I
R.
B.
THOMPSON, J. A. CHENICEK, and TED SYMON
Universal Oil Products Co., Des Plaines, 111.
Sulfur Compounds as Antioxidants An ul o gs of €3 eta-Alkyl m ercaptoketo n es BETA-alkylmercaptoketones are effective antioxidants, using lard as the substrate for testing (4-7), but the a-, ?-, and 6-mercaptoketones are relatively ineffective. Activating groups other than keto or carboxyl /3 to the mercapto function lead to ineffective antioxidants. Availability of acrylamides made them desirable to investigate as intermediates for antioxidants. Acrylamide, N-tertbutylacrylamide, and methylenebisacrylamide reacted with ethyl mercaptan in the presence of basic catalysts, sodium methylate or piperidine. With methylenebisacrylamide apparently a mixture of mono- and di-addition products was formed, as sulfur was intermediate between the two compounds. All these materials were effective antioxidants, but that from methylenebisacrylamide was considerably more potent, in agreement with results obtained with mono- and di-a,P-unsaturated ketones. Of the 6mercaptoketones, those from the di-a, 0unsaturated ketones were more potent. In all previous work, only the carbonyl group P to mercapto group gave good antioxidants. The cyanide a-pyridyl, and nitro groups yielded relatively ineffective antioxidants. Two of these latter materials are incapable of forming the type of six-membered ring which has been suggested as a possibility of explaining the activity of the P-mercapto ketones (73). T h e sulfone group also activates thedouble bond for addition. Ethylvinyl sulfone reacts rapidly with ethyl mercaptan in the presence of a basic catalyst; the resulting P-ethylmercaptoethyl ethyl sulfone is an effective antioxidant, as is analogous sulfoxide. A possible intermediate in oxidation which might occur from the P-ethylmercaptoethyl ethyl sulfoxide is the disulfoxide, bis-1,2-ethylsulfinyl ethane which was synthesized (7). This disulfoxide was an antioxidant. As a monosulfoxide is capable of further oxidation, ethyl sulfoxide was also tested to see whether the P-positions of the sulfoxide groups were necessary. I t is not an antioxidant. The disulfoxide prepared from 1,3-bisethylmercaptopropane was not an antioxidant. The P-mercapto sulfone, sulfoxide, and P-disulfoxide are similar to the P-alkylmercaptoketones in effectiveness. Recent work (9) strongly supports the idea that the sulfur octet is capable of being enlarged, to permit a type of enolization similar to that depicted for ketones. If this is correct,
the potency of the oxygenated sulfur compounds can be explained in the same way as the P-alkylmercaptoketones. The nature of the radical of the mercaptan added to the a$-unsaturated double bond influences potency. Additional variations of this group were obtained by adding hydrogen sulfide to methyl vinyl ketone and to methyl acrylate. If hydrogen sulfide is bubbled into a solution of methyl vinyl ketone containing a trace of piperidine, the sulfide is formed. If the unsaturated ketone or ester is added to an excess of hydrogen sulfide in the presence of a trace of piperidine, satisfactory yields of desired thiol could be isolated. Both compounds were converted to the corresponding mercaptols by reaction with acetone in the presence of anhydrous hydrogen chloride and to the disulfides by oxidation of an alkaline solution with hydrogen peroxide. During alkaline oxidation of the ester it was hydrolyzed to the free acid. Reaction of 6-mercaptoethyl methyl ketone with ethyl vinyl sulfone in the presence of a Table 1.
