stantial reduction manipulations.
in
reagents and
LITERATURE CITED
( 1 ) Ackman, R . G., Burgher, R. D.,
As.1~. CHEY.3 5 , 6 4 7 (1963). ( 2 ) Bartley, W., Biochem. J . 53, 305 (1953).
iv ( l g 5 0 ) . ( 4 ) Hurd, C. D,;) “The Pyrolysis of Carbon ComDounds. DD. 481-6. The Chemical catalog ‘Co:,’Inc., S e w York, 1929. (5) Korff, R . I+’., von, J . Biol. Chem. 210, 477
539 (1954). ( 6 ) Lundquist, F., Fugmann, U., Rasmussen, H., Bzochem. J . 80, 393 (1961). ( 7 ) Virtanen, A. I., Pulkki, L., J . Am. Chem. SOC.5 0 , 3 1 3 8 (1928).
( 8 ) Zorina, L. I., Sb. Tr. IV-oz (Chetvertol) Vses. Konf. Sudebn. M e d i koz,, Riga 1962, 573-4; ‘2.24. 59, 13103h (1963). RECEIVEDfor review March 5, 1964. Accepted April 22, 1964. Supported in part by a grant from the Licensed Beverage Industries Fund. Presented April 16, 1964, a t Federation of American Societies
for Experimental Biology, Chicago, Ill.
Reduction of Aromatic Disulfides with Triphenylphosphine RAY E. HUMPHREY and JERRY M. HAWKINS’ Department o f Chemisfry, Sam Houston State College, Huntsville, Texas
b Aromatic disulfides are reduced to thiols by reaction with triphenylphosphine in aqueous methanol. The reduction is rapid, quantitative, and occurs at room temperature. Water is believed to b e involved in the reduction as a source of the hydrogen. The triphenylphosphine is converted to the oxide. A number of substituted aromatic disulfides were reduced in this manner. The reduction appears to b e more efficient in solutions containing a strong acid.
Barakat ( 1 4 ) . I n the presence of triphenylphosphine and water, phenyl disulfide was reduced to benzenethiol with the phosphine being converted to the oxide. The reaction was carried out in refluxing benzene to presumably form an intermediate compound which, upon extraction with aqueous sodium hydroxide, formed the sodium salt of the thiol and triphenylphosphine oxide. This reaction is shown in Equation 1.
D
The intermediate addition compound was not isolated and no evidence was presented for its existence. Triphenylphosphine oxide was isolated from the benzene solution after extraction with aqueous base. The benzenethiol was determined in the aqueous layer by adding benzoyl chloride to form phenylthiobenzoate. Phenyl disulfide appears to be the only compound reported to react in this manner. Challenger and Greenwood (3) found that allyl disulfide was not reduced in this way but did react to form the nionosulfide and triphenylphosphine sulfide as shown in Equation 2. They found that phenyl disulfide did not react with triphenylphosphine in boiling mesitylene under anhydrous conditions and a nitrogen atmoqihere. However, some triphenylphosphine oxide was produced by refluxing a solution of the phosphine in mesitylene presumably due to air oxidation. The reaction of triphenylphosphine with a number of aromatic disulfides was inveqtigated in aqueous methanol. The disulfides studied were quantitatively reduced to thiols very rapidly a t room tem1)erature. From the results obtained it appears that triphenylphosphine is a more efficient reducing agent for some aromatic disulfides than the hydrogen-producing systems. Triphenylphosphine acts as a reducing agent by removing oxygen from
are commonly determined by reduction to the corresponding thiols followed by titration with silver nitrate (4). The reduction can be accomplished by a number of substances including zinc and acetic acid ( 5 ) ) zinc in alcoholic potassium hydroxide ( I W ) , or sodium borohydride (15). These procedures depend on the generation of hydrogen for the reduction and in some instances require elevated temperatures with reaction times of 30 minutes or longer. The reduction of phenyl disulfide with zinc and acetic acid in an unstirred solution required 16 hours a t room temperature ( 7 ) . However, the time is reduced to about thirty minutes with adequate stirring (9). Disulfides have also been reported to be reduced to thiols by reaction with sodium arsenite and water (6) a i t h the accompanying production of arsenate. The extent of these reductions was not reported. The reduction nith arsenite resembles that reported here for triphenylphosphine in that both apparently require water as a source of the necessary hydrogen. -1somewhat unusual reducing system for phenyl disulfide was reported by Schonberg (13) and by Schonberg and ISULFIDES
