Derivatives of 1 , l -Dimethyl-3-Oxobu tylthiocyanate.
1. 1,4-Dihydro-l-( 2-Mercaptobenzothiazol-6-YI) -
2-T hioxo-4,4,6-T rimethylpyrimidine. JOHN J. D’AMICO, CHING CHEN TUNG, ROBERT H. CAMPBELL and DARRELL D. MULLINS Monsanto Chemical Co., Rubber Chemicals Research Laboratories, Nitro, W. Va.
The reaction of 1 ,I-dimethyl-3-oxobutylthiocyanate with 6-amino-2-mercaptobenzothiazole under acidic conditions gave 1,4-dihydro- 1 -( 2-mercaptobenzothiazol-6-yl)2-thioxo-4,4,6-trimethylpyrimidine, I. Oxidation of I gave 2,2’-dithiobis-[6-( 1,4dihydro-2-thioxo-4,4,6-trimethylpyrimidin-l-yl)-benzothiazole]. Forty-nine deriva. tives of I were prepared. The infrared spectrum of I was obtained.
ALTHOUGH 2-MERCAPTOBENZOTHIAZOLE
was The infrared spectra of I were obtained as Nujol and prepared by Hofman (6) in 1887 it was not until 1921 that halocarbon mulls using a Perkin-Elmer Model 21 Infrared both Bedford ( I ) and Bruni ( 2 ) discovered that it possessed Spectrophotometer. The infrared spectra were consistent accelerating activity for the vulcanization of rubber with with the proposed structure. The C = C stretching vibration sulfur. This great discovery has stimulated many workers assigned to 2-thioxo-4,4,6-trimethyl-1,2,3,4-tetrahydropyto prepare and extensively evaluate its derivatives. Most rimidine (9) was observed a t 1700 cm.-’. Other band of the commercial accelerators, in particular N-cyclohexylassignments in (cm. -I) were as follows: 2-benzothiazolesulfenamide (commercially available as SANTOCURE) ( 5 ) , N-tert-butyl-2-benzothiaxolesulfena- 3247(M) Hydrogen-bonded N-H stretching C-H aromatic and alkene stretching 3030(M) mide (commercially available as SANTOCURE NS) ( 3 ) , 2985(M)2924(W) Aliphatic C-H stretching and 2- (2,6-dimethylmorpholinothio)benzothiazole (comC = C skeletal in-plant-vibrations 1600(M) mercially available as SANTOCURE 26) ( 4 ) are still de1531(S) Thioureide (-N(H)-C=S) rived from 2-mgrcaptobenzothiazole. The 2-mercaptobenzoC-H deformation and C = C skeletal in-plane 1486(S)broad thiazole and its derivatives containing substituents, other vibrations than the ethoxy, hydroxyl and amino radicals, in the 61399(M) -CHs sym. deformation 6osition have been prepared only in a limited number of 1344(S) Unassigned examples. Since 2-thioxo-4,4,6-trimethyl-1,2,3,4-tetrahy-1339(S) C-N stretching as in 2-mercaptobenzothiazole dropyrimidine (7, 8) and its derivatives possess moderate The strong 4-adjacent hydrogen out-of-plane band of accelerating activity, a compound containing both benzothiazolylthio and 2-thioxo-4,4,6-trimethyl-1,2,3,4-tetra-2-mercaptobenzothiazole normally found a t 756 cm.-’ was absent and a 817 cm.-‘ (M) band was observed in the region hydropyrimidinyl radicals would exhibit a synergistic effect of 2-adjacent hydrogen which is in agreement with the and produce a chemical with greater activity than 2-merproposed structure. captobenzothiazole and its derivatives. The new heteroThe postulated,synergistic effect was not observed since cyclic compound was prepared by the reaction of 6-amino-mercaptobenzothiazole with l,l-dimethyl-3-oxobutylthio- the accelerator activity of I and its derivatives was either equal or slightly inferior to 2-mercaptobenzothiazole and its cyanate under acidic conditions producing 1,4-dihydro-1corresponding derivatives. The detailed evaluation data of (2-mercaptobenzothiazol-6-yl)-2-thioxo-4, 4, 6-trimethylI and its derivatives will be reported in forthcoming publipyrimidine, I. The product, a tan colored solid, m.p. cations. 207-209“ C. after recrystallization from ethyl alcohol, was The oxidation of I with either ammonium persulfate obtained in 97.5% yield. The reaction may be represented or sodium hypoiodite furnished 2,2’-dithiobis-[6-(1,4-dias: hydro-2-thioxo-4, 4, 6-trimethylpyrimidin-1-y1)benzothiazOH lCHjlzCCH2CCH~ I C H I CCHpCCH3ICH~IZFCH-~CH~ ole] in yields of 99.5 and 90%, respectively. The product, 3 2 1 II N-C-5 4CN ‘b NCS 0 a tan colored solid, melted a t 266-268” C. with decomposition after recrystallization from dimethylformamide. The condensation of I and formaldehyde with hexamethylenimine or aniline gave 1,4-dihydro-l-(3-hexamethyleniminomethylthiobenzothiazol-6-yl)-2-thioxo-4, 4,:-5 6-trimethylpyrimidine, 11, and 1-[3-(anilinomethylthio) benzothiazol-6-yl]-l, 4-dihydro-2-thioxo-4, 4, 6-trimethylpyrimidine, 111, in yields of 60 and 80% respectively. Products I1 and I11 melted a t 208-210” C. with decomposition and 181-183” C. after recrystallization from ethyl I alcohol, respectively. 446
JOURNAL OF CHEMICAL AND ENGINEERING DATA
ALKALI THIOCARBAMOYL XX
XXVl
X = -CNlCH31z
X
-
x. - y c &
XXVll
X.