basic catalyst yielded a compound having the sulfur to two diffrrent activating groups. I n the presence of piperidine, passing hydrogen sulfide into mesityl oxide gives a very slow reaction. Sodium methylate gives a much more satisfactory reaction. Unlike methyl vinyl ketone, mesityl oxide yields predominantly the mercaptan rather than the sulfide, even when a large excess of the ketone is used, This difference arises from the presence of two deactivating alkyl groups in the P-position (70, 73). Attlempts.to oxidize the mercaptan from mesityl oxide to the disulfide in alkaline solution were fruitless, as the hydrogen sulfide was removed by caustic to yield mesityl oxide and sodium sulfide. Disulfide was obtained by oxidation of mercaptan in acetic acid with hydrogen peroxide. Because of foul odor the mercaptans were not tested as antioxidants; the derivatives of mesityl oxide were not tested. Disulfide and mercaptol derived from methyl vinyl ketone had potencies as antioxidants comparable to those of Antioxidants Y.P.,
Formula C. Conipound Methylene-bis-b-ethyl mercaptopropionamide CHZ(NHCOCHZCHZSCZH~)Z 176-8 6-Ethyl mercaptopropionamide NHzCOCHzCHzSCzHs 65-6 N-tert-Butyl-ðyl mercaptopropionamide (CH3)3CNHCOCHzCHzSCzHs 0-Ethylmercaptoethyl ethyl sulfone CaHsSCzHaSOzCzH6 P-Ethylmercaptoethyl ethyl CzHsSCzH4SOCzHfi sulfoxide 1,2-Bisethyl sulfinyl ethane C2HfiSOC2HaSOCzHs 130-8 Diethyl sulfoxide CzH5SOCzHs 5-6 5,6-Dithia-2,9-diketodecane ( C H ~ C O C L H ~ S ) ~ 5,7-Dithia-6,6-dimethyl-2, (CHJCOCZH~S)~ 10-diketoundecane C(CHa)z Dithiodipropionic acid (-SCHzCH2COzH)z 152-4 Methyl 4,6-dithia-5,5-di(CHs)zC(SCHzCHzCOz12-13 methyl azelate CH3) 2 2-Methyl-Z-mercapto-4(CH3)zC CHzCOCHa pentanone I SH 2 (2-Methyl-4-ketoamyl) (CH3)zCCHzCOCH3 80 sulfide I
B.P., C.
...
77
...
38.5
102-4
...
127-9 (2 mm.)
...
140 (3 mm.)
...
...
...
AOMO Stability Time,Hr.
38.5
...
104 (25 mm.) 130-5 (0.3 mm.) 145-50 (0.3 mm.)
...
27 41 25 6 17 26
141-3 (0.5 mm.)
6.5 20
70-2 (23 mm.)
.. .
130 (11 mm.)
...
S
I
2(2-Methyl-4-betoamyl) disulfide
(CHa)zCCHzCOCH (CH~)~CCHZCOCH~
I
.
, ,
137-42 (0.7 mm.)
S
I
9 (CH3)zC-CHzCOCHs 3-Thia-6-ketoheptyl ethyl C H ~ C O C ~ H ~ S C Z H ~ S O ~51-3 sulfone CZH4 0.02% in 5-hour lard, active oxygen method.
...
56
(I
VOL. 50, NO. 5
M A Y 15158
797
Table II.
Effect of a-Methyl Substituent
AOM'
Stability Time,
Compound a-Methyl-P-ethyl mercaptopropiophenone
Il\t-CO~HCHd3C2Hs
P-Ethylmercaptopropiophenone
A-COCH~CH&~CZHE 45 (m.p.)
a
Formula
B.P.,
O
C,
Hr.
55
98-100 (1 mm.)
91
0.0270in 5-hour lard, active oxygen method.
Table 111.
Substituted Benzylacetophenones
AOMa
67-8
Stability Time, Hr. 45
76-7
47
105-6
44
M.P.,
Compound 1,3-Diphenyl-4-thia-l-hexanone
Formula :/COCH~CHC~HS
O C .
I
SCzHs
' /
I-(2-Hydroxyphenyl)-3-phenyl-4-thia-l-
hexanone
0'
COCHzCHCsH6 gCZH5
"OH 1-(4-HydroxyphenyI)-3-phenyl-4-thia-lhexanone
a
0.0270 in 5-hour lard, active oxygen method.
