nm0691: right when i finally find the relevant slides we can get going okay er 
we were talking are we sort of er the this lecture's being recorded for the 
benefit of mankind so er that's why there's an additional member of the 
audience the form round that's being passed around you should sign which will 
tell us which members of the audience that should be here aren't here er was 
everyone here b-, present when i talked about the exam structure i think most 
of you were if anyone ha-, wasn't present when i discussed the exam structure 
can you see me afterwards 'cause we haven't got a huge amount of time now er 
right let me just recap we were talking about rearrangements the migrating 
group going trans and it occurred to me that you hadn't followed it wholly er 
wholly understood what i was saying let's look at this because this is in your 
tutorial okay [laughter] cyclohexanol if you treat it with er in in in acid 
conditions dehydrating conditions you can get you 
will get the formation of a carbocathion but in actual fact what reacts in 
cyclohexanol in acidic solution is the two groups that are trans antiperiplanar 
to each other so the O-H has got to be pointing down the hydrogen's got to be 
pointing up and it does that and you get an elimination reaction right so 
elimination requires you remember from Dr namex's course or perhaps you don't 
[laughter] er there's was elimination the groups have to be trans 
antiperiplanar now in the case of this weird and wonderful decalin system that 
i showed you er we protonate that now i'm going to save time drawing it i'm 
going to protonate it up there now can we get elimination well the answer is no 
because n-, we need to have a hydrogen obviously we're going to eliminate H-two-
O we need to have a hydrogen in an antiperiplanar arrangement and that means 
that that in this case the ring 
can't flip as you probably recall decalin rings fused rings in general have 
very very little conformational freedom so this ring is fixed and it means it 
can't flip such that the O-H is pointing down in an axial position and so in 
this case you don't get elimination what you get rather is a migration so you 
form a cation and you get a group migrating this group here for example will 
migrate and the O-H will fall off in the normal way and and the product we 
eventually get is the eliminated product but now it's in actual fact that 
compound it seems a bit mysterious really but it's not all it all that we're 
saying is that the groups have to be trans antiperiplanar to each other in 
order to be able to er migrate okay in general rearrangements really come into 
their own in cyclic systems the cyclic systems are where you can get some good 
transformations in particular er you can form five and six member rings and 
you remember last week we were discussing the pinacol arrangement and we had 
two options with a with a one-two-cyclohexanediol depending on the er 
configuration of the diol at the start whether the O-Hs were trans or cis now 
this is a good one here and this is also in your tutorial it's also if i don't 
normally recommend colleagues' books only only my own should i happen to have 
one er [laughter] but Professor namex's little monogram on polar rearrangements 
has all the answers in because that's what i used to write the course before he 
came here even and so er it will have all the answers in it's probably not 
necessary to buy these things we did arrange to have all these Oxford primers 
in the library in the short loan collection so if you go over there you should 
be able to get hold of it but this is er a particularly good one because it b-, 
both of them give the same product oh-oh which i've have 
to draw out properly this spirocyclic compound perhaps i'll put in the er the 
wedge line here from the hash line at the back just to emphasize you see these 
are spiro compounds those spiro systems are are not necessarily very easy to 
form but you often find that rearrangements can give you that sort of unusual 
er cyclic arrangement the other the other type of reaction where you get some 
really strange cyclic compounds are photochemical reactions but it's outside of 
the scope of this series of lectures to talk about that now i'm going to put up 
some alternatives here i'll just er try and because i er i'll have to shut the 
curtains i think because i'm so kind to you and gave you the printed handout 
you don't need to copy this down it's also on the web and some of that's in 
colour and that was brought to my attention yesterday that i'd i'd write on 
this sheet things are blue 
when of course they're black and white but i couldn't afford colour 
photocopying to give to you all here we have some variations on a theme as it 
were and these are all what i would classify as semi-pinacol rearrangements 
right the driving force is always formation of a carbocation with a positive 
charge adjacent to the lone pair on the oxygens that's what causes u-, us to 
get this pinacol arrangement that's what's happening here indeed one of those O-
Hs is being lost and then a group is migrating i haven't put up the mechanism 
