic chemistry were absolutely taboo.

00:21:35 Frank Whitmore, in his seminal papers on carbonium-ion rearrangements,

00:21:40 had to use an ambiguous asterisk,

00:21:43 not a positive charge,

00:21:46 and refer to those entities as reactive species,

00:21:49 not carbonium ions,

00:21:51 in order that his papers might be accepted.

00:21:54 It wouldn't have been accepted with positive charges in carbonium ions,

00:21:58 things of that sort.

00:22:01 Now when I arrived at Harvard,

00:22:04 on the second floor of Converse,

00:22:07 Gus Carlson and Nate Weiner were working in Rome.

00:22:12 They were the last of the private assistants,

00:22:15 we would now call them postdoctoral fellows,

00:22:18 of Arthur Michael.

00:22:24 Now, one of their tasks was the following,

00:22:30 to disprove the classic views of Arthur Lapworth

00:22:35 on the mechanism of cyanohydrin formation.

00:22:40 How did Michael know that Lapworth's views were incorrect?

00:22:45 Very simple. Ions did not exist.

00:22:51 Now, some of you may know about Arthur Michael,

00:22:56 quite a few of you may not.

00:22:59 And so I'm going to digress for a few moments about Arthur Michael.

00:23:05 He was a great organic chemist of the past.

00:23:09 His name is embedded in organic chemistry

00:23:12 Michael addition and Michael reaction,

00:23:18 early examples of which he discovered.

00:23:21 I would suppose that throughout the world,

00:23:24 he is generally assumed to have been one of the

00:23:29 group of German chemists of the last quarter of the 19th century

00:23:34 who did so much to bring organic chemistry forward.

00:23:39 That is not really true.

00:23:43 Michael was an American, a Bostonian,

00:23:47 of a very wealthy family who went to Germany in about 1875.

00:23:52 He was not only wealthy, he was irascible,

00:23:55 and he didn't have to take, nor did he want to take,

00:23:58 any nonsense from anyone.

00:24:00 And the result of that was that he visited

00:24:03 and worked in every major German university.

00:24:09 He'd go to one, do some work, and get thrown out,

00:24:12 then he'd go to another, and that happened many times.

00:24:19 After he spent about 25 years in Germany,

00:24:22 publishing many worthwhile papers,

00:24:24 discovering the Michael reaction and so forth,

00:24:26 misinterpreting its mechanism,

00:24:29 he returned to this country and went to Tufts University.

00:24:34 And then, after he retired from Tufts,

00:24:38 or perhaps they couldn't stand him anymore,

00:24:40 he was appointed some kind of professor here at Harvard.

00:24:43 I thought he was appointed an emeritus professor,

00:24:45 that he was the only case in which a man's first appointment

00:24:48 was an emeritus professor.

00:24:50 That may be true, but I haven't really looked into the details.

00:24:55 He had a lab out in, a private lab out in Newton,

00:24:58 in a large house,

00:25:01 a huge sitting room full of enormously valuable Buddhas,

00:25:07 and Gus Carlson and Nate Weiner working to show

00:25:11 that cyanohydrin formation must take some other course

00:25:15 than that which we all now know it does,

00:25:18 because there were no ions.

00:25:20 Well, you can see from that how far chemistry came.

00:25:23 Michael, by the way, I might say,

00:25:25 in the course of wandering around Germany for 25 years,

00:25:28 achieved a detestation of everything Teutonic.

00:25:33 And he used to say we'd go out to visit him every once in a while,

00:25:36 when he was about 95, I suppose.

00:25:39 That was part of the living history of early organic chemistry.

00:25:44 And he would tell us what a fool Van't Hoff was.

00:25:49 As compared, for example,

00:25:52 with that brilliant, lucid person Libel.

00:25:56 Read the papers of Van't Hoff.

00:25:59 Read the papers of Libel.

00:26:02 See if you agree with Michael.

00:26:06 He didn't have much use for August Wilhelm von Hoffmann.

