Catalytic Synthesis of Thiols M. W. FARLOW, WILBUR A. LAZIER’, AND F. K. SIGNAIGO Experimental Station, E. I . du Pont de Nemours & Company, Inc., Wilmington, Del.
A
new synthesis of thiols, through reductive thiolation of aldehydes, ketones, or nitriles in the presence of sulfactive hydrogenation catalysts, is reported. Improved methods for preparing sulfactive catalysts are described.
I
NDUSTRIAL interest in thiols as polymerization modifiers for synthetic rubbers, as rubber peptizers, and as intermediates for the preparation of surfaee active sulfonic acids, has created a need for economical thiol syntheses. The new procedures described herein are applicable to the synthesis of primary and secondary thiols, and appear to offer a practical route.to certain thiols of this group. The synthesis of thiols by the reductive thiolation of aldehydes, ketones, or nitriles represents the first instance of the use of catalytic hydrogenation techniques for introducing sulfur-containing functional groups into organic compounds. A major factor in opening this route to organic sulfur compounds was the development of a group of metallic sulfide catalysts which are not only resistant to deactivation or poisoning by sulfur and its compounds, but are effective for the hydrogenation of many sulfur-containing functional groups at relatively low temperatures. As compared with orthodox hydrogenation catalysts these “sulfactive catalysts” show relatively little activity for the hydrogenation of sulfur-free functional groups, hence are highly selective in action. [The term “sulftbctive catalyst” has been applied to certain metal catalysts, notably molybdenum sulfide, which have been used for destructive hydrogenation of carbonaceous materials, desulfurization of petroleum fractions, etc., a t temperatures above 300’ C. ( I ) 1 The hydrogenation of glucose-sulfur mixtures to 1-thiosorbitol with the aid of a cobalt polysulfide catalyst has been described in a previous paper ( d ) . The present paper describes in a general way the preparation and properties of sulfactive catalysts and their use in the synthesis of thiols from aldehydes, ketones, or nitriles (5,8). Probably the most generally useful sulfactive catalyst uncovered in this work is cobalt polysulfide, although sulfides of nickel, iron, molybdenum, and certain other metals are active in varying degrees. As in the caae of other heterogeneous-phase or contact catalysts, the sulfactive catalysts appear to be most efficient when produced in a finely divided or porous condition, thereby presenting a large surface area. Methods for preparing typical sulfactive catalysts and brief descriptions of these catalysts are presented below. The conversion of aldehydes, ketones, and nitriies to thiols (Table I), according to the present scheme, may be represented (LS follows: 0
SH
e
-R‘ (or H )
R-
+ H a + Hr catalyst
CHdCH2)aCHO
+ H2S + 2H2
catalyst
RCHaSH
4 NHI
Normally, sulfur is used instead of hydrogen sulfide, for sulfup is more easily handled and is readily hydrogenated to hydrogen 81.11fide in the presence of sulfactive catalysts. It is believed that the synthesis proceeds through the action of Kydrogen sulfide on the aldehyde, ketone, or nitrile to give a sulfur-containing interPrevent addre=. Chaa. Pfieer & Co., Inc., Brooklyn, N. Y.
+ CHa(CH2)aSH + Hz catalyst
CHs(CHs)s--S--(CHt),CH3
+ H?O
However, this reaction is suppressed to the point of being negligible by using excess hydrogen sulfide. In the conversion of simple nitriles to thiols, hydrolysis of the nitrile may produce the corresponding amide, and for this reason the reagents should be as nearly anhydrous as practicable. Aldehydes, ketones, and 111triles usually boil in the same range as the corresponding thiols, and the presence of the starting material may be suspected in aiiv impure thiol prepared by the present procedure. In such a case mhydrogenation of the impure thiol in the presence of hydrogtm sulfide or sulfur usually gives a product of higher purity. If the carbonyl compound or nitrile contains other functional groups, possibilities for side reactions are increat3ed. Hydrogenation of an alpha,beta-unsaturated aldehyde in the preeence of hvdrogen sulfide or sulfur, for example, gives some of the dithiol pissulting from addition of hydrogen sulfide to the double bond aiul conversion of the carbonyl group to the thiol (Table I, experimeiit 12). With certain polyfunctional starting materials, heterocyclic sulfur compounds, such as sulfides and thiolactones (6),ai(& formed (Table I, experiments 13,14, and 16). The use of elementary sulfur as a source of the thiol sulfur is recommended from the standpoint of convenience. Hydrogcri sulfide might be preferable in instances where sulfur causes e\tensive by-product formation. Other sources of sulfur such as carbon disulfide, which undergoes hydrogenolysis to produce hydrogen sulfide, have been used succcssfully but offer no advantagcs.
