(Hive Bee)
09-05-02 02:00
No 352950
      Get that double bond without borohydride
(Rated as: excellent)

This method is from Synthetic Communications, 15(6), 527-533 (1985). Its 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%
(Distinctive Doe)
09-05-02 05:54
No 352991
      More novel nitrostyrene to nitroalkane     

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 80C 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 - 160C), 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
(Distinctive Doe)
09-05-02 06:03
No 352994
      Another reference on the same reaction
(Rated as: excellent)

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
05-30-03 15:51
No 436658
      And this time with a microwave
(Rated as: excellent)

And this time with almost OTC chems and a microwave cool

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 (63-200m) 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. 188-190C 

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.

The candle that burns twice as bright burns half as long
06-01-03 19:42
No 437104
      thats very very nice... thankx...     

thats very very nice... thankx...
06-02-03 09:36
No 437252
      ... and now a practical application
(Rated as: excellent)

Ever mentioned that Lego has a weakness for Chinese journals? wink

A New Approach for Preparation of Various Phenylethylamines

Chinese Chemical Letters Vol. 11, No. 10, pp. 855-856, 2000

Fulltext as PDF (

Abstract: A new approach for preparation of various substituted phenylethylamines from the corresponding nitro compounds with iron powder and NH4Cl in 75% aqueous ethanol solution was developed.

Keywords: Phenylethylamines, nitro compounds, eduction, iron powder.

Phenylethylamines are important intermediates for many biologically active compounds.
As known, phenylethylamines can be obtained by reduction of phenylacetonitrile with Raney nickel or 10% Pd/C1, it also can be prepared from beta-nitro-styrene by hydrogenation under high hydrogen pressure1 or reduction with LiAlH42, borane with catalytic amount of NaBH43 and other methods4.
However, the limits of all above methods are high cost , high toxicity and the need of autoclave apparatus. Additionally, beta-nitro-phenylethanes can be  reduced to phenylethylamine by LiAlH4 , unfortunately, this method is not very attractive because of its high cost and inconvenient work-up. According to literatures, nitroarenes can be easily reduced into aromatic amines by various methods5,6,7. but fewer reagents can reduce aliphatic nitro compounds to the corresponding amines.

In this paper, we would like to report a new method to prepare phenylethylamines from aliphatic nitro compounds (Scheme 1). Beta-Nitro-styrene was reduced with PBI which formed in situ from benzaldehyde and o-phenylenediamine, to give beta-nitro-phenylethanes in high yield8 . 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. The advantages of our system are: the reaction was carried out in mild condition, the starting saturated nitro compounds can be purified by distillation in vacuum and the reagents are considerable cheaper.

Typical procedure for reduction of 4b: 35g (0.12 mol) of 4b , 34g (0.6 mol) of iron powder and 30g (0.6mol) of NH4Cl, 120 ml 75% aqueous ethanol were added by turns. The mixture was heated to reflux for 4 h and cooled to 20C, 20g of Na2CO3 was added , stirred for 0.5 h. The sludge was filtered off and the filtrate was evaporated to give brown solid. This solid was dissolved in 100 ml water and extracted with ethyl acetate 1504 ml, after drying, cooled over ice-bath, ethanol solution of hydrochloric acid was added dropwise to give white precipitate of hydrochloride salt of 4c . It was recrystalized from ethanol . m.p 173-174C9d . yield 79%.

In conclusion, a convenient method for synthesis of various substituted phenylethylamines via the beta-nitro-phenylethanes have been developed.

Table 1 The yields of phenylethylamines from the corresponding beta-nitro-phenylethanes
Entry R group m.p (C, HCl salt, ethanol) Yield(%)
1c 3,4-(CH3O)2 153-154 (154-155)9a 85
2c 3,4-OCH2O 208-210 (210-211)9a 82
3c 4-MeO 209-210 (211) 9a 83
4c 3-MeO-4-PhCH2O 173-174 (173-174)9d  79
5c 4-Cl 213-215 (215)9c 75
6c 2-Cl 202-203 (204)9b 78
7c 2-MeO 140-141 (141)9a 80

1. a) H. L. Finbeiner, J. Am. Chem. Soc. 1963, 85,616; b) D.P. Wagner, Synth. Commun. 1971, 1,47.
2. T. Kametani, K. Kigasawa, J. Chem. Soc. (C), 1971,2632.
3. M. S. Mourad, R.S. Varma, G.W. Kabalka, Synth.Commaun. 1984, 14,1099.
4. G.W. Kabalka, R.S. Varma, Tetrahedron Letter, 1990, 31,7443.
5. a) H.C. Brown, Tetrahedron, 1979,35,567; b) D. Seebach,, Chimia, 1979,33,1; c) R.C. Wade, J. Mol. Catalysis, 1983, 18,273; d) H.N. Borah, J. Chem. Research (S), 1994, 228; e) B.H. Han, Tetrahedron Letter, 1990,31,1181.
6. M. Petrini, R. Ballini, Synthesis, 1987,713.
7. S. Ram, R.E. Ehrenkaufer, Tetrahedron Letter, 1984, 25,3415.
8. H. Chikashita, S. Nishida, Bull. Chem. Soc. Japan. 1987,60(2), 737. Post 352994 (foxy2: "Another reference on the same reaction", Novel Discourse)
9. a) Dictionary of Organic Compounds, (Fith. Ed.), Chapman and Hall, New York; b) Beil, 12(3), 243; c) D.H.Hey, J. Chem. Soc., 1951, 1527; d) R.Tschesche, Tetrahedron, 1964, 20(6), 1435.

