G_Pig (Stranger)
07-13-00 21:23
No 28424
      Benzyl Chlorides from subs. Benzenes  Bookmark   

This is very hypothetical at the moment and needs some work.  It hasn't been attempted by Gp, but it's published, so it MUST work, right... RIiiighhhttt....  OK..  Tell GP if this sounds plausable

0.1M substituted benzene
dissolved in 30mL HCl and 30mL benzene.  Cool to 0C.  With stirring and cooling, saturate with HCl gas.  Add 0.15M formaldehyde.  Gas with more HCl for 15 minutes.  Stir at RT for 2 hours.  Separate the benzene layer, dry (MgSO4) and evaparate the solvent to get the Benzyl Chloride in 30% yield.

That's pretty much straight out of Chem Abstracts.  The paper is:
CA 57, 6721 (1963)
for those interested.
GP is gonna go get it right now and see if there are any more details.

GP wonders how the starting material is separated from the product ??  Wouldn't the unreacted starting material and product BOTH be soluable in the benzene layer?  seems like it to gp.  And you couldn't really distill as the Bp's wouldn't be very far apart.

GP knows... 30% sounds shitty. but p-diMeO-Benzene is dirt cheap and so is formaldehyde.  It's old chemistry, but hey.. this shit is timeless, right?



okay.. GP went to the library.  The above ref is in russian and gp don't speak russian, BUT he did find some interesting papers.

here's another similar synth for chloromethyl derivatives:
Or Sy Collective Vol 3, pp557-559

1.66 moles sub. benzene, 1L of conc. HCl and 63 mL (0.84 moles) of formaldehyde solution (37%).  Bubble HCl at a rate that is "a little faster than you can count the bubbles".  Stir on a water bath at 55C and maintain the bubble rate for 5.5 hours (yikes!).  at the halfway point, another 63 ml of the formaldehyde solution is added.  Extract with Benzene and wash with H20, dil NaOH, H2O; dry over CaCl2.  The residue after solvent striping is distilled under vacuum to obtain the benzyl chloride.  This one claims to get yields around 55-62%.
NOTE: They say the 'formaldehyde solution' used was commercially available "formalin" solution, which is an "aqueous-methanolic solution containing 37% formaldehyde by weight"

What do they mean by "aqueous-methanolic" solution??

This one is interesting in that it doesn't require HCl gassing.  It is however illustrated for naphthalene, which is very similar to benzene.. don't know if it would work.. here it is:
Or Syn Coll Vol 3, pp195-196

2 moles naphthalene (subs. benzene), 110g paraformaldehyde, 260 mL glacial acetic acid, 165 mL 85% phosphoric acid, and 362 mL conc. HCl. (whoa..that's alot of acid!) heat to 80-85C on water bath and stir for 6 hours.
Workup:  cool to 15-20C and pour into 2L sep funnel.  "wash" with two 1L portions of COLD (5-15C) H2O, then with 500mL 10% potassium carbonate, and finally with 500 mL cold H2O.  The bottom layer holds the product in all washings.  Add 200mL Ether and dry over anhydrous potassium carbonate for one hour.  Strip solvent and distill under vacuum to get the chloride.  They claim 75% yield "based on the consumed naphthalene" not all of the starting material reacts, though, as there is a forerun of naphthalene.


another paper uses similar conditions as the second HCl gas method above, but when distilling the product they employ a fractional column or a Vigreux column (you know, those funny lookin' condensors) to purify the product.

Now all that remains is some experimentation...

Gp's on it...
07-14-00 11:25
No 28656
      Re: Benzyl Chlorides from subs. Benzenes  Bookmark   

Beilstein doesn't give a ref for 1,4-dimethoxybenzene chloromethylation. Seems like this doesn't work.
But 1,4-diomethoxybenzene chloromethylation is described, producing 1,4-dimethoxy-2,5-bis-chloromethyl-benzene:
H3PO4, Hg(!!!), aq. HCl; Zh. Obshch. Khim. 29, 1959, 3746; engl. ed. 3704, 3705
aq. HCl, HCl, acetic acid; Bull. Chem. Soc. Jpn, 48, 1975, 497-504

2,5-dimethoxytoluene chloromethylation in concentrated HCl:
Helv. Chim. Acta 39 (1956), 1564, 1575

2-Bromo-1,4-dimethoxybenzene chloromethylation:
Bull. Soc. Chim. Fr. 1953; C46

1,4-dimethoxynaphtalene chloromethylation:
64%, gas. HCl, conc. HCl, dioxane, H2O, 20 min, 55-60C;
J. Org. Chem 48, 19, 1983, 3265-68

Another interesting ref with lots of chloromethylations in it:
Chem. Ber. 80, 1947, 391-399

(Hive Bee)
07-14-00 17:29
No 28726
      Re: Benzyl Chlorides from subs. Benzenes  Bookmark   

Benzyl alcohol and conc HCL react in the cold to produce Benzyl Chloride.
Extraction is the question.Unreacted alcohol and water azeotrope.
Was about to try removing water with dessicant and then distillation, but other things took priority.

07-14-00 21:08
No 28806
      Re: Benzyl Chlorides from subs. Benzenes  Bookmark   

Os- yep, GP was concerned about di-cloromethylation problems with the 1,4MeO Benzene.  The idea of brominating FIRST and blocking one of the ortho sites sounds very good to GP.  GP has worked with bromobenzenes in academia with similar systems, and it would seem that the presence of the Br on the ring doesn't really affect the subsequent reactions to get to the amine.  GP was concerned about the final reduction step with Raney/Nickel.  He KNOWS that it's okay with LAH, so it's probably ok with the R/N.

07-15-00 12:42
No 29038
      Re: Benzyl Chlorides from subs. Benzenes  Bookmark   

LAH is not ok with aromatic bromines! But most other reductions should work.

07-18-00 21:13
No 30129
      Re: Benzyl Chlorides from subs. Benzenes  Bookmark   

In academia, gp has witnessed one of his coworkers reduce a p-bromobenzoic acid down to the alcohol using LAH in 93% yield.  He said that it WILL replace the Br with Hydrogen if you 'aren't careful'.   He performed this at -9C and quenched under ice as well. 

09-09-00 06:02
No 50269
      Re: Benzyl Chlorides from subs. Benzenes  Bookmark   

Dear G_Pig! on 13th July you wrote about making subst. benzylchlorides from benzenes with HCHO/HCl in 30% yield.
And then ...
            >>okay.. GP went to the library. The above ref is in russian and gp don't speak russian ...>>
Oh, my beloved G_Pig! This  ref would do me a great favor, and I am happy to say that I DO speak russian, so if you send me a xerocopy of it I will gladly translate it and post for everyone's use. Best regards,