flipper (Hive Bee)
01-28-02 08:32
No 261748
      isosafrole from benzodioxole  Bookmark   

Does anybody have some literature of this reaction or a more detailed paper about it.

Isosafrole from Benzodioxole
Feugeas (see safrole from benzodioxole) also gives a synthesis for isosafrole (RCH=CHMe) from RMgBr by first reacting with propanaldehyde (EtCHO) with an 81% yield and then with para-tolulenesulfonic acid to give isosafrole in 79% yield. The reported boiling point at 17 mmHg is 13 1C.


I know it's a simple grignard but what's with the para-tolulenesulfonic acid and propanaldehyde. ThanX

Safrole from benzodioxole
 Feugaes[18] reports an 87% yield of safrole (abbreviated R-CH2=CHCH2) from benzodioxole (3,4-methylenedioxybenzene, designated R) by the Grignard reaction of RMgBr with allyl bromide (CH2=CHCH2Br). The reagents in Grignard reactions must be absolutely dry and the glassware flame dried prior to use. The author here uses tetrahydrofuran as solvent which even when purchased dry usually has to be dried by distilling with sodium metal under an atmosphere of dry nitrogen.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
01-28-02 09:01
No 261759
      Re: isosafrole from benzodioxole  Bookmark   

flipper: The reaction produces MD-P1Pol by cycloaddition of the phenyl group to the two-membered ring of the C=O, opening it to form MD-P1Pol, or CH2O2-Ph-CH(OH)-CH2-CH3

This is then reacted with the p-toluenesulfonic acid to dehydrate the alcohol to the alkene. I assume they use this specific dehydrating agent because it will not cleave the formed olefinic bond, by oxidation to aldehydes.

                                                  PrimoPyro

Vivent Longtemps la Ruche!
 
 
 
 
    flipper
(Hive Bee)
01-28-02 11:57
No 261788
      Re: isosafrole from benzodioxole  Bookmark   

Thanx for the reply Primopyro but I have a little problem. I don't understand any of it. This is what I think you wrote: We've got Benzodioxole and we gonna make MDP1Pol of it by addition of a phenyl group to somewhere on the Benzodioxole using the grignard reaction.
When we have MDP1Pol we've gotta dehydrate it with p-toluenesulfonic acid. When that is done we have Isosafrole.smile

Is it something like this or is it just total bullshit  tongue

Thanks and sorry for my dumbness cool
 
 
 
 
    PrimoPyro
(Hive Prodigy)
01-28-02 16:28
No 261828
      Re: isosafrole from benzodioxole  Bookmark   

You are close, but what you actually wrote is incorrect. No need to apologize.

The phenyl group I speak of is the benzodioxole. After this point, anything written in this reply is meant to be informational, not confrontational or sarcastic at all.

Do you know what the benzene ring looks like? It is a 6-membered carbon ring. The carbon atom has the opportunity to make four bonds, and always takes this opportunity to fill them. This means that every neutral carbon must have four bonds coming from it, either to four other atoms, or having less than four different atoms, but multiple bonds to one or two involved. Here are some examples: CH4, where the four hydrogens are each singly bonded to the carbon, totaling four bonds; H2CO, where the oxygen is double bonded to the carbon, and the teo hydrogen atoms (totaling only three atoms) are singly bonded to the carbon; and CO2, which has the structure O=C=O, where each line represents a bond. See how this four bond structure is strictly adhered to?

Well the 6 membered carbon ring, known as benzene, has a very unique, very important structure. The six sets of bonds, holding each of the six carbon atoms together, vary. It can be represented as alternating single and double bonds, like -CH=CH-CH=CH-CH=CH where the first and last carbons are singly bonded together. Each carbon has one hydrogen singly bonded to it. Each carbon obeys the four bond structure.

In benzene, no completely single or double carbon-carbon bonds exist. They are all said to be hybridized between 1 and two bonds. This is because the electrons that cause electronic bonding, do not stay in one place, denoting the number of bonds in that place. Instead, they move around a lot throughout the ring, and each bond is an intermediate strength ~1.5 This structure is very stable, and can prove to be stable in situations where normal C-C bonds tend to fall apart. It is noteworthy that these bonds, which are known as aromatic bonds, are hard to break.

Now you know benzene inside out. The substance benzene refers to the benzene ring, with only hydrogens hanging off the carbons. Six carbon ring, with a hydrogen off each carbon, for the formula C6H6, this is benzene. The phenyl group is the benzene carbon ring, with five hydrogens, and a bond ready for something to be added where the sixth was, C6H5- is the phenyl group. The substance phenyl does not exist. phenyl denotes a part of a molecule, like this place in the molecule. A group is a part of the molecule, or an intermediate entity in a reaction. They are used to describe reactions.

