[CONTRIBUTION FROM THE DEPARTMENT OF RESEARCH IN PURECHEMISTRY, MELLONINSTITUTE]
THE ACTION OF SODIUM IODIDE ON SOME ESTERS OF p-TOLUEKESULFONIC ACID' R. STUART TIPSON, MARY A. CLAPP,
AND
LEONARD H. CRETCHER
Received July 29, 19.48
In 1897 it was observed (1) that potassium iodide (in hot alcohol or acetone) converts ethyl p-bromobenzenesulfonate to ethyl iodide. Many years later, methyl and ethyl iodides (2, 3) and ethyl a-iodopropionate (4)were prepared in good yield by the action of the same reagent (in boiling water or alcohol) on the corresponding p-toluenesulfonates. The method was next applied ( 5 ) to the preparation of diisopropylidene-6-iododesoxygalactosefrom the 6-tosyl derivative, with the improvement of using Finkelstein's reagent (6), namely, sodium iodide dissolved in acetone. Further research has, however, been mainly confined to study of the behavior of tosyl esters of sugar derivatives (7) towards the reagent and it has been found that a primary tosyloxy group is much more reactive than a secondary in such aldo-sugar derivatives as methyl 2,3,4,6tetratosyl-p-D-glucoside. The reaction is usually found to proceed as an alkyl-oxygen fission (8) in accordance with the equation:
0
/I
R-O-S-C7H7
/I
+
NaI
=
RI
+
C7H,S03Na
0 hut a tosyloxy group on the primary alcoholic carbon 1 of certain keto-sugar derivatives is unreactive (9) and if a secondary tosyloxy group is adjacent to a primary tosyloxy group, the formation of an unsaturated substance and free iodine can occur (10). Furthermore, the tosyl esters of naphthol (3), phenol (3, l l ) ,and apocupreine (11) are unreactive, but that of 2,4-dinitrophenol gives rise (11) to p-tolyl 2,4-dinitrophenyl sulfone, together with sodium 2,4-dinitrophenate, sodium p-toluenesulfonate, and free iodine. Now, in attempting to prepare certain P-iodoethyloxyquinolinederivatives we decided to investigate the action of sodium iodide (dissolved in acetone) on the corresponding p-p-toluenesulfonyloxyethyloxycompounds. We found that the reaction proceeded with great rapidity at room temperature, crystallization of sodium p-toluenesulfonate commencing after a few minutes. Intrigued by this reactivity, which is so much greater than that displayed by a tosyloxy group on the primary alcoholic carbon of many aldo-sugar derivatives, we decided to study the behavior of a number of simple esters of p-toluenesulfonic acid, particularly because, in using such esters as alkylating agents by virtue of their alkyl-oxygen fission, it would be advantageous to know their approximate relative reactivities, 1
A brief abstract of part of this work was published in Chem. Eng.News, 22,515 (1944). 133
134
R. S. TIPSON, M. A. CLAPP, AND L. H. CRETCHER
in order to facilitate selection of the optimum conditions for performing any particular alkylation. In addition, possession of this knowledge would permit choice of the best procedure for preparing the ester to be used as alkylating agent. Since a high degree of precision appeared unnecessary for our purposes, a method which appeared to us to hold some promise for estimating approximately the ease of replacement of the tosyloxy group was to determine the per cent of sodium p-toluenesulfonate formed on treatment with sodium iodide under standard conditions-the action of 2 molar proportions of sodium iodide (10% solution in acetone) at room temperature or during 2 hours at 100" (sealed tube). It is assumed that the resulting solutions or suspensions were not supersaturated with respect to sodium p-toluenesulfonate. The question of the mechanism of TABLE I ACTIONOF SODIUMIODIDE IN ACBTONEON ESTERS OF p-TOLUENESULFONIC ACID
I
PEE CENT YIELD OF SODIUM fi-TOLUENXSULFONATE AT ROOY TEXPEBATURE
9-TOLUENESULFONIC ESTER OF
2 hr.
