Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: jayashae on June 21, 2012, 11:50:15 AM
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Given 3 molescules: 1-chloropropane, 1-butyne, and a benzene ring, how do I synthesize 1-butyl-3-propylbenzene?
I'm not sure how to change the 1-chloropropane or 1-butyne to something that will not result in branched products. These 2 must be used to start.
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These 2 must be used to start.
Can you clarify this statement? Do you mean you must propose a synthesis like this:
ClPr + HC≡CEt :rarrow: A
A + PhH :rarrow: 1-butyl-3-propylbenzene
If so, it is either a ridiculous question or you don't mean 1-butyl-3-propylbenzene.
Start by drawing the product and look at the structure. For each carbon atom, or group of carbon atoms, think about which starting material each atom/group came from.
Your product has 13 carbons, and your starting materials have 3, 4 and 6.
Forget about reagents for the moment, think about how you need to clip your starting materials together to make the product. What bonds need to be formed?
Now think about how those bonds could be formed.
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(http://i.imgur.com/nhJL2.jpg)
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Ok, so "these two must be used to start" was not actually in the question. Good, so:
Start by drawing the product and look at the structure. For each carbon atom, or group of carbon atoms, think about which starting material each atom/group came from.
Your product has 13 carbons, and your starting materials have 3, 4 and 6.
Forget about reagents for the moment, think about how you need to clip your starting materials together to make the product. What bonds need to be formed?
Now think about how those bonds could be formed.
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the only way I can think of placing the chloropropane on there is by acylating o.o, but not sure how to do that given the chloropropane already.
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For the third time:
Forget about reagents for the moment, think about how you need to clip your starting materials together to make the product. What bonds need to be formed?
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not sure what you mean by what bonds need to be formed. As for how I should structure it, there needs to be meta-directors. I don't think I'm understanding your question, can you rephrase?
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sorry, I really need help on this :/
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Identify the new C-C bonds that need to be formed. Then think about which C-C bond forming reactions you could use.
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To the poster, this is what I think. Since the pieces required are given and they match the number of carbons in the product, you must do one or more functional group transformations in order to find chemical reactions that are compatible with the chemistry and regiochemistry of the product.
For example, 1-chloropropane can do a Friedel-Crafts alkylation of benzene, but it would give a lot of rearranged product. If the chloride were converted to an alcohol to a carboxylic acid to a acid chloride, it could be used in a F.-C. acylation. This would avoid rearrangement. Then further transformations would be required to convert a C=O to a CH2.
The question is, what functional group transformations are required to convert, either a CH of the benzene ring to couple with an acetylene or what functional group transformations would be required to allow coupling with the benzene ring?
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hmm, if I convert the acetylene to an alkane using metal-catalyzed hydrogenation and then applying the same concept to the deduced alkane with chlorination and follow same steps?
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hmm, if I convert the acetylene to an alkane using metal-catalyzed hydrogenation and then applying the same concept to the deduced alkane with chlorination and follow same steps?
It may be better to use the acetylene in a more useful way. Once it is reduced to an alkane it is effectively useless for further manipulation.
You may like to look up the Sonogashira coupling, although this may be a bit above your Org chem level at the moment.
http://en.wikipedia.org/wiki/Sonogashira_coupling.
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hmm, this is a sample problem I'm studying for an exam for tomorrow. I didn't learn that coupling and so I don't think it wouldn't be expected of us to know for solving this problem. So I guess it wouldn't be feasible to chloronate the alkane because the alkane would yield more secondary substituted. hmm, not sure where to go
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How would you synthesize propylbenzene from benzene and propanoic acid or butylbenzene from butanoic acid?
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from benzene to propylbenzene, I would have to somehow acylate the propane to be added to the benzene.
Ok my exam is tomorrow and I honestly don't know how to do this and won't know it in time if we're only doing Q&A. I need someone to teach me how to get a carbonyl group on that carbon with a chlorine, but I don't know the steps.
also, I'm pretty lost in term of the butyne as well, I can reduce it to an butane, but apparently thats of no help.
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actually for the chloropropane, i can do sn2 attack with an OH group and then use jones for the -COOH then into acid chloride and that would be set.
as for the butyne, I can reduce it to a butene, then I'm not sure how to further it
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Butyne: you can pretty much do the exact same thing you did with the chloroproane (convert it to the acid chloride ultimately). If you start with an oxymercuration step that would get you to 2-butanone. From there it's just 2 steps to the acid chloride.
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hmm, didn't learn the oxymercuration. but I can reduce the alkyne to an alkene through lindlar. then from the alkene do permanganate to form the COOH, then acid chloride and same steps.
would ths work?
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wait but even if i do get those 2 products, one product can't meta-direct an acylation because the beneze would be too deactivated...