00:26:12 Kekulé.

00:26:14 Dopes, all of them.

00:26:19 Nor did he have much use for us.

00:26:22 Paul Bartlett at the time was the leading young light

00:26:26 in this new and blossoming field of physical organic chemistry.

00:26:31 Arthur Michael would fix Paul with a fierce glare,

00:26:35 and he'd say, now, Doctor,

00:26:38 why is butyric acid stronger than propionic acid?

00:26:43 That would throw Paul into something of a state of confusion,

00:26:48 and Michael would say, aha, you see?

00:26:50 Your views are all nonsense.

00:26:57 All right.

00:26:58 That's just a digression about Arthur Michael,

00:27:00 a very interesting character,

00:27:01 a great figure in the history of chemistry,

00:27:03 and part of the Harvard tradition also.

00:27:06 Now, I mentioned a moment ago

00:27:08 Whitmore's interesting papers in the thirties.

00:27:12 Now, those papers were exceptional.

00:27:15 Do an experiment.

00:27:18 Pick up a copy of the Journal of the American Chemical Society

00:27:22 of the thirties at random.

00:27:26 Dollsville.

00:27:29 Really, Dollsville.

00:27:32 With occasional exceptions of the sort that I've mentioned.

00:27:35 By contrast, the chemistry of the present day

00:27:39 is incomparably more exciting,

00:27:42 effervescent, alive.

00:27:45 No month, no week, passes without challenging

00:27:48 and beautiful developments.

00:27:51 And yet, the chemistry of the present day

00:27:55 without challenging and beautiful developments.

00:27:58 I mean, I've lived in both times.

00:28:01 I'm still living in one of them.

00:28:06 And I know the difference.

00:28:08 And it's real. It's tangible.

00:28:10 It's enormous.

00:28:14 I'm just going to mention one,

00:28:17 just one recent example.

00:28:21 During my most recent visit to Basel,

00:28:24 Professor Meyer of Gießen presented a lecture.

00:28:30 By the way, you will realize, of course, most of you,

00:28:33 that my most recent visit to Basel will have been very recent.

00:28:37 Always is.

00:28:40 Professor Meyer of Gießen presented a lecture

00:28:43 in which he described the first,

00:28:47 I think the first authentic tetrahedron derivative.

00:28:53 Tetra tertiary butyl tetrahedron.

00:28:57 I'm going to draw a picture.

00:28:59 I'll try.

00:29:08 Bill During told me this really worked.

00:29:11 Well, it does if you try hard enough.

00:29:16 It does if you try.

00:29:47 There it is.

00:29:50 Tetra butyl tetrahedron.

00:29:54 Four carbon atoms at the corners of a tetrahedron.

00:29:58 This turns out to be a colorless crystalline solid.

00:30:03 Stable indefinitely.

00:30:07 Melts at, I think, about 136 degrees,

00:30:11 but it might have been 163.

00:30:13 It's a high-melting, stable crystalline substance.

00:30:17 Look at it.

00:30:19 Four carbon atoms at the corners of a tetrahedron.

00:30:23 An enormous amount of energy is stored in this molecule,

00:30:28 which, by the way, of course, owes its existence

00:30:31 to Hoffman Woodward imposed barriers

00:30:34 to its transformation into anything else.

00:30:39 Now, the amount of that excess energy is, as I say,

00:30:42 certainly enormous.

00:30:45 It has not yet been measured experimentally.

00:30:48 Various theoreticians have estimated it

00:30:52 at between 120 to 200 kilocalories per mole

00:31:00 stored in that tetrahedral array.

00:31:04 We'll soon know.

00:31:06 Another milestone.

00:31:08 And this sort of thing is happening

00:31:11 in contemporary chemistry frequently.

00:31:14 Didn't have that happen once in a number of years

00:31:17 in the 30s.

00:31:21 Actually, it gives me particular pleasure

00:31:23 that Meyer has prepared this tetrahedron derivative.

