The most interesting CTH reaction ever documented?

[Barium]

2-Nitro-1-(2,5-dimethoxyphenyl)ethanol

2,5-Dimethoxybenzaldehyde, 8,3 g (50 mmol)
Nitromethane, 3 ml (55 mmol)
Sodium hydroxide, 0,2 g (5 mmol)
Aliquat 336, 1,3 g (4 mmol)
Water, 100 ml
MeOH, 15 ml

The sodium hydroxide was dissolved in 100 ml water in a 250 ml beaker containing a magnetic stirbar followed by nitromethane, 2,5-dimethoxybenzaldehyde, and methanol. The finely powdered benzaldehyde started to form big lumps in the stirred solution. The PTC was added and stirring continued. Within one minute a clear yellow oil separated from the lumpy benzaldehyde. After about ten minutes of stirring the lumpy benzaldehyde was gone and the thick yellow oil covered the bottom of the beaker. As the stirring continued the oil solidified to a creamy-yellow solid over 5-10 minutes. The alkaline aqueous solution was removed by decantation, the solid washed with water until neutral, recrystallized from MeOH and dried to constant weight.

Yield: 9,1 g (40 mmol, 80%)


This was a test of the procedure found in J. O. C., vol 62, 425-427 (1997) which can be downloaded from a link on Rhodiums website. Thank you so much for the link.  


Currently another trial reaction is running with 50 mmol 2,5-dimethoxybenzaldehyde and 55 mmol nitroethane.This time with no MeOH added. Damn it, this reaction looks every bit as good as the previous one.  

[GC_MS]

This might be something interesting for you Ba:

Facile synthesis of 2-nitroalkanols by tetramethylguanidine (TMG)-catalyzed addition of primary nitroalkanes to aldehydes and alicyclic ketones

Daniele Simoni et al. Tetrahedron Lett 38(15) (1997) 2749-2752

Abstract - Tetramethylguanidine-catalyzed addition of primary nitroalkanes to aldehydes and alicyclic ketones constitutes a practical means to perform the nitro-aldol reaction (Henry reaction). The very mild conditions employed, together with the short reaction times, make the procedure tolerant of a range of functionalities and highly versatile for the synthesis of a variety of 2-nitroalkanols.

Nitroalkanes are versatile building blocks and intermediates in organic synthesis, primarly due to the ease of carbon-carbon bond forming reactions of derived species such as nitronate anions, silyl nitronates, and nitrile oxides (1-4). Among nitroalkanes, 2-nitroalkanols are particularly versatile intermediates for the synthesis of nitroalkenes, 2-aminoalcohols and alfa-nitroketones; (1-3) moreover, they are of importance because of their biological activity as fungicides. (5)
Classical preparation of 2-nitroalkanols involves base-catalyzed addition of a nitroalkane to a carbonyl compound (Henry reaction), the most widely used condensing agents being alkali and alkaline alkoxides in alcoholic solution. (2,6-9) Improved procedures have been recently introduced by Rosini et al. (9-10) who effected the addition of nitroalkanes to aliphatic aldehydes on an alumina surface, and by Wollenberg et al. (11) through a fluoride ion-catalyzed reaction of nitromethane to aliphatic aldehydes. However, these methods, although efficient, are not of general applicability, being generally limited to aliphatic aldehydes. Therefore, the development of new methodologies for the preparation of 2-nitroalkanols is very attractive owing to their synthetic value.
In this letter we report our preliminary results concerning the tetramethylguanidine(TMG)-catalyzed addition of nitroalkanes to aldehydes and ketones as a practical means to perform the nitro-aldol addition reaction. Our own previous observation of the ability of TMG to catalyze the Michael addition of nitromethane to alfa,beta-unsaturated carboxylic acid esters as well as alfa,beta-unsaturated ketones (12,13) [Scheme 1] suggested to us to extend its utility to bring about the nitroaldol addition reaction [Scheme 2].

