Author Topic: Get that double bond without borohydride  (Read 3588 times)

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  • Guest
Get that double bond without borohydride
« on: September 05, 2002, 02:00:00 AM »
This method is from Synthetic Communications, 15(6), 527-533 (1985). It´s a weird one but it seems like it does the job.

An efficient method for the selective reduction of 2-aryl-1-nitroalkenes to 2-aryl-1-nitroalkanes by 2-phenylbenzimidazoline.

Recently we have reported that 2-phenylbenzimidazoline (PBI) prepared in situ from o-phenylenediamine and benzaldehyde was a good reducing agent for the reduction of alpha,beta-unsaturated dinitriles. Our interest in the selective reducing properties of this reagent promts us to study the capability of PBI for the reduction of 2-aryl-1-nitroalkenes. In this paper we wish to report the facile reduction of 2-aryl-1-nitroalkenes to the corresponding nitroalkanes without side reactions.
In order to optimize the reaction conditions, the reduction of beta-nitrostyrene with PBI was examined in a variety of solvents. The reduction with PBI was accelerated by the use of alcoholic solvent. However the refluxing in butanol gave best results in term of the rapidity, due to a rise of the reaction temperature. Thus, the reduction of various nitroalkenes were carried out with o-phenylenediamine and benzaldehyde in butanol at reflux temperature. The results are summarized in Table 1. Although the kind of aromatic substituent in nitroalkene influenced the rate of reduction, a variety of nitroalkenes employed here were reduced to the corresponding nitroalkanes in excellent yields.

In all cases carbon-carbon double bonds of nitroalkenes were reduced in complete selectivity and no formation of dimer or other by-products could be observed. In particular, the successful reduction of 3-nitrovinylindole to the corresponding nitroethylindole is of interest in conection with the synthesis of functionalized polycyclic indoles and natural products of ergoline class. The use of 1.2 equiv. of o-phenylenediamine and benzaldehyde was sufficient to conduct the reduction, and 2-phenylbenzimidazole formed by the reaction could be easily removed by filtration. An attempt to reduce 1-nitro-2-methylpropene with PBI under the the present conditions did not produce 1-nitro-2-methylpropane. This result suggests the present method may be limited to 2-aryl-1-nitroalkenes.


General procedure

To a stirred solution of beta-nitrostyrene (5 mmol) and benzaldehyde (0.64g, 6 mmol) in 25 ml butanol under nitrogen at room temperature, o-phenylenediamine (0.65g, 6 mmol) was added. After refluxing for the appropriate time (1 hour), the solvent was evaporated under reduced pressure. Methylene chloride (DCM) was added to the residue and insoluble 2-phenylbenzimidazole was filtered off. The methylene chloride solution was washed thoroughly with 0.1 N HCl and concentrated to give a crude product. The crude productc was purified by short column chromatography on sillica gel to give pure reduced product (2-aryl-1-nitroethane). In a large scale synthesis, the purification by distillation was also effective.

Substrate                           Reaction time           Yield  

beta-nitrostyrene                     1 h                     88%
p-NO2-beta-nitrostyrene           1 h                     91%
p-Cl-beta-nitrostyrene              1 h                     82%
p-Me-beta-nitrostyrene             3 h                     85%
p-MeO-beta-nitrostyrene           3 h                     93%
p-OH-beta-nitrostyrene             6 h                     78%
beta-methyl-beta-nitrostyrene    6 h                     91%
3,4-dimethoxy-beta-nitrostyrene  6 h                     84%


  • Guest
More novel nitrostyrene to nitroalkane
« Reply #1 on: September 05, 2002, 05:54:00 AM »
NAD(P)+-NAD(P)H model.  52.  Reduction of olefins by Hantzsch ester on silica gel.    
Nakamura, Kaoru; Fujii, Masayuki; Ohno, Atsuyoshi; Oka, Shinzaburo.
Tetrahedron Lett.  (1984),  25(36),  3983-6.

Olefinic double bonds in a,b-unsatd. carbonyl or nitro compds. are reduced chemoselectively by Hantzsch ester (I) on silica gel in excellent yields. 

In this letter, we wish to report that silica gel is such a good catalyst as to promote the reduction of carbon-carbon double bonds in simple a,B-un-saturated ketones and aldehydes or in a,b-unsaturated nitro compounds.

In a typical run, a mixture of 1 mmole of a substrate, 1.5 mmoles of 3,5-di-carboethoxy-2,6-dimethyl-1,4_dihydropyridine (Hantzsch ester, HEH), and 1 g of silica gel (5) in 15 mL of benzene was kept at 80°C for 17 hr under an argon atmosphere in the dark. Then, the solvent was evaporated from the reaction mixture and the residue was subjected either to a column chromatography on silica gel with an eluent of benzene-hexane mixture or to a preparative GLPC (PEG 20 m, 70 - 160°C), yielding the corresponding product. Results are summarized in the Table.