Instead of saying bromobenzene and acetone enolate make P2P, you can describe the reaction by saying: The enolate group attacks the phenyl group, and couples with it, forming phenylacetone (P2P). Now, what is benzodioxole? Benzodioxole literally is: A benzene ring, where two of the hydrogens have been replaced by oxygens. These replacements have to be right next to each other. Oxygen forms 2 bonds, meaning each oxygen, having one bond now to this ring, is also bonded to one other thing. They are both bonded to the same carbon atom of a methylene group: (H2C=) So as you can see, we have ourselves another ring grafted into this benzene ring. A formula being CH2O2C6H4.

The phenyl group I speak of is contained within the benzodioxole. I imply the addition of the methylene-dioxy part with my statement. The exact compound you speak of that does the reacting, is benzodioxole, with a bromine atom on one carbon in the benzene ring, replacing yet another hydrogen. This bromine is all by its lonesome. I eman there is an ampty space between the oxygens and the bromine on the ring, where a hydrogen sits. The bromine cannot be next to an oxygen, or you have the wrong compound. The grignard of the compound is exactly what I just described, but with a magnesium atom between the bromine and the ring. From here on, I will refer to benzodioxole as Ph, the symbol for the phenyl group. This grignard is Ph-Mg-Br.

Now to explain the other reagent: The propanaldehyde. Simply put, this substance is: CH3-CH2-CH=O, now remember that hydrogen only forms one bond, so even though I write CHO in the end, the oxygen is not bonded to that hydrogen, but to the carbon. Grignards attack aldehydes. Now you know what part of this molecule is attacked by what part of the other molecule: The Mg-Br of the girgnard atacks the C=O of propanaldehyde. This "opens" the two membered C=O ring, so that the carbon in C=O, now has four atoms attached to it, not three. So, how can that happen? Well, the double bonded oxygen is reduced to a single bond. Now the carbon accepts one more atom, and so does the oxygen. The oxygen takes the more electropositive part: the MgBr, to form O-Mg-Br, where the O is now singly attached to our carbon I speak of in propanaldehyde.

The carbon itself, now wanting another atom, takes the electronegative phenyl group and attaches to it. When you quench the grignard, the unstable O-Mg-Br is added to an acid, HBr, which changes to O-H and MgBr2. This O-H is atached to this same carbon I keep speaking about.

This same carbon is the one that had the C=O in propanaldehyde. That C=O has changed into C-O-H, an alcohol. Now the phenyl group is also attached to that very same carbon, that part looking like Ph-C. Our new substance now looks like Ph-C-(OH)-CH2-CH3 the parentheses mean that whatever group thatcomes after them, is also attached to whatever group that comes before them. So the CH2 is also attached to the C that the OH is attached to.

As the estute evil chemist will notice, that alcohol is on the wrong carbon atom in the chain to do anything evil with it. It needs to be one more to the right, off the second carbon. So what do they do? They dehydrate this alcohol to an alkene. An alkene is a molecule with a C=C bond.

The alcohol loses water by losing the OH off the first carbon, and one hydrogen off the second carbon in the chain, forming H2O. Now each carbon, the first and the second, want to form one more bond, so they form one with each other, srengthening their bond from C-C to C=C, this is the alkene. Ph-CH=CH-CH3, isosafrole.

Why is this done with p-Tolenesulfonic acid? I can only guess, but it seems logical to me that it was selected because of its ability to dehydrate the alcohol, without cleaving the formed alkene bond. Olefin means alkene, they are the same. An olefinic bond is C=C just like alkene is. See, these little fuckers are kind of picky about what they want to be exposed to. A lot of dehydrating agents, like sulfuric acid, are also oxidizing agents. Some, like I suspect sulfuric acid, will oxidize this alkene, ripping it in half, forming two aldehydes, by the formula C=C --> C=O + C=O

So it is something you dont want to happen, as it would turn precious isosafrole into piperonal and the other half becomes acetaldehyde. So there you have it, the p-tolenesulfonic acid dehydrates our alcohol we formed with a grignard reaction, but does not rip up our alkene, which happens to be isosafrole. smile

                                                    PrimoPyro

Vivent Longtemps la Ruche!
 
 
 
 
    flipper
(Hive Bee)
01-28-02 16:56
No 261841
      Re: isosafrole from benzodioxole  Bookmark   

PrimoPyro WoW I really apreciate this. Many many Thanks.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
01-28-02 17:04
No 261844
      Re: isosafrole from benzodioxole  Bookmark   

No problem.