[Scheme 1]

                                                   R1
R2--C==C--C==O                 TMG                 |
    |     |      +   MeNO2  ---------->  O2N--CH2--C--CH2--C==O
    R1    R3                 room temp             |       |
                                                   R2      R3

Hence, when an aldehyde (1 mmol) was solubilized at O C in nitromethane (10 mL) in the presence of a catlytic amount of TMG (two drops), the addition reaction took place smoothly giving rise to the 2-nitroalcohols in good yield (Table).(14) The reaction can be applied both to aromatic and aliphatic aldehydes simply through a slight modification of the reaction conditions (see times and temperatures in Table). Attempts to perform the reaction in organic solvents (i.e. dichloromethane, acetonitrile or toluene) in the presence of one equivalent of nitromethane, resulted in somewhat lower yields, the formation of the 1,3-dinitro derivative being concomitant. Moreover, when nitroethane was used, the nitro-aldol addition ocurred in good yields but without diastereoselectivity.

[Scheme 2]

                                                NO2 R2
                               TMG              |   |
R1--CH2--NO2 + R2--C==O ------------------> R1--CH--C--R3
                   |     room temperature           |
                   R3         or O C                OH
   [4]            [5]                            [6]

4a: R1=H
4b: R1=Me

On the other hand, the condensation of aliphatic as well as alicyclic ketones with primary nitroalkanes usually takes place in the presence of alkaline alkoxides in alcoholic solution. The use of aliphatic amines as catalysts has also been tried, resulting in the prevalent formation of 1,3-dinitro-paraffins or the nitroalkene derivatives (15). Furthermore, Lambert and Lowe (15) claimed the preparation of 2-nitroalkanols using triethylamine as the catalyst, without reporting any experimental detail. We observed that TMG catalyzes the Henry addition of nitromethane to cycloalkanones at room temperature producing good yield of the desired 2-nitroalkanols after the required time (see Table). Acetophenone failed to give condensation products, at least under these conditions, whereas the reaction of aliphatic ketones such as acetone, 2-butanone or 2-hexanone, resulted in somewhat lower yield possibly due to the preferential self-condensation reaction.
In summary, as shown in Table, the present methodology is particularly suitable using aldehydes and alicyclic ketones as substrates allowing an easy isolation of the desired adducts in excellent to good yields. Aromatic aldehydes gave the corresponding nitroalcohol derivatives as the only detectable products in good yields.
In conclusion, this method offers significant advantages over existing methods, especially in terms of milder reaction conditions, shorter reaction times, and that anhydrous solvents or reagents and inert atmosphere conditions are not required. Interestingly, the TMG-catalyzed addition of nitromethane to cyclohexanone afforded the corresponding nitroalchol in 71% yield, thus comparing very favourably with the methodology described in "Organic Syntheses".(16)
Finally, considering the ease of operation and the simplicity of workup of the developed methodology one may expect its widespread application for industrial purposes such as generating combinatorial 2-nitroalkanols libraries.

(note: only 'interesting' compounds shown)

1. Benzaldehyde + MeNO2 -> 94%, 30 min, 0 C
3. p-nitrobenzaldehyde + MeNO2 -> 97%, 15 min, O C
4. anisaldehyde + MeNO2 -> 73%, 60 min, O C
8. p-nitrobenzaldehyde + EtNO2 -> 88%, 15 min, O C (*)
9. anisaldehyde + EtNO2 -> 74%, 60 min, O C (*)

(*) no diastereoselectivity was observed.
Experimental procedure: a solution of 0.01 mol of the carbonyl compound in 10 mL of the primary nitroalkane was cooled at 0 C and then two drops of TMG were added. The reaction was allowed to stand at 0 C (or at r.t. in case of ketones) for the time indicated in the table, then it was diluted with brine, acidified with 5% HCl solution and extracted with EtOAc. The combined extracts were dried over anhydrous MgSO4 and after removing the solvent the pure 2-nitroalkanol was obtained by distillation or by flash chromatography.