HtO RCN
1
mediate, which is then hydrogenated catalytically to the thiol. This proposed mechanism is based on the observation that suifactive catalysts are not effective for the hydrogenation of carbonyl compounds or nitriles, alone, under the conditions in question, nor does hydrogen sulfide react with alcohols or amines to give thiols under these conditions. On the other hand, it has been demonstrated in certain cases ,that the isolated reaction products of hydrogen sulfide with ketones or nitriles (thioketones, thioamides, etc.) are hydrogenated to thiols by sulfactive catalysts. Furthermore, the presence of acetic acid accelerates t#he reductive thiolation of carbonyl compounds to thiols, and acids are known to catalyze the reaction of hydrogen sulfide with carbonyl compounds. In the conversion of simple ketones to thiols no serious side reactions have been noted. With simple aldehydes, aldol condensation may occur as a side reaction. In addition, dialkyl sulfides can be formed, apparently as a result of secondary reactions involving the aldehyde and thiol. Sulfide formation is the predominant reaction when an equimolar mixture of aldehyde and thiol is hydrogenated (If ):
PREPARATION O F SULFACTIVE CATALYSTS
The following are examples of typical sulfactive catalyst prcp~trations.
PRECIPITATED COBALT POLYSULFIDE CATALYST (IO). To 1500 nil. of water in a %liter beaker, 240 rams of sodium sulfide hydrate (NazS.9H20) and 64 grams of suyfur were added The misture was stirred until the sulfur dissolved. The filteied solution was added during a 10- to 1.5-minute period to a solution pre ared from 242 grams of cobalt chloride hydrate (CoClz.6H20~ and 1700 ml. of water contained in a 4-liter beaker equipped with a 2547
INDUSTRIAL AND ENGINEERING CHEMISTRY
2548
Vol. 42, No. 12
TABLEI. PREPARATION OF THIOLS Reagent
Grams of Reagent
Heptaldehyde Sulfur Acetic acid a-Ethylcaproaldehyde Sulfur Acetic acid Benzaldehyde Pulfur Acetone Sulfur Acetic acid
100 60 40 100 60 50 118 60 75 45 50
2-Hexanone Sulfur Acetic acid 2-Octanone Hydrogen sulfide 8-Pentadecanone Sulfur Acetic acid 7-Heptadecanone Sulfur Acetic acid Cyclohexanone
90 32 50 114 34 100 33
Erpt,. NO. 1
2
3 4
5 6 7 8
.
Theoretical % of Boilin8 Yield Point, C. From Carbonyl Compound8 90-92 (49 mm.) 1-Heptanethiol 46 Product
% Thiol S Calcd.
Found
24.2
23.7
n f16
2-Ethyl-1-hexanethiol
77
74-80 (19 mm.)
21.9
21.5
Phenyimethanethiol
70
95 (30 mm.)
...
...
2-Propanethiol
5s
2-Hexanethiol
59
122-135
2-Octsnet hiol
12(75)
85 (23 rnm.)
21.9
21.6
1.4474
&Pentaderanethi01
96.
159-180 (10 mm.)
13.1
13.1
1.4582
7-Heptadecanethiol
100
151-153 (1 inm.)
11.8
11.7
...
1,4541
.
I
.
...
