pHarmacist
(Hive Addict)
03-02-03 21:39
No 413136
      Acetylation of Anisole to p-Methoxyacetophenone
(Rated as: excellent)
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pHarmacist's voice: Surprisingly, I haven't seen any Friedel-Crafts acetylation approach to p-methoxyacetophenone discussed by bees yet. Detailed procedure below gives excellent yield (93% of pure product). I have presonaly performed the reaction some time ago and got nearly 90% yield first time I did it, so it's a very forgiving and simple reaction, yet precursor produced is valuable for our purpose.

VOGEL'S Textbook Of Practical Organic Chemistry [Fifth Edition] page 1012, Experiment 6.122


MeO-Ph + (Me-CO)2O ---AlCl3---> p-MeO-Ph-(C=O)-Me + Me-CO2H


Equip a 500-mL 3-necked flask with a double surface condenser, a sealed stirrer unit and a dropping funnel protected with a calciumchloride guard-tube. Connect the top of the condenser to the trap for absorbing hydrogen chloride evolved. Place 75 g (0.56 mol) of anhydrous, finely powered aluminium chloride and 54 g (54.5 mL, 0.5 mol) of anisole in the flask and cool the latter in a bath of ice-water. Add 26 g (24 mL, 0.25 mol) of redistilled acetic anhydride during half an hour while the contents of the flask are thoroughly stirred; much heat is evolved in the reaction. Heat in a boiling water bath for about 30 minutes (or until the evolution of hydrogen chloride almost cases) to complete the reaction, cool and pour the contents of the flask into a mixture of 150 g of crushed ice and 150 mL of concentrated hydrochloric acid contained in a beaker or flask. Stirr or shake until all the aluminium salts are dissolved. Transfer the mixture to a separatory funnel, add 250-30 mL of ether, shake and separate the upper layer. Extract the aqueous layer with 25 mL of ether and add this to organic layer previously separated. Wash the combined organic extracts with 50 mL of 10 % NaOH solution (or until washings remain alkaline), then with water, separate the organic layer and dry it with magensium sulphate or anhydrous calcium chloride. Remove the solvent by distillation under 1 atm and isolate the p-methoxyacetophenone by distillation at reduced pressure through a short fractionating column.

The yield of p-methoxyacetophenone, b.p. 139C/15mmHg, is 70 g (93%). The b.p. under atmospheric pressure is 265C.

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    Nemo_Tenetur
(Analogue Bee)
03-02-03 22:40
No 413161
      para-Methoxypropiophenone
(Rated as: excellent)
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I've used a slightly modificated procedure for the preparation of 1-(4-methoxyphenyl)propan-1-one:

1.2 moles anhydrous AlCl3 is covered with CH2Cl2. 1.1 moles propionylchloride is added in one batch and the mixture is manual shaken until most of the AlCl3 is dissolved (approx. half hour). Now a stirrbar is added and the flask is equipped with a dropping funnel with pressure equalization tube and a connected hose to introduce the evolved HCl gas in a beaker with H20. The flask is externally cooled with ice bath and through the dropping funnel is added 1 mole anisole with good stirring. This takes for larger batch sizes more than one hour, the reaction is very vigorous and exothermic.

After complete addition, remove the hose from the beaker immediately (back-sucktion!) and stirr for additional 5 minutes for complete reaction. Now pour the rxn mixture over chipped ice (careful, HCl and CH2Cl2 fumes are evolved!) and add more ice that the Al salts even dissolve (no excess ice) and stirr well. Pour the mixture in a separatory funnel and discard the lower aqueous phase (a saturated AlCl3 solution has a higher density than the organic layer), make one wash with dilute HCl to remove residual Al salts (now the upper layer must be dicarded!) and finally one wash with dilute NaHCO3 solution to remove acid traces. Dry over Na2SO4 and remove the CH2Cl2 with a hot water bath (recycle solvent), finally vacuum fractionation gives more than 80 % of theory para-methoxypropiophenone.

Notes:

The amount of CH2Cl2 is not critical, but I did not use less than 300 ml/mole for a better temperature control. If the rxn temp. becomes too high (>10C), more ether cleavage and lower yields were obtained.
The complex cleavage is, particulary in large scale rxn, a nasty and noxious thing. Even with slow decomposion a considerable amount of fumes are evolved in the environment.
It is advantageous to remove first a saturated Al salt solution, the phase separation is much easier and fewer solid (partially hydrolized) Al salts are formed in the following steps.


