Author Topic: Novel high-yielding C=C reduction of nitrostyrenes  (Read 35577 times)

0 Members and 1 Guest are viewing this topic.

GC_MS

  • Guest
Yield
« Reply #60 on: October 21, 2003, 03:11:00 PM »
Yes, that's sweet work  So you got a 56% yield in the end right? That's not to shabby all things taken in account.
So the final verdict is 2 molar borohydride per mole of substrate?


2 mol eq NaBH4? Yes.

Yield 56%? Not sure... Just take a look at the "impurity" DCM phase from B. There was quite alot of N-formyl-amphetamine. I don't think this should be simply neglected...  ;) .


starlight

  • Guest
great to have
« Reply #61 on: October 21, 2003, 04:26:00 PM »
GC_MS: great to have some objective measures of reaction performance under different conditions. Takes things further away from guesswork. Thanks for the effort that this entailed.

hest

  • Guest
Thank's
« Reply #62 on: October 21, 2003, 11:21:00 PM »
Nice work GCMS, I'll give thered with Pd/C and H2 or KOOCH a shot.

Bandil

  • Guest
Further tweaking
« Reply #63 on: October 23, 2003, 01:37:00 PM »
GC_MS>
When you say that the N-formyl-amphetamine should not be neglected, what precisely do you mean? Is it possible to salvage that somehow?

Also, where does the formylamphetamine come from? It it some sort of condensation reaction with amphetamine and formic acid? AFAIK formamide is formed at high temperatures from formic acid and ammonia. Could it be problem be that we are using IPA here, which allows the temperature to climb and thus allow the formation of the formylamphetamine?

Could it be an idea to tweak the reaction in the following way:
1: Use 2X borohydride(as you found out of course)
2: Perhaps use a bit less formic acid and keep the temperature in the range from 20-40 degrees, to avoid forming anything wrong?
3: Use potassionformate as they suggest in the original patent(we'll the use ammoniumformate, but AFAIK the potassium salt is a much better hydrogen donor). Maybe a less acidic envirnoment wont facilitate the formation of the formyl compound?

Think of how cool it could be to bring the yield of this reaction up on the side of LAH reductions. That would be close to revolutionary IMO  8)

Regards
Bandil


Rhodium

  • Guest
Alternative Explanation
« Reply #64 on: October 23, 2003, 03:22:00 PM »
N-[2-(1-phenylpropyl)]-ethylidenimine

Where the fuck does this come from?


I have seem Zn/formate catalyze retro-nitroaldol reactions before, giving the starting materials back, in this case benzaldehyde + nitroethane.

Formic acid most certainly is able to catalyze the reaction EtNO2 -> AcOH + NH2OH (see

Post 216169

(Rhodium: "R-CH2NO2 + Acid -> R-COOH + NH2OH", Chemistry Discourse)
)

The acetic acid is reduced to acetaldehyde, and then condenses with amphetamine. Result: N-[2-(1-phenylpropyl)]-ethylidenimine

However, there is something else that bothers me: amphetamine-benzaldehyde imine.

The benzaldehyde gotten in the retro-nitroaldol reaction also condenses with amphetamine. Result: amphetamine-benzaldehyde imine.

Bandil

  • Guest
Boosting yields
« Reply #65 on: October 31, 2003, 12:06:00 PM »
Since the major side reaction is the formation of the N-formyl amphetamine, how about just treating the whole lot like a pseudo-leuckart reaction?

After finished Zn reduction, most of the solvent could be stripped and then the residue mixed with some 15% hydrochloric acid and refluxed to two hours. Wont that hydrolyze the N-formyl compound?

Maybe thats the trick required to boost the yields further...

Regards
Bandil


eve

  • Guest
PTC
« Reply #66 on: October 31, 2003, 05:00:00 PM »
Sorry to bother, any other substitute PTC for the aliquat 336 ??

Bandil

  • Guest
No bother :-) But as you can read in the later
« Reply #67 on: November 01, 2003, 01:55:00 AM »
No bother  :)  But as you can read in the later in the thread, there is no need for a PTC at all...


Vitus_Verdegast

  • Guest
another PTC
« Reply #68 on: November 01, 2003, 05:51:00 PM »
SWIM has tried substituting the easily obtainable cetrimide (hexadecyltrimethylammonium bromide) for aliquat 336 in a water/DCM two-phase NaBH4 reduction of 2,5-dimethoxynitrostyrene, but only tar was obtained.

It might work for nitropropenes, though.


josef_k

  • Guest
Is there a possibility that you could use HCl...
« Reply #69 on: December 13, 2003, 02:11:00 AM »
Is there a possibility that you could use HCl instead of formic acid in the Zn reduction part of the method by bandil in this thread? Zn/HCl can reduce other nitro groups for example phenyl-2-nitropropanol. It would also avoid the formation of N-formylamphetamine.

GC_MS

  • Guest
Activated Zn
« Reply #70 on: December 17, 2003, 08:45:00 AM »
Although the Zn/HCOOH reduction involving inactivated Zn certainly works, I think it is more adventageous to use activated Zn.