Product not easily ae arated from etBer used in extraction; yield baaed on determination of thiol S in b.p. to 5 2 O (3. fraction 27.1 22.5
50
100 33 50
(0:'
1.4594 a 0:8384)
Cyclohexanethiol
(86)
58 (25 mm.)
27.6
26.0
...
6-Fenchanethiol
69
90-105 (30 mm.)
19.7
17.8
...
E:thylbenzane 1-Phenyl-1-ethanethiol 1,3-Butanedithiol
41 (19)
73 (100 mm.) 130 (100 mm.)
. .
...
41
01-93 (30 mrn.)
52 5
51.9
60 45 20
45
126-128
54
2,5-Dimethyltett.ahydrothiophene, (product contained 0.50 equivalent thiol before diutillation)
Ethyl acetoacetate Sulfur Dioxane Levulinic acid Sulfur Benzene
100 35 54 100
Ethyl-3-mercaptobutyrate (plus lower boiling thiols) 4-Valerotliiolactone
26
95-100 (30 mm.)
94
94-95 (22 mm.)
27.6
23.2
4-Ketopimelic acid Sulfur Dioxane
800 300 400
4-Pimelothiolactone
78
185-188 (2 mm.)
-Neutral 175
Equivalent175
17
Lauronitrile Sulfur Xylene
280
1-Dodecanethiol
36(88)
97 (1 mm.)
--
15.5
1s
Palmitonitrile Sulfur
100 32
Thionopalmitamide Palmitonitrile
11
Mixture, 150--165 (3 a m . ) ; m.p., 50-51
Dioxane
30
1-Hoxadecanethiol
(40)
Sebaconitrile Sulfur Acetic acid Daoxane Benzonitrile Sulfur Phenylacetonitrile
fio
1.10-Decanedithiol
47 (74)
9 10 11 12
13
1: 15
16
19
20 21
Sulfur
Isofenc hone Sulfur Acetic acid Acetophenone Sulfur Acetic acid Crotonaldehyde Sulfur Acetic acid Dioxane Acetoiiylacetone Sulfur Acetic acid Dioxane
Sulfur
Xylene
BO 4.5 110 45
50
107 +5 00 55 75 25 40
60
__._
27.6
--yo
%S--
..
27.7
Thiol S18.7
21 . 6
35
90 40
32 45 100 103 45 117 60 30
From Nitriles
(40)
% Thiol 8
15.8
---%S-11.80
-
11.85
(% thiol S, 6 . 5 ; %
N.3.20)
155 (7 mm.)
--
31.1
30.2
1.4950
...
To Thiol S
--
Phonylmethanethiol
57
87 (18 mm.)
25.8
25.3
2-Phenyl-1-ethanethiol
29
96 (2 mm.)
23.2
22.0
large paddle stirrer. The stirring was continued for an additional hour. The precipitated cobalt sulfide was collected by vacuum filtration and washed with water until the filtrate was colorless. The 750 to 1000 rams of hard paste contained approximately 150 grams of solif catalyst. The catalyst prepared as above has the approximate composition Coss. The dry sulfide is oxidized by air with release of sulfur dioxide. The moist solid is reasonably stable toward air and the catalyst may be stored as a paste with water or other diluents. The solid appears to be nonhomogeneous, for extraction with di-
...
