edited by

ARDEN P. ZIPP
SUNY-Conland
Coniand. NY 13045

The Microscale Synthesis and The procedure described here contains and a 3-mL conical vial containing a spin
several changes in addition to reducing vane. Let cool to room temperature in a des-
Purification of N,IY-Diethyl-m the scale of the synthesis. Specifically, iccator. T o the vial add 136 mg (1.00 mmol)
Toluamide [Deet) his(trichloromethyl)carbonate, triphosgene of pure m-toluie acid, 0.50 mL of methylene
(4), is used as the chlorinating agent and chloride (CHC$) and stir until the solid
flash chromatography (5) is employed as a dissolves. T o this solution add 100 mg (0.34
An Experiment for a Project-Oriented ~urificationmethod. Triphosgene (6) offers mmal) of triphosgeneZand one drop of dry
Organic Chemistry Laboratory several advantages over thionyl chloride. dimethylformamide (DMF). Fit the vial
Triphosgene is a solid, which is required in with the Claisen head. Cap the opening
smaller amounts (only 113 equivalent rela- above the vial sndadd the condenser (fitted
tive to 2) and gives a cleaner reaction with- with the drying tuhe) to the other opening
out the formation of Son or dark-colored (4). Connect a piece of Tygon tubing from
impurities. Flash chromatography is espe- the drying tuhe to a small, inverted glass
cially well-suited to the microscale purifica- funnel placed just under the surface of a 10%
Joseph W. LeFevre tion of deet since it provides students with NaOH solution in a beaker to neutralize the
State University 01 New Yak, College at Oswega experience in column chromatography, HCL generated during the preparation of 3.
Oswego. NY 13126 whieh is rapid because air pressure ia used to Heat the solution in a sand bath under re-
speed the separation. Thin-layer chrama- flux conditions for 1h. Buhhles of C 0 2 and
A popular experiment in undergraduate tography (TLC) may he used to choose the HCI can be observed in the gas trap shortly
organic laboratories is the synthesis and pu- correct solvent for the column separation after the reaction begins. The acid chloride
rification of Nfl-diethvl-m-toluamide. deet and to analyze the collected fractions if de- (3) is not isolated but is reacted in situ ac-
( I ) , whieh is the active ingredient in many sired. cording to the procedure below.
commercial insect repellents such as "OFF" The synthesis can be broken down into
and "Jungle Juice 100".L In this paper a two steps; the conversion of rn-toluic acid Conversion of m-Toluyl Chloride (3)
microscale synthesis and purification of (2) into m-toluyl chloride (3) (eq I). into N,N-Dlethylm-toluarnide ( 1 )
deet is described. Previous authors (13) and the conversion of the acid chloride (3)
have synthesized deet on a multigram scale todeet ( I ) by treatment with excess diethy- During the reflux period place 0.50 mL of
by converting m-toluic acid (2) to rn-toluyl lamine (eq 2). CHzClzin a dry 1-mL conical vial and add
0.22 mL (2.15 mmal) of freshly distilled
diethylamine via an automatic delivery pi-
pet. Cool the solution to 0 OC in an ice bath.
After the reflux period has ended, cool the
clear, pale yellow reaction solution to 0 "C.
Using a dry l-mL syringe inserted through
the Claisen head, add dropwise at 0 'C over
several minutes the diethylamine-CHgClz
solution. The acid chloride is quite reactive
and a copious white precipitate of diethyla-
mine hydrochloride forms immediately. Af-
ter all of the diethylamine has been added,
test for basicity with a micropipet and lit-
mus paper, and, if necessary, add more
diethylamine dropwise until the solution is
basic. Let the vial warm to room tempera-
ture to complete the reaction.
Extract the solution with 1 mL of 10%
NaOH to remove any unreacted rn-toluic
acid. Extract the lower CHC12 layer with 1
mL of 3 N HC1 to remove the diethylamine
hydrochloride followed by a l-mL water ex-
traction. Dry the CH2C12layer with 150 mg
of granular anhydrous sodium sulfate
(NarSOn). Transfer the solution to a dry,
tared 10-mL Erlenmeyer flask using a Pas-
teur filter pipet. Rinse the NanS01 with a
fresh 0.30-mL portion of CHzCIz. Evaporate
the CH2C12by leaving the flask unstoppered
in the hood until the next laharatory period
chloride (3) with thionyl chloride. Treat- Experimental leaving crude deet as a pale yellow oil.
ment of (3) with excess diethylamine pro- Synthesis of m-ToW Chloride (3) from
duces deet, which can he purified by either Purification of N,N-Diethylm-toluamide
vacuum distillation or column chromatogra. m-TOIUICAdd (2) (1) by flash Chromtogr~phy
phy on alumina. Following the completion
of our work a microscale synthesis of deet Oven-dry a micro-reflux condenser, a Prepare 250 mL of solvent, 2:3 (by vol-
appeared (4). CaCl2 drying tube, a microClaisen head, ume) ethyl aeetate:petroleum ether (b.p.