s
XXXIII
Y= -$OCP5
XXIV
Y= -COCH3
XXXV
Y.-COCH(CH312 0
XXXVl
Y--COC5HII 0
S
0
n
XXII
X.
-CN
XXVlll
X*-CN
XXlll
x.
-FN
XXIX
x = - C N ~ H ( C H ~ ) ; ~ ~
S
XXlV
X* - C N
XXXVll
X--CN "
Diagram of Compounds
Y=-COCH2CH-CH2
s 3 XXV
sY
/ N
0
- $NlCH31z
C2H5
R O
SSc
OR
C H L O R O T H IOFORMATE
-:N(CZH5I2
0 XXI
ALK4Ll CHLOROFORMATE
OR
CARBAMOYL CHLORIDE
6
P
XXXl
X.--CN(C2H51z
XXXVlll
Y--tSCH3
0
CHJ XXXll
0
X*-CNlC3Hj2
XXXlX
i
Y--CSCzH5 0
AMINE NaOCL
ALKALI
1
R"'CL
A L K A L I AND Z n C l 2
ZINC AND 4MINE SALTS
1
R"'.-CH2CCL-CCL2
XV
R"'--CH3
V
R"'. -CH2CCL.CHCL
XVI
R"'. -CH2CH-CHCH2CCH2ClCH313
VI
R"'.-CH~CH.CH~
VI1
R"'=-CH2CfCH
viii
R'".-CH~CH=CCL~
IX
R"'.-CH~CCL=CH~
x
R'"--CH~CH=CCLCH~
XI
R"*-CH(COCH312
x,,
R"'.
Xlll
R"'~-CH(COOC2H~l2
XIV
R1,"--C2H5
I CH3
XVll
I
I
R',,*o II 0
CL
XVlll
R '". -T;C bOQCL 0
FOOC2H5 -CHCOCH3 XIX
OR C e H 5 N H 2
7H3
IV
R'"--Q
I ALKALI
'O~>SCH2CH2N~R""I2
CLCH2CH2NlR""l2 R""*CH3
R'.
AND C 2 H 5
NHC6H5 ALKALI
4
ALKALI -
C Y A N U R I C CHLORIDE
N-PHENOTHIAZINYL DICHLOROTRIAZINE N
S
R"
*c'
s
VOL. 8 , No. 3, JULY 1963
447
$%$ - m w m i
d
. . . . - . .
