I have some reactions I want to do using N-chlorosuccinimide (NCS) and N-bromosuccinimide (NBS).
The standard solvent for such halogenations is CCl4, mostly because the reagents are highly soluble in it, and the progress of reaction can be
followed by watching the spent succinimide float to the top, from which it is conveniently filtered off in workup.
Sadly CCl4 is banned here, so is chloroform, so are ethylene dibromide and dichloride.
DCM is still available but I am unsure of its suitability as a replacement.
Any suggestions or experience with alternative solvents for these reagents?SecretSquirrel - 28-6-2007 at 23:46
Will acetonitrile work for you?
Halogenation of Aromatic Compounds by N-chloro-, N-bromo-, and N-iodosuccinimide Chemistry Letters, Vol. 32, No. 10, pp. 932-933 (2003)
DOI:10.1246/cl.2003.932
Abstract
An efficient and mild method for the halogenation of aromatic compounds using N-chloro-, N-bromo-, and N-iodosuccinimide in the presence of NH4NO3 of
FeCl3 in acetonitrile was developed.
Experimental
A typical experimental procedure is as follows: A mixture of 1,4-dimethoxybenzene (1.38g, 10 mmol), NBS (1.78g, 10 mmol), and NH4NO3 (80mg, 1 mmol) in
dry CH3CN (5 mL) was stirred at 25°C for 10 min. The reaction mixture was poured into water (50 mL) and extracted with ether. The extracts were
washed with water, dried and evaporated. The residue was chromatographed (hexane-acetone = 10:1) on silica gel to give 2-bromo-1,4-dimethoxbenzene
(2.04g, 94%).
I will post more procedures if I'll be able find them.Sauron - 29-6-2007 at 05:43
That ought to work well, the substrates I have in mind off the top of my head aren't aromatic but they are polar.
2-oxo-i,4-dithiane to be chloribated at the 3-position
and
caproic acid to be brominated at the alpha-position (to convert it innext step to norleucine racemate with NH4OH conc)
Thanks for the help, will give MeCN a go.Pyridinium - 29-6-2007 at 12:25
I have seen quite a few syntheses that used NBS or NCS in CH2Cl2.
Is the spent succinimide soluble in CH2Cl2 to some extent? I know it's insol. in CHCl3.
Or do you think it's simply a question of lowered yield in CH2Cl2 vs. CCl4?Sauron - 29-6-2007 at 15:58
Not sure. Reflux temp (bp) is lower, so maybe rxn time is longer. Anyway if I can find quant solubility data for succinimide then all should be clear.Isomeric_Fred - 4-7-2007 at 15:32
I have used NCS in DCM with success and no apperent solvent chlorination.
EDIT ::
Also I have used NCS in acetic acid and in acetic/formic acid with success. The ref for such usage is -
Preparation and Synthetic Applications of 2-Halotryptamines: Synthesis of Elacomine and Isoelacomine. Fumiko Y. Miyake, Kenichi Yakushijin, and David
A. Horne. ORGANIC LETTERS 2004
Vol. 6, No. 5, 711-713.
[Edited on 4-7-2007 by Isomeric_Fred]flyingbanana - 6-7-2007 at 19:53
I have also used NBS in DCM, and there are some procedures you can find that use this as well. I've also seen procedures that use glacial acetic acid.
I've also tried NBS in acetone/water to get a bromohydrin from an alkene, but I don't know if this was successful or not as I never worked it up for
various reasons.
[Edited on by flyingbanana]BromicAcid - 6-7-2007 at 20:15
I was recently reading through a chemical process book that described using NBS under strictly aqueous conditions. The problem of course being to get
your organic to dissolve to be subject to the bromination. I was honestly surprised by the amount of aqueous organic chemistry going on lately, whole
books on the subject, especially C-C bond formation. But I digress, I can give you more information is you would like.
chlorination of 1,4-dimethoxybenzene.
absramarao - 8-7-2007 at 19:34
Process for the Bromination of 1,4-dimethoxybenzene with NBS and getting 94% yield is interesting.
What would be the yield for chlorination with NCS?What is the extent of dichloro formation and how to prevent it?
I did chlorination of 1,4-DMB with SO2Cl2.The dichloro started building up after the Mono chloro reached about 60%.So we have to stop it there and
recover DMB by rectification.,which is cumbersome.
Chlorination ,with chlorine in CCL4 is also not very encouraging.
Can any body suggest for total conversion of DMB to MCDMB without /or minimum possible(not more than 2%) dichloro content using chlorine
preferably.How to recover Succinamide if you use NCS.
Thanks & Regards
rama RaoSauron - 8-7-2007 at 20:45
You would preclude dichlorination by using the exact stochiometric qty or reagent for monochlorination and stirring the mixture well.
That was you should get little or no dichlorination. I assume you follow the progress of reaction instrumentally or by TLC?absramarao - 8-7-2007 at 21:11
I am conducting chlorination neat. i.e, DMB melts at 55 deg.C
adding SO2Cl2 at 55-60 and monitoring by GC.Stopping addition of chlorinating agent when the dichloro reaches around 3 to 4%
By that time the MCDMB would be around 65 to 70% and balance DMB.
Is there any way to convert entire DMB to MCDMB without getting much dichloro?
The same trend I observed when I used solvent as diluent.
Regards
rama raoNicodem - 8-7-2007 at 22:58
Quote:
Originally posted by absramarao
Is there any way to convert entire DMB to MCDMB without getting much dichloro?
Not really. You might minimize it by reducing the reaction temperature , but there will always be a considerable amount of the dichloro product.
Generally that is no big problem as it is easy to remove by vacuum distillation with a short column. However, I have the impression you want to
optimize a production process and want high yields.
I was wandering how come you don't report any side product resulting from the ipso electrophilic attack? In my experience this is more annoying than
the dichloro product since it distills together with 2-chloro-1,4-dimethoxybenzene. I have not bothered in determining the structure, but according to
literature these products have a 4-chloro-4-R-cyclohexa-2,5-dien-1-one structure where R is the substituent at which the ipso attack occurs. They are
base labile and can be washed away with diluted NaOH, yet they are quite a nuisance, since if not removed they tend to decompose to some dark brown
colored stuff during the distillation (benzoquinone or whatever).
Succinimide can be removed/recovered by extracting it in NaOH solution (pKa 9.6 in H2O).absramarao - 9-7-2007 at 03:16
Thank you for the info.
I am washing the chloro compound with a mild cold alkali at the end of reaction.May be some of the impurities are being washed away.May be some may
get carried away to distillation still.I have not done a thorough analysis.hence not able to report its contents.After the removal of unreacted DMB ,
the remaining oil is nitrated and washed with methanol. By this work up, getting sufficiently pure nitro compound.(MP 140 deg.C).
My interest is to find out a method where by there is no unreacted DMB with high conversion to MCDMB.
Thanks & Regards
Ramarao