The candle that burns twice as bright burns half as long
(Hive Bee)
06-02-03 11:51
No 437277


What a find!

Great Lego!

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

Thank you man!laughwink

I cant believe it! so good! so nice!
(Hive Bee)
06-02-03 12:12
No 437280
      These nitro compounds were reduced with iron...     

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 smile!!!

And what a nice procedure smile, brilliant!

Lego, thank you girl, you 've just made my day smile.  I think you're going to receive alot of fan-mail for this reaction  -LOL smile
(Hive Addict)
06-02-03 13:09
No 437291

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..

Infinite Radiant Light - THKRA
(Hive Addict)
06-03-03 01:44
No 437443

shocked 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 50C 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.

(Hive Addict)
06-04-03 07:41
No 437773
      Bad yield     

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.

(Chief Bee)
06-04-03 14:05
No 437815
      Try again?     

Ouch... That is just a little bit over 20% yield, right? Will you try it on another substrate, known to be easier to reduce?
(Hive Addict)
06-05-03 01:18
No 437923
      That is a 14% overall yield only.     

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.

06-05-03 01:47
No 437927
      Where's the rest? Byproducts? Which?     

Where's the rest? Byproducts? Which?
(Hive Addict)
06-05-03 02:15
No 437937
      I don't know     

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.

06-05-03 07:39
No 437971
      No TLC data?     

No TLC data?
(Hive Addict)
06-05-03 07:44
No 437972
      I actually didn't bother :-o :-S     

I actually didn't bother blushcrazy

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.

(Chief Bee)
06-05-03 10:55
No 438016
      Oxalic acid against iron-stained glass     

Dilute aqueous oxalic acid makes cleaning iron-stained glassware much easier... (Mechanism: Post 294852 (Rhodium: "red rust", Stimulants))
(Hive Addict)
06-05-03 11:22
No 438028

Tell my buchner funnel about that. It seems to disagree wink
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.

06-06-03 08:35
No 438257
      Perhaps this will work better     

Barium, you are great! Thanks a lot for trying this synthesis! cool
You did Lego a great favour... wink

Lego is really sorry for your funnel crazy

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.......

The candle that burns twice as bright burns half as long
(Chief Bee)
06-06-03 15:22
No 438326
      Zinc/sulfuric acid for nitroalkanes     

Here they use Zn/H2SO4 to reduce a related nitroalkane in high yield: Post 438325 (Rhodium: "Norpseudoephedrine synthesis & optical resolution", Methods Discourse)
(Hive Addict)
06-08-03 07:06
No 438634

Mg, Al, Fe and Zn can all be used together with a acid to reduce nitroalkanes to aminoalkanes. The difference is the yield and the agony associated with the workup.

07-03-03 15:26
No 444306
      Formic acid and triethylamine
(Rated as: excellent)

In Chem. Pharm. Bull., 1979, 27(1), 198-203 ( the reduction of the double bond of phenylnitropropenes is described.

Formic acid reduction of beta-nitrostyrenes
General procedure

A mixture of Ia - f and 5.2 g (0.06 mol based on HCOOH) of TEAF in 40 ml of DMF was stirred at appropriate temperature. Dry air free from CO2 was introduced in order to check evolution of CO2 by saturated Ba(OH)2 solution. After CO2 evolution almost ceased, DMF and excess TEAF were destilled off under reduced pressure. The residue was dissolved in benzene. The benzene solution was washed with water and dried over anhyd. MgSO4. Evaporation of benzene under reduced pressure gave the crude reaction product. Recrystallization or distillation under reduced pressure gave pure reduction product. In the run with If, the production was purified was purified by passing through a basic column using benzene-ethyl acetate as an eluent. Physical and analytical data of the reduction products are summarized in Table III.

Yield for P2NP (phenylnitropropene): 70%, reaction time: 6.0 h, reaction temp: 120-122 C

Note: This will not work for nitrostyrenes!

Preparation of TEAF (adopted from Chem. Pharm. Bull., 1977, 25, 135-140):

A mixture of 80% formic acid and trialkylamine (triethylamine), roughly in the azeotropic molar properties, was carefully distilled under a reduced pressure. After removal of a lower boiling distillate, a fraction at constant higher boling temperature was collected. This distillate was dried over anhydrous MgSO4 an redistilled.

In the above reaction 5.2 g of the azeotrope are used, equal 0.06 mol HCOOH (2.76 g). Therefore 2,44 g of TEA should be added carefully to 2.76 g of pure formic acid or a solution in water containing 2.76 g of pure formic acid.

A formic acid:triethylamine 5:2 solution is commercially available.

The candle that burns twice as bright burns half as long
(Chief Bee)
07-03-03 18:45
No 444353

Great post!
(A Truly Remarkable HyperLab Bee)
04-14-04 10:17
No 500814
      reduction with Hantzsch ester/SiO2 (full article)
(Rated as: good read)

A Highly Chemoselective Reduction of Conjugated Nitro Olefins with Hantzsch Ester in the Presence of Silica Gel
M. Fujii
Bull. Chem. Soc. Jpn.
, 61, 4029-4035 (1988).

   An effective system to reduce conjugated nitro olefins into the corresponding nitroalkanes is described. The system composed of Hantzsch ester (HEH) and silica gel in benzene exerts high yield and excellent chemoselectivity under almost neutral conditions. Facile applications of the system to the syntheses of natural products are also described.

An earlier work by the same author is mentioned in
Post 352991 (foxy2: "More novel nitrostyrene to nitroalkane", Novel Discourse).