These syntheses, employing readily available a n d commercially important starting materials, provide useful assignm e n t work. In this, groups of students a r e involved i n differe n t svntheses of "trans-ethvl isoeuaenol". T h e students are t h e n required t o m a k e a comparison of their analyses a n d vielda a n d assess t h e advantaaes a n d disadvantages of t h e procedures.
Experimental
one (100 cm?). Introduce a magnetic follower, and fit the flask with a water condenser. Assemble the flask on a magnetic stirrerhot plate, stir the contents. and adiust the heat so that the contents of the flask are -..warm hut n i t refludins -~~~~~~~Down the condenser add hromoethane (10 g. 0.09 mol) a h t t b at a time. When this ndditim is complete, raise the temperature until the contents of the flask reflux gently. Continue refluxing for about 2 h. If the carbonate goes lumpy, it will be necessary to temporarily turn off the heat source, disconnect the condenser, and break up the Lumps with a spatula or glass rod: then reconnect the apparatus, and continue the reflux. Filter the warm reaction mixture. and wash the residue with orooanone. Evaporate -~~~~~ the .... filtrate under xeduced pressure to ~roviheahout 3 e of oastv . yellow solid. Disperse this solid in dirhloromethane (50 cm 1. Pour thc solution inlo a small srparating funnel, and w a ~ hnith dilute potassium hydroxidesolution (2 X 50cm',0.05 MI. Dry the dirhlor;methane extract with anhydrous sodium sulfate, and evaporate under reduced pressure at ti0 T.On cooling. the product forms a pale yellow solid (2.8 g, 784). Recrydtailire irom industrial ethanol i m o 5 H T ~The . ouritv oithe oroduct ma\, he assessed bv'l'LC rR, = 0.41, silica gel, 2:l ether /pe&oleum spirit (4M0), uv visualiktion). The characteristic 314 pattern of the ethylgroup is prominent in the PMR. Summary of PMR: (TMS, CDCLJ 6 1.43, t, CHa; 6 3.81, s, CHBO;6 4.12, q, CH20; 6 6.82-7.38,m, CsH3; 6 9.80, s, CHO. ~~~
~
.
~
l-Etbxy-2-methoxy-4-prop-2'~ylbenzene('Ethyl Eugenol") Introduce eugenol (10 g, 0.063 mal) into a 100-cm", two-necked, round-bottomed flask. Add a solution of potassium hydroxide (4 g KOH in 8 g water), and warm the mixture to homogenize. Fit the flask with condenser and dropping funnel, and, by means of an electric heater, heat the contents to boiling while adding bromoeth: ane dropwise (8 g, 0.073 mol) from the dropping funnel over about 10 miu. Following this addition, hoil the contents of the flask for 45 min. Cool, and add 50 &'water. Extract with dichloromethane (2 X 50 c d ) . Wash the organic extract with potassium hydroxide solution (0.5 M, 3 X 30 em" then with water. Dry the organic extract with anhydrous sodium sulfate, and evaporate under reduced pressure at 60 "C. This provides 9.5 g of crude product. If stored in the freezer for a few days, it will set solid but will melt in the range 6-9 OC. TLC (silica gel, 1:1petroleum spirit (4MO)/ether, dodecaphosphomolybdie acid spray (5% in industrial ethanol)) indicates good conversion (maior ~ 0.70). Distill the . . component a s a bluesoot a t R = crude product at atmospheric pressure, collecting the fractwn boiling in the range 255-256 T.Thir provides approximately d.5 g (71Di)of purifird material. IR and PMR confirm that the product has the required structure. Summary of PMR: (TMS, CDCI3) 6 1.40, t, CH3; 6 3.27, d, CH2; 6 3.80, s, CHIQ 6 4.00, q,CHsQ 6 5.00, d, CHFC; 6 5.8, m, -CH=C; 6 6.62.. m.. CEH-. . . ( ~ e.v t: = triplet, d = doublet, s = singlet, q = quartet, m = multiplet.)
