Max_Entropy
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Amination of Primary Alcohol
I am trying to synthesize nanoparticles
For this experiment i need to have an aliphatic (at least 10 carbons) terminating with an amino group as well as an amide
At the other end is a thiol
I was considering using SOCl2 to convert a COOH to a
C=O
\Cl
Then add NH3
I have not done too much research but if anyone has any ideas as to the methodology and conditions for the SOCl2
conversion
and the NH3 conditions, solvents etc
I would appreciate it
It looks like this
H-S-(CH2)10 -COOH
Then H-S-(CH2)10-C=O
\
Cl
So the final result is:
H-S-(CH2)10-C=O
\
NH2
Its an aliphatic and will have functional groups including the above
My question is how susceptable is the Thiol to any Nucleophilic Attacks SN2
via Ammonica
[Edited on 27-6-2005 by Max_Entropy]
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sparkgap
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You're gonna use ammonia? 
Try researching on phthalimide (Gabriel's the name  ) or azide; they are way
better to use in such syntheses.
The thiol linkage is quite labile; would you happen to have the structure of your molecule of interest so that we can answer your question better?
sparky (~_~)
[Edited on 27-6-2005 by sparkgap]
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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runlabrun
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Just explain a little better what your trying to do...?
You need to end up with a 10 carbon chain with terminating groups of one end a amine (NH2) and the other end a amide (CONH2) right? So you want this
->
NH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CONH2
Correct?
"At the other end is a thiol" ?
Oh do you mean the amine and the amide are on the same end carbon and the thiol is on the other end? Like ->
(NH2)(NH2OC)-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-SH
Which is correct???
And what you have is a starting unit with a carboxyl group (COOH) which your turning into your amide.
Ok using thionyl chloride you can convert to the acyl chloride, this must be totally water free or the prodcut will immediatly breakdown back to the
carboxyl and your thionyl chloride will decompose.
As for the NH3 addition you need to use anhydrous ammonia or sodium amide.
But in the first place, your making nanoparticles however "I have not done too much research"....? Anyway
-rlr
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sparkgap
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rlr, I'm hazarding that he has an omega-mercapto C<sub>10</sub> alpha-amino acid that he wants to turn into an amide.
Looks like it's time to use protecting groups...
sparky (~_~)
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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Max_Entropy
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Not Too much research
On the chemical rxn necessary to correctly complete this rxn.
So far it appears that either a gabriel syn or addition of ammonia (anhydrous) will do.
I would venture that this must be under basic conditions?
We don;t want any keto-enol tight-o-mers
(tautomers?) being teleological about this but can;t spell worth a crap.
Any further details?
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Nicodem
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The Gabriel synthesis is a method for preparing the primary amines and this has nothing to do with what you want.
You want an amide, don't you?
If you just desperatly want to use SOCl2 you will probably have to protect the -SH group (as sparky already said), the easiest way being by oxidazing
it to the disulphide (R-S-S-R). Then you should be able to prepare the acid chloride and quench it with aqueous ammonia. You will then have to reduce
the disulphide which makes it for a multistep reaction (I would personaly never choose such a route for a simple amide).
But you could skip the nasty SOCl2 and the unpredictabilities in its use on an mercaptane, by using alternative methods. You can esterify your
mercapto acid with MeOH and then ammonolize the ester.
Or you can use 2-3 equivalents of urea at 170°C for 3-4h (a single step to your amide, the fastest and most practical in my opinion).
PS: Why is the subject of this thread called "Amination of Primary Alcohol"?
[Edited on 27-6-2005 by Nicodem]
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unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
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Max_Entropy
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desparato
I don;t desperatly need to use thiolnyl chloride
The purpose of this forum is to exchange information for those of us who may not have a total grasp of the subject of chemistry.
I am open to suggestion (hence the post)
do you have a suggestion (specific to a substitute for the amination or conversion of a primary alcohol?
I need a method to change a COOH to an amide as well as to aminate a primary alcohol hence the title of this post.
Amination of a primary alcohol.
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runlabrun
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ok well i got on the wrong track...
COOH --> CONH2
COOH + SOCl2 --> COCl + SO2 + HCl
Acyl chlorides and thionyl chloride, as i said must be protected from water otherwise the prodcut will decompose. This reaction occurs at room
temperature, vent the produced SO2 and HCl vapours as they are obviously noxious.
COCl + NH3 --> CONH2 + HCl
The ammonia needs to be anhydrous so you dont cause decomposition of the acyl chloride. Vent the produced HCl vapours.
COH --> CNH2
Many paths..
Oxidation to aldehyde by PCC + Reductive amination to primary amine..
COH --> PCC --> CO --> RedAm --> CNH2
HBr gas to get the halide then hexamine with the depline reaction to get the primary amine (depline works well for primary halides only!)..
COH + HBr --> CBr + H2O
3CBr + Hexamine (urotropine, hexamethylenetetramine) --> Depline rxn --> CNH2 + other crap
Sorry to busy to remember how that one balances right now.. check google for info on the depline rxn.
-rlr
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sparkgap
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tss, tss, I must've been stoned yesterday; phthalimide and azide aren't good for your particular situation... sorry. 
With regards to making the amide, rlr already gave the textbook way of doing it. I will reiterate, protect the mercapto group before any fooling
around with that acid of yours.
