I wrote detailed description of substituted nitrostyrene preparation for those who are interested in 2C type phenylethylamines and have some issues with this step (@Rabidreject) or want to increase yield and purity of this precursor.
** That is ~1.1 molar equivalent (~10% excess) of GAA relative to Ethylenediamine, as we need 2 moles for every mole of amine to get diacetate salt in situ. A bit excess necessary to guaranty full neutralization so there is no free amine left in the reaction mixture, as it will induce byproducts formation.
- NM (1.137 g/ml) => 4.4g / 1.137 = 3.87ml; 11g / 1.137 = 9.67ml
- EDA (0.9 g/ml) => 1.4g / 0.9 = 1.56ml
- GAA (1.05 g/ml) => 3.2g / 1.05 = 3.05ml
2) As you already noticed here is given wide range of Nitromethane to aldehyde ratio, it’s done intentionally to demonstrate reliability of this reaction, as excellent yields was achieved with as small as 1.2 equivalent (20% molar excess) of NM and remains stable within all that range, so if you have pure dry NM and it’s hard for you to get, do not take large excess, this EDDA catalyzed reaction will greatly save you both money and time.
3) If you get great yields with your current quality of precursors, next runs you can reduce catalyst load up to 2 times or even more, until it not affect your yields, for example take 0.3/0.675 eq. or 0.2/0.45 eq. of EDA and GAA respectively.
4) In case of methanol as a solvent, reaction rate is greatly increased, 5-10mins at 60°C is enough. This also can be attributed to the increased concentration of reactants, as aldehyde has greater solubility in MeOH. When dark red color is obtained, all aldehyde is mostly consumed. Holding it more at that temperatures after all aldehyde is reacted will decrease yield. Don’t use more solvent than necessary. But reflux condenser with water flowing in this case is a must.
Add 1.4g(1.6ml) of dry fuming EDA, then slowly 3.2g (3.1ml) of GAA (fumes), when everything become homogeneous add 4.4g (3.9ml) of NM and preferably attach reflux condenser (could be without water flow) and stir magnetically or swirl it from time to time by hand with gentle heating on water bath or hotplate so that internal temperature remains near 60°C* for up to 1h (5-10 mins for MeOH solvent). Cool down to RT, in most cases crystallization will occur, if not, try to scratch the inner walls with glass rod and place it in refrigerator for a few hours or overnight. Brake crystals in a still cold reaction mass with rod or spatula or by shaking/stirring, vacuum filter the nitrostyrene product (2,5-DMNS), wash with small amount of cold 1:1 v/v IPA:Water solution (or 1:2 v/v MeOH:Water) and air dry. Yields are up to 95% (12g, 1.2 w/w). M.P. after recrystallization is 118-120°C.**
* For convenience you can control just outer bath temperature, usually it should be 5-10°C higher, so hold it within 65-70°C.
** In most cases recrystallization is not necessary, but can be done from a minimum amount of hot IPA or IPA-Water solution.
If there is given enough time for crystals growth, you will obtain orange to orange-reddish thin crystalline material, sometimes reminiscent of glass wool, or just as a long needles.
WARNING: Skin irritant! Wear gloves, glasses and avoid dust of this product.
@Rabidreject, I wish you the best yields and waiting for your feedback.
trans-2,5-Dimethoxy-beta-nitrostyrene (2,5-Dimethoxynitrostyrene, 2,5-DMNS, CAS 40276-11-7)
Preliminary quality control:
Best yields of up to 95% in this reaction are achievable if the purity of precursors, especially aldehyde and NM are high enough.- 2,5-Dimethoxybenzaldehyde (2,5-DMBA) m.p. should be 50°C or close to that. If it was made by yourself or by other cook and m.p. value is far from that or you cannot achieve high yields, better purify it by high vacuum distillation or via bisulfite adduct, or at least recrystallize once.
- Nitromethane (NM, MeNO2) b.p. should be 101°C at 760mmHg. If it's not from original bottle, redistill it and collect middle fraction with as narrow as possible range, preferably within 1°C, e.g. 101+-0.5°C, it can deviate +-2C from literature data, depending of atm. pressure in your region.
- Ethylenediamine (EDA) should fume in open air, if no smoke seen, than it's highly contaminated with water or is not what you think it is. You can dry it by NaOH/KOH, decant and then extra dry by sodium metal or molecular sieves and then distill it or try to prepare diacetate salt (EDDA) in cold dry diethyl ether. It’s very hygroscopic salt. Pure EDA has b.p. 117°C at 760mm.
- Glacial acetic acid (GAA) also should be as dry as possible, place it in refrigerator at 2-5°C and wait for crystallization, if it's not occurred within 1-2 days = too much water. In that case place it in freezer. If it become only partially solid – decant liquid and save crystalline mass, you get relatively dry GAA. I works only if acetic acid content is already at least 80%+.
