Making a nitropropene with a Organohalide

[Vibrating_Lights]

Can 4bromo 2,5 dimethoxybenzyaldehyde be used with nitroethane. will the bromine react with the nitroethane at all.  And will the bromine be affected through a NaBH4/AlHg reduction?
VL_

[Rhodium]

2,5-Dimethoxy-4-Bromobenzaldehyde will indeed condense with nitroethane to form 2,5-Dimethoxy-4-Bromophenyl-2-nitropropene, and neither sodium borohydride or aluminum amalgam will dehalogenate it to any noticeable extent under normal conditions.

2,5-Dimethoxy-4-bromobenzaldehyde¹

2,5-Dimethoxybenzaldehyde (66.5 g, 0.4 mole) was dissolved in 300 ml of CH₂Cl₂. Anhyd SnCl₄ (115 g, 0.44 mole) was added, followed by 64 g of Br₂ over a 1-hr period. The resulting solution was refluxed for 2 hr arid stirred overnight at room temp. The orange suspension was poured over 500 g of ice, and the layers were separated. The CH₂Cl₂ layer was washed with 10% NaHCO₃ and H₂O and dried (Na₂SO₄). After filtration the solvent was removed in vacuo, and the solid residue recrystd from MeOH-H₂O to yield 64g (66%) of the aldehyde, mp 132-133°C.

1-(4-bromo-2,5-dimethoxyphenyl)-2-nitropropene¹

2,5-Dimethoxy-4-bromobenzaldehyde was refluxed with EtNO₂ and NH₄OAc in AcOH as described by Gairaud and Lappin² to give a 57% yield of 1-(4-bromo-2,5-dimethoxyphenyl)-2-nitropropene, mp 113.5-115°C.

Condensations with ammonium acetate in acetic acid²

The aldehyde (5g), 5 ml of the nitroalkane, and 2 g. of ammonium acetate were added to 20 ml of glacial acetic acid. The resulting solution was refluxed for two hours and then poured into ice-water. If a solid product was obtained it was collected and recrystallized from methanol, ethanol, or acetic acid. If the product was an oil it was separated and crystallized, if possible, from one of the above solvents.

References:
[1]

J. Med. Chem. 14(4), 370-372 (1971)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/nichols/nichols-bromomethoxyamphetamines.pdf)
[2]

Gairaud and Lappin,  JOC 18, 1 (1953)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitrostyrenes.gairaud-lappin.html)

[Vibrating_Lights]

How about Using MeOH/NaOH Nitroethane.  As in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdp2np.html

How would i put 100gms of the 4 bromo-2,5dimethoxyaldehyde into that synth.  I'm not to lazy to do it  I just dont have the equations.  Could one Methylate the 4 position of the benzyaldehyde with Methyl iodide or perhaps MeOH/H2SO4?   
VL_
Thanks VL

[Rhodium]

How about Using MeOH/NaOH Nitroethane.

Should work too.

How would i put 100gms of the 4 bromo-2,5dimethoxyaldehyde into that synth.

You calculate how many moles piperonal was used in that synthesis (the weight used divided with its molecular weight), then multiply with the molecular weight of 4-bromo-2,5-dimethoxybenzaldehyde. Then scale up all reagents X times so that the amount of 4-bromo-2,5-dimethoxybenzaldehyde arrives at 100g. It is however very foolish to run a 100g batch when the synthesis hasn't been tested on that particular aldehyde yet, so better make a 5-10g test batch first, then if everything goes all right, you can scale up.

Could one Methylate the 4 position of the benzyaldehyde with Methyl iodide or perhaps MeOH/H2SO4?

Yes, protect the carbonyl group by preparing the dimethyl acetal of 4-bromo-2,5-dimethoxybenzaldehyde as in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/345labrat.html

and then lithiate with BuLi and alkylate with MeI as in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2cbde.html

Workup with dilute HCl will hydrolyze the acetal and give 4-Methyl-2,5-dimethoxybenzaldehyde. MeOH/H2SO4 is of no use here though.

[wyndowlicker]

Just throw a dash of this,and a dash of that in there like you normally do VL!    

[Vibrating_Lights]

Dash of this and dash of that only works when you have done it so many times that you  cna weigh the dash in the palm of your hand.  Or when you know how far to spread your arms for 28gms off a rynolds roll.  Thanks Rhod  ALdehydes are the shit.  Can you think of any other examples online of NaOH and MeOH being used to make the nitropropene?  What is the name of that rxn that i would search for??

[Vibrating_Lights]

Re:


Yes, protect the carbonyl group by preparing the dimethyl acetal of 4-bromo-2,5-dimethoxybenzaldehyde as in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/345labrat.html

and then lithiate with BuLi and alkylate with MeI as in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2cbde.html

Workup with dilute HCl will hydrolyze the acetal and give 4-Methyl-2,5-dimethoxybenzaldehyde. MeOH/H2SO4 is of no use here though.
  

Can one protect the aldehyde with potassium bisulfite
FOr the methylation?
VL_ 
 

[Rhodium]

I have a very hard time believing that a bisulfite adduct would stand up to BuLi...

Making an acetal is very easy, either you reflux the aldehyde with trimethyl orthoformate (yields the dimethylacetal), or ethylene glycol and a catalytic amount of p-toluenesulfonic acid in toluene, while removing the water formed using a dean-stark trap (yields the ethylidene acetal).