With turning a primary alcohol into an amine, my original suggestion stands. Go look into azide or phthalimide. Your thionyl chloride should also come
in handy. 
BTW, you haven't shown us what your "primary alcohol" looks like, so maybe our suggestions might not apply directly.
sparky (~_~)
P.S. ASCII chemical structures are OK if you can pull them off, but maybe, just maybe, you can a) do line formulae, or b) attach an image containing
the structure of your substrate (there's a thread here on how to post pictures, search) instead, 'no?
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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Nicodem
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Try this, it is the simplest experiment that I could propose. Report back if it works:
Just heat one equivalent of your mercaptoacid with 3 molar equivalents of urea in a flask on oil bath heated at 170°C for 3 to 4h. Then dissolve the
reaction mixture in ethyl acetate, filter the off the solids, wash the filtrate twice with water, then twice with 5% NaHCO3*, brine, and dry over
MgSO4 (or Na2SO4). Remove the solvent in vacuum and you should have the crude amide (I don't know how pure you want it to have).
HS-(CH2)10-COOH + H2N-CO-NH2 ={170°C}=> HS-(CH2)10-CONH2 + NH3 + CO2
I only attempted a similar reaction once (with a very different aliphatic carboxylic acid) and it gave excellent results.
*Do not use any base stronger than NaHCO3 to wash the unreacted mercaptoacid out or you will remove the amide as well (mercaptanes, R-SH, have a
pKa=10 and are thus slightly acidic).
Runlabrun, the ammonia does not need to be anhydrous. NH3 is way more nucleophylic than H2O and acidchlorides thus react preferentially to amides with
aqueous ammonia. The hydrolysis is a way slower reaction.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Max_Entropy
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I seem to be.......
Unable to determine the time constant for a reduction from the c=o group (when I want to go from cooh to cnh2
if I use sodium borohydride or something else
the experiments I have planned would work better if I could do the following:
s-ch2)10- cooh --> s-ch2)10-c=o-nh2
---> c+oh-nh2
---> choh-cl-nh2
---> ch nh2
would like reduce the ketone to primary alcohol to amine
any suggestoins
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Nicodem
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OK, I give up and will say:
I don't understand what you are talking about. Please describe what is it that you want to do, what is your goal and how come you speak of
alcohols and ketones while you always have a carboxylic acid in your (often difficult to decifer) schemes.
Sorry for these complaints, but your last post got me so confused that I was beginning to think that all those who replied up to now, including me,
completely misunderstood your problem.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Kinetic
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Impossible Functional Groups
I suggest you do some background research before asking any more questions. Not only has you
initial question - at least the question I and others have read your post as asking - been answered and you have not acknowledged the fact, but your
latest post does not make sense. By the way your question is structured, it appears you do not really understand what you are asking. The functional
group 'choh-cl-nh2' can not exist (nor could the group CHOH-Cl-NH2, as you should have written it). Sodium borohydride would certainly not
turn COOH to CH2NH2 either.
If you want to turn you amide into an amine, then you will have to reduce it with a more powerful reducing agent. Try making the amide as Nicodem
suggested, then use lithium aluminium hydride or maybe NaBH4-H2SO4 to give the amine. But to be honest, your question does not make enough sense for
me to be sure if I have answered it or not.
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Max_Entropy
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THree two mini
Fair enough. My goal is to make nanoparticles with the following objectives:
varying ligand length and functional end groups
This is to complete my research for a tech conference where I will be presenting my results
the functional end groups FEG's must vary from electron withdrawing to electron donating
the scheme I have so far I use cooH to start and convert this to an amide then to an amine
the reason for this is to examine the chemical interactions from these FEG's
the question then is how to do the following sequence on one starting material i.e.
11 mercapto undecanoic acid
1) COOH
2) C=O
\
NH2
3) C-OH ---> CH
\ \
NH3 NH2
4) C-OH
eliminating the amine group
I can start with undecanol rather than the carboxylic acid
This would be far simpler? for me to make this sequence or order the undecanol
Its a simple question then if I can do this synthesis using just thionyl chloride and ammonia
the reducing agent I have on hand is borohydride
the questions pertaining to why use those is that I have a limited budget and a lead time for new chemicals that is longer than I prefer
So the suggestions I have received so far are useful.
The one thing that is usually missing are the exact details only one person here provided those.
I have seen many text books that discuss how to make a specific chemical and yet they leave out what solvents to use how long the rxn takes and more
iimportantly the conditions of state.
STP?
I read in one book to use thionyl chloride to halogenate a carboxylic acid but I saw no mention of what solvent and how to determine the end point
etc.
These are vital questions and the answers are more important and solvents can influence (no duh!!) the rxn .
Hopefully this last post will illuminate (whats nu , why lambda over c of course)
my objectives.
In line with my previous rant, I am in the process of making a nanoparticle with cooh end groups. the author of the paper did not provide any clues
as to how the rxn went, any details etc.
Again this can make or break any rxn.
What I have found is that significant amounts of research is/are required before partaking any chemical synthesis.
As this is part of my research to effect a solution, I find it comical that anyone would presume that this is the only research I am carrying out.
To those that have helped and especially them that provided details (times, temps, solvents etc) I am dutifully grateful and humbled.
thanks
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