Benzyl alcohol., . . . . . . . . . . . . . . . Methanol ...................... Ethanol. . . . . . . . . . . . . . . . . . . . . . . n-Propyl alcohol, . . . . . . . . . . . . . . ,%Ethoxyethanol. . . . . . . . . . . . . . . 8-Phenoxyethanol . . . . . . . . . . . . . . 0-Benzyloxyethanol . . . . . . . . . . . . Dimethyl carbinol. . . . . . . . . . . . . Diethyl carbinol.. . . . . . . . . . . . . . Di-n-propyl carbinol. . . . . . . . . . . Ethylene glycol (diester). . . . . . Borneol. . . . . . . . . . . . . . . . . . . . . . . 2-Menthol . . . . . . . . . . . . . . . . . . . . . Cyclohexanol . . . . . . . . . . . . . . . . . . Thymol. ......................
97 96.5 51 49.5 14.5 12 13 7.5 23 24 16* 0 0
a* 0
I
24 hr.
IN SEALED TUBE AT 100'
2 hr.
97 99 99 9s 68 67 69 53.5 85 73* 0 1.9* 15* 0
61.5* 91* 98* 0
I
* Free iodine liberated.
reaction of the various p-toluenesulfonates with sodium iodide will not be considered here. The results are given in Table I, from which it may be seen that, with a variety of simple esters of p-toluenesulfonic acid, the order of their activities is comparable with that observed by Conant et al. (12) for the corresponding organic chlorides treated in a somewhat similar manner. They did not study the behavior of methyl chloride but it has been shown that methyl benzenesulfonate is more reactive than the ethyl ester towards alcohols (13). The p-toluenesulfonates of some phenols, like the simple aryl chlorides (12), do not react. Thus, the thymyl ester is devoid of activity but its hexahydro derivative, the menthyl ester, is more reactive than bornyl and only slightly less reactive than cyclohexyl p-toluenesulfonate. Iodine was liberated in the re-
SODIUM IODIDE WITH TOLUENESULFONIC ESTERS
135
actions with the last three, presumably owing to the presence of an adjacent labile hydrogen atom and resulting formation of the corresponding unsaturated hydrocarbon. This behavior resembles that of certain vicinal ditosyloxy derivatives (lo), a further example of which, ditosyl ethylene glycol, is given in Table I. The benzyl and methyl esters are very reactive, the ethyl and n-propyl esters considerably less so. The activity of the ethyl ester is diminished by introduction of a P-alkoxy group; the ethoxy, phenoxy, and benzyloxy derivatives have about the same reactivity. The esters of the secondary alcohols are less reactive than those of the primary alcohols, and diethyl is more reactive than dimethyl carbinol. Conant (12) remarked on the low reactivity of cyclohexyl chloride; the p-toluenesulfonate is similarly of rather low reactivity. It is well known that the highly reactive ethyl and benzyl p-toluenesulfonates cannot be prepared by the reaction of p-toluenesulfonyl chloride on the respective alcohol in pyridine at room temperature, owing to formation of their pyridinium salts, but can be prepared from these reagents under appropriate conditions (14). We now find that the esters of isopropyl alcohol, menthol, cyclohexanol, and thymol, which prove to be less reactive toward sodium iodide, can be prepared in excellent yield by tosylation at room temperature. Attempts to isolate the p toluenesulfonates of phenyl methyl carbinol and diphenyl carbinol were fruitless, confirming similar work by Kenyon et al. (15). EXPERIMENTAL
Esters of p-toluenesulfonic acid. These were prepared by one or other of the methods previously described (14). Benzyloxyethyl p-toluenesuZjonate was prepared and purified as described by Clapp and Tipson (16). The following information appears t o be new. Benzyl p-toluenesuljonate was recrystallized from chloroform (2 vol.) plus hexane (10 vol.); m.p. 55-56'. It was kept a t room temperature in a vacuum desiccator over phosphorus pentoxide and soda-lime for over three days before decomposition, as evidenced by change in melting point, set in. Ethyl p-toluenesulfonate was recrystallized from ether (2 vol.) plus pentane (4 vol.); m.p. 33-34 O. n-Propyl p-toluenesulfonaie boiled at 106-108" a t 0.06 mm. (bath temp., 120"); i t was a colorless liquid. Dimethyl cdrbinyl p-toluenesuljonate was obtained in 75% yield by the general method (14) (2 hours at 0') ; in 60.5% yield after 24 hr. at room temp.; in 90% yield after 2 hr. a t room temp. It showed a tendency to decompose on distillation at high vacuum. However, a portion which distilled as a colorless syrup, before decomposition set in, boiled a t 107-109" at 0.4 mm. (bath temp. 114-115'). On cooling, i t gave a solid mass of colorless crystals, m.p. 20'. A n a l . Calc'd for C I O H I ~ O ~S,S 14.97. : Found: S, 14.53. Itj could be crystallized, without distillation, from ether (2 vol.) plus pentane (12 vol.) by cooling in solid carbon dioside-chloroform and then keeping overnight in the ref&verator (5"). Di-n-propyl carbinyl p-toluenesulfonate was obtained as a pale yellow syrup in 60.5% yield (24 hr. a t room temp.). It was freed from traces of solvent under a high vacuum at rooni temperature, since i t decomposed on attempted distillation. A n a l . Calc'd for C14HZ208S:S, 11.86. Found: S, 11.47, 11.35. 1-Menthyl, cyclohexyl, and thymyl p-toluenesulfonates were prepared as described for the bornyl ester (14) in yields of 96.5%,98.5%, and loo%,respectively.
