Z+
4 tkc New England Association of Chem William 0. Foye
Massachusetts College of Phorrnacy Boston, 021 15
chers
Condensation Reactions of Carbon Disulfide
T h e chemical reactivity of carhon disulfide has escaped general notice. Possibly because of its use as a solvent in Friedel-Crafts or other reactions, or as a solvent for spectroscopy, the possibility of reaction with carbon disulfide is not often considered. Recently, a variety of reactions of this compound, surprising both in number and complexity, have been found which show the carbon to function as an active electrophile, and, in some cases, the sulfur as an active nucleophile. Carbon disulfide should now he considered a reagent as well as solvent. The following review catalogs a number of condensations involving carbon disulfide for which no parallel appears to exist in carhon dioxide chemistry. Whereas carbon dioxide reacts with such strong nucleophiles as hydroxide ion, organometallic compounds, and phenoxide ion, carbon disnlfide shows a much wider reactivity. Several factors can probably account for this difference. One is the greater bond distance for C-S ( 1 . ~ 2 Athan ) for C-0 (1.43 A), which results in greater steric accessibility for compound or complex formation with carbon disulfide. Another factor is that the difference in dissociation energies between C=S and C-S (45 kcal mole-') is less than that between C=O and C-0 (73 kcal mole-'). Thus carbon disulfide has a much greater tendency to assume the dithiolate dianion structure
having a highly electrophilic carbon, than carbon dioxide has to assume the dioxide dianion. I n addition, stretching force constants for bonds with second row elements are generally lower than for bonds with first row elements; this allows a lower energy for the same extent of bond stretching in carbon disulfide and therefore a lower energy in formation of the transition state for a given reaction. Condensation reactions of carbon disulfide with amines, alcohols, and mercaptans to give, respectively, dithiocarbamates, xanthates, and trithiocarbonates are generally known. That carbon disulfide can also condense with carbon, generally as carbanion, has more recently become apparent. The purpose of this review is to point out the instances where carbanion condensations with carbon disulfide have been found, as well as Based on a lecture presented to the 346611 Meeting of the New Eneland Association of Chernistrv Teachers at Canton, Mama chietts, May 1968.
show the nature of the products where more than one group is present. which is capable of undergoing condensation with carbon disulfide. Neither of these topics has been considered a t length or at all in recent monographs (1,s). Reaction of carbon disulfide with diamines is expected to follow the generalization of Losanitsch (.!?), which states that the condensation takes place with the less basic amine, and the more basic amine appears as the cation of the salt. Recent evidence that this is the case was found with p-aminoetbylpiperazine, where infrared absorption showed the primary amino group to undergo condensation, and the secondary amine to undergo zwitterion formation (4). Also, in the case of 2-hydroxyethylaminoethylamine, where the possibility exists for condensation with primary amine, secondary amine, and hydroxyl, infrared evidence again showed condensation with primary amine and zwitterion formation with secondary amine (4). Where the amino groups of a diamine are of equal basicity, this postulation is not applicable, although on the basis of the foregoing results, it might be expected that zwitterions might again result. Piperasine, however, in the absence of added base, forms a bis-dithiocarbamate, isolated as the his-piperazinium salt. Formation of the mono-dithiocarbamate of piperazine has also been claimed (5) in the absence of added hase. Cystamine, however, forms a mono-dithiocarbamate zwitterion (I) in the presence of ammonia (4). It has
been stated that addition of an aliphatic amine to a suspension of carbon disulfide in ammonium hydroxide gives rise to the ammonium salt of the dithiocarhamate (6). This generality does not appear to hold in the foregoing case, where the unreacted amino group is more basic than ammonia, or in several cases mentioned later. Ethylenediamine has also formed both a mono-dithiocarbamate zwitterion (7) in the absence of added hase, and the bis-dithiocarbamate in the presence of sodium hydroxide (8). Hydrazine and carbon disulfide form the hydrazinium salt of the mono-dithiocarbamate (4), although two moles of carhon disulfide in the presence of alkali can form hydrazine-bis-dithiocarhonate (9). Ethanolamine forms the dithiocarbamic acid, rather than the xantbate, which goes to 2-mercaptooxazoline on standing (10). If ethanolamine is heated under pressure with carbon disulfide, however, the product is 2-mercaptothiazdline (I I). Reaction with 2-mercaptoVolume 46, Number 72, December 7969
1 841
ethylamine, in presence of ammonia, however, gives the trithiocarbonate zwitterion (12). This was shown by characteristic absorption in the ultraviolet both for this compound and t,he X,N-diethyl derivative; t,he S-methyl d e r i v h v e formed a rather unstablc dithiocarbamate. The nmr spectrum also showed the presence of NHa+ in the 2-mercaptoethylamine product (IS). Reaction wit,h cysteine in presence of ammonia gave the dithiocnrhamate trithiocarbonate isolated as the triammonium salt(I1) (14).