- The END -

[Barium]

Thank you GC_MS. May I tempt you with this one;

Tetrahedron, 52, 1677-1684 (1996)

Nitroaldol (Henry) reaction catalyzed by Amberlyst A-21 as a far superior heterogenous catalyst

...We found that Amberlyst A-21 is far superior as general catalyst for the nitroaldol reaction [1], in fact it is possible to obtain beta-nitroalkanols in high yields (70-95%), by limited reaction times, and from a wide variety of starting materials. The Amberlyst A-21 avoids the dehydration of the 2-nitroalcohols into nitroalkenes even if aromatic aldehydes are used.
The reaction has been performed by adding 8-10 g of Amberlyst A-21 to 50 mmol of aldehyde and 50 mmol of nitroalkane, however, unlkie other methods the yields are substantially independent from the ratio catalyst/starting materials. It is important to point out that, after recycling, the catalyst can be reused withouta considerable loss of efficiency. Different solvents can be used (Et₂O, CH₂Cl₂, THF) without a substantial change of the yield.

By our method both primary and secondary nitroalkanes gives god results. Compared to other processes our procedure gives, generally, better yields. Moreover, this catalyst does not affect labile funtional groups and its mildness is demonstrated by the stablilty of the bromohydrin to epoxide formation, under basic conditions.

General procedure for the synthesis of nitroalcohols, without solvent.

A 100 ml two-necked flask equipped with a mechanical stirrer was charged with the nitro compound (30 mmol) and cooled with an ice-water bath. The aldehyde (30 mmol) was added, and the mixture was stirred for 15 minutes. Amberlyst A-21 (5-7 g) was added, and stirring cotinued for the right time. The Amberlyst was washed with CH₂Cl₂ (4 x 25 ml). The filtered extract was evaporated and the crude nitroalcohol was purified by chromatography or used as it is.

General procedure for the synthesis of nitroalcohols, with solvent.

The nitro compound (30 mmol) and the aldehyde (30 mmol) were added to the solvent (30 ml), then Amberlyst A-21 (5-7 g) was added and the mixture was magnetically stirred for the right time. After filtration the Amberlyst was washed with the solvent used and the extracts were evaporated. The crude nitroalcohol was purified as above.
[1] From J. Chem. Soc., Perkin Trans. 1, 107-110 (1999)
...The utilisation of Amberlyst A-21 proved to be not very efficient in our hands. Instead of Amberlyst A-21, Amberlite IRA-420 (OH-form) or DOWEX-1 (OH-form) can be used.
Barium´s voice In this article the authors first converted benzyl alcohol, p-MeO-benzyl alcohol, p-NO2-benzyl alcohol, p-F-benzyl alcohol and o-F-benzyl alcohol to the benzaldehydes by oxidation using polymer supported permanganate (PSM) [2], then the benzaldehydes were condesed with either nitromethane or nitroethene (a large excess of nitroalkane, serving as solvent and reagent, was used) to the corresponding beta-nitroalcohols using either Amberlite IRA-420 or DOWEX-1. Immediately after that the nitroalkenes were formed by esterifying the alcohols with trifluoroacetic acid in DCM, then the nitrostyrenes was formed by reaction with triethylamine.

[2] Polymer supported permanganate (PSM) was prepared by filtering an aqueous solution of potassium permanganate through Amberlyst A-27, subsequent washing of the obtined brick-red material with water and acetone and drying of the beads in vacuo.

Benzyl achohol --> benzaldehyde (95%) --> beta-nitrostyrene (27%)
p-MeO-Benzyl achohol --> p-MeO-benzaldehyde (95%) --> p-MeO-beta-nitrostyrene (23%), p-MeO-beta-methyl-beta-nitrostyrene (25%)
p-NO₂-Benzyl achohol --> p-NO₂-benzaldehyde (95%) --> p-NO₂-beta-nitrostyrene (45%), p-NO₂-beta-methyl-beta-nitrostyrene (77%)
p-F-Benzyl achohol --> p-F-benzaldehyde (95%) --> p-F-beta-nitrostyrene (60%)
o-F-Benzyl achohol --> o-F-benzaldehyde (95%) --> o-F-beta-nitrostyrene (65%)