ethylmercaptoethyl methyl ketone. Dithiodipropionic acid, which is practically ineffective, is much poorer than thiodipropionic acid ( 8 ) . The 3-thia6-ketoheptyl ethyl sulfone is an effective antioxidant but is not greatly improved by extra activating group. An a-alkyl substituted P-alkylmercaptoketone should be easily available from the Mannich base of propiophenone by the method used to make P-alkylmercaptopropiophenone (73). The free Mannich base was treated with the mercapto compound under relatively mild conditions, such as boiling ether solution, and the desired alkylmercaptoketone was isolated; dimethylamine was evolved as a gas. This reaction has been successfully carried out with compounds as varied as ethyl mercaptan, hydrogen sulfide, and thiophenol. Reaction of the Mannich base from dimethylamine and propiophenone gives a /3-mercaptoketone having a methyl group in the a-position (Table 11). The a-methyl group decreases the potency of mercaptoketone as a n antioxidant. To prepare a di-(alkylmercapto) ketone, benzalacetophenone was converted to the dibromide, which was treated with two equivalents of sodium ethyl mercaptide. No sulfur-containing ketones could be isolated, but benzalacetophenone in better than 90% yield was obtained (77). I n this case, the sodium mercaptide behaved like sodium iodide, which is capable of regenerating double bonds in dibromides. To see whether the carbonyl group is necessary for this reaction, debromination of 2,3-
798
dibromo-2,3-dimethylbutane was
attempted with the sodium ethyl mercaptide. Sodium bromide, tetramethylethylene, and ethyl disulfide were isolated. The reaction can be formulated as
I I I 1
+ 2NaSCaH5
-C-C-
-+
Br Br 2NaBr f -C
I
1
= C-
0-Ethylmercaptoethyl Ethyl Sulfone. p-Chloroethyl ethyl sulfide (75) was oxidized to sulfone with hydrogen peroxide and dehydrochlorinated with triethylamine (3). Ethyl mercaptan added vigorously in the presence of benzyl trimethyl ammonium hydroxide. p-Ethylmercaptoethyl Ethyl Sulfoxide. p-Chloroethyl ethyl sulfide (0.2 mole) was oxidized in acetic acid (25 cc.) with 30% hydrogen peroxide (24 grams) below 40" C. Unchanged starting material was extracted with petroleum ether. Afrer evaporation of the water and acetic acid, the 6-chloroethyl ethyl sulfoxide distilled at 137-239" C. at 26 mm. The sulfoxide (4.2 grams) was heated briefly with a methanolic (50 cc.) solution of sodium methylate (2 grams) and ethyl mercaptan (2.5 grams). The product was distilled in vacuo after filtering to remove the sodium chloride. a-Ketobut 1 Mercaptan. Methyl vinyl ketone mole, 85%) was added to hydrogen sulfide (45 grams) condensed in a stainless steel bomb. A test tube containing 10 drops of Triton B was supported in the bomb so that it did not come in contact with the reactants. After sealing, the bomb was shaken vigorously and allowed to stand overnight. Product was separated by distillation. a-Methyl-p-ethylmercaptopropiophenone. Equivalent amounts of propiophenone, paraformaldehyde, and dimethylamine hydrochloride were boiled in alcohol 1 hour. After the solvent had been removed in vacuo and aqueous solution, the residue was extracted with ether to remove unchanged propiophenone. The Mannich base treated with sodium hydroxide was dissolved in ether and boiled gently with excess ethyl mercaptan for 16 hours; dimethylamine was liberated.
6
Ordinarily AOM times were detcr+ ( C P H ~ S ) ~mined two to three times for each com-
This is an interesting method of removing bromine to form a double bond. 6-Alkylmercaptoketones having aromatic hydroxy groups on the phenyl ring bearing the keto group were prepared from the corresponding chalcones (4-7) * The aromatic hydroxy group is essentially without effect on inhibitor potency. The P-alkylmercapto sulfones are laborious to prepare and the yields are poor in some of the steps. A better method would appear to be through the Mannich bases, as the Mannich reaction can be expected to occur where the reactants have a hydrogen a to an activating group ( 2 ) . Attempts to prepare a Mannich base from methyl phenyl sulfone, formaldehyde, and dimethylamine were unsuccessful.
pound; the results checked well in practically all cases. Literature Cited (I) Bell, E. V., Bennett, G. M., J . Chem. SOC.130, 1803 (1927). (2) Blicke, F. F., Org. Reactions 1, 306 (1942). (3) Buckley, G. D., Charlish, J., Rose, J. L., J . Chem. SOC.1947, p. 1514. (4) Feuerstein, W., Kostanecki, St. V., Ber. 31, 715 (1898). (5) Kostanecki, St. V., Tambor, J., Zbid.,32,1924 (1899). (6) Miller, E., Hartung, W.H., Organic Syntheses, Coll. Vol. 11, 543 (1943). (7) h2,ozingo, R., Zbid.,21, 45 (1941). (8) 0 Leary, D. K., U. S. Patent 2,397,976 (April 9, 1946). (9) Szmant, H. H., Suld, G., J.Am. Chem. SOC. 78, 3400 (1956). (10) Thompson, R. B., I N D . ENG.CHEW 43,1638 (1951). (11) Thompson, R. B., U. S. Patent 2,553,797 (May 22,1951). (12) Zbid.,2,677,617 (Mav 4, 1954). (13) Thompson, ThoniDson. R. B., 'Chenicek. 'Chenicek, J. A. Symon, T., IND. ENG.CHEM.44, 1659 (1952). RECEIVED for review June 22, 1957 ACCEPTED September 20, 1957 Division of Agricultural and Food Chemistry, 131st Meeting, ACS, Miami, Fla., April 1957. I
Experimental
Mercaptans were added to the activated a,p-unsaturated system in the presence of piperidine, quaternary ammonium hydroxides, or sodium methylate.
INDUSTRIAL AND ENGINEERING CHEMISTRY
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