5) Silica gel was purchased from Nakarai Chem. Co. Ltd., (silica gel 60, 35-70 mesh).

beta-nitrostyrene  yield% 100 (84)

b) Determined on GLPC.
c) Numbers in parentheses are isolated yields after
column chromatography or preparative GLPC.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety


  • Guest
Another reference on the same reaction
« Reply #2 on: September 05, 2002, 06:03:00 AM »
In situ generation and synthetic application of 2-phenylbenzimidazoline to the selective reduction of carbon-carbon double bonds of electron-deficient olefins.
Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi.
Bull. Chem. Soc. Jpn.  (1987),  60(2),  737-46. 
In English.  

The title compd. (I), a mild, selective, and convenient reducing agent, was prepd. in situ from o-(H2N)2C6H4 and BzH in alcs.  A general method for the selective redn. of C-C double bonds of a variety of electron-deficient olefins with an alc. soln. of I is described.  The redn. of a,b-unsatd. ketones to the corresponding satd. ketones was accomplished less effectively with I and a Lewis-acid catalyst.  Condensation of 2-O2NC6H4CHO with 2-MeNHC6H4NH2 gave benzimidazoline II in 92% yield.  Redn. of PhCH:C(CN)2 with II gave PhCH2CH(CN)2 and benzimidazole III in 85 and 97% yields, resp.  This shows the validity of I to be the actual reducing species in the redn. system.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety


  • Guest
And this time with a microwave
« Reply #3 on: May 30, 2003, 03:51:00 PM »
And this time with almost OTC chems and a microwave  8)

The double bound of several substituted styrenes was reduced e.g. nitrostyrene to 2-phenylnitroethane in short times with good yields and cheap chemicals.

Hydrogen Transfer from Hantzsch 1,4-Dihydropyridines to
Carbon-Carbon Double Bonds under Microwave Irradiation

Molecules 2002, 7, 528-533


Abstract: 1,4-Dihydropyridines (DHPs) have been used in the reduction of carbon-carbon double bonds under microwave irradiation without solvent. The efficiency of the reactions is dramatically dependent on the steric effects in the DHPs and on the electronic effects in the olefins. [/b]

Microwave irradiations were performed in a Synthewave 402 Prolabo instrument (monomode) or in a Normatron Normandie-Labo oven (multimode). Silica gel 60 Merck (63-200µm) was used in the reduction of olefins.

Diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1a).
A mixture of ethyl acetoacetate (20 mmol), hexamethylenetetramine (8 mmol) and ammonium acetate (10mmol) is irradiated for 100s (45W, Synthewave S402). After cooling, the solid is filtered, washed with ethanol and dried under vacuum; m.p. 188-190°C 

Typical procedure for the reduction of olefins by DHP
Silica gel (4g), nitrostyrene (0.6g, 4 mmol) and DHP 1a (1.5g, 6 mmol) are diluted in methylene chloride (20 mL). The solvent is quickly evaporated in vacuo. The resulting solid is irradiated for 4 min (150W, Synthewave S402) under a nitrogen atmosphere, cooled and filtered. The filtrate is stirred for 20 min with 6N HCl (20 mL). The organic layer is dried on MgSO4 and concentrated in vacuum to afford 2-phenylnitroethane (yield 78%).

Lego's voice: All these methods mentioned in this thread offer a serious alternative to LAH reductions or hydrogenations of nitrostyrenes. In the second step the nitro group has to bee reduced with any method you can imagine to get the desired phenethylamine.


  • Guest
thats very very nice... thankx...
« Reply #4 on: June 01, 2003, 07:42:00 PM »
thats very very nice... thankx...


  • Guest
« Reply #5 on: June 02, 2003, 11:51:00 AM »

What a find!

Great Lego!

Truly excellent! 80% with iron!! No need of Pd/C anymore!  ;D

Thank you man! ;D  ;)

I cant believe it! so good! so nice!


  • Guest
These nitro compounds were reduced with iron...
« Reply #6 on: June 02, 2003, 12:12:00 PM »
These nitro compounds were reduced with iron powder and NH4Cl in aqueous ethanol to give the corresponding phenylethylamines in high yield. To our knowledge, the above approach to prepare phenylethylamine is not reported in the literature yet.

Indeed: WOW!!!

The iron / HCl reduction is commonly used to reduce aromatic nitro compounds.  Now, iron can also bee used to reduce aliphatic nitros.  This is simply fantastic  :) !!!

And what a nice procedure  :) , brilliant!

Lego, thank you girl, you 've just made my day  :) .  I think you're going to receive alot of fan-mail for this reaction  -LOL  :)


  • Guest
« Reply #7 on: June 02, 2003, 01:09:00 PM »
Wow! what an excellent find... this really opens up a whole new realm of possiblities...

 hmm lego your ratio of good karma to posts (18/37) is just about 50% ... amazing!! thx for all the excellent work..