Carbon disulfide can also condense with the NH3 group of sulfonamides to give N-sulfonyliminodithiocarbonates (111) which can be isolated as either monoor di-ethers (16). Sulfanilamide, under the same conditions (using carbon disulfide and aqueous sodium hydroxide), gave only the p-ditbiocarhamate (16). Either one or both of the S-alkyl groups of the di-ethers are easily replaced with amino (15) or chloro groups (17) to provide syntheses of S-alkyl sulfonylisothioureas, sulfonylguanidines, N-sulfonyldithiourethans and Nsulfonyliminothioesters.
ArSOlNHs
Nz ArS02N=C H \/~ CS.
111
from such compounds as ethylene glycol or dichlorofumaronitrile. Mono-S-ethers are usually impossible to isolate, although they have been claimed in one case (21). The resonating forms of the condensation product from malononitrile and carbon disulfide have been pointed out (V) (23). Salts and ethers from the condensation product with nitromethane (24) have also been isolated. The condensation product with benzoylacetonitrile showed no infrared absorption for G O but the absorption spectrum was characteristic of an en01 salt (VI) (22).
Condensation of carbon disulfide with disubstituted methylenetriphenylphosphoranes has been reported to give the Wittig products, e.g.,thioBetenes and triphenylphosphine sulfide (26). With monosubstituted methylene triphenylphosphoranes, either no product or triphenylphosphine sulfide was obtained, except where the mono-substituent was cyano. Here, the dithiocarboxylic acid (VII) was isolated (26).
S-Na+
1
NHa 50'
NH
NIT, // 3 ArS02NHC,
/SR ArSOnN=C,
Carbanion condensations with carbon disulfide have taken place with such reactive species as those derived from malononitrile ( I S ) , cyanoacetic ester and amide (19), sulfonylacetonitriles (19), 1,s-diketones, P-keto esters, and malonio esters (20), phcnyl benzyl ketone (Sf), phenylacetonitrile (21) and heterocyclic acetonitriles (22). The condensation product is generally the methylene dithiolate dianion IV, but these products cs,
R
RCHSCN -+ NaOH
\
/
C=C
NC
,S-Ne+ \ S-Na+
IV
are often difficult to isolate. Most frequently, the products isolated are di(alkyl)ethers, sometimes referred to as ketene mercaptals, or cyclic ethers derived 842
/
Journal o f Chemical Education
Condensation of carbon disulfide with the active methyl groups of 2,F-dimethylpyridine and 2-methylquinoline has been claimed to give the salts of the dithiocarboxylic acids (20). With pyridinium ylids (having a carbanion adjacent to the pyridinium nitrogen), carbon disulfide condensation occurs with the carhanion to give a solution of the dithiocarboxy betaine (VIII) ; in the presence of methanolic alkali, loss of the aryl or aroyl substituent occurs with formation of dithioacetic acid pyridinium betaine (IX) (27). This compound is stable for a short t,ime and may be converted to pyridinium dithioacetic ester salts or ylids. Ketene mercaptals (X) may also be obtained. Corresponding pyridinium salts having ester or amide substituents in the 3 or 4 position underwent formation of the arylcontaining betaine with carbon disulfide and alkali; the aryl or aroyl substituent was retained on treatment with alkali, however, except in the case of N-phenacyl-3carbamylpyridinium ylid (28). Carbon disulfide condensation also took place with N-phenacylisoquinolinium bromide in the presence of alkali, but the dithio-
hon disulfide in the presence of potassium hydroxide gives the ditbiolate dianion (XV) (SS), frequently con-
,
cs-
VIII
NaOH
CHaOH
+
CsBNC&CE!-
RX
IX
+ C~H~NCHZCSIRX-
\
NaOH
verted to the cyclic dithioles. 1More complex products result from condensation of active methylene ketones and carbon disulfide in the presence of amines. With cyclohexanone in the presence of ammonia, for instance, compounds XVI, XVII, and XVIII (after acidification)
carhoxylic hetaine immediately cyclized to Z-mercapto3-henzoylthiazolo[2,3-a]isoquinolinium hetaine (XI) (29).
