Sciencemadness Discussion Board - benzyl chloride

benzyl chloride

gopal - 4-9-2018 at 22:43

Dear sir,
how to prepare benzyl chloride from benzene

From
Gopal indrara

JJay - 4-9-2018 at 22:52

Supposedly, Blanc chloromethylation works. Formaldehyde and hydrogen chloride in excess benzene with a Lewis acid catalyst (e.g. zinc chloride) in anhydrous conditions at 25 C.

Edit: Note: This supposedly produces some really serious carcinogens as a byproduct. A fume hood is required.

[Edited on 5-9-2018 by JJay]

Metacelsus - 5-9-2018 at 17:06

Why not prepare it by the chlorination of toluene? That's how it's done industrially.

NeonPulse - 5-9-2018 at 21:46

Pretty sure it’s done with toluene and chlorine in the vapour phase. The two chemicals are pumped steadily as gaseous form into a glass reactor where they react and if you designed the apparatus well you should have a collection flask or something similar to get the product. But this just makes it sound much simpler than it actually is. The device design is probably the biggest hurdle here since chlorine will destroy most materials except glass. If you pull it off it would be very interesting to know how you did so and how the apparatus design went.

Loptr - 6-9-2018 at 10:27

Quote: Originally posted by JJay

Supposedly, Blanc chloromethylation works. Formaldehyde and hydrogen chloride in excess benzene with a Lewis acid catalyst (e.g. zinc chloride) in anhydrous conditions at 25 C.

Edit: Note: This supposedly produces some really serious carcinogens as a byproduct. A fume hood is required.

[Edited on 5-9-2018 by JJay]

IIRC, this requires a concentrated solution of HCl at 0C, so a lot more HCl than first glance. Bromomethylation might be easier to handle.

Also, whats wrong with benzyl bromide? Toluene and bromine, using toluene in excess as solvent, and a radical catalyst (hv, etc.)

[Edited on 6-9-2018 by Loptr]

Dan Vizine - 6-9-2018 at 12:35

I've done this photochemically catalyzed chlorination reaction numerous times with m-xylene. Toluene should react in the same way. Chlorine is generated by adding HCl to stirred liquid NaOCl bleach. The tube from the generator leads to an anti-suck back trap and from there to a tube well below the surface of stirred, refluxing substrate. The reaction mixture is illuminated (sunlight would be much better). Trapping of evolved HCl is done by a base trap (another anti-suck back trap!). You follow the reaction by the reflux temperature. After the desired temperature (approximately equal to the bp of your desired product) is reached, the crude product is distilled through a Vigreaux column under reduced pressure.

For your desired target, chloromethylation of benzene should be avoided! You risk forming highly carcinogenic O(CH2Cl)2. NEVER heat HCl with HCOH.

[Edited on 9/6/2018 by Dan Vizine]

Loptr - 6-9-2018 at 12:42

Quote: Originally posted by Dan Vizine

Chloromethylation of benzene should be avoided! You risk forming highly carcinogenic O(CH2Cl)2.

I have always been curious about this. Is it volatile? Can it be hydrolyzed? Any way for it to easily be separated from the mixture?

It does scare me though.

TGSpecialist1 - 6-9-2018 at 12:54

It would be easier to make it using toluene and TCCA:
https://www.youtube.com/watch?v=G_4kfY0dR2A
But personally I would just distill off the unreacted toluene.

zed - 6-9-2018 at 12:54

Gopal, here, terminology may be confusing. Benzyl Chloride is not naturally derived from Benzene, AND Chlorobenzene and Benzyl Chloride, are not the same material.

If you actually want to produce Benzyl Chloride , the easiest method is probably via Benzyl Alcohol.

It is pretty easy to make. https://en.wikipedia.org/wiki/Benzyl_chloride

Benzyl Alcohol, at least in the U.S.A., is probably more easily to obtain than Benzene. https://www.ebay.com/itm/Benzyl-Alcohol-Gallon-HDPE-Bottle/1...

LoAAOSwsZJaWwGh

https://www.youtube.com/watch?v=mK9_MDn2dN0

[Edited on 6-9-2018 by zed]

Dan Vizine - 6-9-2018 at 12:59

Loptr,

The chemical is bis(chloromethyl) ether.

It is volatile, dangerous in almost any amount ( A gc with a Ni-63 detector is required to measure the concentration at its lowest dangerous level in air), and it is hydrolyzable. In fact, the window for this hydrolysis is just right to give you cancer. It survives the transport into your body but the nitrogen bases in DNA are readily cross-linked right across the two strands. The "bite" is just right for this. I have always refused to do any reaction involving BCME.

[Edited on 9/6/2018 by Dan Vizine]

Loptr - 6-9-2018 at 13:13

Quote: Originally posted by Dan Vizine

Loptr,

The chemical is bis(chloromethyl) ether.