00:31:27 We've had some connection

00:31:31 with the tetrahedron problem ourselves.

00:31:36 Actually, this is not, although I believe this to be

00:31:40 the first authentic tetrahedron derivative,

00:31:44 it's not the first that has been reported.

00:31:48 In fact, another substance was reported a long time ago

00:31:56 in Britain by Jocelyn Field Thorpe

00:32:06 and Richard Moore Beasley.

00:32:09 It was not quite this substance.

00:32:12 It had the tetrahedron skeleton, their substance,

00:32:18 but methyl group here and carboxyl groups

00:32:22 at the other three positions.

00:32:27 That substance was first reported,

00:32:33 or preparation of that substance,

00:32:35 was first reported in 1913 by Beasley and Thorpe

00:32:40 in a note in the Proceedings of the Chemical Society.

00:32:45 It was in 1913.

00:32:50 Subsequently, a long paper was published.

00:32:59 The long paper, let's see, that's a much later paper.

00:33:09 If you'll be patient, I'll find when the later paper was.

00:33:19 Well, it was submitted in 1919, six years later.

00:33:30 I don't think it appeared, however.

00:33:33 There might have been some sensible referees in England.

00:33:40 Where does it appear?

00:33:50 Goodness, the Journal of the Chemical Society doesn't let you know.

00:33:54 You have to look on the back cover, you can't look on the page.

00:33:57 I think it was 1920 or 21.

00:34:00 All right, a long paper, detailed paper,

00:34:03 describing the preparation of this substance,

00:34:06 the tetrahedron derivative,

00:34:09 with a methyl group and three carboxyl groups.

00:34:13 Now, that became a famous, perhaps one might say a notorious paper.

00:34:22 And this tetrahedron derivative found itself,

00:34:26 made its way into the textbooks,

00:34:29 almost all of the standard organic textbooks

00:34:32 of the period from 1930 to 1950.

00:34:43 Now, I have to tell you a little chemistry here.

00:34:46 The way it was prepared, by Beasley and Philip,

00:34:49 was the following.

00:34:52 There's one of the carbons, that's the one at the top of the tetrahedron.

00:34:56 See, corresponding to that.

00:34:59 And then they had, we'll write a CH2

00:35:04 of an acetic acid chain here,

00:35:08 and another CH2 of an acetic acid chain here,

00:35:13 and another CH2 of an acetic acid chain here.

00:35:17 So you see, what we have is carbon with three acetic acid chains.

00:35:22 Now, what they did is treat that triacid

00:35:26 with the right amount of bromine and phosphorus pentobromide,

00:35:30 to replace hydrogen.

00:35:36 Here's another color here.

00:35:38 To replace the hydrogen on each of those CH2 groups

00:35:41 by a bromine atom.

00:35:44 You know, you just use the stoichiometric amount, and obligingly,

00:35:48 you put in a bromine there, and a bromine there,

00:35:51 and a bromine there.

00:35:54 And then you treat that with potassium hydroxide.

00:35:57 I'll have a little more to say about that in a little while.

00:36:00 You take out three moles of HBr, that's what you get.

00:36:05 In the pig's eye.

00:36:16 Now, that structure looked pretty strange to me

00:36:20 for some years, in spite of its firm embedment

00:36:24 in the textbook literature,

00:36:28 and this very long and detailed paper,

00:36:32 which I may say, by the way, has an eight-page addendum,

00:36:36 or appendix, or something of the kind,

00:36:40 written by Mr. C. K. Ingold.

00:36:45 Here's the first of the eight pages.

00:36:48 Now, that also is a very interesting part of this paper.

00:36:55 Mr. Ingold shows,

00:36:59 this is the theoretical chemistry,

00:37:02 Mr. Ingold shows that all this work of Beasley and Thorpe

00:37:06 is really very reasonable.

00:37:09 Purely by simple trigonometric methods,

00:37:13 he showed that if you made any two of these three rings,

00:37:17 which you could see here, four altogether,

00:37:20 but if you make any two of them, then the fourth one

00:37:23 will just close itself automatically.