N-Methylpicolinium iodide was believed to react with alkali to give the methylene "pyridan" which underwent condensation with carbon disulfide to give a dithiocarhoxylate inner salt (XII) ($0). Recent investigation of this reaction showed that in the presence of carbon disulfide and alkali, the 2-methyl group was eliminated and N-methylpyridine-2-dithiocarhoxylic zwitterion resulted (XIII) (51). The proton nmr spectrum of the compound revealed complete loss of the 2-methyl protons. A corresponding reaction was not given by N-methylquinaldinium iodide, hut the zwitterion of the 2-dithiocarboxymethyl derivative resulted
have been isolated and characterized by meansof their ultraviolet absorption spectra (34). Condensation with cyclohexanone in the presence of sodamide, however, also gave products XVI, XVII, and XVIII along with XIX and XX. Condensation with acetone and
s
n
(31).
ammonia also gave a mixture of cyclization products (XXI, XXII) (55) as did methyl ethyl ketone (XXIII, XXIV) (55). I n these reactions, condensation with both active methylene and nitrogen has occurred.'
AH,+ XIII
Reaction of active methylene ketones with carbon disulfide and potassium hydroxide was found in 1904 to give colored compounds postulated as 2,5-dimercaptothiapyran-Cones (XIV) (52). Acetophenone and car-
XXI
X X ~
X X ~
XXN
An azomethine represents another situation where both nitrogen and active methylerle are present for possible reaction with carbon disulfide. With 3,4dihydroisoquinoline, for example, the hexahydrothiadiazine XXV was obtained (56). 1,2,3,4-Tetrahydroiso'condensation of enamines with carbon disulfide and sulfur to give various heterocycles has been reviewed (64) Also, reaction of ketene acetals with carbon disulfide to give stable adducts has been reported (66).
Volume 46, Number 12, December 1969
/ 843
or
R-C-N
(&
h
I
NH
XXXII \
\
XXV
quinoline, on the other hand, gave the tetrahydroisoquinolinium salt of the dithiocarbamate. A further example of reaction with both nitrogen and active methylene may be found in the condensation with the dimethyloxosulfonium methylide XXVI where the dihydro-2-mercaptoquinolone (XXVII) resulted (57).
Cyclization of thiocarbohydrazide also takes place with carbon disulfide in pyridine to give both 3,s-dimercaptn4-amino4,1,2-triazole (XXXIII) and 2,4-dimercapto[4,1,2]triazolo[3,4-b] [1,3,4]thiadiazole (XXXIV) (44). Reaction of carbon d~sulfidewith strong heterocyclic
n NH,-NrSH
HS
AN,N
HS
XXXIII XXVI
I n these cases the carbon of carbon disulfide has reacted preferentially with nitrogen. With a mixture of an amine and formaldehyde, however, condensation with methylene occurs to give tetrahydro-1,3,5-thiadiazines (XXVIII) (38). I n the reaction with alkylene oxides, alkylene trithiocarbonates (XXIX) result (39). These trithiocarbonates can react with amines to give dithiocarbamoylalkyl disulfidcs (59).
+
RNH,
CH,O
+
CS1
XXXN
bases (pKa valuesof 8-12) of the N-alkyl aminopyridine, -pyrimidine, -quinoline, and -acridine series provides iminodithiocarbonates (XXXV) which have been isolated as salts of the added base, salts of the aminoheterocycle, or esters in unpredictable fashion (45).
R XXXV
I n contrast to most dithiocarbamate formations, which are rapid reactions, the formation of iminodithiocarbonates is quite slow. This is in agreement with the nbservation that electron-withdrawing substituents hinder dithiocarbamate formation of amines (46). p-Nitroaniline, for example, does not form a dithiocarbamate
+
(46).