 
 
 
 
    GC_MS
(Hive Addict)
03-03-03 11:12
No 413289
      Acylation of alkyl aryl ethers with I2 as catalyst
(Rated as: excellent)
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Not long ago, I sent this article to a fellow-researcher since it might be helpful for his research on Friedel-Crafts techniques. It is special in this aspect that it uses iodine as catalyst. The published chemical literature contains a handful of potentially (and certainly!) interesting synthesis pathways. For instance, if one could do Post 361260 (Regis: "Internal aryl alkenes from aryl ketones (WOW!)", Novel Discourse), well, what do you want me to add? Indeed, the actual article...

Acylation of Alkyl Aryl Ethers with Iodine as Catalyst

by: Xorge Alejandro Dominguez, Beatriz Gomez, J Slim, Dora Giesecke and Ernesto Ureta B

Journal of the American Chemical Society 76 (1954) 5150

Introduction: Acylation with iodine 1,2 as catalyst, gives good yields of some alkoxy-substituted aceto-, propio-, isobutyro- and carprophenones, although the acylation of phenyl acetate, guaiacol, guaiacol acetate and bromo- and iodobenzene is unsuccessfull. We have confirmed the report that anisole does not react with succini anhydrdide in the presence of iodine 3. The preparation of 4-methoxyacetophenone, reported by Chodroff and Klein 3, who used a mole excess of anisole, has been improved.
Our experiments and those of Kaye et al 4, indicate that iodine can be used as a catalyst for the acylation of aromatic ethers by aliphatic or aromatic monocarboxylchlorideds or anhydrides, and that this method is better for the preparation of alkoxy aryl ketones than the conventional Friedel-Crafts procedure. In successful acylation, the violet colored vapors of the refluxing mixture disappeared after 15-30 minutes, but when there was no reaction, the color persisted.

Experimental 5: General procedure, 4-methoxyacetophenone - A mixture of 21.6 g (0.2 mole) of anisole, 22.5 g (0.22 mole) of acetic anhydride and 1.0 g (0.004 mole) of iodine was refluxed for three hours. The dark brown solution was poured into 100 mL of water. The mixture was extracted with ether; the ether solution was washed successively with dilute sodium carbonate, sodium bisulfite and water and then dried over sodium sulfate. After removal of the solvent and distillation of the residue under vacuum, 24 g (80%) of 4-methoxyacetophenone was obtained, bp 120-125 (5 mmHg). The yield was 50% when acetyl chloride was used. After crystallization from aqueous methanol, the compound melted at 37-38 and its semicarbazone at 197-198; reported mp 38, semicarbazone at 198-198.5 3. In the presence of 0.8 g (0.00278 mole), 1.2 g (0.0047 mole), 1.6 g (0.0063 mole), 0.2 g ( 0.00079 mole) of iodine, a mixture of 0.2 mole anisole and 0.22 mole acetic anhydride, gave yields of 68.7, 66, 61.2 and 45% respectively.
2-Methoxy-1-acetylnaphthalene - A mixture of 15.8 g (0.1 mole) of 2-methoxynaphtalene, 11.3 g (0.11 mole) of acetic anhydride and 0.5 g (0.00196 mole) of iodine gave after recrystallization from dilute alcohol, 13.2 g (63%) of 2-methoxy-1-acetylnaphthalene, mp 57; its mixed mp with an authentic specimen was 57-58; reported by Noller ans Adams, 57-58 5.

     Y
          |
          C==O
          |
          C
        /   \
       C     C--R"
       |     |
       |     |
       C     C--R'
        \   /
          C
          |
          R
         
    R         R'    R"     Y     Yield   mp
 ----------------------------------------------
   CH3O     CH3O    H   methyl    66.5  47-48
   CH3O      H    CH3O  methyl    71    42-43.5
   CH3O      H      H   methyl    66    36-37.5
   CH3O      H      H   ethyl     50    26-27
   CH3O     CH3O    H   ethyl     46.5  56-58
   C2H5O     H      H   ethyl     57    29-30
   CH3O      H      H   propyl    68    19-21
   CH3O     CH3O    H   propyl    74    59-61
   CH3O      H      H   i-propyl  42
   CH3O      H      H   penyl     49.3  38-39



Acknowledgment: We express our appreciation to Ings Carlos Lopez, Carlos Duhne and Elliot Camarena for their interest and invaluable collaboration and to Amelia Saldana and Ernesto Alatorre for their assistance - Laboratorio de Quimica Organica, Instituto Tecnologico y de Estudios Superiores de Monterrey. Monterrey, NL, MEXICO

References:
1. HD Hartough and AI Kosak, JACS 68 (1946) 2639
2. AI Kosak and HD Hartough, JACS 69 (1947) 3144
3. S Chodroff and HC Klein, JACS 70 (1948) 1647
4. IA Kaye, HC Klein and WJ Burlant, JACS 75 (1953) 745
5. *the melting points are uncorrected*
6. CR Noller and R Adams, JACS 46 (1924) 1889


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