00:37:27 There's a very beautiful trigonometric proof of that proposition here.

00:37:31 It's only eight pages long,

00:37:34 and the trigonometry is fairly simple.

00:37:37 Well, now, in about 1950 or so,

00:37:40 I managed to persuade Harold Larson

00:37:43 to repeat the experiments

00:37:46 that had been done by Beasley and Thorpe,

00:37:49 or to attempt to do so.

00:37:52 Now, that was an act of great bravery,

00:37:55 if not foolhardiness, on Harold Larson's part,

00:37:58 because,

00:38:01 just,

00:38:04 even on the face of it,

00:38:07 there are peculiar things about these papers.

00:38:10 If one looks at the 1913 paper,

00:38:14 we should have gotten separated better here,

00:38:19 I'm having a little clumperous problems.

00:38:22 But I'll get there,

00:38:25 and as Dudley told me,

00:38:28 I have plenty of time.

00:38:34 I will find that first paper,

00:38:37 because it is here.

00:38:40 I have confidence.

00:38:44 Good Lord.

00:38:55 Robert Robinson used to do this when he wanted to stall.

00:38:58 He didn't know what to say.

00:39:01 I'm not doing that. I know what I want to say.

00:39:04 I need to find this paper.

00:39:07 Ah, here it is.

00:39:10 I put it in a special place where I'd be sure to be able to find it.

00:39:13 Now, the first paper was a short communication.

00:39:16 There's a discrepancy, for example.

00:39:19 The substance is given as melting at

00:39:22 entirely different temperatures.

00:39:25 I won't bother to look for them,

00:39:28 50 degrees apart in the two papers.

00:39:31 So there was that discrepancy.

00:39:34 And then in this first preliminary communication,

00:39:37 the following statement.

00:39:40 The reaction is carried out by adding the bromoester,

00:39:43 that's that tribromoester,

00:39:46 to a very concentrated aqueous solution

00:39:49 of potassium hydroxide at 130 degrees.

00:39:52 The reaction is very violent.

00:39:55 But the more violent it is,

00:39:58 the better is the yield of the ring compound.

00:40:02 All right.

00:40:05 Now, that's the preliminary communication in 1913.

00:40:08 Now, the experimental part

00:40:11 of the detailed paper,

00:40:14 published in 1920 or so,

00:40:17 let me read you a bit from that.

00:40:25 I won't bother with the propaganda

00:40:29 which precedes this experimental description.

00:40:32 I'll just read the description.

00:40:35 60 grams of potassium hydroxide

00:40:38 are dissolved in 50 cubic centimeters of water.

00:40:45 Wait.

00:40:49 And the solution is evaporated

00:40:53 over the free flame

00:40:58 until it reaches a temperature of 150 degrees.

00:41:04 15 grams of the dibromoester

00:41:07 mixed with an equal volume of alcohol

00:41:13 are now added as quickly as possible.

00:41:23 Consistent with safety.

00:41:31 And the very vigorous reaction

00:41:34 is allowed to subside.

00:41:37 It is well to use a large flask

00:41:40 for this operation

00:41:43 as the reaction is almost explosive in its body.

00:41:46 And some of the material

00:41:49 is apt to be lost by spurting.

00:41:52 Well, that's really the best part of it.

00:41:55 But, you know, it does go on.

00:41:58 You get some acids out of this thing.

00:42:01 How do you get them out?

00:42:04 You take the well-dried mixture,

00:42:07 if there is any of it.

00:42:10 You grind it with an equal volume

00:42:13 of clean white sand.

00:42:16 And the ground is transferred

00:42:19 to a Soxhlet apparatus

00:42:22 and extracted with carefully dried and purified ether.

00:42:25 God, why would one bother?

00:42:28 Well, the ethereal extract on evaporation

00:42:31 yields the mesoacid or what have you.

00:42:34 We won't go on with that.

00:42:37 And you fool around some more.