l-Ethoxy-2-methoxy-4-prop- 1'-enyibenzene ("trans-Ethyi Isoeugenol") Ethyl eugenol (4 g, 0.02 mol) is introduced into a boiling tube. Carbitol (diethyleneglycolmonoethyl ether, 1.5 cm", triethanolamine (0.2 g) and potassium hydroxide (0.2 g, 2 smell pellets) are added to the tuhe and stirred with a glass rod. The tube is supported in a clamp on a retort stand in a fumehood and heated gently, using a Bunseu burner, so as to raise the contents of the tuhe to 190°C (the contents hoil at 210 "C). The contents of the tube are maintained at this temperature for 5 min. The contents of the tube are then poured into 20 c m b a t e r . On cooling, a yellow solid is formed. This is recrystallized from industrial ethanol to provide the product as a white crystalline solid (2.8 g, (70%),mp 6 3 " ~ ) . A comparison of the UV apectra (1.0 X 10-6 M in ethanol) shows clearly the enhanced conjugation in the product. Conjugation between the ring and the side chain moves the electron transfer band (ET band) from 230 nm to 257.5 nm and the local excitation band (LE band) from 280 nm to 293 nm. The PMR confirms the structure of the product. Summary ofPMR: (TMS, CDCb) 6 1.38, t, CH3; 6 1.80, d, CH3; 6 3.80,s, CH1O; 6 4.00, q, CH20; 6 6.1, m, CH=CH; 6 6.78, m, CsH3.
4-Etho@-methoxybenzenecarbaIdehyde (4-Ethoxy-manisaldehyde)
~~~~~~~~
~~~~~
~~~~~~~~~
.~
- .
Winig Synthesis of I-Ethoxy-2-methoxy-4-prop- 1'enylbenzene ("trans-Ethyl /soeugenol") Introduce a magnetic follower and ethyltriphenylphosphonium iodide (6) (4.2 g,0.01 mol) intoa two-necked, round-bottomed flask. Fit the small neck of the flask with a septum cap and the larger, central, neck with a nitrogen reservoir (provided by a nitrogen-filled balloon (6)).Insertasyringe needle into the septum, and allow some nitrogen to escape so as to flush air from the reaction vessel. Having withdrawn the needle, inject dry tetrahydrofuran (35 cm:'). Stir the contents of the flask using a magnetic stirrer. Inject a solution of butyllithium ( 7 d , 1.6 Min hexane). Stir the reaction mixture for 30 min a t room temperature. The mixture will acquire a rich redbrown color at the end of this period. Cool the reaction vessel in a troogh of ice-salGwater so as to reduce the temperature of the reaction mixture to -7 "C. Inject a solution of ethyl vanillin (1.6 g, 0.0089 mol in 5 em" dry THF) dropwise, with stirring, over about 5 min. Following this addition, stir the reaction mixture for 1 h. During this latter period it is the coolant can be allowed to melt unnecessary to maintain -7 T; a t its own rate. At the end of the stirring the reaction mixture normally contains whitish solid. Add water (20 cm"), and isolate the ether layer. Extract the aqueous phase with dichlarometbane (2 X 20 em3).Combine the organic phases, wash with water, and dry with anhydrous sodium sulfate. Evaporate the organic extract under reduced pressure a t 40 'C. At this stage the required product is contaminated with triphenylphosohine oxide. This mav be senarsted from the ethyl isoeueenol bv column chrometo~.r&hv eel 60-120 mesh.-ethedietbanil , (&a . (200:lO)eluant); the ethyl isoeu&ol elutes first. Final purificatim is achieved by recrystallization from industrial ethanol (the product is soluble in hot solvent hut only sparingly soluble in cold). A yield of purified material in the order of 1g (59%)is expected. Melting point and spectral characterization is as previously recorded. ~
~~
~~~~~
"~~.~
Lfleraiure Cited 1. Uniiaver Ltd. E~trnrfiono/Clova
Oil and the Isolation of Eugenol; Information Division, Unilever Hause: Blaekfriars, London. 2. Mann. d. Sacondory Metabolism; 2nd ed.: Oxford Univ.: Oxford, 1980; Chapter 4. 3. Tiemsnn. F.: Mends1sohn.B. Deul. Chem. Gas.Ber. 18'76.9.127a1284.
Introduce vanillin (3g, 0.02 mol) into a 250-cm' conical flask. Add anhydrous potassium carbonate (10 g, small granules) and propan-
Volume 66
Number 8
August la91
699