lute sulfuric acid results in a solution of a minor amount of cobalt, and the insoluble residue has the approximate composition, CoSg.8. The extraction was carried out by suspending a water paste prepared as above in 1300 ml. of water and adding portionwise during 15 minutes a solution of 170 grams of 95% sulfuric acid in 500 ml. of 'water, followed by boiling the suspension for 3 to 4 hours, washing, and pasting as above. The solid prepared in this way contained extractable sulfur, removal of which by extraction with hot benzene produced a solid having the composition CoSs. Cobalt polysulfide is an excellent sulfactive hydrogenation
December 1950
INDUSTRIAL AND ENGINEERING CHEMISTRY
catalyst. As a rule i t undergoes artial reduction during use giving lower sulfides-for example, &SI.* I.r-which are also catalytically active. PRECIPITATED NICKELPOLYSULFIDE CATALYST.An active nickel polysulfide catalyst was prepared by a procedure analogous to that described in the first paragraph of the preceding section, from a solution of 90 grams of nickel sulfate hydrate (NiS04.6H20) in 250 ml. of water, usin as recipitant a solution of 80 grams of sodium sulfide hydrate f k a d 9 H ~ Oand ) 21 grams of sulfur in 300 ml. of water. The precipitate, after thorough washing with water, then with glacial acetic acid, was stored as an acetir acid astc. It had a nickel-sulfur ratio corresponding approxim a t e k to Ni&. ALLOY-SKELETONCOBALTSULFIDECATALYST (4). Two hundred and twenty-seven grams of a finely divided cobalt-aluminum alloy rontaining approximately 35% cobalt were suspended in lo00 ml. of water. The mixture was heated t o boiling with vigorous stirring and a solution of 226 grams of hydrated sodium sulfide (Na&9H20) in 375 ml. of water was added slowly over a period of 1.25 hours. A vigorous reaction accompanied by the evolution of hydrogen and traces of hydrogen sulfide ensued, and the alloy was converted to a gray dud e. After boiling for an additional 4 hours the mixture was allowe! to settle, the supernatant liquid decanted and the residue washed twice with water to remove soluble saits. The solid was resuspended in a solution containing lo00 ml. of water, 226 grams of hydrated sodium sulfide, and 113 grams of sodium hydroxide, and boiled for an additional period of 4 hours. The water which w m lost by evaporation was replaced from time to time. The slurry was then allowed to settle, the supernatant liquid was decanted, and the solid was washed with water by decantation until essentially free from alkali, sodium sulfide, and hydrogen sulfide. The resulting aqueous paste was washed with ethyl alcohol and stored under absolute ethyl alcohol. Analysis for cobalt, sulfur, and alumina indicated a weight ratio of 1.94 parts of cobalt, 1.0 part of sulfur, and 1.8 parts of alumina, correspondin approximately to a composition of 33% cobalt sulfide and 67# hydrated alumina. SULFIDED MOLYBDENUM CATALYST (9). Sulfactive catalysts may be prepared by the controlled low-temperature sulfidation of the finely divided metal with hydrogen sulfide or elementary sulfur. For example, finely divided molybdenum was prepared by suspending 36 grams of a powdered alloy containing equal parts of molybdenum and aluminum in 300 ml. of boiling water and adding gradually, over a period of 1 hour, a solution containing 130 grams of sulfuric acid .and 100 ml. of water. The suspension was boiled for an additional 4 hours, cooled, and filtered. The resultin pyrophoric molybdenum was washed with water, then wit% methanol. During the filtering and washing operations, care was taken to avoid exposure of the pyrophoric metal to air. The molybdenum-methanol paste was suspended in additional methanol, and hydrogen sulfide gas was passed through the suspension for 8 hours at room temperature. The resultin molybdenum sulfide catalyst has a molybdenum-sulfur weigit ratio of approximately 6 to 1. METALSAS SULFACTIVE CATALYSTS.I n some instances the sulfactive metal sulfide can be formed in situ by introducing the corresponding finely divided free metal into the reaction mixture. This variation is not enerally applicable, because the sulfides formed by uncontrollef sulfidation of finely divided metals have a relatively low degree of catalytic activity.
-
HYDROGENATION PROCEDURE
The reaction mixtures indicated in Table I, together with catalyst, were charged into a chrome-vanadium steel, high-pressure vessel having a capacity of 400 ml. (except in experiments 16 and 17, in which the pressure vessels had capacities of 12.5 and 1.0 liters, respectively). Hydrogen was admitted a t a pressure of about 1000pounds per square inch, and the vessel was heated with agitation to the reaction temperature of 150” to 200” C., after which hydrogen was added as required to maintain a pressure of 1500 to 2000 pounds per square inch. When hydrogen absorption was complete, as evidenced by no further decrease in pressure ( I to 8 hours), the vessel was cooled, and the pressure was released in a hood adequate for disposal of the excess hydrogen sulfide. The pressure vessels used in the authors’ laboratory showed definite corrosion as a result of hydrogenations involving sulfur and its compounds. The vessels were examined frequently and were discarded before they were judged to be unsafe for further use.