00:42:40 You don't get it all out.

00:42:43 You have to mix it with a sufficient quantity

00:42:46 of acetic anhydride, either 220 degrees or 6.

00:42:49 Then you extract again.

00:42:52 Well, Harold Larson was mad enough to try all that.

00:42:55 Needless to say,

00:42:58 he never saw anything resembling

00:43:01 any one of the compounds

00:43:04 that had been reported by Beasley and Thorpe.

00:43:07 Now, while he was doing this,

00:43:10 Jocelyn Field Thorpe,

00:43:13 as many Englishmen had done and do,

00:43:16 not so much perhaps these days,

00:43:19 gravitated around various English universities,

00:43:22 Manchester, Sheffield, Imperial College,

00:43:25 working their way up slowly.

00:43:28 And so I had friends

00:43:31 in each of these places,

00:43:34 and I thought, well,

00:43:37 I wonder if it's possible that we could get any notes

00:43:40 or notebooks or samples

00:43:43 from any of these people

00:43:46 or just some information.

00:43:49 That line of investigation

00:43:52 drew a complete blank.

00:43:55 Absolutely nothing was to be had whatsoever.

00:43:58 No samples,

00:44:01 no notebooks, no notes,

00:44:04 no indication whatsoever of any kind

00:44:07 that any work of this kind had ever been done.

00:44:10 Now, you recall that Ingold

00:44:13 wrote an eight-page section of this paper.

00:44:16 So I thought perhaps

00:44:19 Ingold might be able to shed some light on the matter,

00:44:22 and I wrote to him.

00:44:25 And he replied as follows.

00:44:28 I'm sorry I cannot help about the Beasley and Thorpe compounds.

00:44:32 I remember Thorpe showing me a specimen of his cage compound

00:44:35 when I was an undergraduate,

00:44:38 but I never knew what happened to it.

00:44:41 Well, that was the end of that.

00:44:44 I did speak to him later, and he said the same thing.

00:44:47 Then I had an inspiration.

00:44:50 Where is Beasley?

00:44:55 I found him

00:44:58 in a fish club in Mexico City.

00:45:08 And I wrote to him then.

00:45:11 Of course, I apologized for intruding

00:45:14 upon memories so long past,

00:45:17 but explained our predicament

00:45:20 and said that although I didn't suppose

00:45:23 he would be able to help,

00:45:26 he would give us great delight if he could

00:45:29 in any way throw any light on what seemed to be

00:45:32 rather a difficult situation.

00:45:35 And I received from Beasley the following reply.

00:45:38 Dear Dr. Woodward,

00:45:41 this is the 7th of January, 1950.

00:45:48 Today I received your letter of the fourth.

00:45:51 I fear I can be

00:45:54 of little direct help to you.

00:45:57 After obtaining my MSc in 1913,

00:46:00 I was employed by Professor,

00:46:03 later Sir, J.F. Thorpe,

00:46:06 as his paid laboratory assistant,

00:46:09 first at Sheffield University

00:46:12 and later at the Imperial College of Science,

00:46:15 South Kensington.

00:46:18 Our association ceased

00:46:21 in the month of August, 1914

00:46:24 when he decided that I had not

00:46:27 the necessary academic mind

00:46:30 and I had the urge to go off to the wars.

00:46:33 Some of you perhaps

00:46:36 have heard of August, 1914.

00:46:39 I finally devoted myself to petroleum chemistry

00:46:42 in Mexico with no small measure of success,

00:46:45 thus justifying Thorpe's judgment

00:46:48 of my capacities.

00:46:51 Actually,

00:46:54 I had no idea that my name had been associated

00:46:57 with any publications of Thorpe

00:47:00 until

00:47:03 in the way of business

00:47:06 I purchased a copy of

00:47:09 The Principles of Motor Fuel Preparation and Application

00:47:12 by Nash and Howes, published by Chapman and Hall,

00:47:16 You must have obtained my name

00:47:19 from reports of the British Chemical Society

00:47:22 or my address from the register of the Royal Institute of Chemistry.

