PrimoPyro (Hive Prodigy)
10-24-02 16:08
No 372155
      Friedel-Crafts Acetonylation of 1,3-Benzodioxole  Bookmark   

Which would make MDP2P of course. Is there any specific reason it couldn't be done?

Now I know that traditional FC reactions will produce tar from destruction of the MD bridge. But consider Rhodium's proposal to acylate 1,3-benzodioxole with propionic acid as the acyl donor and polyphosphoric acid (PPA) as the lewis acid, forming 3,4-methylenedioxypropiophenone.

Now I wonder. Could chloro/bromoacetone be used in place of propionic acid, forming MDP2P? Or is there a specific reason that this could not occur? I don't think the traditional reason of "it will ruin the MD bridge" suffices this time.

The use of the free acid in the reaction I speak of makes me curious however. Is the action of PPA that of removing a hydroxyl ion from the free acid, forming the O=C(+) electrophile that attacks the ring, followed by removing a proton from the ring to have a net loss of H2O, which hydrates the PPA a little. That is one really weird question. tongue

But what I am saying is: Does the method of action of PPA provide the need for a free acid over an acyl chloride? Would propionyl chloride react with PPA in the same manner the free acid does?

The reason I ask is because I know of no method, or no citation or topic including, the preparation of alpha-hydroxyacetone. If there is one downfall to the proposed reaction, I would think that this might be it.

Can PPA extract Cl- from compounds in normal FC catalyst fashion, or only hydroxide ions? I would think this crucial to the reaction at hand. If Cl- can be extracted by PPA, then perhaps benzodioxole can be acetonylated with chloro/bromoacetone and polyphosphoric acid, forming MDP2P.


(Synaptic Self-Mutilator)
10-24-02 17:25
No 372171
      I don't think so?  Bookmark   

Don't you need a resonance-stablized acyl cation to do a Friedel's-Crafts acylation? I've never heard of a F-C acetonylation, that would have to be a free radical reaction...

Here's a refresher of the mechanism for a F-C reaction:

If you were to put the halogen alpha to the carbonyl, it will no longer be resonance-stabilized.
(Hive Prodigy)
10-24-02 17:38
No 372176
      FC "acetonylation"  Bookmark   

"Acetonylation" is an alkylation reaction specifying acetone as the alkyl function.

Don't you recall the old benzene + chloroacetone --> P2P method employed in ages past? It's low yielding, but I know it works.

(Synaptic Self-Mutilator)
10-24-02 18:31
No 372189
      Oops!  Bookmark   

Ahh! I'm kinda slow sometimes. I'm confused why that reaction works (carbons alpha to carbonyls don't make happy carbocations). Anyways, I'll duck out of this thread before I try and predict where the substitution will occur. smile
(Hive Bee)
10-24-02 22:31
No 372284
      bromoacetone  Bookmark   

will bromoacetone work as well as chloro?  better?  will KF sub as a catalyst? 
(Hive Prodigy)
10-24-02 22:41
No 372286
      *IF*  Bookmark   

*If* the reaction works, I would think that:

1.Bromoacetone would work better than chloro, since bromide is easier to remove than chloride, and

2.No, I don't think KF would work as a suitable catalyst, since I think I've read about using it as a FC catalyst for the very purpose of hydrolyzing phenylalkyl ethers, which is precisely what we are trying to avoid here. I would think it would be quite efficient at doing what we do not want happening at all, so I would not recommend it's use.

Polyphosphoric acid appears to have the curious characteristic of not tearing the shit out of arylalkyl ethers, such as methoxy substituted benzene rings, and methylenedioxybenzenes, etc. This is what would make it a desired catalyst here, for MDP2P production, or also for 2,5-dimethoxyphenylacetone production for DOX compounds.

10-27-02 20:55
No 373260
      Bromoacetone.  Bookmark   

If bromoacetone is to be used, then the correct choice of Lewis acid is AlBr3.
(Hive Prodigy)
10-27-02 21:50
No 373297
      No  Bookmark   

As was stated, aluminum halides tear up the MD ring, forming crapola. This is why 'traditional' FC reactions do not work on benzodioxole.

11-05-02 00:51
      Yes, well.
(Rated as: insignificant)
(Hive Prodigy)
11-05-02 03:29
No 376549
      Severely Off Topic  Bookmark   

Man, don't even get me started on the, "Use the common precursor." attitude.....
(Stranger / Eraser)
11-28-02 01:01
No 384026
      JACS 63,3527(1941)
(Rated as: excellent)

 Here´s an article about a quite "non-traditional"smile FC reaction I came across a while ago. I can see no reason why it shouldn´t work on substituted benzenes and Al/Hg shouldn´t be a problem for the MD bridge. What do you think?

The Use of Amalgamated Aluminum as a Catalyst in the Friedel and Crafts Reaction

It has been shown by the writer(1) that a series of alkylbenzenes could be prepared via Friedel and Crafts procedure using amalgamated aluminum catalyst. Isolated examples of the use of amalgamated aluminum or aluminum have been reported but no systematic investigation under carefully controlled conditions in which the structure and yields of products were carefully established has been carried out.(2) The identity and yields of principal products obtained were carefully established and by using this catalyst in the alkylation type reaction it was shown that the alkylbenzenes could be prepared in general with less rearrangement, formation of tars, disproportionation and dimerization than by the use of aluminum chloride in the usual Friedel and Crafts alkylation reaction.
The following series of alkylbenzenes and also s-butyl-a-naphthalene were prepared in good yields : ethylbenzene, isopropylbenzene, s-butylbenzene, t-butylbenzene, and s-butyl-a-naphthalene.

