Tricky (Stranger)
03-29-02 13:43
No 289460
      Condensation  Bookmark   

Hi, bees!
Does somebody knows something about possibility of condensation rxn of Benzaldehyde and Acetonitrile???
A.f.a.i.k. it's something like this:
PhCHO + CH3CN __> PhCH=CH-CN + H2O
It's very interesting moment, because it may be new way to old 2cb cool

Matrix... may tricks?
03-29-02 15:20
No 289469
      I doubt it, strongly in fact.  Bookmark   

I doubt it, strongly in fact. Anyone knows that the nitrile group is electron withdrawing thus the methyl carbon wont be elctronegative enough to attack the carbonyl carbon. How's about benzyl bromide + KCN/ethanol.
(Distinctive Doe)
03-29-02 15:30
No 289475
      too many carbons  Bookmark   

even IF it did work, which it won't, you wouldn't get 2CB since there are too many carbons.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety
(Sector G)
03-29-02 15:42
No 289485
      Simple  Bookmark   

Benzyl bromide + sodium cyanide --> phenylacetonitrile + sodium bromide

PhCH2Br + NaCN --> PhCH2CN + NaBr


Vivent Longtemps La Ruche!
(Distinctive Doe)
03-29-02 15:51
No 289492
      Then  Bookmark   

Recycle the NaBr to brominate you 2CB

Those who give up essential liberties for temporary safety deserve neither liberty nor safety
03-29-02 16:05
No 289500
      NB! we need just 3-carbon chain !  Bookmark   

Because, I thinkin' about that:
1) 2,5DMPhCHO + CH3CN __> 2,5DMPhCH=CH-CN
2) 2,5DMPhCH=CH-CN __> 2,5DMPhCH2CH2CN (sim. red.)
3) 2,5DMPhCH2CH2CN __> 2,5DMCH2CH2CONH2 amid! (hydrolisis!)
4) 2,5DMCH2CH2CONH2 + NaOBr __> 2,5DMCH2CH2-N=C=O + NaBr + H2O
5) 2,5DMCH2CH2-N=C=O + NaOH   __> 2CH + Na2CO3

Matrix... may tricks?
(Sector G)
03-29-02 16:17
No 289502
      No, I don't think so....  Bookmark   

1.I'm not so sure this reaction will take place at all. I'm not 100% discounting it, but I personally doubt it.

2."Simple" reductions tailored to reduce the double bond will very likely reduce your nitrile (the CN) to an amine (-CH2-NH2)

3.Oxidation of the nitrile, followed by hydrolysis, would yield the carboxylic acid, COOH, not CONH2. This can be corrected by re-reacting with an amine-donating group to reform CONH2. (Or just don't do a reaction that involves hydrolysis in the first place)

4&5. I believe it was psychokitty that shot through my wanting to use this reaction for a very very similar purpose, if not the same, by showing that it has very low yields for this type of amide.

My personal advice? If you have the benzaldehyde, why go through all these steps when it's just a simple condensation with nitromethane to form the nitrostyrene, and a reduction of the nitrostyrene (easy remember?) forms the phenethylamine directly: 2C-H


Vivent Longtemps La Ruche!
03-29-02 18:22
No 289528
      Dreamin'  Bookmark   

Primo, I don't dare to make 2CB this method. It's all only for a sake of love to chemistry smile
I'm interesting in possibility of condensation, that's all. smile
By the way about hydrolysis of nitriles, I saw!!! the procedure, there amide was make directly from nitrile! I'll post it, as find.
And what about reduction. Hmmm, IMHO, double bond is more easy to reduce than the nitrile. But anyway, it's just theoretical chemistry and my fantasy smile
Best regards.

Matrix... may tricks?
(Official Hive Translator)
03-29-02 19:29
No 289541
      Electronegativity???  Bookmark   

Anyone knows that the nitrile group is electron withdrawing thus the methyl carbon wont be elctronegative enough to attack the carbonyl carbon.

Please, explain something to an ignorant!

I always thought that -NO2 group, as well as -CHO - was also electron-withdrawing... And both nitroalkanes and aldehydes condense w/ald's perfectly well...

Of course, that doesn't knit w/the fact that the carbon atom of -CHO IS electropositive and thus it would bee natural to assume one'd need smth nucleophyllic to attach it there...

Please, bear w/SWIM - he has very little knowledge of theoretic chemistryblush


03-29-02 20:52
No 289550
      (empty)  Bookmark   

Both nitriles and nitro compounds do react with carbonyls, provided they have alpha hydrogens, to give aldol products. But you cant just throw them in a pot and expect them to react together. Why? Because you have to abstract an acidic proton from the alpha carbon using the appropriate base. Therefore one needs a benchmark appreciation of relative pKa values.
(-)CH2-CN <-> CH2=CH=N(-)
(-)CH2-N+(=O)-O(-) <-> CH2=N+(-O(-))2
Nitromethane has  pKa = 10 and is a very suitable reagent for this reaction.
Now if spontaneous dehydration of the ‘aldol’ product occurs as we would expect to isolate this product Ar-CH=CH-NO2. Note that the double bond is conjugated with the aromatic ring. Reduction by either catalytic hydrogenation or some electrochemical reaction that I am not aware of could do the business for this second step.
(Hive Bee)
03-30-02 17:55
No 289892
      some remarks
(Rated as: excellent)

hi tricky,

otto likes your thoughts on phenethylamine-synthesis. further otto is pretty sure that most of the steps will work. drawback might be that the synth is somewhat lengthy.

to the 1. step:

it is possible. check out Tetrahedron Letters 1976, p 3495.