00:47:25 So far as I can remember at this late date,

00:47:28 the paper to which you refer

00:47:31 was published in the joint names of R.M. Beasley,

00:47:34 J.K. Ingold, and J.F. Thorpe.

00:47:37 Now, Ingold certainly has the academic mind.

00:47:40 In fact,

00:47:43 when I visited

00:47:46 the Imperial College of Science in 1916,

00:47:49 I found him sporting the uniform

00:47:52 of a full lieutenant in our old laboratory

00:47:55 whilst I was still a mere sergeant,

00:47:58 Royal Engineer's after 18 months service

00:48:01 on the fighting front.

00:48:04 Probably we were both in our proper places.

00:48:07 I'm sure Ingold can give you whatever information you may require

00:48:10 since, according to my latest information,

00:48:13 he is now Professor Christopher Kelk Ingold,

00:48:16 D.S.C., A.R.C.S., B.I.C., F.R.S., F.R.I.C.,

00:48:19 etc., etc.

00:48:22 In due course, I shall be glad to know

00:48:25 whether my suggestions have been of any use

00:48:28 in solving your difficulties.

00:48:31 Well, that was the end of the road.

00:48:34 Not quite the end of the road

00:48:37 Among Jocelyn Field Thorpe's

00:48:40 many interests and capacities

00:48:43 was a powerful interest in and belief in

00:48:46 spiritualism.

00:48:49 And his relic, Lady Thorpe, was still alive.

00:49:00 So I seriously considered getting in touch with Lady Thorpe,

00:49:03 but I decided it would be in bad taste.

00:49:07 And perhaps also I felt it might not be a very

00:49:10 profitable line of investigation.

00:49:13 So that was, in fact, the end of the story.

00:49:18 Now, where were we?

00:49:21 Oh, goodness.

00:49:25 Well, that old tetrahedron, of course,

00:49:28 should be expunged from literature, but I think the new one

00:49:31 is exciting and it's real.

00:49:34 Now, what are

00:49:37 some of the factors which have brought about

00:49:40 or accompanied the really fantastic

00:49:43 efflorescence of chemistry in the last 40 years?

00:49:48 There are many.

00:49:50 I would start with what you might

00:49:53 express in a single word, rationalization.

00:49:56 That is, the bringing of theory most broadly

00:49:59 defined into practice.

00:50:02 What that amounts to, you might say,

00:50:05 is a

00:50:08 extension of the

00:50:11 conceptual schemes which chemists use

00:50:14 and their application

00:50:17 to real experimental cases.

00:50:20 And that's going on. It has facilitated

00:50:23 the work of the chemist a great deal

00:50:26 and it continues to expand and

00:50:29 to make the science a more powerful one.

00:50:32 In addition to these,

00:50:35 what you might loosely call theoretical developments,

00:50:38 there have been

00:50:41 developments on the experimental side

00:50:44 of very great importance.

00:50:47 One of those is the introduction of physical methods

00:50:50 of all kinds

00:50:53 into chemistry.

00:50:56 I'm concentrating on organic chemistry.

00:50:59 That is perhaps not

00:51:02 unconnected with the fact that I know a bit more about

00:51:05 organic chemistry than some of the other branches.

00:51:08 In organic chemistry, certainly, the use of physical

00:51:11 methods has led to a

00:51:14 tremendous increase in the power

00:51:17 of the organic chemist to accomplish objectives

00:51:20 of all kinds.

00:51:23 To give a rough list,

00:51:26 we can take ultraviolet and visible

00:51:29 spectroscopy, infrared spectroscopy,

00:51:32 nuclear magnetic resonance spectroscopy,

00:51:35 and then, of course, the ultimate method,

00:51:38 x-ray crystallography.

00:51:41 In many of these areas, this department has

00:51:44 played a major role in bringing these things into

00:51:47 everyday use, and I think we can feel very pleased

00:51:50 about that.

