Sciencemadness Discussion Board - synthesis of 2-bromobenzoyl chloride

synthesis of 2-bromobenzoyl chloride

jmister28 - 18-12-2018 at 15:30

Hi, I was wondering if any of you know a reaction to form 2-bromobenzoyl chloride because I can't seem to be able to find any resources for it. Any help is much appreciated.

Tsjerk - 18-12-2018 at 15:57

What are you resources? 2-bromobenzoic acid?

Loptr - 18-12-2018 at 16:00

Sure. What do you have?

SOCl2 + 2-bromobenzoic acid

You have SOCl2, right?

jmister28 - 18-12-2018 at 16:03

yes I have SOCL2 Thanks

jmister28 - 18-12-2018 at 16:08

how do I preform the reaction, reflux?

jmister28 - 18-12-2018 at 16:15

As I am a beginner I am not sure

walruslover69 - 18-12-2018 at 16:26

If you are a beginner, and don't know what you are doing, you should probably find a literature source for a similar reaction before working with something moderately dangerous like SOCL2. Whats the context for you making it?

jmister28 - 18-12-2018 at 16:28

I am using the 2-bromobenzoyl chloride in a reaction with 4-chloroaniline with a ZnCl3 catalyst to produce 2-Amino-2’-bromo-5-chlorobenzophenone

walruslover69 - 18-12-2018 at 16:49

What do you plan to do with the 2-Amino-2’-bromo-5-chlorobenzophenone? Seems like a series of complicated steps/reactions if you are just beginning to do amateur chemistry

jmister28 - 18-12-2018 at 16:58

It is a synthetic pathway that I am trying to work out *Theoretically* to reach a new compound that uses the 2-Amino-2'-bromo-5-chlorobenzophenone

As I don't plan to carry the reaction in real life anytime soon I am just gathering the literature necessary for it

walruslover69 - 18-12-2018 at 17:01

Have you typed it into scifinder (if you have university access)?

jmister28 - 18-12-2018 at 17:10

no, I have not(I don't have university access) But I am using well known pathways and the only reagent that I needed to synthesize is the 2-bromobenzoyl chloride

CuReUS - 18-12-2018 at 17:55

Quote: Originally posted by jmister28

I am using the 2-bromobenzoyl chloride in a reaction with 4-chloroaniline with a ZnCl3 catalyst to produce 2-Amino-2’-bromo-5-chlorobenzophenone

won't the acyl chloride just react with aniline rather than the ring ? ZnCl₂ would also react with aniline

UC235 - 18-12-2018 at 18:27

Quote: Originally posted by CuReUS

Quote: Originally posted by jmister28

I am using the 2-bromobenzoyl chloride in a reaction with 4-chloroaniline with a ZnCl3 catalyst to produce 2-Amino-2’-bromo-5-chlorobenzophenone

won't the acyl chloride just react with aniline rather than the ring ? ZnCl₂ would also react with aniline

Yes. Also, it looks like OP is looking to make benzos, albeit poorly.

jmister28 - 19-12-2018 at 09:01

If you were to react 4-chloroaniline, 2-bromobenzoyl chloride, and pyridine, take the product and react it with more 2-bromobenzoyl chloride and catalyze it with ZnCl2. would it not work to synthesize 2-Amino-2'-bromo-5-chlorobenzophenone.
Also, I am not trying to synthesize any benzodiazepines if I were, this would be a terrible method to do so.

Metacelsus - 19-12-2018 at 10:49

CuReUS is correct. You'll need a protecting group on the aniline, or else the amine will react with the acyl chloride.

It might be possible to acetylate the amino group, do the Friedel-Crafts acylation on the N-acetyl 4-chloroaniline, and then hydrolyze off the acetyl group.

[Edited on 2018-12-19 by Metacelsus]

clearly_not_atara - 19-12-2018 at 11:12

I think it would be better to use 2-bromobenzonitrile and p-chloroaniline together in a Sugasawa reaction:

https://en.chem-station.com/reactions-2/2015/03/sugasawa-rea...

No protection and no acyl halide is required in this case.

jmister28 - 19-12-2018 at 11:39

does anyone have a good procedure for the sugasawa reaction?

jmister28 - 19-12-2018 at 11:57

what about this
https://www.researchgate.net/figure/Synthesis-of-2-amino-5-c...

clearly_not_atara - 19-12-2018 at 12:35

Haha, you're not trying to make benzos. You're interested in open-chain benzo analogs optimized for muscle relaxant activity. At least this is an interesting spoonfeed.

Do you have any plans for a skeletal muscle relaxant? Those kinds of things could be very dangerous in the wrong hands. The paper is here:

https://www.researchgate.net/publication/230795410_Synthesis...