No experimental procedures was given by the assholes  

[GC_MS]

Thanks for the 1996 Tetrahedron article. When I went up to the chemistry library, the whole year 1996 was *missing*. And as usual, the librarian had no idea what I was talking about...
The J Chem Soc Perkin Trans 1 (1999) article is nice as well, especially for smaller batches (i.e. if you want to organize a drug party with your friends    )

[gsus]

again from Kumar, but this time with the 2-nitroalcohol as product instead of nitroalkene. this is better than most of the above rxs on the basis of its speed and low cost of catalyst. no amberlyst or weird complexes here! the yield is only 75%.
  the reaction time is 5 minutes, there is no solvent and no side reactions, only unreacted precursors. the catalyst is silica.
  they use a fine SiO2 and mention "activation" but give no details. it would be interesting to compare results from ground-up sand, commercial SiO2, dried silica gel, ground-up diatomaceous earth, and SiO2 from home dehydration of homemade (from sand) silicic acid.
  the procedure isnt spelled out exactly step-by-step as some bees would want. what was added to what first? what was the exact size of the container? tough.
  equimolar amts. of benzaldehyde and nitroethane were adsorbed onto SiO2 in a test tube, placed in the microwave, and cooked for 5 min. (1min. pulses with 30 sec. rests) @ 600W. product extracted with DCM, which was evap'd and product chromatographed for isolation of the 2-nitro-1-phenyl-1-propanol in 75% yield:

SiO2 Catalyzed Henry Reaction: Microwave-Assisted Preparation of 2-nitroalcohols In Dry Media
by Kumar, Reddy, and Yadav

Chemistry Letters vol 27(7), 637-638 1998)

(http://www.jstage.jst.go.jp/article/cl/27/7/637/_pdf)

 makes you wonder what else is lurking out there for the experimenter, using things like sand instead of exotics.

[Rhodium]

I have used that procedure with 4-MeO-PhCHO/MeNO₂, and it is OK, but you need to separate the nitroalcohol from byproduct nitroalkene by column chromatography, which might be a hassle for some.

The size of the container or addition order aren't critical, as you adsorb the reactants on silica gel before putting it into the test tube. It is a waste of time trying to use sand/diatomaceous earth, as you really need to use fine silica gel (= activated SiO₂) for it to work.

[gsus]

thanks for the edit Rhodium, looks much better. my point about procedure was intended as a gentle flame after reading so many posts in lesser forums. about the various forms of 1000 mesh silica, pure, not, crystalline or not, we'll see. you never know for sure unless you try, even if others have. but the main thing- you find the article in error about the lack of side reactions in the real world on a real scale? guess so since thats what you said. someone should kindly volunteer to test this.
  in other words, is this article crap that should be flushed?

[Rhodium]

I merely stated that the nitroalkene invariably formed probably needs column chromatography to be removed. I'd guess that the amount of nitroalkene will not be as large if using less activated benzaldehydes (without methoxy groups).

[mellow]

[foxy2]

This will be the first illegal compound I've ever made if I succeed.

Great, But this board is not here to help you make illegal chemicals.  Its  just for theoretical information exchange.

[mellow]

Apologies, it was just a moment of misplaced bravado. I've never made any illegal compounds and I never intend to. I was just interested in finding out if these chemical reactions worked. I still am.

[Kinetic]

I'll assume for the sake of argument that you are going to try this method on an ephedrine analogue which will give a legal analogue.

A literature search gave no hits for the O-acetylation of ephedrine or phenylpropanolamine with acetic acid. Extending the search to other benzylic alcohols gave for 1-phenylethanol to O-acetyl-1-phenylethanol:

Cu(NO₃)₂*3H₂O/AcOH in 90% yield after 2 hours: Synth.Commun.; 28; 11; 1998; 1923-1934.

SiO₂/AcOH in DCM giving an 88% yield after 4 hours: Synth.Commun.; 26; 14; 1996; 2715-2722.