00:51:53 The situation really has changed fabulously.

00:51:56 Some of those working with me right now,

00:51:59 as it happens in the last few weeks,

00:52:02 have by chance asked me what

00:52:05 chemistry was like in the old days, and really, you know,

00:52:08 they can't believe what it was like

00:52:11 when I, for example, began.

00:52:14 Just take a couple of

00:52:17 contrasting examples.

00:52:20 The determination of the structure of

00:52:23 strychnine involved work

00:52:26 by many groups, two extremely active ones,

00:52:29 over a period of 50 years.

00:52:32 It would certainly be a problem

00:52:35 which would be solved now in a matter of days

00:52:38 without any question whatsoever.

00:52:42 Without any question whatsoever.

00:52:47 I'll tell a story from my own past about

00:52:50 the synthesis of quinine.

00:52:53 Now, this is perhaps a bit of fun because

00:52:56 Max Tischler is here.

00:52:59 When we were attempting to synthesize quinine,

00:53:02 we had one step which involved

00:53:05 an elimination of a quaternary ammonium nitrogen

00:53:08 to give a double bond.

00:53:11 And that double bond might a priori have been in either of two positions.

00:53:14 One of them would have been an ethylidene position.

00:53:17 The other would have been a vinyl position.

00:53:20 We wanted the vinyl position.

00:53:23 The analogies which presented themselves suggested that we had the vinyl compound.

00:53:26 But how did we know?

00:53:29 How could we tell?

00:53:32 Any student today would give us the answer

00:53:35 to that question in not days, but seconds.

00:53:38 So easy in any number of ways.

00:53:41 In those days, there was only one way.

00:53:44 Do a Kuhn C-methyl analysis.

00:53:47 Oxidize it with chromic acid

00:53:50 and determine the acetic acid that's formed

00:53:53 if it's the ethylidene compound.

00:53:56 What a cumbersome way.

00:53:59 And in this department, we didn't have the facilities to do it.

00:54:02 We just said one acetic acid, the ethylidene compound.

00:54:05 What we wanted was the vinyl compound.

00:54:08 And we spent a couple of very, very unhappy weeks

00:54:11 until Max wrote us and told us that Merck had made a mistake.

00:54:14 They got some nitric acid there instead of acetic acid

00:54:17 and it was the vinyl compound.

00:54:20 So we were happy again.

00:54:23 But just think of the contrast between those days and now.

00:54:27 Pellipscomb told us

00:54:30 of how extremely powerful,

00:54:33 demonstrated to us,

00:54:36 how extremely powerful x-ray methods are.

00:54:39 And of course, he's played a great role

00:54:42 in making them more and more powerful.

00:54:45 They are in the organic chemistry of the kind that I do

00:54:48 now the ultimate weapon

00:54:51 because they don't involve arguments.

00:54:54 If you know the x-ray crystallographic structure, you know it.

00:54:57 You don't have to argue that the coupling constant is this or something,

00:55:00 or what have you.

00:55:03 And that is a relatively recent development.

00:55:06 I made a wager with Linus Pauling in the early 1950s

00:55:09 that I would determine the structure of terramycin

00:55:12 by chemical methods before anyone would do it

00:55:15 by crystallographic methods.

00:55:18 Now, I won the wager.

00:55:21 By the way, it may appear that I make wages casually,

00:55:24 but I don't.

00:55:27 I knew perfectly well that if I won that wager,

00:55:30 it would be the last one of that sort that I would win.

00:55:33 It was perfectly obvious even then

00:55:36 that x-ray methods would achieve the status that they now have.

00:55:39 An extremely powerful weapon.

00:55:42 Let me give you just one other example

00:55:45 of how the methods have advanced.

00:55:49 Just a short while ago, we were able to get

00:55:52 a C13, natural abundance C13,

00:55:57 spectrum on one milligram

00:56:00 of totally synthetic vitamin B12

00:56:03 at a molecular weight of about 1,500, I suppose.

