06-11-02 08:08
No 319830
      Knoevenagel with various catalysts
(Rated as: excellent)

As you can see there is great many catalysts which can be employed in the Knoevenagel-Walter.

Benzaldehyde                      Nitroethane   n-butylamine      EtOH reflux         85%  Ref 1
Benzaldehyde                      Nitroethane   ethylenediamine   50 deg C            76%  Ref 2
4-OH-benzaldehyde              Nitromethane  anilline          100 deg C           79%  Ref 3
Piperonal                            Nitromethane  ethylamine        8-10 deg C          97%  Ref 4
Piperonal                            Nitroethane   ethylamine        20 deg C            87%  Ref 5
Piperonal                            Nitroethane   n-pentylamine     20 deg C            87%  Ref 5
Piperonal                            Nitroethane   methylamine       20 deg C            87%  Ref 5
3-MeO-benzaldehyde           Nitroethane   n-butylamine      EtOH reflux         54%  Ref 3
4-MeO-benzaldehyde           Nitroethane   ethylenediamine   80 deg C            100% Ref 2
4-MeO-benzaldehyde           Nitropropane  n-butylamine      EtOH reflux         90%  Ref 1
4-MeO-benzaldehyde         1-Nitrobutane   n-butylamine      EtOH reflux         90%  Ref 1
3-OH-4-MeO-benzaldehyde     Nitromethane  methylamine       0-20 deg C          80%  Ref 6
3-MeO-4-OH-benzaldehyde     Nitromethane  methylamine       20 deg C            81%  Ref 6
3-MeO-4-OH-benzaldehyde     Nitromethane  ethylenediamine   20 deg C            95%  Ref 2
3-MeO-4-OH-benzaldehyde     Nitroethane   methylamine       20 deg C            79%  Ref 5
3-MeO-4,5-MDO-benzaldehyde  Nitromethane  n-pentylamine     20 deg C            90%  Ref 8
3,5-diMeO-4-OH-benzaldehyde Nitromethane  methylamine       MeOH/20 deg C       97%  Ref 9
3,5-diMeO-4-EtO-benzaldehyde Nitromethane  NH4 acetate       MeOH reflux         65%  Ref 9
2,3,4,6-tetraMeO-benzaldehyde Nitromethane  NH4 acetate       MeOH reflux         93%  Ref 10

Ref 1  J. Org. Chem., 15, 8 (1950)
Ref 2  Zh. Prikl. Khim., 31, 663 (1958)
Ref 3  J. Am. Chem. Soc., 74, 4489 (1952)
Ref 4  J. Am. Chem. Soc., 73, 5556 (1951)
Ref 5  JOC., 16, 221 (1951)
Ref 6 J. Am. Chem. Soc., 72, 2781 (1950)
Ref 7 JOC. 16, 221 (1951)
Ref 8 J. Am. Chem. Soc., 71, 2211 (1949)
Ref 9 J. Am. Chem. Soc., 76, 5556 (1954)
Ref 10 JOC. 20, 104 (1955)
(Official Hive Translator)
06-11-02 09:40
No 319845

.......but why there's no mention of dialkylammonium salts?

Can they bee used as bases in this rxn? Can they not?

Antoncho's asking 'cause there's some guy who isn't Antoncho who has a practical interest in this rxn using dimethylammonium acetatesmile

BTW, Barium, congratulations w/your new title!wink Keep up the good workwink Your posts are quite interesting to read, shall i saywink

(Chief Bee)
06-11-02 09:44
No 319849
      Yes, dialkylammoniums can also be used, there are ...     

Yes, dialkylammoniums can also be used, there are MANY possible catalysts out there.

Are the aldimines true intermediates even in the one-pot syntheses, or does the amines simply act as a base?
06-11-02 09:46
No 319850
      Ill bet     

Thanks Antoncho..wink
Ive seen dimethylamine, diethylamine and triethylamine, as free bases and salts, be used as catalysts. Lets see if I have some of the references nearby. Ill post what I find.
(Chief Bee)
06-11-02 10:22
No 319858
      What is this about Knoevenagel-Walther?     