Synthesis of Alkylbenzenes

Six hundred cc. of thiophene free-benzene was placed in a liter round-bottom flask and 100 cc. distilled off to thoroughly dry the benzene and the flask. One hundred cc.of the dry benzene was mixed with 1 mole of the alkyl chloride and set aside in a stoppered bottle until ready for use. The liter flask was fitted with a 250-cc. graduated dropping funnel and a reflux condenser with a hydrogen chloride absorption device(3) connected to the lop of the condenser through a calcium chloride tube. The activated aluminum catalyst(4) was added to the benzene in the reaction flask, the dropping funnel and condenser placed in position and the chloride-benzene mixture poured into the dropping funnel. A calcium chloride tube was inserted in the top of the funnel and about 25 cc. of the chloride solution allowed to run into the flask a t room temperature. The reaction ordinarily began immediately. After the evolution of hydrogen chloride began to subside, the addtion of the chloride solution was continued at the rate of 1cc. per min. This maintained a fairly vigorous evolution of gas. About four hours were required for the addition after which the reaction mixture was allowed to stand overnight. If any moisture was present a flocculent precipitate of aluminum hydroxide formed and heating was necessary to start the reaction. After the completion of the reaction the solution was a reddish brown color and a small brown oily layer about the thickness of the catalyst was present in the bottom of the flask. After the decomposition with dilute hydrochloric acid approximately one-half of the unreacted aluminum catalyst was present. After standing overnight, the reaction was heated to gentle refluxing for five to ten minutes, cooled and washed with a 5% solution of hydrochloric acid and with water twice. The benzene layer was separated and dried over calcium chloride for distillation.
           Separation and purification of the alkylbenzenes was accomplished by means of fractional distillation using a highly efficient column 60 X 1 cm. inside dimensions. The column(5) was packed with glass helices, and fitted with a partial take off type distillation head. A column6 with a similar packed section 41 X 1 cm. has been found by Fenske to have an efficiency of 11-12 plates. The inner tube containing the packings was surrounded by an electric heater which was in turn enclosedin a Pyrex vacuum jacket. Solid p-acetamino derivatives of some of the alkylbenzenes were prepared according to the procedure of Ipatieff and Schmerling.(6)
              In conclusion, amalgamated aluminum has been shown to have certain decided advantages over aluminum chloride in alkylation reactions of aromatic hydrocarbons. (a) Higher yields of the desired product are obtained in most cases than those cited in literature using aluminum chloride(7). (b) The reaction proceeds smoothly with the formation of smaller amounts of rearranged products and tars(8). (c) The use of this catalyst affords certain manipulative advantages. 1. Temperature remains fairly constant during the entire reaction and the use of the catalyst simplifies experimental procedures. 2. Reaction may be allowed to proceed overnight without observation.

(1) Research work completed under the supervision of Dr. W, T.
Miller, Cornell University, in partial fulfillment of the requirements
for the degree of Master of Science (Thesis, 1939).
(2) Boeseken and Bastet, Rec. trav. chim., 32, 184 (1914); von Korczynski, Ber., 35, 868 (1902); Radziewanowski, ibid., 28, 1135(1895).
(3) H. Gilman, “Organic Syntheses,” Vol. 14, p. 2.
(4) The amalgamated aluminum catalyst was prepared by Washing 2 g. of granulated Aluminum metal (30 mesh) with dilute sodium hydroxide and water, then treating with 10 cc. of a 5% solution of mercuric chloride in a test-tube for two to three minutes. Small globules of mercury were visible on the surface of the aluminum after this treatment. The supernatant liquid was poured off and the catalyst washed with water, two 5-m. portions of ethyl alcohol, and several portions of dry benzene. Alternately, the benzene could be distilled from the catalyst to ensure absolutely anhydrous conditions. To activate this amalgam 3 cc. of an equal volume of the alkyl chloride to be used in the preparation was added to the amalgam in a test-tube, warmed if necessary to start the reaction and allowed to react until the gas evolution slowed down, then added quickly to the reaction flask. The activated catalyst must be used immediately.
(5) Fenske, Ind. Eng. Chem., 26, 1213 (1934).
(6) Ipatieff and Schmerling, J . Chem. Soc., 59, 1056 (1937).
(7) Schreiner, J . prakt. Chem., 81, 558 (1910); Bert, Ber., 36,
3086 (1903); Radziewanowski, ibid., 28, 1137 (1895); 33, 439 (1900),
Boedtker, Bull. Soc. Chim., 45, 647 (1929); 25, 844 (1901); 31, 966
(1904); Chem. Zentr., VIII, 12, 1112 (1904).
(8) Calloway, Chem. Rev., 17, 327 (1935); Read, THIS JOURNAL,
49, 3153 (1927); 48, 1606 (1926); Wagner, Ber., 11, 1251 (1878).