Have a good look at the schematic on this wikipedia page. Also take into account that the major product (from all reports) from the acid hydrolysis of acetaminophen/paracetamol is hydroquinone. No need to fuck around with anything else here, just follow the old industrial procedure for making phenacetin via the alkylation of that p-hydroxy group on the non-etherified precursor available in massive quantities from every drugstore/pharmacy on the planet, fuck it - here is a procedure from a school by the looks:

Conversion of Acetaminophen into Phenacetin

Background: Over 20 million pounds per year of aspirin are consumed in the US. Yet acetaminophen and ibuprofen are gradually taking over as pain relievers. In 1887 phenacetin was found to have analgesic properties, but in 1949 phenacetin's metabolite, acetaminophen, was found to be the true pain reliever. Although phenacetin still remains on the market in many mixed formulations, Tylenol and Datril contain only acetaminophen in various amounts.

Preparation: M&B Sect 6.20. The conversion of acetaminophen (H-O-paraC6H4-NH-COCH3) into phenacetin (C2H5-O-paraC6H4-NH-COCH3) is an example of the Williamson ether synthesis using a phenol as the alcohol. The net reaction is:

H-O-paraC6H4-NH-COCH3 + K2CO3 + C2H5I ---> C2H5-O-paraC6H4-NH-COCH3 + KI + KHCO3

("paraC6H4" denotes a benzene ring, C6H6, that is substituted on opposite sides. One substitution is -NH-COCH3 and the other is either H-O- for acetaminophen or C2H5-O- for phenacetin)

Set up a reaction table according to this reaction (see "Common Practices..") giving molar masses and the density of ethyl iodide. Calculate the theoretical yield based on 1.0 g of acetaminophen, 1.9 g of K2CO3 and 1.4 g of ethyl iodide. Calculate the volume of ethyl iodide needed.

The Williamson ether synthesis actually a two-step conversion to form an ether. Initially the acetaminophen reacts with carbonate to form the corresponding phenoxide ion:

HO-C6H4-NH-COCH3 + CO3-2 ---> -O-C6H4-NH-COCH3 + HCO3-

The phenoxide ion then acts as the nucleophile in the SN2 reaction with ethyl iodide to form phenacetin:

CH3CH2I + -O-C6H4-NH-COCH3 ---> CH3CH2-O-C6H4-NH-COCH3 + I-

Procedure: Crush two tablets each containing 500 mg acetaminophen (using a mortar and pestle from the stockroom). Set up the reaction in the hood with 50 mL round bottomed flasks and water cooled condensers (for several students, connect the exit hose of one condenser to the entry of the next.) Add the acetaminophen, K2CO3, 12 mL of MEK (methyl ethyl ketone or 2-butanone, b.p. 80 oC), and the ethyl iodide. Connect the condenser and reflux using a water bath on a hot plate for 1 hr.

Cool the flask in an ice bath and gravity filter the contents of the flask into the separatory funnel. Rinse some ether through the flask and filter to carry additional product into the separatory funnel. Wash the organic phase with 20 mL of 5% aqueous NaOH to remove any unreacted acetaminophen. Dry the organic layer over anhydrous Na2SO4, filter into a tared 100 ml beaker and evaporate the MEK (using a boiling stick) on the steam bath in the hood*. Record the weight.

Recrystallize the crude phenacetin from water. Collect the crystals with a small Buchner funnel and let them air dry. Record the final weight and melting point. Calculate the % yield.

*This evaporation can be hastened by using a hotplate (in the hood) but the process must be carefully watched to avoid burning the product. Just before the last of the MEK has evaporated, remove the flask from the hotplate and tip it to allow the vapors to pour out but not so much as to let the liquid pour out. The beaker is eventually tipped enough so that its rim is on the bench. If the beaker is still hot all the vapors will leave so that only crystals of phenacetin will remain at the bottom of the beaker.

Reference:

Morrison, R.T., and Boyd, R.N. Organic Chemistry, 6th ed., Prentice Hall: Englewood Cliffs, NJ, 1992

Rev. Winter, 1997

Acid hydrolysis of the phenacetin will, mind this is just a guess, give good yields of the p-methoxyphenol.

@no1uno

I don't really understand what you're getting at. That seems much longer and more difficult, never mind the use of alkyl iodides.

Everything from here down should be split... this thread is about a specific procedure.

Yeah, but no fucking around with catalysts - surely that has some benefit? That and the fact that one side, soon to the unmodified phenol side, is protected during the alkylation?

Insofar as hard to get agents - you still need alkylating agents even with hydroquinone, just paracetamol is decidedly easier to acquire (and a fucking sight cheaper) than photo-chems.

Tincture is still available - seems they still use it heaps at racing stables

Also take into account that the major product (from all reports) from the acid hydrolysis of acetaminophen/paracetamol is hydroquinone.

  could you please tell more about that?