A278 Journal of Chemical Education

30-60 "C). These solvents should he dis- m-toluvl chloride (3) and. oresumnhlv. m- iect. T.indn LeFevre for helo in orranizinc
tilled prior t o use. Pack a chromatography
column (30 em long, i.d. 7 mm) with -15 gof
silica gel using the slurry technique. Silica diethylamine, and anew spot corresponding York, College a t Oswego for its support of
Gel 60 (E. Merck #9385) particle size to deet ( I ) appears a t Rr = 0.30. After flash the Chemistry Department.
0.040-0.063 mm (230-400 mesh) was used. chromatography the deet is detected no ear-
Prepare asimple air flow controller by plac- lier than fraction 6 and is usually ~ foff the Literature Clted
~~ ..
ine,. a number-two rubber s t o ~ o e rwith a column by fraction 15, Student yields of pu. I.Pavia.D. L.iL~mpman.GM.:Kriz,G.S. Introduction
to Orpnnic L o b o r a t o r y Techniques, 3rd ed.:
hale runraining a glass Y joint i r m l v in t h e rified deet ranged from 22 to 68% with an Saundes: Phiiadelphia. 1988:pp 123-126.
top 001t h e c o l u m n . C o n n e c t apiece oi'l'ygon average of 51%. 2. ~ehmsn.J. w opwotionai organic chemistry, 2nd
tubing from one opening of the Y joint t o the A proton NMR temperature dependence ed.: AM and &con: ~oston.1988:pp 365-377.
study in CDC& easily he performed to 3. W a w B.J-S. J. ChmEduc. 1974.51.631.
air valve. Open the air valve slightly and use 4. Pavia.D.L.;Lampmsn.G. M.:Kiiz.G.S.:En8el,R.G.
an index finger to adjust the pressure so that illustrate the hindered rotation around the Introduction to Orgonic Labomtory Techniyucs-A
solvent flows through the column a t a rate of C-N amide bond (7). The two quartets ex- ~icrnscole~pproaeh:~sundor~: ~hiladelphis.1990.
1in.130 s (5). Collect 20 10-mL fractions in petted for each nonequivalent methylene 5 . St3i.C. W.: Kahn, M.;Mitra,A. J. Org. Chsm. 1978.43,
numbered test tubes. Check for the pres- group at room temperature and a 2923.
6. &kerf, H.;Forster. B. Angaw. Chem. Inf. Ed. Engi.
ence of deet in the fractions by TLC. Thin- broad m u l t i ~ l e tare observed. As the tem- ."
-.,-.
,us7 98,4, 1196
layer chromatograms were run on 0.2-mm perature is raised and free rotation begins to 7. Stowan. W. E : Siddi, T H. Chsm. Re". 1970, 70,517.
occur about the C N bond, the two methyl- 8. Silueira, A . Jr. J. Chem. Educ. 1978.55.57.
thickness Silica Gel 60 F254 plates with a 9. Silueira.A..Jr.:Satra,S.K.J.O~g.Chrm.1979,41.873.
plastic backing (E. Merck #5735). The ene groups condense into a single sharp LO. Silveira.A.,dr.: Bretherick, H. D.; Negi8ht.E. J. Chem.
spots were visualized hy a UV lamp a t 254 quartet a t 90 T. Educ 1979,56,560.
nm. Combine the deet-containing fractions Oswego has been quite active in recent 11. Silueira.A..Jr.; Koehier, J.A.;Beadei,E.F., JI.:M~"-
roe.P.A. J. Chem.Educ. 1984.61.264.
and evaporate the solvent under reduced years in there types of project-oriented l a b s 12. Siluelra.A..Jr.;Oriando,S.C.J.Chem.Educ.1988.85,
pressure leaving pure deet as a colorless oil. (6-12,. Thw project was performed h) pairs 630.
A proton NMR spectrum (in CDCls) end/or uf srlrdents in our ad\,anrerl rhemi;tru lab- 13. Mayo, D. W.; Pike, R. M.; Butcher, S. S. Microrroie
oratorv in a series of three 3-h labs. The OrsonieLaboratnry.2nd ed.; Wiley: New York, 1989.
an IR spectrum (neat) can be run.
micro&ale techniques employed are de-
Discusslon scribed in detail by Mayo, e t al. (13). The ' Jbngle Ju CB 100 is 9 5 % pure oeet and can os
experiment provides students with valuable p ~ c h a s e IromRecreat
d onal Eqwpment. 1°C.. P 0
Valuable TLC experience can he gained experience in functional group conversion, Box 88125 Seance. WA 98138-0125 1 servesas
by having students determine the correct acid-base chemistry, flash and thin-layer an excellent TLC standard.
composition of the flash chromatographic chromatography, and NMR interpretation. * Triphosgene can be purchased horn Aidrlch
solvent, which should give an Rr value of Because the materials are low-cost, the pro- Chemical Company. Inc., PO. Box 2060, Mllwau-
0.35 (5) far deet. Also. the Droeress of the ject can easily he incorporated into the mi- kee, Wi 53201 (Catalogue number 33,075-2).
reaction can be convenientl; monitored bv
~~ ~~~~ ~

croscale organic laboratory. The spot at R, = 0.71 has an Identical Rr value

obaervmg t h e disappearance o f t h e spot cor- t o that which results from the treatment of m t o i u i c
rr~pondingto m-tduic acid (2) a t R = 0.40 Acknowledgment acid with 0.5 equlvslent.of dicyclohexylcarboai-
(solvent-ethyl acetate:petroleum ether, 1:2 imide at room temperature In tetrshydmfuran.
by volume) and the appearance of two new J. W. LeFevre thanks the students in These conditions are known t o produce anyhy-
mots s t Rr = 0.79snd 0.71 corresponding to Chem. 334L for their hard work on thjs pro- drides.

Volume 67 Number 11 November 1990 A279