You'll note that the FC acylation described in the diagram does not appear anywhere in the text of the paper; instead, they take the 2-aminobenzophenones as a starting point and add various groups to the nitrogen, of which o-tolyl (3e) seems to be the most successful.

As such, I think the acylation is provided only as a pictive example, and may not refer to a workable procedure. If I had to guess the ZnCl2 is actually catalyzing a Fries-type rearrangement, similar to this procedure:

http://anonym.to/https://www.tandfonline.com/doi/abs/10.1080...

[Edited on 19-12-2018 by clearly_not_atara]

hacker - 19-12-2018 at 22:28

You could start by brominating toluene with a Lewis acid catalyst, trichlorinate the methyl group under ultraviolet radiation. and then follow the procedure in US1557154 to hydrolyze to the target compound with water and a zinc chloride catalyst.

CuReUS - 20-12-2018 at 05:07

Quote: Originally posted by Metacelsus

It might be possible to acetylate the amino group, do the Friedel-Crafts acylation on the N-acetyl 4-chloroaniline, and then hydrolyze off the acetyl group.

wouldn't there be steric hindrance at the o-position ?

Quote: Originally posted by clearly_not_atara

I think it would be better to use 2-bromobenzonitrile and p-chloroaniline together in a Sugasawa reaction

Good find atara.I was also thinking of using nitrile but more in the lines of a hoesch reaction.

Quote: Originally posted by clearly_not_atara

As such, I think the acylation is provided only as a pictive example, and may not refer to a workable procedure.

My thoughts exactly.The lewis acid used would react with the NH₂ of aniline -https://chemistry.stackexchange.com/questions/87145/why-does...
jmister,could you tell us for target molecule.Then maybe easier reactions or a better starting compound could be suggested

jmister28 - 20-12-2018 at 06:47

2-Amino-2’-bromo-5-chlorobenzophenone is the target molecule

Loptr - 20-12-2018 at 13:58

Quote: Originally posted by jmister28

I am using the 2-bromobenzoyl chloride in a reaction with 4-chloroaniline with a ZnCl3 catalyst to produce 2-Amino-2’-bromo-5-chlorobenzophenone

Where are you getting this ZnCl3 from? I am not familiar with that one....

(doesn't exist outside of solution, IIRC)

jmister28 - 20-12-2018 at 18:31

sorry, typo ZnCl2

CuReUS - 21-12-2018 at 06:11

Quote: Originally posted by jmister28

2-Amino-2’-bromo-5-chlorobenzophenone is the target molecule

I have good news and bad news.
the good news is that phenyl benzamides can be rearranged to amino benzophenones via a fries reaction.
the bad news is that the ref is not online - Ravi, Subban; Saravanan, Nagusamy; Shanthi, Andy; Dharmaraj, Nallusamy; Lakshmanan, Akoni J Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1991 , vol. 30, # 4 p. 443 - 445 (83% yield)

another paper from the same authors - http://nopr.niscair.res.in/bitstream/123456789/8970/1/IJCB%2...

Chemi Pharma - 27-12-2018 at 07:46

Hi @jmister28,

I agree with other members that thinks you want to synthesize benzos, but it's not my business at all make you questions about that, cause I'm only interested in the chemical reactions.

What can I do for you? at your other thread you ask members from the Sciencemadness how to sinthesize 2-bromobenzoyl chloride. I've already posted at that thread how you can achive this chemical from salicylic acid. Look here: http://www.sciencemadness.org/talk/viewthread.php?tid=114280... and here: http://www.sciencemadness.org/talk/viewthread.php?tid=114280...

As you can see in that links, you don't need the nasty SOCl2 at all to do this reactions, like some members said.

To do the condensation beetween chloro-benzoyl chloride and 4-chloro aniline with ZnCl2, I have two ilustrative papers to give to you, I'm attaching below.

Don't forget you have two common ways to close the benzodiazepinic ring: one using chloroacetyl chloride, and I have a good and easy sinthesis for it, that I'm attaching too. Other way is using glycine ethyl ester hydrochloride.

But this is another step and I will reserve to me the right opportunity to bring the right papers for this synthesis here in Sciencemadness anytime in the future.

Attachment: chloroacetyl chloride from trichloethylene, chloroacetic acid and p-tolueno sulfonic acid.pdf (361kB)
This file has been downloaded 320 times

Attachment: 2-amino-5-chlorobenzophenone.pdf (676kB)
This file has been downloaded 416 times

Attachment: 2-amino-5-chlorobenzophenone II.pdf (269kB)
This file has been downloaded 356 times

[Edited on 27-12-2018 by Chemi Pharma]