And by the way, I forgot to mention a comment about the statements regarding flamedrying glassware and distilling THF over sodium metal. In a word: bullshit. You dont need to do all that. Flame drying your glassware is fine, but its easier to just put it in the oven at 80C for 15 minutes (preheated) then remove and attach the unit to your already prepaired rig with moisture guard tube. As for dry THF, I think you can dry it over CaO enough for it to work. The main issue with grignard success is not the ether, but rather the cleanliness of the magnesium and the absence of any acid.

                                                   PrimoPyro

Vivent Longtemps la Ruche!
 
 
 
 
    ChemicalSolution
(Hive Bee)
01-31-02 22:34
No 263388
      Re: isosafrole from benzodioxole  Bookmark   

Primo-- TSII mentions the use of KHSO4 as a dehydrating agent.

After the Grignard product has been isolated and solvent removed, 1g KHSO4 is added and heated until H2O ceases to distill over.  Then the iso compound is distilled.

Any bee try this one?  Also, what about NaHSO4?  Would you expect this to work as well?

xoxo--Julia
 
 
 
 
    PrimoPyro
(Hive Prodigy)
01-31-02 22:44
No 263396
      Re: isosafrole from benzodioxole  Bookmark   

I would suspect NaHSO4 to be better. Isn't it more hygroscopic than the potassium salt?

                                                    PrimoPyro

Vivent Longtemps la Ruche!
 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
01-31-02 23:14
No 263412
      Re: isosafrole from benzodioxole  Bookmark   

I think KHSO4 is used because it crystallizes out, along with its water of crystallization, at a higher temperature than NaHSO4. That's another Half-a-Pint guess.

~ ~ ~ C U N D C ~ ~ ~
~ ~ 4 / 20 / 003 ~ ~
1000000 heads high
 
 
 
 
    Rhodium
(Chief Bee)
02-01-02 00:11
No 263430
      Re: isosafrole from benzodioxole  Bookmark   

KHSO4 is always used for these kind of dehydrations, but I don't know exactly why. I have a procedure here which uses CuSO4 which is oven dried to remove the waters of crystalization, and it gives good yields - the downside is the high molecular weight of CuSO4 compared to KHSO4.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
02-01-02 00:14
No 263434
      Re: isosafrole from benzodioxole  Bookmark   

Would dehydration of the P2Pol yield allylbenzene, propenylbenzene, or a mix?

Vivent Longtemps la Ruche!
 
 
 
 
    Osmium
(Stoni's sexual toy)
02-01-02 00:16
No 263437
      Re: isosafrole from benzodioxole  Bookmark   

Propenylbenzene.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
02-01-02 00:21
No 263440
      Re: isosafrole from benzodioxole  Bookmark   

Would it be possible to have you, in all your graciousness, kindly tell me why this is so? wink I honest to God believe you, but you know me, Im curious regarding the why behind the what.

Is there a definite law or mechanism that results in this specific formation of the alkene?

                                                  PrimoPyro

Vivent Longtemps la Ruche!
 
 
 
 
    Rhodium
(Chief Bee)
02-01-02 01:20
No 263459
      Re: isosafrole from benzodioxole  Bookmark   

The rule is called Zaitsev's Rule.

http://www-class.unl.edu/chem251/alkenes-1/zaitsevs_rule.htm
http://www.chem.wsu.edu/chem240/AlkeneElim.html

This is a good illustration: http://www.molecules.org/experiments/Moores/Moores.html

 
 
 
 
    ChemicalSolution
(Hive Bee)
02-01-02 05:13
No 263548
      Re: isosafrole from benzodioxole  Bookmark   

There is a similar isosafrole synthesis in TSII that starts with piperonal and uses etBr.

SWIM's only question is...

Can THF be used here?  How would this affect the workup since THF is more soluble in water than ether?

xoxo
Julia
 
 
 
 
    terbium
(Old P2P Cook)
02-01-02 07:09
No 263607
      Re: isosafrole from benzodioxole  Bookmark   

There is a similar isosafrole synthesis in TSII that starts with piperonal and uses etBr.
If one can buy piperonal then just buy safrole instead and prepare the isosafrole from safrole - a heck of a lot easier.
 
 
 
 
    ChemicalSolution
(Hive Bee)
02-01-02 08:58
No 263664
      Re: isosafrole from benzodioxole  Bookmark   

If SWIM were only so lucky!!!!!!!


SWIM takes her di-hydroxybenzene and first makes benzodioxole and THEN the procedure would apply...  Still... she finds this procedure to be more economical than brominating the subsituted benzene..

etBr is much easier to come by than subsituted bromobenzene.

STRIKE boasts 96% yield of the OH compound and 91% yield of the propenylbenzene.

xoxo
Julia