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oh right totally missed the part about you wanting to make propylbenzene first
well, you need a meta director, which means you can't really get rid of the C=O group (yet), so keep it there after you do the FC acylation with propionic chloride, then brominate the aromatic to put a Br in the meta position
I'm not going to walk you through everything but suffice to say, you can form the last C-C bond via a Grignard reaction from the brominated aromatic and an aldehyde that could be derived from butyne
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you guys are making this way too complicated.
first, do NOT do an oxymercuration of the alkyne. this will give you a ketone, effectively making your butyne worthless.
you should instead do a hydroboration so you get butanal, which you can easily convert to an acid chloride by oxidixing with chromic acid and then treatment with SOCl2.
do a FCA with your new acid chloride and you'll have a meta directing, 4 carbon containing chain.
do a FCA with your chloropropane and you'll have your molecule with the carbonyl still in it, which can be easily gotten rid of by a wolff-kishner reduction.
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^actually it would take exactly the same number of steps had an oxymercuration been performed -- from 2-butanone you do a haloform reaction to get the carboxylic acid (granted probably not a great reaction), which would then get converted to the acid chloride
the issue with the route you suggested, is that FC acylations on deactivated aromatics tend not to work so great, which is where the roundabout synthesis came from. otherwise yes that would be the most straightforward way to do it
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you can't do a haloform on MEK because then your resulting acid only has 3 carbons and you're still stuck with how to add a 4 carbon chain to the benzene ring, which is why you have to use an anti-markovnikov addition of water to the triple bond.
but people are talking about converting chloropropane to an acid chloride which is completely unnecessary, adding a halogen to the phenyl ring to direct a specific way which is completely unnecessary, and trying to add a o,p-directing substituent first, which is just going backwards. we obviously need a m-directing substituent, and yes, even though you're deactivating your phenyl ring, it's better than killing your yield by going through 9.3784 steps to get to a product that isn't correct anyway.
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yes you're right about the butyne, my bad
the whole point about the chloroproane is to convert into into an m directing substituent
the problem with doing a straight FC alkylation with chloropropane after putting on the butanal fragment is that you will most certainly get the rearranged product (isopropyl) as the major isomer rather than the desired n-propyl chain, there's just no way around this and it'll end up being very messy.
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the problem with doing a straight FC alkylation with chloropropane after putting on the butanal fragment is that you will most certainly get the rearranged product (isopropyl) as the major isomer rather than the desired n-propyl chain, there's just no way around this and it'll end up being very messy.
Agreed. The most reliable-looking route I can see is to make propionyl chloride, F-C acylation, brominate, Sonogashira, reduce, reduce. I think it's 8 steps total.
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sure you're going to get some rearrangement, but this is also something coming out of an ochem 2 text, so...
but if you really want to do it that way, you should be iodinating, not brominating, and you only need one reduction step.
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sure you're going to get some rearrangement
I was taught is was mostly rearrangement rather than some rearrangement, but I may be mistaken.
but if you really want to do it that way, you should be iodinating, not brominating, and you only need one reduction step.
Why iodination? There is a large amount of literature addressing Sonogashira coupling with aryl bromides (and chlorides), which are easier to make than iodides.
What did you have in mind for the one step reduction?
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This is an interesting problem in that several functional group transformations are required for the overall transformation and the constant, predict the reactions for a class we did not attend. It looks as though a Sonogashira may have been discussed as a butyne is one of the starting materials, but 1-chloropropane was the other.
As the poster suggested, chloride to alcohol to acid to acid chloride to propiophenone is a plausible route.
This would be a route from there, and assuming Sonogashira was not covered.
Propiophenone to m-bromopropiophenone, Clemmensen reduction, magnesium to Grignard reagent.
Butyne + disiamylborane then NaOH/H2O2 to butyraldehyde. Add Grignard reagent to butyraldehyde and a catalytic hydrogenolysis or a second Clemmensen reduction.
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Sometimes simplicity is best. This looks like an undergraduate problem on the benzene and aromaticity chapters. Metal-catalyzed cross couplings would not have been covered at this point in the course.
Convert the [1] alkyne to an aldehyde via hydroboration-oxidation, [2] oxidize the aldehyde with Jones reagent, [3] convert to the acid chloride, then do the [4] Friedel-Crafts. The second step is a simple [5] Friedel-Crafts alkylation. Finally, finish it off with [6] a Clemenson Reduction.
When a prof looks at most of the problems in an undergraduate organic chemistry textbook, TONS of flaws can be spotted. There's always the possibility for rearrangements, especially with Friedel-Crafts. Most textbooks still give the primary attachment as the major product.
Check Vollhardt & Schore, Streitwieser & Heathcock.
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well would you look at that.
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sure you're going to get some rearrangement
I was taught is was mostly rearrangement rather than some rearrangement, but I may be mistaken.
but if you really want to do it that way, you should be iodinating, not brominating, and you only need one reduction step.
Why iodination? There is a large amount of literature addressing Sonogashira coupling with aryl bromides (and chlorides), which are easier to make than iodides.
What did you have in mind for the one step reduction?
iodine rate>bromine rate>chlorine rate and yields as well.
and for one step reduction all you have to do is catalytic hydrogenation. just don't use Rh or Ru or too excessive pressures/temperatures that you reduce the aromatic ring basically.
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and for one step reduction all you have to do is catalytic hydrogenation.
Sorry, I was being slow and forgot the alcohol after ketone hydrogenation is benzylic and will undergo hydrogenolysis.