136
R . S. TIPSON, M. A. CLAPP, AND L. H. CRETCHER
I-Menthyl ester. The crude, colorless crystals (m.p. 91-93') were recrystallized from hexane (5 vol.), m.p. 93-95'. Again so recrystallized i t had m.p. 94-95', [CY] -68.2' (in chloroform). Hilditch (17) gave m.p. 97", [CY] -66.8" (in chloroform). Cyclohexyl ester. The crude, colorless crystals (m.p. 4243") were recrystallized twice from ether (1 vol.) plus pentane (2 vol.), m.p. 45-46". Huckel (18) gave m.p. 44-45". T h y m y l ester (20.2 g.) was reorystallized by dissolving in 1.5 volumes of dry ether a t room temperature, adding 1.5 volumes of pentane, filtering, and cooling, t o give a first crop of 10.6 g. of colorless crystals, m.p. 69-70'. On recrystallization from 3 volumes of ether plus 3 volumes of pentane, i t had m.p. 71-72'. A n a l . Calc'd for ClrH,oO8S: S, 10.54. Found: S, 10.60. Attempted preparation of diphenyl carbinyl p-toluenesulfonate. (9) In pyridine during 2 hours at 0"or 84 hours at 86". No crystals of pyridine hydrochloride formed. The original weight of unchanged, crystalline diphenyl carbinol was recovered, m.p. 65-66'. Recrystallized from chloroform (1 vol.) plus hexane (10 vol.) it had m.p. 68" and was devoid of sulfur. (B) I n boiling ether containing dimethylaniline (19). No apparent reaction took place on adding 1 equivalent of dimethylaniline to the ether solution of reactants and boiling for 5 hours. ( C ) 8 Hours in boiling benzene. A solution of diphenyl carbinol (m.p. 68"; 5 g.) and p toluenesulfonyl chloride (5.7 g.) in 35 cc. of benzene was boiled under reflux ("Drierite" tube) for 2 hours. The yellow solution (containing a trace of a liquid layer) was washed with distilled water, the water becoming strongly acid to Congo Red, and then successively with aqueous sodium bicarbonate solution and water until neutral. It was dried with sodium sulfate and evaporated t o dryness, giving 10.7 g. of pale yellow crystals, partly melting a t 53-55' and completely molten a t 80". I n order to ensure decomposition of any p toluenesulfonyl chloride, it was dissolved in 50 ee. of pyridine and 50 cc. of water was added. On cooling in ice, a yellow oil separated and crystallized. The colorless crystals were filtered off, washed Rith water until free from pyridine, and dried; wt. 4.4 g.; m.p. 106-108". It was recrystallized from 10 volumes of absolute ethanol, giving 4.3 g. of crystals, m.p. 110", which were devoid of chlorine or sulfur. A n a l . Calc'd for C:eH2,0: C, 89.10, H, 6.33. Found: C, 88.51, H , 6.32. These results indicate a yield of over 90% of s-tetraphenyldimethyl ether [for which Ward (20) gave m.p. llOO]. On repeating the preparation, with boiling for only 30 minutes, a quantitative yield of crude product, m.p. 106108", was obtained. Attempted preparation of phenyl methyl carbinyl p-toluenesulfonate. No apparent reaction occurred between tosyl chloride and phenyl methyl carbinol in pyridine during 2 hours either a t 0" or 65-70'. Action of sodium iodLde o n p-toluenesulfonates. Anhydrous sodium iodide (0.5 9.) was weighed into a test tube, and one-half the theoretical weight of ester and 5 cc. of acetone were added. The tube was tightly stoppered and gently swirled at room temperature until the reactants had dissolved completely. The time for the first appearance of crystals was noted and, after the elapse of a suitable period of time, the sodium p-toluenesulfonate was filtered off, washed with acetone, dried, and weighed. It was then treated with water, t o make sure that i t contained no water-insoluble material, and the solution was tested for inorganic iodide (which was invariably absent). At room temperature, crystals appeared instantaneously with the benzyl and methyl esters; in less than 5 minutes with the ethyl and n-propyl esters; and in 10 to 20 minutes with the other reactive esters shown in Table I. I n those cases where reaction did not proceed appreciably at room temperature, a solution of the same composition was sealed in a tube which was then heated in a boiling waterbath during two hours. The tube was cooled and the sodium p-toluenesulfonate isolated as above.
