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Nucleophilic Substitution by Benzodithioate Anions Chantal Bonnans-Plaisance and Jean-Claude Gressiw Laboratoire de Photochimie Organique, Faculte des Sciences, Universite du Maine, 72017 Le Mans, France Nucleophilic substitutions are often misunderstood hv the average student. Numerous concepts that are theoreti"cally introduced often remain ill-assimilated. A practical illustration is a good means to improve the student's knowledge, hut it is often difficult to find literature examples of nucleophilic suhstitution, without side reactions, that lead to easily isolated products and that are suitable for the limited time of the lab session. Recently, we have perfected the synthesis of quaternary ammonium salts of carhoxydithioic acids. Three papers devoted to their reactivity have been published (1-3). These compounds which are strong nucleo~hilesand sliehtlv - .basic reagents, do not lead to eli&ation &en with very sensitive compounds such as poly(vinylchloride) (4). Students in the third year of chemistry in our university take a course entitled "Mechanisms in Organic Chemistry", which exposes them to the different problems of nucleophilic suhstitution. The following experiment has been used to illustrate the Grignard reaction and nucleophilic suhstitution. Procedure A complete study requires two sessions. In the first the henzodithioic quaternary ammonium salt is prepared, and in the second the reaction of this salt is examined with different halogenated compounds. The resulting products are analyzed by 'H NMR. In addition, a kinetic study using UV-visible spectrometry can he used to show the S Nreac~ tion with epichlorohydrin. First Session Each student prepares a quaternary ammonium salt of a henzodithioic acid. Aromatic compounds are used because their stabilities are greater than those of alinhatic compounds (5). The synthesis consists of adding CS2 to the Grignard reagent of an aromatic halide in a tetrahvdrofuran solution (6).~ i t h i o a c i d sare unstable and are n i t isolated hut are extracted with hexane iust after hvdrolvsis of the magnesium salt. A commercial alcoholic solution-of quaternary ammonium hydroxide (tetramethyl or henzyltrimethylammonium) is added to form the quaternary ammonium benzodithioic salt; the reaction is fast and quantitative. This four hours for eood vields. The formation first step . reauires . of phenylmagnesium bromide &d the addition of CS2 are the slow steps. This svnthesis also illustrates the effect of solvent in the rig nard reaction since no reaction occurs if diethyl ether rather than tetrahydrofuran is used (6).
character of the quaternary ammonium salt (dichloromethane exhibits a similar reaction with thiolate anion (8)). 3-Chloro-l-hutene to show the allvlic rearrangement. Epichlurohydrin to show the rearrangement durrng the S N ~ reartion and fc,r the kinetic study using the strung ahsorbancrs near 320 nm tr n' transitiun) and 520 nm rn n' transition) due to the thiocarbonyl group. The bicyclic compound I , synthesized from eniehlorohvdrin. ~-~ . . does not absorh in the visihle ranee: the kinetics of its formation is monitored hv -,the ---decreasini nbsorbance of th? salt at 516 nm, usmg such condition, at w h ~ hthr internal nucleophilic substitutim leading to brni.yldithrohenaoa1r (2) (91, is wry slow (temperature below 25 T I .
