Author Topic: Benzaldehydes to Propenylbenzenes (STP/DOM)  (Read 648 times)

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Benzaldehydes to Propenylbenzenes (STP/DOM)
« on: September 26, 2002, 05:57:00 PM »
Synthesis of 2,5-Dimethoxy-4-methyl-propenylbenzene

(a) With 1 Equiv of Base.

Ethyltriphenylphosphonium bromide (11.10 g, 0.03 mol) in 50 mL of dry THF was stirred under a N2 atmosphere with 3.36 g (0.03 mol) of commerical potassium tert-butoxide. The mixture was stirred for 2 h, resulting in an orangered colored solution. A solution of 2,5-dimethoxy-4-methylbenzaldehyde (5.40 g, 0.03 mol) in 25 mL of dry THF was added dropwise to the reaction mixture. As the addition proceeded, the color changed to bright yellow. The mixture was stirred a t room temperature for 0.5 h and refluxed overnight under an N2 atmosphere. The reaction mixture was filtered, diluted with water, and extracted three times with CHCl3 The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was taken up into a minimum of Et20, and the solution was decanted to remove triphenylphosphine oxide, which separated as a solid. The solid was washed with ether, and the combined ether solutions were concentrated and passed through a short silica gel column eluted with ethyl acetate-hexane (l:l), to remove remaining traces of triphenylphosphine oxide. The required olefin, along with some unreacted aldehyde, was rapidly eluted from the column. Concentration of this material gave a residue, which was taken up into 10 mL of EtOH and treated with 10 mL of saturated NaHSO, solution. The bisulfite adduct was removed by filtration and was repeatedly washed with ether. The combined filtrate and washings were concentrated to give the required product as a yellow liquid: yield 3.56 g (62%); bp 110-125°C (0.15 mm); GC analysis indicated the product to be 72% Z isomer and 28% E isomer.

(b) With 2 Equiv of Base.

The Wittig reaction was repeated as above but using 2 equiv of potassium tert-butoxide. Thus, 5.4g (0.03 mol) of the aldehyde and 11.1 g (0.03 mol) of ethyltriphenylphosphonium bromide with 6.72 g (0.06 mol) of potassium tert-butoxide yielded, after distillation, 2.89 g (50%) of the pure olefin, bp 105-110°C (0.05 mm). GC analysis showed it to be 97% E and 3% Z.

Reference: J. Med. Chem. 25, 526-530 (1982)


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4-Methyl-2,5-Dimethoxypropiophenone (STP/DOM)
« Reply #1 on: September 26, 2002, 06:50:00 PM »

To a solution of 15.2g (0.1 mole) of 2,5-dimethoxytoluene and 9.2g (0.1 mole) of propionyl chloride in 125ml carbon disulfide was added portionwise 13.4g (0.1 mole) of AlCl3 at such a rate that the temperature of the reaction mixture remained between 0-10°C. The addition required about 30 minutes. After stirring at room temperature for three hours, the dark green mixture was decomposed by pouring into 80ml of crushed ice and 5ml conc HCl and then filtered to yield 3.1g of a solid, mp 76-77°C. The filtrate was extracted with 2x50ml CHCl3, the extracts combined, dried over Na2SO4 and evaporated in vacuo leaving 15.6g, mp 76-77°C, which was recrystallized from 95% Ethanol to give 8.4g ketone, mp 76-77°C. Concentration of the mother liquor gave a third crop of 5.6g, mp 76-77°C, together adding up to a total yield of 17.1g (82%).

Reference: J. Med. Chem. 13(5), 1022 (1970)


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« Reply #2 on: September 26, 2002, 06:57:00 PM »
Hey Rhodium, you can use NaOH as a base for that very reaction.  the Phosphonium salt acts as it's own PTC.  DCM, Chloroform, Tetra... whatever low boiling you want to use.  probably can get away with using toluene.  you can also use acetaldehyde and the respective phosphonium salt to give the very same product.