Activated Zn is very reactive towards the added HCOOH. Adding HCOOH to Zn produces heat and lots of gas within a second. This is not the case for inactivated Zn. When you add HCOOH to inactivated Zn, it may be that no or little reaction is noted, resulting in adding more HCOOH. However, this will lead to a fountain making Trevi look like a pile of shit. The Zn starts reacting (after "in situ activation") with HCOOH "all the sudden" resulting in a reaction you don't have under control anymore.

It's a practical tip. If you doubt it, you are kindly invited to come to my lab for a cleaning session (interpretation of the latter depends on your gender).


Rhodium

  • Guest
Rh-catalyzed hydrogenation of nitroalkenes
« Reply #71 on: December 17, 2003, 11:22:00 PM »
Procedure for the Homogeneous Catalytic Hydrogenation of alpha,beta-Unsaturated Nitro Compounds using Triarylphosphine-Rhodium Complexes
Robert E. Harmon, Jack L. Parsons, and S. K. Gupta
Organic Preparations and Procedures 2(1), 25-27 (1970)

In recent years the homogeneous hydrogenation of carbon-carbon double bond in the presence of other reducible functional groups such as carboxylic acids, esters, aldehydes, ketones, nitriles, etc. has received increased attention1-5. The selective catalytic hydrogenation of an olefin in the presence of a nitro group is especially difficult. In this paper, we wish to describe a detailed procedure for the homogeneous hydrogenation of alpha,beta-unsaturated nitro compounds using tris(triphenylphosphine)chlororhodium(I) (1)1 and trichlorotris(4-biphenylyl-1-naphthylphenylphosphine)rhodium(III) (2)6. For instance, the hydrogenation of 3,4-methylenedioxy-ß-nitrostyrene (3) using the catalyst 1, afforded a 84% yield of 2-(3,4-methylenedioxyphenyl)-nitroethane (4). Similarly, the hydrogenation nitrostyrene (5) gave a 90% yield of 2-(2,5-dimethoxyphenyl)-2-nitropropane (6). Under identical reaction conditions (temperature 50°C, hydrogen gas pressure 80 psi, and reaction time 8 hr.), the catalyst 2 was found to be as effective as the well known Wilkinson's catalyst, 1.



Experimental

3,4-Methylenedioxy-ß-nitrostyrene (3) was prepared by the condensation of piperonal and nitromethane according to the procedure of Lange and Hambourger7. 2,5-Dimethoxy-ß-methyl-ß-nitrostyrene (5) is commercially available. Tris(triphenylphosphine)chlororhodium(I) was prepared by the reaction of an excess of triphenylphosphine with rhodium trichloride trihydrate according the procedure of Wilkinson and co-workers3. Trichlorotris(4-biphenylyl-1-naphthylphenylphosphine)rhodium(III) was prepared by the reaction of 4-biphenylyl-1-naphthylphenylphosphine with rhodium trichloride trihydrate2.

All solvents were deoxygenated by refluxing under a stream of argon for 3 hours, followed by storage under argon. Melting points were taken on a Thomas-Hoover melting point apparatus and are corrected. The hydrogenations were performed in a medium pressure hydrogenation apparatus.

The Hydrogenation of 3,4-methylenedioxy-ß-nitrostyrene (3)

The compound 3 (2.5 g, 13.0 mmol) and tris(triphenylphosphine)chlororhodium(I) (1) (0.40 g, 0.44 mmol) were dissolved in 300 ml of benzene under an argon atmosphere. The solution was transferred to the medium pressure reaction vessel and flushed with hydrogen gas 5 times. The reaction mixture was stirred for 9 hours at 60°C under a hydrogen gas pressure of 60 psi. After completion, the benzene was evaporated under reduced pressure. The oily residue was mixed with 50 ml of ethyl ether and filtered to remove the insoluble catalyst. The filtrate was evaporated to dryness. The residue was redissolved in ether, filtered, and the ether removed to give 2.1 g (84%) of 2-(3,4-methylenedioxyphenyl)-nitroethane (4), mp 53-54°C.   

The Hydrogenation of 2,5-Dimethoxy-ß-methyl-ß-nitrostyrene (5)

The compound (3.0 g, 13.4 mmol) and trichlorotris (4-biphenylyl-1-naphthylphenylphosphine)rhodium (III) (0.40 g, 0.29 mmol) were dissolved in 300 ml of benzene-ethanol (1:1) under an argon atmosphere. The resulting clear red solution was transferred to the reaction vessel and after flushing 5 times with hydrogen gas, stirred for 12 hours at 60°C under a hydrogen gas pressure of 100 psi. Then the solvent was removed under reduced pressure and the remaining oil vacuum distilled to give 2.7 g (90%) of 2-(2,5-dimethoxyphenyl)-2-methyl-nitroethane, bp 135-140°C (0.1 mm). 

