Para-Nitration of Toluene

[shock_flame]

Hi. I am interested in ultimately synthesizing Benzocaine (R) from toluene scratch, as lab practice. Benzocaine's formal name is 4-Aminobenzoic Acid Ethyl Ester. Here's the link to see its structure http://www.genome.ad.jp/Fig/compound/C07527.gif

I would like some help on the para-nitration of toluene. In the explosives section of the website I have already found good procedures for mono-nitration of toluene; however, the posters were merely concerned with just getting toluene nitrated once, and weren't concerned if it was ortho or para nitrated.

1) From my organic chemistry textbook, I know that the nature of toluene itself will cause the mononitration reaction to create a 2:1 ratio of ortho:para nitro groups. As I am poor like many college students, I really don't want to waste 60% of my yield. I have investigated many patents and scientific papers (used SciFinder to locate articles, and then read them on freepatentsonline). There's a lot of methods that tell you how to make para percentage increase significantly, but unfortunately many of their materials are too sophisticated (such as an ultrasound generator).

The most feasible methods I saw were to use zeolite catalysts on the reaction at around 100+ degrees Celsius. If I were to use this, though, does anyone know where to buy zeolite (hardware stores, maybe?)? Also, I'm worried about the strong temps implied in association with nitric/sulfuric acid/toluene. Is this a serious hazard that I should back away from?

Ultimately, I'd like to know if anyone knows of a good, accessible nitration method that favors para-nitration.

2) Should I synthesize the nitric acid myself or should I order it online? I know of an online site that charges 9.99/16 oz. of 60% nitric acid (plus $20 special shipping by UPS). I guess this is a price and safety issue combined here. Is it more cost effective to make it myself or to buy it? Also, I have read on the forums about a black-list that people get put on if they order chemicals online, especially nitric acid. Am I at risk of getting on this list if I buy this stuff online?

I'd appreciate any assistance.

[shock_flame]

Thank you, admin and moderators, for allowing this thread.

I have done some work ever since the last synthesis. I hesitated to purchase any zeolite rock off of eBay to perform a para-favoring mono-nitration, since I wasn't sure if the crude form was the zeolite of choice used for zeolite "cages" in para-nitration favoring synthesis procedures. Therefore, I decided to manipulate temperature instead. Knowing that activating power of an electrophilic aromatic substitution can be increased by raising temperature, I decided to lower the temperature to achieve the opposite result. For those of you not too familiar with the theory and mechanism of EAM with toluene, toluene's enormous activating power creates a nearly ideal 2:1 ortho para ratio in product for nitration. Usually, if you do an EAM with a ortho/para directing group (like chlorobenzene), the result is almost exclusively para, because the ortho positions are disfavored due to their close proximity to the large chlorine atom's (a steric effect). The methyl group in toluene is small enough to make steric effects negligible, and thus a 2:1 ratio is achieved.

Now that I've set the stage for everyone, this was my procedure. I measured out KNO3 (from Green light, which I've read is supposedly pure stuff) and mixed it in with 3 equivalents of sulfuric acid to make HNO3 while keeping a H2SO4 environment. I must have added in the KNO3 too quickly, as the crystals just clumped up in the acid. I had to break them up and try to stir/swirl to make the KNO3 dissolve. I then added in 1-equiv of toluene. Similar to a post in the "Synthesis of TNT thread", the mixing of all 3 chemicals creates a opague yellow oil on top and a viscous brown layer on the bottom. This reaction was carried out in a propylene beaker that was in an ice bath. Since I currently don't have a stirrer, I swirled for compensation (for about 1.5 hrs). I then realized that I was losing product due to evaporation (strong smell), and quickly poured everything into a glass vial, covered it tightly with vinyl plastic wrap (the plastic wrap used for food), and left it alone for the night.

The next morning, I was met with a strange scene. There were now 3-4 layers! On the top was the oil from last night, but now a dirty brown instead of a light yellow. Directly below this was a vicous looking brown/white layer that looked distinctly different. Next was a clear brown liquid. The bottom layer had crystals, as well as a strange gooey yellow substance. This bottom layer confused me very much. According to solubity rules learned in general chemistry, the alkali metals should be soluble! While I have thought of the possibilty of unreacted KNO3, I'm suspicious that the crystals could be KHSO4. The strange gooey yellow substance is a complete stumper. I have read in the "Synthesis of TNT" thread that one guy, when making TNT from DNT, woke up to find a mass of TNT crystals sitting at the bottom of the jar. This shouldn't have happened with me: I know I didn't add enough KNO3 for this to happen. My quantities were: 15 mL H2SO4, 5 mL Toluene, and 5 g KNO3 (the actual stoichiometric equivalence of KNO3 to toluene should have been 4.93 g, but I added 5 g to try to get better yields).

I then extracted the top layer and conserved the contents of the original vial for later work. To separate the p-nitrotoluene from the o-nitrotoluene, I decided to take advantage of MP's (they have a difference of over 50 degrees Celsius). I used a 99% isopropyl alcohol solvent for this, obtained from a auto store. This turned out to be a BIG BIG BIG mistake, because of a dye that they add to the alcohol. Using a purification by recrystallization method, I got a reasonable precipitate. I used a syringe to take out the liquid and decided to leave the solid to dry out. BIG mistake #2. Now I will explain why I said they were mistakes. First of all, when I boiled the liquid to get rid of alcohol and leave o-isomer product, the liquid turned black/brown. This should NOT have happened: the o-isomer ought to remain yellow, and shouldn't decompose; the only thing that decomposed was the dye, I suspect. Now with a black product, I'm don't know what to do with it. The 2nd mistake was not using gravimetric filtration or vacuum filtration to separate the solid. The liquid left in the solid must have inevitably contained some o-isomer, hence it wouldn't dry after 20 hours. When I got impatient and heated it, the solid turned black, again probably because of the dye. Now I have a black fluid and a black powder, and these two equal to reflect a poor design of experiment.

Lessons:

1) Don't use auto-shop isopropyl alchohol: it screws you over when it mixes with the nitrotoluene. Boiling it by itself doesn't turn the alcohol black, however. It probably reacts with the nitrotoluene somehow.

2) Use proper filtration to separate isomers. Drying sucks, as I have illustrated.

3) Add KNO3 in minute amounts to H2SO4, to prevent clumping.

Now, I do have some questions that I hope the Rogue Science community can help me with. Can somebody please tell me where to get these zeolite "cages", or at least how to make them from the zeolite rocks found on eBay? These zeolite cages, when used with HCL and acetic acid solvent, will give almost 60-70% para nitration, reversing the ortho:para 2:1 ratio. (it also uses milder conditions, which makes it safer for us).

Also, I'm deciding to make a fume hood (to prevent killing of self and family/friends with toluene fumes and other gases). The plan is to suck exhuast air through a Volvo car filter that has activated charcoal layer, and then bubble exhaust through a thick layer of activated charcoal about 1 cubic foot in volume. I have read a filtration archive file in which a member remarked that plans like these will be too expensive, since the charcoal rapidly saturates. Can somebody give me an estimate on how long would an average saturation period would be?