00:56:08 It took 995,000 transients

00:56:13 collected over a period of four days.

00:56:17 Now, just think of the stability of that machine

00:56:20 that can do that, accomplish that task.

00:56:23 So we have these fantastic physical methods

00:56:26 available to us which enable us to do

00:56:29 in the twinkling of an eye things that would

00:56:32 before have taken many years.

00:56:35 And then, in the third group, I'll put separation methods.

00:56:38 We have now

00:56:41 tremendously powerful separation methods

00:56:45 which enable us, above all,

00:56:48 to carry out reactions on a relatively small scale

00:56:51 and still to know what we're doing

00:56:54 to separate the components of any reaction mixture

00:56:57 and then use these physical methods to find out

00:57:00 what those components are.

00:57:03 So these extremely powerful separation methods

00:57:06 have made it possible to do just incomparably more

00:57:09 than we could do in the old days.

00:57:15 There again, I'll just tell a story

00:57:18 to liven things up a bit.

00:57:22 Some of our early work was on the substance cantharidine.

00:57:25 Now, that's the active principle of the so-called

00:57:28 Spanish fly.

00:57:34 Now, people had been working on that for many years,

00:57:37 on cantharidine, and then when we looked at the old literature

00:57:40 we would find that people had taken 75 grams

00:57:43 of cantharidine, 500 grams of cantharidine,

00:57:46 boiled it with hydrobromic acid

00:57:49 in order to see what products were formed

00:57:52 in an attempt to determine what the structure was.

00:57:55 Just think of it, 500 grams of cantharidine.

00:57:58 There are many people who would think that would be an absolute tragedy,

00:58:01 realize that would be enough to keep the entire population

00:58:04 of Spain in a state of quasi-erotic excitement

00:58:07 for a period of a full year.

00:58:10 Period of a full year.

00:58:13 Here they're boiling it up with hydrobromic acid.

00:58:16 You see, you don't have to do that now.

00:58:19 You could do it on a couple of milligrams of cantharidine

00:58:22 and find out everything that they found out from the 500 grams.

00:58:30 Look, this has been a lot of fun, but Dudley said he wants

00:58:33 to do something at 5.30 and at 20 to 6. Thanks a lot.

00:58:40 APPLAUSE

00:59:10 Let me start with a few words of thanks

00:59:13 and then move on to apologies.

00:59:16 As you know from my letter,

00:59:19 I did not intend to speak.

00:59:22 I have something else prepared,

00:59:25 which I hope comes off in a few minutes.

00:59:28 But I did not intend to speak.

00:59:31 I have something else prepared,

00:59:34 which I hope comes off in a few minutes.

00:59:37 But with this opportunity,

00:59:40 I want to repeat the thanks

00:59:43 I expressed in the letter

00:59:46 to everyone involved in organizing this symposium.

00:59:49 Ed Wasserman, your president

00:59:52 and incredibly vigorous

00:59:55 and enterprising president.

00:59:58 APPLAUSE

01:00:08 Of the Association of Harvard Chemists,

01:00:11 who had the original idea

01:00:14 for this symposium.

01:00:17 He joined forces with Max Tischler,

01:00:20 who of course has long served Harvard

01:00:23 in many, many ways, and again

01:00:26 as our symposium chairman today.

01:00:29 The very many details

01:00:32 that had to be handled

01:00:35 were taken care of by Don Ciapponelli

01:00:38 and his team,

01:00:41 including our department secretary,

01:00:44 Teddy Lytle, and her assistant,

01:00:47 Michelle Thompson.

01:00:50 We all owe them very much thanks

01:00:53 for many things that are not as

01:00:56 readily seen to the naked eye

01:00:59 as some of the sights you've seen

01:01:02 and displayed today.

01:01:05 Finally, of course, we owe major thanks

01:01:08 to our speakers.

01:01:11 I think they conveyed more than science,

01:01:14 but also a great deal

01:01:17 of the marvelous spirit

01:01:20 that we cherish so much at Harvard.