Sodium borohydride/AcOH at 85^oC - 90^oC for 3 hours (unspecified yield): Indian J.Chem.Sect.B; 19; 9; 1980; 822-823.


There were no refs for the sulfuric acid catalysed acetylation until the side chain had been further shortened to phenylmethanol, giving O-acetylphenylmethanol upon treatment with acetic acid/sulfuric acid. For this transformation see:

Justus Liebigs Ann. Chem.; 88; 1853; 130.

Patent DE529135

I don't know whether the absence of references for sulfuric acid catalysed acetylations on longer chains than that of phenylmethanol is an indication of potential dehydration or not, but since the process is an equilibrium when applied to ephedrine derivatives according to

Phenyl-2-propanone from Ephedrine Derivatives

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#ephedrine) then use of sulfuric acid shouldn't cause a problem. But that is by no means a certainty, and the only way you can be sure is by trying it out.

You don't need to separate the ester from the unreacted alcohol. Once the CTH reduction is over you will be left with any unacetylated ephedrine derivative, whose freebase is soluble in water, and the methamphetamine derivative whose freebase is not. The freebases of the products can also be separated by steam distillation; see

Steam volatility of methamphetamine, amphetamine and ephedrine

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/meth.ephedrine.steam.html).

Your assumption that the amino group won't react under the conditions for esterification is not entirely correct, and the side reactions caused by the presence of the amino group is in my opinion the biggest drawback of this otherwise excellent patent. You will notice that with the acetic anhydride/acetic acid O-acetylation used in the original patent that the hydrocholride salt of the phenylpropanolamine derivative is used and, even then, there is some amide formation. You will end up with a majority of O-acetylephedrine analogue, but there will be a small amount each of unreacted ephedrine analogue, N-acetylephedrine analogue, and N,O-diacetylephedrine analogue. Beginning from a vicinal aminoalcohol, as you are, there is probably no way to entirely control the acetylation, even when it is in the non-basic salt form. This is why it Barium got so excited about the possiblilty of acetylating the nitroalcohol, which can't form any acetylated byproduce. But then there is the serious threat of dehydration (for example

Post 395584

(Barium: "Oh my!", Novel Discourse)).

If you could instead make your nickel carbonate into nickel bromide, you could try the article posted above by Rhodium:

Nickel bromide as a hydrogen transfer catalyst

(https://www.thevespiary.org/rhodium/Rhodium/pdf/cth.nickelbromide.ipa.pdf), although the article doesn't mention whether the system reduces esters to the respective alkanes. With Raney-Nickel you could do worse than try the process in

Post 393077

(Rhodium: "(pseudo)Ephedrine to Meth w/ Raney-Nickel", Stimulants), which doesn't even require O-acetylation.

The patent in question uses ammonium formate, but sodium formate is a more powerful hydrogen donor. I plan on attempting a modification of this patent (for which I have my own set of questions), and I plan on using potassium formate. A better hydrogen donor should theoretically give better yields, but the problem in this case is the better hydrogen donor is also a stronger base, which may well lead to the acetyl group migrating from the oxygen to the nitrogen - in which case you'll end up with a good yield of pretty useless N-acetylephedrine analogue..

Good luck, and be sure to report back if you have any news.

[Kinetic]

The idea of O-acetylating the formed nitroalcohol to prevent N-acetylation is a clever one, as is the simultaneous CTH reduction of the O-acetyl and the nitro groups to give the amphetamine. It's unfortunate that under the conditions employed for acetylation, dehydration to the nitrostyrene is a major side-reaction.

If however an azidoalcohol is used, such as 2-azido-1-phenyl-1-propanol, the less electron withdrawing azido group will allow for O-acetylation without the risk of dehydration to the azidostyrene, overcoming this problem.

However, I cannot figure a way around the next potential problem. Assuming that the acetylated nitroalcohol is stable in the same way as the acetylated azidoalcohol is, it would seem both will suffer the same problem upon CTH reduction in any attempt to give the amphetamine.