- Alcoholic solvents (methanol, isopropanol) in most cases are dry enough for this reaction directly from commercial suppliers, but if any doubt, better buy from another source or distill it (for methanol only) via Vigreux column.
You need:
- 2,5-DMBA – [MW = 166.17 g/mol] – 1 eq.
- Nitromethane – [MW = 61.04 g/mol] – 1.2-3 eq. (0.44-1.1 w/w; 0.39-0.97 v/w)
- Ethylenediamine – [MW = 60.10 g/mol] – 0.4 eq. (0.14 w/w; 0.16 v/w)*
- GAA (acetic acid) – [MW = 60.05 g/mol] – 0.9 eq. (0.32 w/w; 0.31 v/w)**
- Solvent – abs. iPrOH(IPA) (x7 v/w) or abs. MeOH(methanol) (x3 v/w)
- 2,5-DMNS (product) – [MW = 209.2 g/mol]
** That is ~1.1 molar equivalent (~10% excess) of GAA relative to Ethylenediamine, as we need 2 moles for every mole of amine to get diacetate salt in situ. A bit excess necessary to guaranty full neutralization so there is no free amine left in the reaction mixture, as it will induce byproducts formation.
Notes:
1) Proportions are given by weight (w/w = weight-to-weight) relative to aldehyde, except for solvent, so for example if you start with 10g of 2,5-DMBA, then you need 4.4-11g of NM, 1.4g of EDA, 3.2g of GAA and 70ml of IPA or 30ml of MeOH. If you want measure NM, EDA and GAA by volumes, that is less precise but more quick technique with pipette/syringe, then divide their weight values by their relative densities for pure compounds at 20°C:- NM (1.137 g/ml) => 4.4g / 1.137 = 3.87ml; 11g / 1.137 = 9.67ml
- EDA (0.9 g/ml) => 1.4g / 0.9 = 1.56ml
- GAA (1.05 g/ml) => 3.2g / 1.05 = 3.05ml
2) As you already noticed here is given wide range of Nitromethane to aldehyde ratio, it’s done intentionally to demonstrate reliability of this reaction, as excellent yields was achieved with as small as 1.2 equivalent (20% molar excess) of NM and remains stable within all that range, so if you have pure dry NM and it’s hard for you to get, do not take large excess, this EDDA catalyzed reaction will greatly save you both money and time.
3) If you get great yields with your current quality of precursors, next runs you can reduce catalyst load up to 2 times or even more, until it not affect your yields, for example take 0.3/0.675 eq. or 0.2/0.45 eq. of EDA and GAA respectively.
4) In case of methanol as a solvent, reaction rate is greatly increased, 5-10mins at 60°C is enough. This also can be attributed to the increased concentration of reactants, as aldehyde has greater solubility in MeOH. When dark red color is obtained, all aldehyde is mostly consumed. Holding it more at that temperatures after all aldehyde is reacted will decrease yield. Don’t use more solvent than necessary. But reflux condenser with water flowing in this case is a must.
Procedure for 10g of aldehyde:
In a 250ml flask dissolve 10g of 2,5-DMBA in 70ml of abs. IPA (or 30ml abs. MeOH in 100-250ml flask) by warming and stirring/swirling a bit.Add 1.4g(1.6ml) of dry fuming EDA, then slowly 3.2g (3.1ml) of GAA (fumes), when everything become homogeneous add 4.4g (3.9ml) of NM and preferably attach reflux condenser (could be without water flow) and stir magnetically or swirl it from time to time by hand with gentle heating on water bath or hotplate so that internal temperature remains near 60°C* for up to 1h (5-10 mins for MeOH solvent). Cool down to RT, in most cases crystallization will occur, if not, try to scratch the inner walls with glass rod and place it in refrigerator for a few hours or overnight. Brake crystals in a still cold reaction mass with rod or spatula or by shaking/stirring, vacuum filter the nitrostyrene product (2,5-DMNS), wash with small amount of cold 1:1 v/v IPA:Water solution (or 1:2 v/v MeOH:Water) and air dry. Yields are up to 95% (12g, 1.2 w/w). M.P. after recrystallization is 118-120°C.**
* For convenience you can control just outer bath temperature, usually it should be 5-10°C higher, so hold it within 65-70°C.
** In most cases recrystallization is not necessary, but can be done from a minimum amount of hot IPA or IPA-Water solution.
If there is given enough time for crystals growth, you will obtain orange to orange-reddish thin crystalline material, sometimes reminiscent of glass wool, or just as a long needles.
WARNING: Skin irritant! Wear gloves, glasses and avoid dust of this product.
@Rabidreject, I wish you the best yields and waiting for your feedback.