Phenylhydrazine reacts with carbon disulfide and base to give the dithiolate dianion (XXVI) (47), but
XXIX
XXXVI
Aromatic o-amino halides and o-diamines react with carbon disulfide to give cyclic thinnes of fused ring thiazolines (XXX) (40) or imidazolines (XXXI) (41). C1
NH,
XXXI
.Infrared spectra in some of these cases have shown evidence of amino thiol zwitterions (42). A convenient synthesis of 8-mercaptopurine results from reaction of carbon disulfide with 4,5-diaminopyrimidine (42). Carboxylic acid hydrazidcs cyclize with carbon disulfide to form nxadiazoline-5-thiones (XXXII) (45). 844
/
Journal of Chemical Education
N-aminoquinolinium iodide undergoes l,3-dipolar cycloaddition with carbon disulfide (48) to give a zwitterionic thiadiazole thiol (XXXVII). I;&-Dipolar cy-
cloaddition was also found to occur with 2,4,6-trimethylbenzonitrile oxide to give the 1,4,2-oxathiazoline5-one (XXXIX) rather than the expected thione (XXXVIII) (49). Reaction with anthraccne-9-nitrile oxide gave only the isothiocyanate, however.
-
XXXVIII
~.
+
0-N
ArN=C=S
XXXM
+ CS2 4
I
XL
NC-CS-Na+
11
4
-
-
NHnCN
1
NCCSn-Na+
NC-CS-Na+
FK+ + CS2 + NCN=C KOH \
8-K+
XLI
(51). Reaction of cyanamide, carbon disulfide, and base leads to formation of the cyanodithioimidocarhonate dianion (XLI) (52). This anion has recently been found to react with dihalides to give various heterocycles (55). No attempt has been made to compare the electrophilic reactivity of carbon disulfide with that of other electrophiles, but from the number and variety of the foregoing examples, it would appear to be appreciable. Literature Cited (1) REID,E. E., "Organic Chemistry of Bivdent Sulfur," Vol. IV, Chemical Publishing Co., Inc., New York, 1962. G. D., AND LUDWIG, R. A,, "The Ditbiocarbsmates (2) THORN, and Related Compounds," Elsevier Publishing Co., New York, 1962. S. M., J. Chem. Sac., 119, 763 (1921). (3) LOSANITSCH, (4) FOYE,W. O., AND MICKLES,J., J. Med. Pharm. Chem., 5, -RZR - - 119R?> - - - ,. (5) CHAEONNAT, R., Atti X o c m ~intern. . chim., 3, 65 (1939). J., MOYLE,M., AND (6) BAXTER,J . N., CYMEEMAN-CRAIG, WHITE,R. A,, J . Chem. Soc., 659, (1956); SCHMIDT, E., ZALLER,F., MOOSMULLER, F., A N D KAMMERL, E., Ann., 585, 230 (1954); YOSHIDA,S., AND UNOKI,J., Japan. oat,. 6630 11953). A. W., Ber., 5, 240 (1872). (7) HOFMANN, A. Y., AND KLIMOVA, V. A., J. Gen. Chem. (8) YAKUBOVICH, (U.S.S.R.), 9, 1777 (1939). A. Y., AND GINSBURG, V. A,, J . Gen. Chem. (9) YAKUBOVICH, (U S.S.R), 28, 1031 (1958). P. G.. A N D IVANOVA. S. N.. J. Gen. Chem. (U.S.(10) SERGEEV. \
WILLIAMS, T.. i pat. 547 F@YPW 1
,
(15) GOMPPER,R., (1966).
.
.
,,nco\ ('V"",.
Further illustration of the electrophilic reactivity of the carbon in carbon disulfide is found in the reaction with sodium cyanide. Here, the dithio acid is first formed, but readily dimerizes to give dimercaptomaleonitrile (XL) (50). This compound forms dithioles with either methylene iodide, phosgene, or thiophosgene NaCN
.