As the nitro and azido groups reduce readily under the conditions, these will reduce first, leaving the O-acetylated phenylpropanolamine freebase. Even with the amine as its hydrochloride salt, as in the patent, only a very weak base such as the formate salt is sufficient to cause migration of the acetyl group to the nitrogen. This problem will be far worse with the acetylated PPA as freebase, which it will be as it is formed during the course of the reaction. Adding an equivalent of HCl at the beginning of the reaction will of course react with the formate salt instead. From the patent:

Ammonium formate appears to catalyze the rearrangement of O-acetylnorephedrine hydrochloride to N-acetylnorephedrine. Three samples of O-acetylnorephedrine hydrochloride (Experiment Z recrystallized) were stirred with water for six hours respectively at room temperature, at 60 degree C., and at 60 degree C. with ammonium formate added. [...] With the ammonium formate mixture at 60 degree C., the percentage of O-acetylnorephedrine hydrochloride dropped to 91.23% within 30 minutes and to 77.20% by 6 hours while the amount of N-acetylnorephedrine increased from 7.51% to 20.95%.

Is this problem surmountable, or should I instead think of brominating the azidohydrin to the azidobromide and then performing a one-pot CTH to the amine from there? Which will of course present its own potential problems of aziridine formation if nothing else.

The only thing I can think of is to exchange the formic acid salt for formic acid, to which an equivalent of HCl could be added. But I don't know what effect this will have on the yield. Before thinking of this problem I had my heart set on a yield of 90% for a beautiful one-pot reduction...

[Nicodem]

I see the problem, but I can't imagine how you can deal with it since formic acid works as a CTH hydrogen donor only as a formate anion (I think). That is in buffered conditions that lead to the O- to N-acetyl migration. I don’t know much on CTH but since this is so interesting I will let my imagination go wild so somebee can enjoy using his imagination to correct mine.

Maybe you can use a HCOOK/HCOOH acidic buffer? But I don’t know if it HCOOK would retain its CTH hydrogen donor properties.

Or maybe you can try using an O-formyl-ephedrine hydrochloride (from ephedrine×HCl in refluxing formic acid?) while first adding only a part of potassium formate (maybe 1/4 mol. equivalent). This would form some O-formyl-ephedrine formate (and KCl) which would hopefully bee a hydrogen donor as well as the substrate. The point is that once the reduction starts new formic acid would form neutralizing the basic amino group of the O-formyl-ephedrine or the amphetamine and again forming a hydrogen donor formate (thus replacing the consumed formic acid which lefts the reaction as CO2). I guess this could bee called autocatalysis but who knows if amphetamine can substitute for ammonia or potassium. At the end, while checking the pH, you can slowly add some more potassium formate to keep it going faster and to the end.
I hope I wrote this in an understandable form. The key point is that as soon as a formate anion is consumed a new one forms keeping the pH buffered at the only slightly acidic point due to the constant presence of some O-formyl-ephedrine/amphetamine hydrochloride.

Anyway, maybe it would be better to simply find a hydrogen donor that works in acidic medium. Maybe cyclohexene or tetraline?

Thinking of this I came to a crazy or stupid idea (still haven’t decided on that ) that probably isn’t even new. Why not hydrogen? (I don’t mean like bubbling H2, it wouldn’t be CTH anymore then.) I mean in situ formed hydrogen from a dissolving metal. Maybe strong acids like HCl would dissolve aluminum or zinc too vigorously, but formic or acetic acid should do well even at higher temperatures. This would prevent the problem of the O to N acetyl migration by allowing acidic conditions. However, recycling the catalyst might be more difficult (not impossible though). Does too much of Al or Zn salts poison the catalyst? Also, I don’t know how to classify such a system. Is it a dissolving metal reduction, CTH, or a hydrogenation?

[Barium]

I would try the reduction with 25-50% aq. HOAc as solvent. Voilá, great acidic solvent.