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Experimerital Synthesis of BenzyltrimethylammonlumBenzodithioate Operate in a fume hood. Glassware must he oven dried just before use. Asolution of bromobenzene (15.7 g,0.1 mol) in anhydrousTHF (100 mL) is added for 30 min to magnesium turnings (2.5 g, 0.105 mol) under nitrogen flow at 40 OC. A crystal of iodine or a drop of bromine may help to start the reaction. The mixture is stirred for 30 min more at 50 "C to complete the reaction. After cooling to 20 "C, CS2 (7.8 g, 0.1 moll in anhydrous THF (40 mL) is slowly added (cooling with a water bath may be necessary), and the mixture is allowed to react for 1.5 h. (Caution: Keep all flames away from CSg, and be certain the system is kept well back in the hood to prevent escape of the CSz into the laharatory.) Two-thirds of the solvent is removed by a rotatory evaporator without warming (helow 25 OC). The remainder is poured into a mixture of ice (100 g), 10 N hydrochloric acid (50 mL), and hexane (80 mL). The free dithioacid is extracted with hexane (2 X 50 mL) and the collected organic phases are dried by anhydraus magnesium sulfate. After filtration, the
Second Session During the session each student uses the ammonium henzodithioate salt to demonstrate a parii(.uIar facet of the Su2 mechanism. Several alkyl halidescan he used (see figure);'
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1-Bromo-3-chloropropane to show the selective reactivity of the halogens. 1,2-Dihromoethane to show the anchimeric assistance of the first introduced benzodithioate group to the second bromine substitution; even with a large excess of dibrominated eompound, the reaction always leads to the disubstituted product. This mechanism is similar to the hydrolysis of 2-chloroethyl ethyl sulfide (7). Dichloromethane (often inert) to show the strong nucleophilic
Reaction mechanisms
Volume 65
Number 1 January 1988
93
solution is concentrated to about 50 mL. In order to avoid an excess, which prevents the crystallization of the salt, a lack versus the stoiehiometric amount of benzyltrimethyl ammonium hydroxide (35 g of a commercial 40 wt % solution in methanol) is added to the henzodithioie acid solution. The mixture is evaporated to dryness under vacuum. The deep purple or violet crystals of benzodithioic ammonium salt are washed with cold hexane and dried at room temperature (yield 70-80%). Characteristics:mp = 87 'C; 'H NMR (6, CDsOD, TMS): 3.05 (s, 9H N(CH&); 4.50 (8, 2H, CH2); 7.30 and 8.20 (m, 5H phenyl ring); 7.55 (s, 5H, henzyl ring). UV-visible (THF) A,, = 516 nm (log c = 2.12); 368 nm (log c = 3.83).
ume is adjusted at 100 mL with the solvent mixture. Methanol facilitates the dissolutionof the salt 1 and prevents the precipitation of the quaternary ammonium chloride during the reaction, which disturbs the measurements. The kinetics is monitored at 516 nm (cell 1cm, ref. THF); theabsorbance (At)ofthe solution ismeasured ever" 5 min for an hour. Absorbance for t = 0 (An)and fort = ( A J can be determined graphically by extrapolstion can the curve A, = f(1,. According tu theslope of the curve
Nucleophilic Substitution of Halogenated Compounds with 1 Salt 1 (3.03 g, 10 mmol) in THF (30 mL) is stirred with the stoiehiometric amount of halogenated compound at room temperature for 2 h. It does not matter if some crystals remain undissolved, since dissolution will occur during the reaction. The color of the solution changes from deep purple to bright red (discolorationwith epichlorohydrin) as the henzyltrimethylammonium halide precipitates. After filtration and evaporation of the solvent, the reaction mixture is diluted with several milliliters of hexane and cbromatographed on Si01(-15 g in a 0.5-in.-diameter column), using hexane or hexsneTHF according to the solubility of the product. Red products are collected and are recrystallized from methylene chlaride and hexane, with yields around 75%. Physical ondlHNMR characteristics ( 8 , CDCb, TMS) of benzodithioates: 3-Chlorupropylbenrudithioatr (3). Eluant: hexane; redoil bp = 104 'C tdec) 2.10(m, 2H,(.Hz,; 3.50 and :I60 (dl, 4H, CH-CI, nnd C H.A I..: 7.GOand 8.10 lm. ohenvl . . 5H. .. . erounr .. Ethylene his(benzodithioate) (4). Eluant: hexsneTHF 80-20, mp = 105 'C; 3.70 (s, 4H, CH2); 7.50 and 8.10 (m, 5H, phenyl rind. ~ e t h ~ l ehis(benzodithioate) ne (5). Eluant hexane-THF 80-20, mp = 124 O C ; 5.40 (a, 2H, CH2),7.50 and 8.10 (m, 5H, phenyl
a second-order rate constant is easilv found (first order toward each reactant). Found: k = 3 . i 0 - ~mollmin a t 25 O C ; ordinate for origin: 0.96; (correlation coefficient 0.993).