because i'm sure you will all be capable of doing that yourself now i hope so 
anyway right these are diols and and the er the classic pinacol arrangement is 
the rearrangement of a one-two-diol we can generate w-, there's a ready source 
of diols we can generate diols from v-, via the dimerization of er ketones 
dimerization of ketones using mediated by n-, normally magnesium magnesium and 
mercury or something 
like that would be suitable but we can also generate diols from alkene plus 
osmium tetroxide should we so desire and that that way we can actually get a f-,
er a handle on some unsymmetric diols there are other ways of producing diols 
of course osmium tetroxide always in cyclic systems gives you cis diols if you 
want trans diols then you can s-, also generate them from you can generate them 
from alkenes by epoxidization followed by er nucleophilic attack and ring 
opening with base so we we got a handle on diols there's there's plenty of them 
around so synthetically this has got enormous utility 
if you want to make that type of compound and and really the gist of what i'm 
i'm trying to get across is that in a-, in aliphatic systems i mean that's all 
very well ver-, very interesting but in cyclic systems you can often use this 
to change the way in which the ring looks now we're not restricted to diols we 
are we have this range of other systems which generate in the last case a 
similar in the other cases the same carbocation intermediate here so where we 
have an amine there we treat with nitrous acid and we diazotize we then lose 
the nitrogen as gas it's entropically driven it's a very rapid reaction you 
remember in in aliphatic systems at least so we lose the nitrogen and we 
generate the carbocation similarly we can ring open an epoxide with a Lewis 
acid lithium iodide for example ring open the expoxide and we will somehow 
magically 
presumably from solvent pick up a proton and we will l-, get once again a 
cation the same cation once again a Lewis acid and a alcohol halide the the 
silver m-, mops up the chloride silver c-, silver chloride being insoluble 
disappears from the the phase th-, from th-, from from availability as it were 
as a precipitate and we get this cation here proteination gives us the most 
stable driven by m-, Markovnikov's rules gives us the most stable cation right 
none of those cations exist very long er er they're all similiar cations but 
they don't exist very long because a group's going to migrate one of these 
groups is going to migrate depending on the migratory aptitude and we're going 
to get a cation there on this carbon which is adjacent to the lone pair on the 
oxygen which then delocalizes pumps electrons into the system and gives us a 
relatively stable cation okay is that does that make sense is everyone happy 
with that fine so these are all variations on a theme semi-pinacol type 
rearrangements and i have got a few more examples here and we we we we have to 
sort of rush through them i'm afraid once again this should be i'll just check 
yes it's in your handout so i-, probably i-, more likely to be correct if you 
just leave it with-, without copying it down once again these these are all 
semi-pinacol rearrangements nitrous acid diazonium cation once it falls off and 
we then get this group migrating round note it's the trans antiperiplanar 
arrangement that allows migration because yo-, th-, stress the antiperiplanar 
because of course these are actually in a trans arrangement aren't they but 
they're not in a suitable arrangement for migration so it's got to be this 
group here and that group there which are going to be are going to be the 
relevant er s-, have the relevant stereochemistry and of course we then get 
loss of a proton from the rearranged cation to give us a ketone 
so we've made converted a six member ring to a five member ring here we get two 
different stereochemistry in this case we've got s-, the O-H and the N-H-two-
cis and now we have the possibility of two conformations mediating the the 
process here we can have this one formations of a cation migrating group trans 
to the leaving group note the the the f-, the fact is and i must admit t-, 
confess to being slightly surprised or even baffled by this that that the the 
azo group falls off and it appears this group does migrate selectively even 
though we don't get any of this neighbouring group participation and and 
compare the aliphatic example based on er neopentyl cation that i gave you last 
week where where one got really a quite a mixture of products so so even though 
this is going to fall off very very quickly you'd still get this this trans 
group migrating and we get the same similar product to previously the same 
product but we've got this other 
conformational arrangement available here and in this case we now get migration 
and it's easier for the hydride to migrate because it's trans to the leaving 
group and so that's what happens and now we get a six member ring there of 
course if we get ring-flipping then we still are left with the the ring 