  • Guest
« Reply #8 on: June 03, 2003, 01:44:00 AM »
:o  I think I just crapped my pants!! I told Rh some years ago that I was sure there was a way to reduce nitroalkanes to amines using Fe. Yieldwise I hope this method holds what it promise. Zn/NH4Cl sure doesn't.


A trial batch has been started now. Freshly made 100 mmol 2,5-dimethoxy-beta-nitrostyrene was reduced to the nitroalkane with aq sodium borohydride/Aliquat 336. The yield was as good as always.
The nitroalkane, Fe, and ammonium chloride was added to 100 ml 75% EtOH and reflux started.
As I write this the reaction has a few more hours to go. The reaction started at 50°C with the formation of black iron oxide thickening the reaction mixture considerably. I don't think reflux is necessary at all but I'll follow their directions during this trial.


  • Guest
Bad yield
« Reply #9 on: June 04, 2003, 07:41:00 AM »
The yield from last nights reduction was only 3g 2C-H*HCl. The workup was nasty, as all the metal reductions are. I'm not shooting this method down now. Only saying that it didn't give a good yield of 2C-H. The yield might be better with other PEA's.

If no Pd/C is avalible this method might be something to consider. But a CTH is preferable if the nitroalkane is already at hand.


  • Guest
Try again?
« Reply #10 on: June 04, 2003, 02:05:00 PM »
Ouch... That is just a little bit over 20% yield, right? Will you try it on another substrate, known to be easier to reduce?


  • Guest
That is a 14% overall yield only.
« Reply #11 on: June 05, 2003, 01:18:00 AM »
That is a 14% overall yield only. In comparison the sodium borohydride-PTC reduction followed by CTH gives more than 80% overall yield. I'll wait a while before I try it again with another substrate. I'm not looking forward to clean up another reaction vessel and buchner funnel from the post-reaction sludge.


  • Guest
Where's the rest? Byproducts? Which?
« Reply #12 on: June 05, 2003, 01:47:00 AM »
Where's the rest? Byproducts? Which?


  • Guest
I don't know
« Reply #13 on: June 05, 2003, 02:15:00 AM »
When my MS is up and running I can give you an answer. The crap stayed behind in the acidic wash, that much I know.


  • Guest
No TLC data?
« Reply #14 on: June 05, 2003, 07:39:00 AM »
No TLC data?


  • Guest
I actually didn't bother :-o :-S
« Reply #15 on: June 05, 2003, 07:44:00 AM »
I actually didn't bother  :-[  ::)

What I did though, was to divide the reaction in two equal volumes after 4 hours reflux. One worked up immediately and the other one allowed to reflux for another two hours (while the first portio was taken care of). They contained equal amounts of 2C-H, about 1.5g in each portion. So the extended reflux time didn't improve anything. With those results and the horrible workup I wasn't too keen on doing anything more at that point.


  • Guest
Oxalic acid against iron-stained glass
« Reply #16 on: June 05, 2003, 10:55:00 AM »
Dilute aqueous oxalic acid makes cleaning iron-stained glassware much easier... (Mechanism:

Post 294852 (missing)

(Rhodium: "red rust", Stimulants)


  • Guest
« Reply #17 on: June 05, 2003, 11:22:00 AM »
Tell my buchner funnel about that. It seems to disagree  ;)
The sludge is black iron oxide. Most of it goes away but enough remains, and refuses to fuck off, to make the funnel unattractive for amine HCl filtration in the future.


  • Guest
Perhaps this will work better
« Reply #18 on: June 06, 2003, 08:35:00 AM »
Barium, you are great! Thanks a lot for trying this synthesis!  8)
You did Lego a great favour...  ;)

Lego is really sorry for your funnel  ::)

Another visit in the library brought this information:

Tetrahedron Letters, 1982, 23(12), 1281-1284

15 was further reduced with NaBH4 in diglyme (0°, 1h) to a saturated nitro compound (16) in 65% yield, which was finally converted into 3-bromo tyramine p-methoxybenzyl ether (17), in almost quantitative yield, on treatment with Zn powder in dioxane containing AcOH (0-5°, 40 min).

15: 3-bromo-4-methoxy-(4-methoxyphenyl)-nitrostyrene

Unfortunately no experimental details and no references for this kind of reaction are given.

Perhaps 2 eq zinc powder carefully added to a cooled solution of acetic acid in dioxane and nitroalkane might work.......


  • Guest
Zinc/sulfuric acid for nitroalkanes
« Reply #19 on: June 06, 2003, 03:22:00 PM »
Here they use Zn/H2SO4 to reduce a related nitroalkane in high yield:

Post 438325

(Rhodium: "Norpseudoephedrine synthesis & optical resolution", Methods Discourse)