1 Present address, The Dow Chemical Co., Freeport, Texas.
1 8 12
ANALYTICAL CHEMISTRY
CsHsS-SCsHs -k (C&)3P -I-H20 2 CsHjSH (CsHs)3PO (1)
+
+
peroxides or nitro groups, and by re moving sulfur from episulfides and certain disulfides (8). I n these reactions triphenylphosphine oxide or sulfide is formed. The reaction with disulfides in anhydrous hydrocarbons, shown in Equation 2, has been reported for a number of such substances, most of which were acyl or alkenyl compounds. One aromatic disulfide, 4,4’dithiobis(S,N-dimethylaniline) was reported to react with triphenylphosphine in benzene in this way :
A number of other disulfides, some aromatic, did not react with triphenylphosphine in boiling benzene (14 ) . EXPERIMENTAL
Apparatus. Polarograms were recorded with a Sargent Model XV recording Polarograph. h saturated calomel electrode was used as reference. Solutions were purged with helium to remove oxygen and a helium blanket was maintained over the surface when recording polarograms. ;Imperometric titrations of the thiols were conducted using a Sargent synchronous rotator and platinum electrode. Current mas measured with a HewlittPackard 412A vacuum tube voltmeter. The reference electrode contained mercury in contact with a solution containing 1.3 grams of Hg12 and 4.2 grams of K I in 100 ml. of saturat,ed KC1 as described by Kolthoff and Harris (10). Infrared spectra were recorded with a Beckman IR-5 spectrophotometer. Reagents and Solutions. Disulfides were obtained from Eastman Organic Chemicals and Chemicals Procurement Laboratories and were purified by re c r J- s t a1li z a t ion from et ha no 1 where possible. A11 chemicals used were the best available reagent grade. The solvent used was methanol containing 107, water. Sodium acetate, ammonium acetate, ammonium nitrate, or perchloric acid were used as electrolyte.-.
I -04
4 2
E
vs.S.CE,
I
I
9.6
6 .
I
-0 1 E
vo/fs
Figure 1 , Polarogram of solution containing phenyl disulfide and triphenylphosphine showing incomplete reaction
Acetic acid was also present in most cases in those solutions containing acetates. Silver nitrate solutions were approximately 0.01M. Procedure. For quantitative reduction the aromatic disulfide a n d triphenylphosphine were usually p u t in a small a m o u n t ( I ml.) of benzene or acetone a n d diluted with methanol, 0.lN in HCIOa, t o 13 final volume of 100 ml. The triphenylphosphine should be present in 10% excess, on a mole basis, relative to the disulfide. The solutions were allowed to age for 15 minutes and were t’hen titrated amperometrically with AgN03 using the rotating platinum electrode. The end point determination and calculations were done in the usual way (IO). RESULTS AND DISCUSSION
Polarographic Study of the Reaction. Aromatic diaulfides show a reduction wave (11) a t the dropping mercury electrode a t about -0.6 volt us. S.C.E. producing the corresponding thiols. Aromatic thiols are oxidized (11) a t the D.M.E. in the range from 0 t o -0.6 volt vs, S.C.IE. with the formation of the mercurous salt. I n solutions containing thiols, oxidation current is observed at potentials more positive than the half-wave value with no reduction current al, more negative potentials. Disulfides exhibit no oxidation current but do show reduction current a t potentials more negative than the half-wave potential. Hence a solution containing both thiol and disulfide shows oxidation current from zero volts v s . S.C.E. to the half-wave potential and reduction current at potentials more negative than the halfwave value. I n solutions containing phenyl disulfide and triphenylphosphine, the extent of reaction could be determined by observing; the decrease in reduction current due to the disulfide group and the appearance of oxidation current due to the thiol (Figure 1). For the nitro-substituted disulfides the
I
I
I
-0.4
-0.6
J
-0.8
v s r S . C E . volts
Figure 2. Polarogram of solution containing p-toluenethiol from reduction of p-tolyl disulfide with triphenylphosphine