methylenes being trans to the leaving group so ring-flipping doesn't really 
matter there right now i have a huge range of other examples so right ring 
expansions it's a good way to make to get ring expansions or contractions to 
give us er er by using rearranged materials here we start with cyclo- hexanone 
we then react it with diazome-, with sorry with nitro-, nitromethane in base 
nitromethane of course is er is somewhat acidic so in base we form this highly 
delocalized anion have to be very careful with diazomethane in base and don't 
let it dry out of course because one interesting when i for my sins used to do 
E-S-R spectroscopy i er we used to 
use nitromethane as a s-, as a spin trap and if you shake the flask containing 
the nitromethane in the base you see a huge amount of radicals being produced 
in your E-S-R spectrometer from goodness knows what source but to me the 
production of radicals spontaneous-, er spontaneous-, spontaneously indicates 
something alarming could be happening and certainly is it says on the bottle 
that it is quite explosive that but that is a good er er a good nucleophile and 
it will react with cyclohexanone there to give us that alcohol which then we 
reduce er i really don't have to remind you the difficulties of making amines 
aliphatic amines you can't do it simply by er just er just whacking in ammonia 
and and doing a nucleophilic substitution type reaction because there's you get 
all these er quarternarized ammonium ions and that sort of thing so you this is 
a good way to do to to get an amine there we then we have that we then reduce 
it it would seem hydrogenation is the method of 
choice here and then we treat with nitrous acid to give us the n-, the the nit-,
the N-two falls off the cation the er the methylene group from the ring 
migrates and gives us the the ring-expanded product so we've got a seven member 
ring now alternatively we can use diazomethane right now we can get a migration 
but in actual fact we get two migrations happening we get one path gives us 
gives us cycloheptanone the other path is gives us that that epoxide ring in a 
spirocyclic system again of course you can then treat that with lithium iodide 
as we mentioned earlier and produce the cyclohexanone 
i guess the trick is somewhere in the the more basic conditions you use in the 
er diazomethane synthesis it seems to fall apart into sort of more more readily 
i guess would be would be the answer there's more i-, it's n-, there's not so 
much thermodynamic control of the product but the important point is that the 
root at which you do this does affect what products you get even though 
nominally you're getting the same intermediate there but of course the 
intermediates are being formed in a different way in one you f-, you generate 
the N-two-plus in highly acidic media in the other i it is it it is actually 
according to to my notes done in in acid but i guess it's not as quite as 
acidic as as previously another example right do you get that occurring no what 
you get is that exclusively gives us that exclusively right i think we should 
leave the semi-pinacol 
rearrangement there and move on rapidly to the Beckmann rearrangement and rel-, 
related analogues right i hope you're all happy with that idea of the semi-
pinacol rearrangement we've seen the pinacol rearrangement guided governed by 
the formation of this er highly stable cation adjacent to the oxygen we've seen 
that we can modify that using these semi-pinacol type system where the classic 
the best example is where we have an amine on the the adjacent group carbon 
rather than er an O-H and then we get rid of that by diazotization and you can 
see how one can use that particularly to form rings that wouldn't that are 
larger to form ring-expanded systems or ring-contracted systems depending on 
the precise conditions you use but you can change the ring size it's actually 
very useful to be able to form a cyclo-, er heptanone or a er seven member ring 
it's a good it's a good skill to le-, to have in our armoury as as synthetic 
chemists okay so it's useful to be able to know that these types of reactions 
lead us to seven member rings albeit with some complications particularly with 
the the diazomethane the diazomethane is a is a good is a really good reagent 
'cause you can buy it from Aldrich and so that means that you don't have to go 
through several steps and it means that that that it much quicker than the ste-,
the the the a-, the alternative methods i've shown you which require you to 
synthesize you know where does that come from well goodness only knows look at 
the look at the the m-, the the two steps you have to get to even to get to the 
amine in the first synthesis right so bit of a downer that you get a side 
product but you can convert the side product synthetic utility of semi-pinacol 
rearrangements and pinacol rearrangements it's particularly to my mind where 
you want to form larger rings okay right so summarizi-, i've summarize that as 
i always do after i've started the 