1161 W. 0.. , ~FOYE. , ~, AND LASALA. , E. F.. un~ublisheddata. (17) NEIDLEIN,R., HAUSSMANN, W., AND HEUKELBACH, E., Chem. Ber., 99, 1252 (1966). H. D., A N D KENDALL, J. D., US. pat. 2,533,233 (18) EDWARDS, (1950). M., U.S. pat. 3,057,875 (1962). (19) BROWN, (20) SCHEFFER,F., AND KICKUTH,R., Ger. pat. 1,136,697 (21) GOMPPEE, R., AND T ~ P F LW., , Chem. Ber., 95,2861 (1962). J. M., J . P h a m . Sci., 57, (22) FOYE,W. O., AND KAUFFMAN, 1611 (1968). E., A& Chem. Seand., 17, 362 (1963). (23) SODEEBACK, (24) GOMPPEE,R., AND SCHAEFER,H., Chem. Ber., 100, 591 (1967). H., RATHSAM, G., AND KJELSBERG, F., Helu. (25) STAUDINGER, Chim. Ada, 3, 853 (1920); SCH~NBERG, A,, F'RESE,E., AND BROSOWSKI, K.-H., Chem. Ber., 95,3077 (1962). E., J. 079. Chem., 31, 3877 (26) PAPPAS,J. J., AND GANCBER, (1966). (27) KRGHNKE,F., AND GERLACH,K., Chem. Ber., 95, 1108 (1962). (28) OH, K. H., MS. thesis, Mass. College of Phsrmacy, 1967. E , A N D STEUERNAGEL, H. H., Chem. Ber., 97, (29) K R ~ H N KF., 1118 (1964). W., GAERTNER, K., AND JORDAN, A,, Be?., (30) SCHNEIDEE, 57B, 552 (1924). J. M., AND LANEILLO, J. J., un(31) FOYE,W. O., KAUFFMAN, published data. (32) APITZSCH, H., Ber., 37, 1559 (1904); 38, 2888 (1905). (33) KELBER,C., Ber., 43, 1252 (1910). T., HAYASHI, T., MURAOKA, M., AND MATSU(34) TAKESHIMA, OKA., T.., J . Ora. Chem.. , 32. 980 (1967). . . (35) TAKESHIMA, T., IMAMOTO, T., YOKOYAMA, M., YAMAMOTO, K., A N D AKANO, M., J . OTQ.Chem., 33, 2877 (1968). M., BEESLOW, D. s., AND Gnas(36) HUISGEN,R., M~EIKAWA, HEY, R., Chem. Ber., 100, 1602 (1967). E. C., J . Org. Chem., 33, (37) VANLEOSEN,A. M., A N D TAYLOR, 66 (1968). G., MARTINI,A,, NEJEDLY, O., AND (38) RIECHE,A., HILGETAG, SCHLEGEL, J., Arch. Pharm., 293, 967 (1960). J. A., JR., STANSBURY, H. A,, JR., AND CATLETTE, (39) DURDEN, W . H . , J . Am. Chem. Soc., 82, 3082 (1960); CULVENOR, C. C. J., DAVIES,W., AND PAUBACKER, K. H., J. Chem. Soc., 1050 (1946). T. P., AND (40) BALSIGER,R. w., FIKES, A. I., JOHNSTON, MONTGOMERY, J. A,, J . Org. Chem., 26, 3386 (1961). V., AND SAFER,J., J . Chem. Soc., 1389 (194%). (41) PETROW, J. M., unpublished data. (42) FOYE,W. O., AND KAUFFMAN, (43) AINSWORTH, C., J . Am. Chem. Soe., 78, 4475 (1956). J., Acta Chern. Scand., 15, 1295 (1961). (44) SANDSTROM, (45) FOYE,W. O.,A N D KAY,D. H., J . Pharm. Sci., 57, 345 (1968); FOYE,W. O., KAY, D. H., A N D AMIN,P. R., J . Phann. Sci., 57, 1793 (1968). H., J . prakt. Chem., 14, (46) . . FISCHER,F., AND FEUERSTEIN, 51 (1961): E., J . pvakt. Chem., 65, (47) B u s c ~ ,M., AND LINGENBRINK, 473 11902). ~, (48) HUISQEN,R., GRASHEY, R., A N D KRISCHKC,R., Telrahedmn Letters, 387 (1962). J. M., J . Org. Chem., 31, (49) FOYE,W. O., A N D KAUFFMAN, 2417 (1966). , Angew. Chem., 70, 606 (1958). (50) B ~ RG., (51) . . WOLF.W.. DEGENEE. . E... AND PETERSLN, . S... Anqew. . Chem., 72, '963 '(1960). A., AND WOLVEKAMP, M., Ann., 331, 265 (52) HANTZSCH, 11904)~ - - - ., . (53) TIMMONS, R. J., AND WITTENBROOK, L. S., J. 079. Chem., 32, R. H., 1566 (1967); D'AMICO,J. J., A N D CAMPBELL, J . Org. Chem., 32, 2567 (1967); SELTZER,R., J. Org. Chem., 33, 3896 (1968). (54) MAYES,R., A N D GEWALD,K., Angew. Chem. (Inl. Ed. Eng.), 6 , 294 (1967). (55) GEEUPPER,R., AND ELSER, W., Angew. Chem. (Int. Ed. Eng.), 6, 366 (1967).
.
\
w.,Chem. Ber.,
AND H ~ ~ G E L E , '
99, 2885
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