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2-Butenyl benzodithioate (6). Eluant: hexane; red oil hp (0.1 mm) 130-132 ' C ; 1.70 (d, 3H, J = 6 Hz); 3.90 (d, 2H, J = 7.5 Hz); 5.40 and 6.10 (m, 2H, alefinic H); 7.20 and 8.10 (m, 5H, phenyl ring). l-Phenyl-7-oxa-2,6-dithiahicyelo[2.2.l]hept(7). Eluant: hexane:. mn: . 82-83 "C. The ABX svstem exhibits a null eoupling constant between two protons making a 909 dihedral angle (JAX= 0)according tothe Karplusrule (10).Thisis easily shown witha Dreiding model; 3.30 (d,2H, JAB = 9 HZ);3.70 (dd, 2H, JAB = 9 HZ,JBX = 5.5 HZ);5.80 (t, lH, JBX = 5.5 Hz); 7.50 and 7.70 (m, 5H, phenyl ring). Kinetic Study with ~ ~ i c h l o r o h ~ d r ~ i n In a 100-mL volumetric flask, 1 0 mmol (0.303 g) of salt 1 is dissolved in 80 mL of THF-methanol (80-20). The stoichiometric amount of epichlorohydrin (0.096 g) is added quickly and the vol-
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Quaternary ammonium benzodithioates provide a variety of possibilities for student experiments. T h e time required for each experiment is convenient for laboratory session, and collecting the results obtained by students working on homologous benzodithioates or with different reagents affords the possibility of obtaining a broader view of the multiple facets of the nucleo~hilicsubstitution. Different hrominated compounds ran be used for the synthesis of the salt (bromochlorot~enzene,bromoanisole, bromntoluene,etr.) in order tosrudy further the influenceof the suhstituent on the reactivity of the salt (1.2). Starting materials are inexpcnsiw, commerrially availat~lecom~~ounds.'l'hey are used without further purification. Synthesized productsaresafe: somedithiocarboxylates have been patented for skin protection from IJV radiation (11). In 1985. the averaee cost for the svnthesis of a benzodithioate salt and its reaction with a halogenated compound is estimated t o FF. 60.00 (-US58). t h a t is. FF. 30.00 (US54) for one student per session. Literature Clted I. Bonnsns-Plaiaance, C.; Gr-ier, J. C.: Leuesque, G.:Mshjoub, A. Bull. Soc. Chim. Fmnce 198L5.891. 2. ~onnsna-Plai&n&& Iavesque, G. Makromol. Chsm., 1986,187,2841. 3. Bonnsns-Plai-ce. C.; Gressier, J. C.; Levesque. G. Mokromol. Chem. Rapid Corn. mun. 1983.4.337.Gr-ier.J.C. J.MoeromoleeulorSri.Chem. 1986.A23(11),1263. 4. Roth, J.P.; Rempp,P.:Psrrod,J. J.Polym.Sci. 1984,Cd.1347. 5. Schoufs, M.; Meijer, J.;Verrneer, P.: Brandsma,L.Synthesis 1978,439. 6. Beiner, J. M.: Thui1licr.A. C. R. Acod. Sei. Pork 1912,274,642 and references cited. 7. 86hrne. H.;Sall, K.Bsr. 1948,81,123. 8. Cohen,T.;Ruffnor.N. J.:SchuU,D.M.:Fogd.E.R.:Falek. J.R.Orp.Synlh.1979.59, 202.
9. Leon, N. H.: Asquith, R. S. Tefrnhadran 1970,26,1719. 10. Bovey, F. A. Nuclear Magnetic Resonome Spectroaeopy;Autdemie: New York, 1969: P 135. 11. Reneh Patent
2396545, 1977: Mullcr.
D.; Leveaque,
0. Cham. Abatr. 1919, 90,
P127404v.
A "Tea Bag" Drying Technique Drying organic liquids implies in most cases a tedious filtration step in order to remove the drying agent. We have simplified this procedure by placing the drying agent in a "tea hag" made with filter paper and tied with a suitable fiber such as nylon, polypropylene,or cotton. The organic liquid is introduced into a flask along with the "tea bag", whose string is caught by a stopper or a septum. Once the liquid is dry, the drying agent is simply pulled out. Nicholas M. lrvlng CINDEV
Apartado 282-C, Zona 15 Guatemala. Guatemala
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J. rnal of Chemical Education