in a 200 ml RBF equipped w/ stirrer, reflux condenser and dropping funnel a mixture of 6.6g (0.1 mol) solid powdered 85% KOH, 80 ml freshly destilled acetonitrile and 2 ml aliquat 336 (PTC!) was added. after having reached reflux a solution of 0.1 mol of the aldehyde in 15 ml acetonitrile (fr. dest'd.) is added. reflux was maintained for additional 10 min. then, the solution was poored onto 200 g of crushed ice.
the product was extracted using 2 portions of DCM, the extracts dried over Na2SO4 and the solvent removed in vacuo.

yields of the corresponding cinnamonitriles (ArCH=CH-CN)

p-(CH3)2-C6H4-CHO               55%

piperonal                       45%

p-CH3O-C6H4-CHO                 30%

to the 2. step:

this can be done by catalytic hydrogenation using Pd/C at r.t. the nitrile won't be affected.

to the 3. step:

this is known to work too. it is normally done by reacting the nitrile w/ conc. H2SO4 at r.t. (then aqueous workup). otto has no idea though, how aromatic ether groups would behave under such conditions.

however, uemuras epoxidation procedure (acetonitrile/MeOH/H2O2/alkene) gives acetamide as a byproduct. thus the use of H2SO4 could be circumvent.
otto means: make a solution of your product from step 2 in MeOH, add an alkene and H2O2, each of the latter 1 mol per mol of nitrile to be hydrolyzed.

t the 4. and 5. step:

this is a one-pot reaction. it gives variing yields and is tricky.


1.2 mol Br2 is added to a solution of 6 mol NaOH in 2 l of water. this solution is then cooled to -5°C and 1 mol of the amide is added under stirring. the temp. should not exceed 40°C, otherwise cooling is applied.
the mixture is stirred overnight and the reaction then quenched w/ 20 g Na2SO3. then, the mixture is acidified to pH 2 under cooling, stirred for 15 min, and made basic again w/ 50% NaOH or KOH. the solution is extracted w/ ether, the etheral phase dried over Na2SO4 and then evaporated. the residue is destilled in vacuo.

yields of the amines from corresponding carboxylic acid amides:

acetamide to methylamine         70%

phenylacetamide to benzylamine   80%

this reaction can be found on rhodiums page too. just look for methylamine.

otto has some suggestions on the synthesis route, too. instead of acetonitrile one could use simple acetone giving the benzalacetone:


then catalytic reduction:


then schmidt-rearrangement:

Ar-CH2CH2COCH3 + NaN3 + H2SO4 -->

Ar-CH2CH2NHCOCH3 + N2 +  NaHSO4.

the resulting acetyl derivative of the corresponding phenethylamine must then only be hydrolyzed. otherwise one could do some chemistry to the aromatic ring while the amine is protected.

03-31-02 18:07
No 290395
      Thanx  Bookmark   

Thanx, alot, Otto smile
Method with acetone is even more interesting than with acethonitrile, but Sodium Azid... There can I get it???  frown
Thanx one more time. smile

Matrix... may tricks?
(Official Hive Translator)
03-31-02 21:11
No 290441
      This is absolutely astonishing!!!  Bookmark   

Otto, friend!

Or anyone who can help!

Can you give us some info (an exp. procedure would bee idealsmile) on this last step - Schmidt rearrangement?

This looks absolutely awesome!

(Hive Bee)
03-31-02 22:34
No 290459
      schmidt-rearrangement  Bookmark   

hi antoncho and everybody,

general procedure for schmidt-rearrangement:

in a 500 ml 3-necked RBF equipped w/ stirrer and reflux condenser w/ gas-exhaust a mixture of 0.1 mol carbonyle compound, 50 ml H2SO4 and 150 ml CHCl3 is made and cooled to r.t. to this mixture is added 0.12 mol NaN3 in small portions under intense stirring so that rxn doesn't become violent. after that the mixture is heated to 50 °C for 6 h. the mixture is then allowed to cool to r.t. and poored onto 400 g of crushed ice, intensely mixed and the CHCl3 -layer is separated.
the aqueous phase is neutralized using ammonia (cooling!). the amide seperates either as crystals which are filtered and recrystalized or as liquid, which is extracted using CHCl3. unified CHCl3-extracts are dried (MgSO4) and evaorated to give the product(the proc. is somewhat uncertain here, additional product? only for liquid products?), which is then vac-dest'd.


cyclopentanone    a-piperidone       60%

cyclohexanone     caprolactam        80%

acetophenone      acetanilide        97%

propiophenone     propionanilide     65%

benzophenone      benzanilide        80%

fluorenone        phenanthridone     90%

the product is the same as from the beckmann-rearrangement of the corresponding oxime. during the reaction highly poisonous HN3 may evolve. so make sure you have taken precautions (like running the reaction outdoor).

you may start from a carboxylic acid. then the reaction will give you amines, the workup has to be modified though.

instead of using azide a two step-procedure is imaginable: first haloform-reaction on the ketone (Ar-CH2CH2COCH3) to give the acid and then hofmann-degradation of the amide.
but otto is rather sceptic about its feasibility. to the 2 steps another one is necessary: formation of the amide. besides that hypohalogenites tend to halogenate activated aromatic systems in undesired manner. (o.k. if the 4-bromo is selectively introduced, still otto has his doubts)

so far

(Official Hive Translator)
04-01-02 07:23
No 290706
      Massive endorphine emission :)  Bookmark   

Thank you a lot! very cool!

Just to add a little tidbit to this, Patent US5208002 and Patent US5098597 describe a facile preparation of NaN3 from MeONO2 and hydrazine hydrate.

This is of course a somewhat lengthy route then the one already knownsmile, but its chemistry is simply awesome!smile I'm sure someday it will bee made use of.