title of the next bit the Beckmann rearrangement like i say i d-, i don't like 
all these named reactions but it is helpful to have a title for a section and 
this is the rearrangement now to my ignorant poi-, er point of view the 
Beckmann rearrangement's the only sort of really big rac-, reaction of oximes 
of course in actual fact i will be hauled over the coals if i said that in the 
presence of so-, genuine synthetic chemists because they have all sorts of 
reactions and there's all sorts of chemistry of oximes that goes on but this is 
this is this is the biggie er perhaps i'm bias because this is the way that 
nylon is formed for example now what is the Beckmann rearrangement i'm just 
reminding myself ah yes an oxime there is an oxime now you can get an oxime 
from the reaction of a ketone with a hydro-, with hydroxyl xylamine ketone plus 
hydroxylamine goes to oxime so we have we would have our er 
normally we use hydroxylamine hydrochloride and buffer it with er sodium 
acetate just like your first year practical you remember the one that doesn't 
work well no [laughter] but well perhaps there are more of them that don't work 
but the one where you make the semi-carbazone and you were adding in buckets of 
sodium acetate and buckets of er semi-carbazone hydrochloride it's s-, very 
similar so you buffer it with sodium acetate easy to produce oximes now if 
you've got an oxime with a specific stereochemistry then like that then that's 
that's quite important because in fact the stereochemistry will follow through 
in the process what happens now we protonate we go to to that make that a good 
leaving group and that's going to fall off and as it falls off the group trans 
to the leaving group migrates so we're left with that horrible intermediate 
which then picks up water 
or i should say picks up hydroxide from water to give us that which then 
tautomerizes so the net result is we've generated an amide from our from from 
our oxime 
right now pay attention the group trans to the leaving group migrates if you 
get some of a mixture of material which doesn't contain just one group 
migrating it means either you started off with something of mixed 
stereochemistry or the system has somehow er isomerized in situ now this one 
for example let's show you what i mean oh sorry what am i doing C you get 
exclusively the phenyl group migrating but certainly there are there is some 
evidence to suggest that you w-, you might you get a trace of that where both 
groups are aliphatic particularly according to er March March being a 
particularly useful textbook for sort 
of detailed synthetic information so there but what's happening there well it's 
not possible that that that group can migrate it's not trans what happens is 
that you get H-plus and you can hydrolize the oxime back to the ketone and the 
hydroxylamine and then you reform it you reform it as the other isomer in 
actual fact you don't need to even go that far you don't need to go that far as 
soon as you protonate it then you you you y-, y-, if you protonate across here 
then you've got the option of the bond rotating of course but you're aware 
because you did this practical in the first year of the danger of adding H-plus 
to these sorts of derivati-, derivatives because they are it is a reversible 
reaction and i guess here the the exception to the rule is only because somehow 
you're getting some isomerization in the presence of the acid but on the whole 
the trans migration is a is a golden 
rule so we can we can we can stick to that now you could do you could do other 
things for example you can use s-, sorry P-C-L-five you use P-C-L-five in which 
case you get one of these inorganic you get that which is a really whizzo 
leaving group as it were because of course it's going to form the phosphorous-
oxygen double bond or you can make the tosylate or you can use boron 
trifluoride perit-, t-, er toluene sulf-, sulfinyl chloride forms a tosylate 
which also is a good leaving group as you remember the S-O-three-minus because 
para-toluenesulfonic acid is extremely acidic now the last point i wanted to 
make on the er sorry on the Beckmann rearrangement is nylon right epsilon 
caprolactam seven member ring formed from this oxime the oxime is of course 
produced from from that then we treat that with heat and er it can be acidic or 
basic conditions but largely heat and that polymerizes to form nylon-six the 
six is the number of carbons there in the monomer repeat unit nylon-six-six is 
where you have two monomers and that's the one that you may have seen the rope 
trick where you ra-, react adipoyl chloride with he-, hexane diamine but this 
is a commercial production of nylon epsilon caprolactam is a seven member ring 
formed from cyclohexanone and in nineteen-seventy-five this was a compound that 
was in the news when i was relatively young was most of you weren't even born i 
suspect er because it was the appr-, epsilon caprolactam plant at Flixborough 
that blew up creating certain amount of local rearrangement as it were 
[laughter] okay well i think we better finish there thank you for your attention