It is volatile, dangerous in almost any amount ( A gc with a Ni-63 detector is required to measure the concentration at its lowest dangerous level in air), and it is hydrolyzable. In fact, the window for this hydrolysis is just right to give you cancer. It survives the transport into your body but the nitrogen bases in DNA are readily cross-linked right across the two strands. The "bite" is just right for this. I have always refused to do any reaction involving BCME.

[Edited on 9/6/2018 by Dan Vizine]

Thanks, Dan Vizine. I knew it was bis(choromethyl) ether. There is another reagent that might be possible to be used here, but I don't know much about it.

Chloromethyl chlorosulfate

Apparently it eliminates the risk of producing bis(chloromethyl) ether as a by-product.

Quote:

The reaction of liquid (gamma-) SO3 with CH2Cl2 at room temperature leads to SO3 insertion into the C-Cl bonds, giving the useful chloromethylating agent chloromethyl chlorosulfate (CMCS). The process is very slow but becomes rapid on addition of catalytic quantities of trimethyl borate. The product mixture consists almost entirely of CMCS and the product of further sulfation, methylene bis(chlorosulfate)(MBCS), in a ratio of ca. 2 : 1, but typical yields of CMCS, isolated by distillation, are only 30-35%. The catalysed reaction in the homogeneous liquid phase at -45 degrees C has been followed as a function of time and of reactant concentration by 1H nmr spectroscopy. It is observed that, besides CMCS and MBCS, three additional, transient products (designated A, B and C) are formed. Products A, B and C decompose slowly at -45 degrees C but much more rapidly if the reaction mixture is raised to room temperature, giving additional CMCS and MBCS. From an analysis of the SO3 balance, it is inferred that products A, B and C arise from the reaction of one molecule of CH2Cl2 with respectively two, three and four molecules of SO3; they are suggested to be chloromethyl chloropolysulfates. By measuring initial rates of CMCS formation or total CH2Cl2 consumption, it is shown that the reaction is first order in the catalyst and roughly third order in SO3. A mechanistic scheme is proposed in which SO3 forms equilibrating zwitterionic molecular complexes with CH2Cl2. of 1 : 1, 2 : 1 and higher stoichiometries. The boron-containing catalyst can activate these complexes towards nucleophilic attack at carbon by the negatively charged oxygen of another zwitterion. An analogous mechanism can be written for the conversion of CMCS into MBCS by SO3 in the presence of trimethyl borate. CMCS reacts rapidly with anionic nucleophiles, such as halide or acetate ions (X-), in homogeneous solution of their tetrabutylammonium salts in CD3CN, or in a two-phase system (CDCl3/H2O) using alkali-metal salts in conjunction with a phase-transfer catalyst. In both situations the products (ClCH2X) arise by rapid nucleophilic displacement of the chlorosulfate moiety; this then more slowly liberates chloride ion, which converts further CMCS into CH2Cl2. The reactivity of CMCS has been compared with that of MBCS and methyl chlorosulfate (MCS) in competitive experiments; the reactivity order is MCS > MBCS > CMCS >> CH2Cl2. Evidence is also presented suggesting that, in contrast to the halide nucleophiles, reaction of CMCS with sodium phenoxide in tetrahydrofuran solution leads to nucleophilic displacement of the sulfur-bound chloride.

[Edited on 6-9-2018 by Loptr]

Dan Vizine - 7-9-2018 at 07:25

Hi Loptr,

Well, CMCS is certainly far safer than HCl/HCOH mixtures. Thanks for the reference.

A general note to all those people who may use alkylating chemicals of any kind....BEWARE! They are more dangerous than they may appear on the surface.

While not as obviously harmful as things like SO3, Cl2, HCN and other laboratory-based boogiemen, alkylating agents (especially volatile ones) are very detrimental to long-term health. Nitrogen bases are the building blocks of your genetic blueprint. Once you alkylate these you have introduced a "mutation" of sorts and cancer is a common result.

Avoid and/or minimize exposure to things like Me2SO4, labile halides like MeI, EtI, BzCl etc. Always think ahead, the offending agent can always form in situ as does BCME. Some dangerous alkylating agents are "hidden". All chloroacetyl chloride, for example, should be viewed as containing traces of BCME.

[Edited on 9/7/2018 by Dan Vizine]

S.C. Wack - 7-9-2018 at 14:39

Is bromomethylation less tragic?

Loptr - 7-9-2018 at 17:32

Quote: Originally posted by S.C. Wack

Is bromomethylation less tragic?

My thought was that bis(bromomethyl) ether would be less volatile. I don't know that as a fact.

Dan Vizine - 8-9-2018 at 09:00

You're correct, Loptr. The bp of the bromo analog is almost 50 C higher.

The more labile bromines would be hydrolyzed faster by the body and so it wouldn't be quite as optimized to do biological damage as BCME is, but it would certainly be a potent carcinogen. It hard to quantify the relative risks, and so it's best to avoid these compounds if at all possible.