References
[1] J. A. Osborn, F. H. Jardine, J. F. Young, and G. Wilkinson, J. Chem. Soc., A, 1711 (1966)
[2] A. J. Birch and K. A. M. Walder, J. Chem. Soc., C, 1894 (1966)
[3] C. Djerassi, J. Gutzwiller, J. Amer. Chem. Soc., 88, 4537 (1966)
[4] F. H. Jardine, J. A Osborn, and G. Wilkinson, J. Chem. Soc. A, 1574 (1967)
[5] A. S. Hussey and Y. Takeuchi, J. Amer. Chem. Soc., 21, 672 (1969)
[6] R. E. Harmon, J. L. Parsons, and S. K. Gupta, Organic Preparations and Procedures, this issue
[7] N. Lange and N. Hambourger, J. Amer. Chem. Soc., 53, 3865 (1931)


josef_k

  • Guest
I tried Bandils method, but I used 2 eq of...
« Reply #72 on: February 03, 2004, 04:36:00 PM »
I tried Bandils method, but I used 2 eq of NaBH4 instead. Otherwise to the letter. But I only got 1g amphetamine sulphate.

Then I instead tried GC_MS method B, but scaled up to use 80g phenyl-2-nitropropene, and I used only 6.66 eq of zinc. After I boiled down the solution after the zinc reduction I added some 20% HCl and refluxed for 2 hours to convert the N-formylamphetamine to amphetamine. But in the end I only got 9g amphetamine sulphate.

I can't understand why I get so lousy yields. In the last reaction my mag stirrer couldn't really keep up, so there was some unreacted zinc. But that wasn't an issue in the first reaction. Could it be some impurity in the IPA? Perhaps I used to little 10% HCl in the A/B? The NaBH4 is of general purpose grade from Fischer, but they usually make quality chemicals, so that shouldn't be the problem.

Anyone have any hints?

Bandil

  • Guest
I would like to try that particular reaction...
« Reply #73 on: February 04, 2004, 08:31:00 AM »
I would like to try that particular reaction with potassium formate instead of formic acid, as they seem to get higher yields in the original patent while using KHCOO. The reaction also runs less hot AFAIK, which might give this reaction an advantage.

But great initiative on trying to reflux in hydrochloric acid...

I'll post once i have tried the KCOOH scheme to see how that works in i comparison to!

Regards
Bandil


Rhodium

  • Guest
Not novel, but a classic reference
« Reply #74 on: March 03, 2004, 12:13:00 AM »
Silica Gel-Assisted Reduction of Nitrostyrenes to 2-Aryl-1-Nitroalkanes with Sodium Borohydride
Achintya K. Sinhababu and Ronald T. Borchardt

Tetrahedron Letters 24(3), 227-230 (1983)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ns.nabh4-silicagel.pdf)

Summary
Reduction of a variety of nitrostyrenes with sodium borohydride in the presence of silica gel in a mixture of chloroform and 2-propanol furnished the corresponding nitroalkanes free of dimers in near quantitative yields.


Rhodium

  • Guest
2,5-DMNS --Ru/H2--> 2C-H (95%)
« Reply #75 on: June 02, 2004, 01:22:00 AM »
Preparation of 2,5-dimethoxyphenylethylamine by liquid-liquid catalyst hydrogenation of 2-(2,5-dimethoxyphenyl)nitroethene
Shi, Ying; Du, Xi; Chen, Hua; Li, Xian-jun; Hu, Jia-yuan.
Faculty of Chemistry,  Sichuan University,  Chengdu,  Peop. Rep. China.
   
Shiyou Huagong 32(12), 1051-1054 (2003)
CODEN: SHHUE8  ISSN: 1000-8144.  Journal  written in Chinese. CAN 140:289167 AN 2004:38137

Abstract
2-Nitro-(2,5-Dimethoxyphenyl)ethene (I) and its hydrogenation product are widely used in fine chem. synthesis.  Catalytic performances of RuCl3 - TPPTS (P(C6H4SO3Na)3) as catalyst precursor for selective hydrogenation of both C=C and -NO2 groups in I had been studied in biphasic catalytic system (aq./org. phase).  After a long reaction time of about 20 h, conversion inctreased substantially and the selectivity for hydrogenation of both C=C and -NO2 groups increased.  Reaction conditions were: c(Ru) = 3 mmol/L, TPPTS/Ru mole ratio = 6, pH2 = 4.0 MPa and 90°C. Hydrogenation of arom. ring was not found (or did not occur).  Addn. of a surfactant (cetyltrimethylammonium bromide, CTAB) to the system obviously decreased the hydrogenation activity as welt as the selectivity for hydrogenation of both C=C and -NO2 groups although, in general, presence of the surfactant (CTAB) was known to increase hydrogenation activity.  Steric hindrance of the surfactant micells formed might possibly decrease the soly. of 2-(2,5-dimethoxyphenyl)nitroethene in biphasic catalytic system.  Under the best reaction conditions, the conversion of substrate reached 95.0%.  It was easy to sep. the hydrogenation product from the catalyst after the reaction.