[Kinetic]

Thanks to both of you for your your replies; I have everything but the 1-(5-indanyl)-2-azidopropane to try this out. I'll give your suggestions a try once I get my hands on some.

While searching for acetylations, I found three references for the acetylation of nitroalcohols with acetic anhydride. The product in all cases is 1-acetoxy-2-nitro-1-phenylpropane:

J. Org Chem; 57; 18; 1992; 4912-4924, giving a 58% yield using acetic anhydride and DMAP in ether;

Bull Chem Soc Jpn; 61; 11; 1988; 4029-4036, using acetic anhydride and pyridine. No yield is given in the abstract;

J. Heterocycl Chem; 31; 4; 1994; 707-710 with acetic anhydride, sulfuric acid in DCM. Again, no yield was given in the abstract.

I should be able to get hold of any of the 3 articles if anyone is interested.

[Barium]

All three, pretty please.   

[Ganesha]

Can't get the others...

Inter- and intramolecular [4 + 2] cycloadditions of nitroalkenes with olefins. 2-Nitrostyrenes

Scott E. Denmark, Brenda S. Kesler, Young Choon Moon;

J. Org. Chem.; 1992; 57(18); 4912-4924.

[azole]

Bull Chem Soc Jpn; 61; 11; 1988; 4029-4036, using acetic anhydride and pyridine. No yield is given in the abstract


The article is now placed into an appropriate thread:

Post 500814

(azole: "reduction with Hantzsch ester/SiO2 (full article)", Novel Discourse).

   Indeed, acylation of an aliphatic nitro alcohol with Ac₂O/Py gave the acetate which was converted into nitroalkene (the target compound) without isolation.
   However, acetylation of nitroalcohols derived from aromatic aldehydes is hardly possible due to easy elimination. The product (nitroalkene) will be stabilized by conjugation with the aromatic ring. For examples of such elimination see

Post 369067

(Ritter: "reference", Novel Discourse)
and

Post 395584

(Barium: "Oh my!", Novel Discourse).

[Kinetic]

The interesting part of it, anyway - interesting being the operative word. The rest of the paper is on the use of the nitroacetates for substituted pyrrole syntheses.

The authors use the method with a number of starting aldehydes. Benzaldehyde and p-chlorobenzaldehyde were the only aromatic aldehydes used. Nitroethane was used in the condensation in the case of both of these aldehydes.


Regioselective Synthesis of 5-Unsubstituted Benzyl Pyrrole-2-carboxylates from Benzyl Isocyanoacetate
Noboru Ono, Hiromi Katayama, Siho Nisyiyama and Takuji Ogawa
Journal of Heterocyclic Chemistry, 31, 707 (1994).


Abstract

A general synthesis of 5-unsubstituted benzyl pyrrole-2-carboxylates was developed based on the reaction of beta-nitroacetates with benzyl isocyanoacetate. The advantage of this route over other pyrrole syntheses was the regiochemical control of the substitution pattern on the pyrrole ring.


General Procedure for the Synthesis of Nitroalcohols and beta-Nitroacetate (2).

To a stirred solution of nitro compounds (10 mmoles) and aldehydes (10 mmoles) in 5 ml of tetrahydrofuran was added DBU (0.1 g) at 10-20°. The resulting mixture was stirred at room temperature for 5-10 hours depending on the substrates. The mixture was then diluted with ether and water. The organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine. The aqueous layers were back-extracted with diethyl ether, dried with magnesium sulfate, filtered, and concentrated in vacuo to afford oils. The crude nitroalcohols were taken up in dichloromethane and treated with acetic anhydride and sulfonic acid (0.1 g). After being stirred for 1-3 hours at room temperature, the reaction mixture was poured into water. The organic layer was washed with aqueous sodium hydrogencarbonate and then concentrated. Purification by short column chromatography (silica gel, hexane-ethyl acetate) gave 2 in 80-90% yield, which was used directly in the next step. Most of the compounds 2 are known except for 2i.

(DBU is 1,8-diazabicyclo[5.4.0]undec-7-ene)