Sciencemadness Discussion Board - Phenyl p-dioxane synthesis

Phenyl p-dioxane synthesis

gl92038 - 18-3-2012 at 02:14

After I saw this synthesis ( http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv4... ) I came up with the idea of making phenyl p-dioxane but I'm not sure if my route is correct. So could you please correct me if I'm wrong.

AndersHoveland - 18-3-2012 at 02:51

sometimes bromoalkanes can react with a strong base to pull out an HBr rather than substitute a hydroxyl group.
For example, bromocyclohexane can react with KOH to form cyclohexene.
http://d.web.umkc.edu/drewa/Chem321L/Handouts/Lab9E2Cyclohex...

from wiki...

Quote:

Dehydrohalogenation of Haloalkanes
Dehydrohalogenation is a very common method for creating alkenes. It uses the E2 elimination mechanism. The base used is generally a strong base such as KOH (potassium hydroxide) or NaOCH3 (sodium methoxide). The haloalkane must have a hydrogen and halide 180° from each other on neighboring carbons. If there is no hydrogen 180° from the halogen on a neighboring carbon, the reaction will not take place.

Dehalogenation of Vicinal Dibromides
The dehalogenation of vicinal dihalides (halides on two neighboring carbons) is another method for synthesizing alkenes. The reaction can take place using either sodium iodide in a solution of acetone, or it can be performed using zinc dust in a solution of either heated ethanol or acetic acid.

[Edited on 18-3-2012 by AndersHoveland]

kavu - 18-3-2012 at 03:49

Sulphur is a much softer nucleophile and less basic than oxygen, the route you presented would probably lead to a gunky mixture of all sorts of things. In an article by R. K. Summerbell and L. N. Bauer J. Am. Chem. Soc., 1935, 57 (12), pp 2364–2368 a viable home chemistry method for the preparation of phenyl p-dioxane is presented. PhMgBr is coupled with monochloro-p-dioxane, prepared by addition of HCl to p-dioxene.

[Edited on 18-3-2012 by kavu]

bbartlog - 18-3-2012 at 05:13

Interestingly the picture shown in the Org Syn prep you link to does not match their procedure (picture shows sodium phenoxide while the described prep uses elemental sodium). First time I've seen an error like that in Org Syn (or maybe I'm confused).
As for your route, I think it could work, but a route is not a procedure. You might need a lot of trial and error to achieve any kind of success. I notice that the Org Syn prep you reference uses 2 liters of ethanol for about 20ml of each of the other two reagents (100:1:1 by volume, more or less), which looks like an attempt to maximize the proportion of intramolecular reactions via dilution.

PHILOU Zrealone - 19-3-2012 at 02:07

In the present case you describe, Anders is right...there is a big chance that instead of a cyclisation product you get an elimination or even a bis-elimination...straight to phenylacetylen...via an intermediary alfa- or beta- bromostyren...

C6H5-CHBr-CH2Br + NaO-CH2-CH2-ONa --> C6H5-CBr=CH2 + NaBr + HO-CH2-CH2-ONa
C6H5-CBr=CH2 + HO-CH2-CH2-ONa --> C6H5-C#C-H + NaBr + HOCH2-CH2OH

Nicodem - 19-3-2012 at 05:39

Indeed, there appears not to exist a slightest chance that 1-phenyl-1,2-dibromoethane could react with something so basic as the bis-deprotonated ethylene glycol. A cursory search of the forum would give evidence of this.

2-Phenyl-1,4-dioxane is most easily prepared via the usual route for 1,4-dioxanes, that is by acid catalysed cyclisation of the appropriate diol, the 2-(1-hydroxy-1-phenylethoxy)ethanol. This compound should be easily accessible by the base catalysed solvolysis of styrene oxide in ethylene glycol.
A more straightforward approach is the direct sulfuric acid catalysed reaction of styrene oxide with ethylene glycol, which under appropriate conditions gives 2-phenyl-1,4-dioxane as the major isolable product (see DOI: 10.1021/jo01093a039 for the procedure and further details). Admittedly, the yield is only moderate and might be lower in comparison to the equivalent two step process, but it avoids the isolation of the water soluble 2-(1-hydroxy-1-phenylethoxy)ethanol. Styrene oxide is easily made from styrene.

gl92038 - 19-3-2012 at 10:03

Thank you all for your replies, especially for the last 2

I'll try the described method with styrene oxide