What is this about Knoevenagel-Walter? I thought this specific case of a Knoevenagel reaction (RNO2 + RCHO) was called "Henry reaction".
(Hive Addict)
06-11-02 10:43
No 319861
      google finds it all :)     

none of my oc books knows it under that name, but:

../rhodium /mda.dalcason.html:

"If the appropriate piperonals are available to react with nitroethane, the Knoevenagel-Walter condensation, will permit the synthesis of ring-substituted analogs [24,29] through nitropropene intermediates (Fig. 5). "
06-11-02 12:16
No 319881

Walter co-authored Ber 37 4502 (1904) with  Knoevenagel, in which it was first reported nitrostyrenes were obtained in good yield using amine catalysts smile
(Chief Bee)
06-11-02 12:24
No 319884
      Aha - and the "Henry Reaction" reference is from ...     

Aha - and the "Henry Reaction" reference is from where?
06-11-02 12:50
No 319891
      re-Henry reaction     

Henry reaction;Kamlet reaction.
L.Henry, Compt. rend. 120,1265 (18950; J. Kamlet, US. PAT. 2,151,517 (1939);C.A. 33,5003 (1939)
Formation of nitroalcohols by an aldol-type  condensation of nitroparaffins with aldehydes in the presence of base(Henry) or by the condensation of sodium salts of acinitroparaffins with the sodium bisulfite additon products of aldehydes in the presence of a trace of alkali or weak acid (Kamlet). widely used in the surar chemistry    Ref. Merck Index 9th edition  Organic Name reactions page 42[b]
06-11-02 17:30
No 319979
      Shulgin mentions performing this reaction on ...     

Shulgin mentions performing this reaction on piperonal with reactants in MeOH solution and aqueous NaOH as a base under the MDA entry, PiHKAL 100

Whether this would work well with other aldehydes is beyond me. 
(Chief Bee)
06-11-02 18:27
No 320001
      NaOH catalyzed condensation     

Here is a detailed description of such a procedure: ../rhodium /mdp2np.html
06-12-02 18:34
No 320535
      i like that one alot too Rhodium, any reason to ...     

i like that one alot too Rhodium, any reason to think it wouldn't work for nitromethane condensation as well?
(Chief Bee)
06-12-02 20:22
No 320567
(Rated as: excellent)

Vogel's "Practical Organic Chemistry" 5th Ed.p 1035-1036

Experiment 6.136 NITROSTYRENE

Ph-CHO + Me-NO2 -NaOH-> PhCH=CHNO2

Equip a 1500-ml three-necked flask with a thermometer, mechanical stirrer and a dropping funnel. Place 61 g (54 ml, 1 mol) of nitromethane (1), 106g (101 ml, 1 mol) of purified benzaldehyde and 200 ml of methanol in the flask and cool it with a mixture of ice and salt to about -10 C. Dissolve 42g of sodium hydroxide in 40-50 ml of water, cool and dilute to 100 ml with ice and water; place this cold solution in the dropping funnel. Add the sodium hydroxide solution, with vigorous stirring, to the nitromethane mixture at such a rate that the temperature is held at 10-15 C. Introduce the first few ml cautiously since, after a short induction period, the temperature may rise to 30C or higher; check the rise in temperature, if necessary, by adding a little crushed ice to the reaction mixture. A bulky white precipitate forms; if the mixture becomes so thick that stirring is difficult, add about 10 ml of methanol. After standing for about 15 minutes, add 700 ml of ice-water containing crushed ice; the temperature should be below 5C. Run the resulting cold solution immediately from a dropping funnel and with stirring into 500 ml of 4 M hydrochloric acid contained in a 3-litre flask; adjust the rate of addition so that the stream just fails to break into drops. A pale yellow crystalline precipitate separates almost as soon as the alkaline solution mixes with the acid. The solid settles to the bottom of the vessel when the stirrer is stopped. Decant most of the cloudy liquid layer, filter the residue by suction and wash it with water until free from chlorides. Transfer the solid to a beaker immersed in hot water; two layers form and on cooling again, the lower layer of nitrostyrene solidifies; pour off the upper water layer. Dissolve the crude nitrostyrene in 85 ml of hot ethanol. (CAUTION: nitrostyrene vapours are irritating to the nose and eyes, and the skin of the face is sensitive to the solid.) Filter through a hotwater funnel and cool until crystallisation is complete. The yield of pure nitrostyrene, m.p. 57-58C, is 125 g (85%).