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Some of the vessels were in almost daily use for periods of many months. Soft iron or aluminum gaskets were used in assembling the vessels after several failures with copper gaskets. The operations were all conducted in an area where mechanical failure, with resultant release of considerable amounts of hydrogen sulfide, would not be dangerous. Except as otherwise ihdicated below the catalyst used for t h e experiments in Table I was precipitated cobalt polysulfide. I n experiment 9 the catalyst was alloy-skeleton cobalt sulfide; i l l experiment 3, alloy-skeleton iron (6, 7, 12). When experiment 7 was repeated using precipitated nickel polysulfide arid sulfided molybdenum as catalysts the conversions to 8-pentadecanethiol were 79 and 76%, respectively. Amounts of catalyst equivaknt to 5 to 15% of the weight of carbonyl compound or nitrile were used. In a few cases, catalysts recovered from previous runs have been reused, with no apparent loss of activity. EXAMINATION OF T H E PRODUCTS
In general the product containing excess hydrogen sulfide and suspended catalyst was filtered, preferably with the help of one of the commercial filter aids, such as kieselguhr. From an aliquot of the crude product hydrogen sulfide was removed by boiling with ether until a lead acetate paper in t,he vapors no longer showed a positive reaction. (Volatile thiols sometimes interfere with the lead acetate test; usually they form yellow lead derivatives in contrast to the black lead sulfide.) The sample was then titrated with standard iodine solution and the thiol calculated from the equation: 2RSH
+ Iz --+ RSSR + 2HI
The major portion of the product was then subjected to fractional distillation or other operations appropriate t o the individual case. Isolated fractions containing thiol were also analyzed for thiol sulfur by iodine titration. The examples given in Table I are in many cases the results of single experiments, and the yields of thiols are undoubtedly below the maximum obtainable. The yield figures enclosed in parentheses refer to total thiol formed as determined by an iodine titration of an aliquot of the crude reaction mixture, after removal of hydrogen sulfide, as described above. Other yield figures refer to the isolated products having the properties indicated in the next vertical columns. Low thiol sulfur analyses for isolated products probably indicate that the thiol is contaminated with starting material (carbonyl compound or nitrile). LITERATURE CITED
(1) Ellis, Carleton, “Hydrogenation of Organic Substanoes,” Chap. 111, paragraphs 4814 and 6360, New York, D. Van Nostrand Go., 1930.
(2) Ferlow, M. W., Hunt, Madison, Langkammerer, C. M., Laiier, W. A., Peppel, W. J., and Signaigo, F. K., J. Am. Chem. SOC., 70,1392-4 (1948).
(3) Farlow, M. W., and Signaigo, F. K. (to Du Pont), U. S. Patents 2,402,613, 2,402,615 (June 25, 1946). (4) Howk, B. W. (to Du Pont), Ibid., 2,402,626 (June 25,’1946). (5) Lazier, W. A., and Signaigo, F. K. (to Du Pont), Ibid., 2,402,639 (June 25,1946). (6) Paul, R., and Hilly, G., BztZZ. SOC. chim., 6, No. 5, 218-23 (1939). (7) Raney, Murray, U. S. Patent 1,628,190 (May 10, 1927). (8) Signaigo, F. K: (to Du Pont), Ibid., 2,230,390 (Feb. 4, 1941). (9) Ibid., 2,402,683 (June 25,J946). (10) Ibid., 2,402,684 (June 25, 1946). (11) Ibid., 2,406,410 (Aug. 27, 1946). (12) Tanner, H. G. (to Du Pont), Ibid., 2,402,694 (June 25, 1946). R E C ~ ~ W January ED 24, 1850. Contribution No. 243 from the Chemica1 Department, Experimental Station, E. I. d u Pont de Nemours t Company, Ino.,Wilmington, Del.