reduction wave for the nitro group occurred in the same region as the disulfide wave. However, the thiol oxidation wave was evident on reaction of these disulfides with triphenylphosphine. On the other hand, p toluenethiol (Figure 2) and 2-hydroxy6-thionaphthol apparently do not show a definite oxidation wave. The polarogram of the solution containing p-tolyl disulfide and triphenylphosphine was identical to t h a t of a solution containing p-toluenethiol. For p-tolyl disulfide arid 2,2’-dihydroxy-6,6’-dinaphthyl disulfide, reaction could be detected by observing the decrease in wave height for the disulfide group. The reaction of phenyl disulfide with triphenylphosphine was studied i n greatest detail since i t was more favorable for polarographic observation. I n solutions containing acetic acid with sodium acetate or ammonium acetate, reaction between phenyl disulfide and triphenylphosphine was very rapid. The disulfide was completely reduced under these conditions when the mole ratio of phosphine to disulfide was 2 : 1 or greater. This was confirmed by amperometric titrations. I n methanol 0.1N in perchloric acid, complete reduction of the disulfide occurred when the mole ratio of phosphine to disulfide was 1 : l . This seems to confirm that the reaction does proceed as shown in Equation 1. The mechanism of the reaction is not known but it is apparent that acid catalysis is necessary in order to obtain rapid and quantitative reduction of the disulfide group. Infrared Studies. I n the original investigation of this reaction ( 1 4 ) triphenylphosphine oxide was shown to be a product by isolation from the reaction solution and identification by melting point determination. Challenger and Greenwood (3) stated that triphenylphosphine is oxidized under these conditions when there is no phenyl disulfide present. I n the present
investigation triphenylphosphine oxide was isolated in the same manner as reported by Schonberg and Barakat ( 1 4 ) and was identified by melting point and infrared spectrum. No oxide could be isolated from a blank solution containing triphenylphosphine only. Since our reactions were carried out at room temperature it is doubtful whether triphenylphosphine would undergo rapid air oxidation to a significant extent under these conditions. Triphenylphosphine oxide shows strong infrared absorption a t 1190 cm.-I and a t 1110 cm.-I The band a t 1190 cm.-I was stretching mode assigned to a P-0 (1). There were only small interferences at these frequencies due t o disulfides or thiols which were present in the reaction solutions. These experiments were carried out by shaking benzene or chloroform solutions of triphenylphosphine and phenyl disulfide or p-tolyl disulfide with distilled water. The infrared absorption of the organic layer was then determined between 1250 cm.-I and 1050 cm.-I From 35 to 50Oj, of the phosphine was oxidized in these disulfide solutions in a period of three hours. A solution of triphenylphosphine only shaken with water showed essentially no infrared absorption a t the P-0 stretching frequency. The yield of phosphine oxide in this reaction is of doubtful significance since theoretically a small amount of disulfide could oxidize almost any amount of phosphine given sufficient time. The ease of oxidation of triphenylphosphine under these conditions is perhaps unusual in view of recent work ( 2 ) which showed that very little triphenylphosphine oxide was found after passing oxygen for three hours through a refluxing solution of the phosphine in benzene. I t is evident that oxidation of the phosphine is not caused by dissolved oxygen but derives from the reaction with the disulfide bond. This is additional support for the reaction VOL. 36, NO. 9, AUGUST 1964
1813
Table I.
Reduction of p-Tolyl Disulfide in Acetate Medium
11 5 14.3 11.9
12.5 30.2 41.2
1 0 20 3.2
7.4 13.9 12.6
64 97 106
Table II. Reduction of p-Tolyl Disulfide in Solutions Containing Perchloric Acid Reduction, RSSR, mg. (CaHs),P, mg. (CaH,)aP/RSSR RSH, mg. 70 0.5 12.9 6.9 6.5 50 10.1 1.2 12.5 101 10.0 1.7 21.4 12.2 11.7 104
shown in Equation 1. Water is the most probable source of the hydrogen and oxygen required for the final products.
Table 111. Reduction of Aromatic Disulfides with Triphenylphosphine” in Acetate Solutions
TiPresent, trated, Per mg. cent Compound mg. 1 0 . 3 104 Phenyl disulfide 9.9 12.3 100 p-Tolyl disulfide 12.3 Bis(o-nitrophenyl j94 disulfide 12.4 11.6 Bis(4-chloro-2nitropheny1)15.4 103 disulfide 15.0 Dimethyl-2,2’dithiodiben13.0 105 zoate 12.3 2,2’-Dihydroxy6,6’-dinaphthyl 12.0 109 disulfide 11.0 The mole ratio of triphenylphosphine t o disulfide was 2 : l or slightly larger In all cases.
Table IV. Reduction of Aromatic Disulfides with Triphenylphosphine” in Perchloric Acid Solutions
Compound Phenyl disulfide p-Tolyl disulfide Bis(o-nitrophenyl jdisulfide Bis(4-chloro-2nitrophenyl jdisulfide Dimethyl-2,2 ‘dithiodibenzoate 2,2’-Dihydroxy6,6’-dinaphthyl disulfide 4,4’-Dithiodianiline
TiPresent, trated, Per mg. mg. cent
9 7 10 0
9 6 10 1
99 101
11 0
10 8
98
13.3
13.0
98
9.2
8.9
97
11 9
12 0
101
14.5
14 2
98
a The mole ratio of triphenylphosphine to disulfide was 1: 1 or only slightly larger in all cascs.