Note 1: The commercial material may be redistilled and the fraction having b.p.100-102C collected.

Cognate preparations.


In a 250-ml round-bottomed flask mix 30g (0.20 mol) of 3,4-methylenedioxybenzaldehyde (piperonal), 13.4 g (0.22 mol) of nitromethane, 7.8 g (0.1 mol) of ammonium acetate and 50 ml of glacial acid. Attach a reflux condenser, and boil the mixture under gentle reflux for 1 hour. Pour the reaction mixture with stirring into a large excess of ice-water (about 1 litre). When all the ice has melted, filter off the crude product under suction and recrystallise from a mixture of absolute ethanol and acetone (about 2:1 v/v). Almost pure yellow crystals of the nitrostyrene, m.p. 161 C, are obtained. The yield is 23.3 g (60%). Further recrystallisation from the same solvent yields the pure compound, m.p. 162C.


Follow the above procedure, but use 33.2g (0.20 mol) of 2,4-dimethoxybenzaldehyde as the starting material. The yield of recrystallised product (yellow crystals, m.p. 103C) is 28.5 g (68%). Further recrystallisation gives pure product of m.p. 105C.
(Chief Bee)
06-13-02 15:16
No 320904
      2,5-Dimethoxynitrostyrene w/ NaOH catalyst
(Rated as: excellent)

JOC 52, 2945-2947 (1987)

A mixture of 2,5-dimethoxybenzaldehyde (1.97 g, 11.8 mmol) and nitromethane (0.72 g, 11.8 mmol) in methanol (200 mL) was stirred at room temperature until the solids dissolved. The solution was cooled to 0C and a 10.5 M NaOH solution (2 mL) was added dropwise over 20 min. The alkaline solution was added slowly to a 4% HCl solution (200 mL) maintained at 60C. The pale yellow amorphous solid that formed was filtered and washed with water (200 mL). The crude product was recrystallized from absolute ethanol to give yellow needles (2.11 g, 85%).
mp 121-123C; IR 3100, 1620, 1500, 1351 cm-1; 1H NMR (CDCl3) δ 7.9 (dd, J=14 Hz, 2 H), 6.88 (d, J=3 Hz, 3 H), 3.85 (s, 3 H), and 3.75 (s, 3 H).

Preparation of 10.5 M NaOH: Dissolve 10.5g sodium hydroxide under cooling in 20ml water, and after cooling dilute the solution to exactly 25ml.
(Chief Bee)
05-13-04 16:50
No 506995
      Knoevenagel's first Nitrostyrene article
(Rated as: good read)

Condensation aliphatischer Nitrokrper mit aromatischen Aldehyden durch organische Basen
E. Knoevenagel & L. Walter
Chem. Ber. 37, 4502-4510 (1904) (../rhodium/pdf /knoevenagel.condensation.pdf)

The first article on nitroalkene preparation with amine catalysts, by Mr. Knoevenagel himself. Among the examples, the alkylamine catalyzed condensation of nitroethane with benzaldehyde (76%) and piperonal (80%) are described.

The Hive - Clandestine Chemists Without Borders
(Hive Addict)
05-13-04 22:52
No 507068
      Post 320904 06-13-02.     

Post 320904 (Rhodium: "2,5-Dimethoxynitrostyrene w/ NaOH catalyst", Methods Discourse)06-13-02. Has been added to mdp2np.html on the archive site but not in the 02-26-04 zip? I know your busy and all and maybe it's on your list of things to do for your next archive zip? In case it has been overlooked, I just thought I should point it out seeing as two years have gone by laugh.