SODIUM IODIDE WITH TOLUENESULFONIC ESTERS
137
SUMMARY
The reaction of certain esters of p-toluenesulfonic acid with sodium iodide dissolved in acetone has been studied. Their reactivities are found to be in the same relative order as those of the corresponding organic chlorides towards the same reagent. The tosyl esters of isopropyl alcohol and thymol have been obtained in crystalline condition. The less reactive esters studied may be prepared in good yield in the presence of pyridine a t room temperature. PITTSBURGH 13, PA. REFERENCES (1) KASTLE, MURRILL, AND FRAZER, Am. Chem. J.,19, 894 (1897). (2) PEACOCK AND MENON, Quart.J. Indian Chem. SOC.,2,240 (1925). (3) RODIOXOV, Bull. SOC. chim., 39, 305 (1926). (4) KENYON, PHILLIPS,A N D TURLEY, J. Chem. SOC.,127,399 (1925). (5) FREUDENBERG AND RASCHIG, Ber., 60, 1633 (1927). (6) FINKELSTEIN, Ber., 43, 1528 (1910). (7) OLDHAM AND RUTHERFORD, J. Am. Chem. Soc., 64,366 (1932). ( 8 ) D A YAND INGOLD, Trans. Faraday Soc., 37,686 (1941) ; BALFE,KENYON, AND TLRNOKY, J . Chem. Soc., 446 (1943). et al., Helv. Chim. (9) LEVEKEAND TIPSON,J. Biol. Chem., 120,607 (1937); REICHSTEIN, Acta, 21,263,1028 (1938); Helv. Chim. Acta, 29, 343 (1946). (10) TIPSONAND CRETCHER, J. Org. Chem., 8, 95 (1943); VISCHER AND REICHSTEIN, Helv. Chim. Acta, 27, 1332 (1944); HANN,NESS,AND HUDSON, J. Am. Chem. Soc., 66, 73 (1944). (11) TIPSONAND BLOCK, J . Am. Chem. SOC.,66,1880 (1944). (12) CONANT AND KIRNER, J. Am. Chem. Soc., 46, 232 (1924); CONANT AND HUSSEY, J. Am. Chem. SOC.,47, 476 (1925); CONANT, KIRNER,ABD HUSSEY,J. Am. Chem. Soc., 47, 488, 587 (1925). (13) ROSENFELD-FREIBERG, J. Russ. Phys.-Chem. Soc., 34, 422 (1902); Chem. Zentr., 11, 86 (1902). J . Org. Chem., 9, 235 (1944). (14') TIPSON, AND TAYLOR, J . Chem. Soc., 173 (1933). (15) KENYON, PHILLIPS, (16) CLAPPAND TIPSON, J . Am. Chem. SGC.,68, 1332 (1946). J. Chem. Soc., 99, 238 (1911). (17) HILDITCH, (18) H ~ C K E et Lal., Ann., 477,99 (1930). et al., J. Am. Chem. Soc., 66,986 (1943). (19) ABRAMOVITCH (20) WARD,J . Chern. Soc., 130, 2290 (1927).