181 4
ANALYTICAL CHEMISTRY
Amperometric Titrations. The yields of thiols formed by the reaction of the several disulfides with triphenylphosphine were determined by amperometric titration with silver nitrate using a rotating platinum electrode. The amount of phosphine required for complete reduction of the disulfide depended upon the supporting electrolyte used. I n solutions containing acetic acid and sodium acetate or ammonium acetate, two moles of phosphine per mole of disulfide were necessary for complete reduction (Table I). However, with solutions 0.1N in perchloric acid 100% reduction of the disulfide occurred when the ratio of phosphine to disulfide was 1 : l . This is shown in Table 11. The yield of thiols for the various disulfides is shown in Table I11 for the acetate media and in Table IV for perchloric acid solutions. 4 considerable number of titrations were carried out for each disulfide in each medium. Good agreement was found for replicate determinations. Quantitative reduction of the disulfides was found by titration within 15 to 20 minutes after preparing the solutions. All evidence indicates that triphenylphosphine reacts with aromatic disulfides in aqueous methanol according to Equation 1. For one compound, bis(o-nitrophenyl)disulfide, reduction occurred on reaction with triphenylphosphine in aqueous methanol whereas no reaction was reported to take place in benzene (1.4). The reaction of 4,4’-dithiobis(N,Sdimethylaniline) with triphenylphosphine in refluxing benzene yielded the corresponding monosulfide (1.4) while the unsubstituted compound, 4,4’-dithiodianiline, was quantitatively reduced to the thiol in aqueous methanol in this work. Characteristic odors of some of the thiols were evident in the reaction solutions. Triphenylphosphine oxide and the various thiols were established as reaction products. Since the reduction occurs in aqueous solvents and does not take place in dry solvents, water must be involved in the reaction.
High results were found in the solutions containing acetic acid when the mole ratio of triphenylphosphine to disulfide was much higher than 2 : 1, Investigation revealed that while neither disulfides nor triphenylphosphine oxide showed any interaction with silver ion, there was some attraction in the case of triphenylphosphine. Hence, if a significant amount of unreacted phosphine was present, high results were found. This effect was not so pronounced in the solutions containing perchloric acid. The results with excess phosphine present can be improved by careful location of the end point. The slope of the line past the end point is much less steep with unreacted triphenylphosphine present and appears to change as the current increases more sharply, apparently after the phosphine has complexed with the silver ion. Best results are obtained if a large excess of phosphine is avoided. This reduction may have some advantages in certain instances from the standpoint of speed, room temperature conditions, and simplicity of procedure. From the rather limited number of aromatic disulfides reduced by triphenylphosphine in this work, there was no effect on the reaction due to the presence of the various functional groups. LITERATURE CITED
(1j Bellamy, L. J., “The T,nfrared Spectra
of Complex Molecules, p. 312, Wiley, New York, 1958. ( 2 ) Buckler, S. A., J . Am. Chem. Soc. 84, 3093 (1962). (3) Challenger, F., Greenwood, D., J . Chem. Soc. 1950, 26;< ( 4 ) ,Dal Nogare, S., Organic Analysis,” Lol. 1, p. 359, Interscience, New York, 1953. (5) Faragher, W. F., Morrell, J. C., Monroe, G. S., Ind. Eng. Chem. 19, 1281 (1927). (6) Gutmann, A., Ber. 56B, 2365 (1923). (7) Harnish, D. P., Tarbell, D. S., ANAL. CHEM.21, 968 (1949). (8) Homer, L., Hoffmann, H., “Neuere Methoden der praparativen organischen Chemie,” Vol. 11, p. 108, Verlag Chemie, 1960. (9) Hubbard, R. L., Haines, W. E., Ball, J. S., ANAL.CHEM.30, 91 (1958). (10) Kolthoff, I. M., Harris, W. E., IND. ENG. CHEW,ANAL.ED. 18, 161 (1946). (11) Milner, G. W. C., “Principles and Applications of Polarography,” pp. 619-24, Wiley, New York, 1957. (12) Rosenwald, R. H., Petrol. Processzng 6,969 (1951). (13) Schonberg, A , , Be?. 68B, 163 (1935). (14) Schonberg, A,, Barakat, M. Z., J . Chem. Soc. 1949 892. (15) Stahl, C. R., Siggia, S., ANAL. CHEM.29, 154 (1957).
RECEIVEDfor review March 5 , 1964. Accepted May 4, 1964. Division of Analytical Chemistry, 145th Meeting, ACS, K . Y., September 1963. The support of the Robert -4. Welch Foundation of Houston, Texas, is gratefully acknowledged.