: : : : % : :
oN
2 z>
I
, s = I x ,=I 3>3clxxx
zx zx >x z
e
h
Y
clu I
c (
JOURNAL OF CHEMICAL AND ENGINEERING DATA
The reaction of the potassium salt of I with cyanuric chloride or N-phenothiazinyl'dichlorotriazine in an acetone 4, 6medium gave 2,4, 6-tris-[6-(1,4-dihydro-2-thioxo-4, trimethylpyrimidin-1-yl) benzothiazol-2-ylthio]-S-triazine and 10-[2, 6-bis[6-(1,4-dihydro-2-thioxo-4, 4, 6-trimethylpyrimidin-1-yl) benzothiazol-2-ylthio]-S-triazin-4-yl]phenothiazine in yields of 98 and 94.576, respectively. The melting points of both products was greater than 300" C. The reaction of an aqueous solution of the sodium salt o f 1 with zinc chloride furnished the zinc salt of I in 99% yield. The hexamethylenimine salt of I, m.p. 185-187" C. was prepared in 79.2% yield by stirring an ether slurry of I with hexamethylenimine. The 1-(2-substituted-thiobenzothiazol-6-yl)-l, 4-dihydro2-thioxo-4, 4, 6-trimethylpyrimidines (IV-XIX) were prepared by the reaction of the sodium or potassium salt of I in either an aqueous or acetone medium with the agpropriate halogen compounds which are listed in Table I. The use of 1,4-dichloro-2-butene in this reaction furnished 2,2'(2-butenylenedithio) bis [6-(1, 4-dihydro-2-thioxo-4, 4, 6trimethylpyrimidin-1-yl)benzothiazole],m.p. 158-160' C., in 98% yiel'd. The sodium salt of I in an aqueous solution reacted with 6-diethyl or dimethylaminoethyl chloride hydrochloride to form 1, 4-dihydro-l-[2-(diethylaminoethylthio) benzothiazol-6-yl]-2-thioxo-4, 4, 6-trimethylpyrimidine and the corresponding dimethyl derivative. The former compound, m.p. 160-162" C. after recrystallization from ethyl alcohol and the latter compound, m.p. 185-187" C. after recrystalli-
zation from ethyl alcohol, were obtained in yields of 97.5 and 94.576, respectively. The 6-(1, 4-dihydro-2-thioxo-4, 4, 6-trimethylpyrimidin1-yl)benzothiazol-2-yl ester of N,N-dialkylthiol (or dithio) carbamic acids (XX-XXXII) were prepared by the reaction of the potassium salt of I with the appropriate N,N-disubstituted thiocarbamoyl or carbamoyl chloride which are listed in Table 11. The substitution of alkyl chloroformate or alkyl chlorothioformate for the N,N-disubstituted thiocarbamoyl or carbamoyl chlorides in the above reaction furnished the S-[6-(1,4-dihydro-2-thioxo-4, 4, 6-trimethylpyrimidin-1-yl) benzothiazol-2-y1] 0 (or S')-alkyl thiol (or dithio1)carbonates (XXXIII-XXXIX) which are listed in Table 111. The oxidative condensation of I with hexamethylenimine, morpholine or cis- and truns-2,6-dimethylmorpholinefurnished the thiazolesulfenamides in yields of 77 to 98% (Table IV). The reaction of the alkali salt of I with the sodium salt of chloroacetic acid followed by neutralization of the reaction mixture with concentrated hydrochloric acid gave 4, 6-trimethylpyrimidin6-(1,2,3, 4-tetrahydro-2-thioxo-4, l-yl)benzothiazol-2-yl thioacetic acid, m.p. 196-198" C. with decomposition, in 79% yield. ACKNOWLEDGMENT
The writers wish to acknowledge their indebtedness to
M. Steele, E.E. Null, and C. Raynes for analyses performed.
Table II. 641,4-Dihydro-2-Thioxo-4,4,6-Trimethylpyrimidin-l -yl) Benzothiazol-2-yl Ester of N,N-Dialkylthiol (or Dithio) Carbamic Acids n
No.
X
R
xx
XXI
0 S
(CHdzNC6H5N-
XXII
0
d~H5 Pyrrolidyl
XXIII
S
XXIV
S
xxv
S
XXVI XXVII XXVIII
S S S
XXIX
S S
xxx
XXXI XXXII
0
S
Disubstituted Carbamoyl or Thiocarbamoyl Chloride (CH3)zNCOCl CsH5NCSCl
J*Hj 1-Pyrrolidinecarbonyl chloride Pyrr o1id y1 1-Pyrrolidinethiocarbonyl chloride 1-PiperidinethioPiperidyl carboFy1 chloride 4- (2,6-Dimethylmor2,6-Dimethyl morpholinyl pholinethiocarbony1)chloride (CzH5)zNCSCl (C2H5)PN(CH3)zNCSCl (CH3)J'JMorpholinyl 4-Morpholinethiocarbonyl chloride [ (CHg),CH]?N- [(CHs)&H]zNCSCl (C4Hs)JJ(CaH9)zNCSCl (C2Hs)zNCOCl (CzH5)zN(C3Hi)*NCSCl (C~H;)PN-
Yield Crude, %
M.P., "C.
Empirical Formula
N, 7' Calcd. Found
s, % Calcd.
Found
61.4 97.5
196-198" 173-175*
C17HnNaOS3 C23Hz4N4SI
14.27 11.56
13.70 11.82
24.51
24.99
52.5
181-183b
C19HnN40S3
13.39
12.96
...
...
11.5
218-220
CigHzzNA
12.89
12.16
...
...
89.4
151-153'
CnHzaNaSa
12.49
11.93
28.59
28.44
41.9
173-174*
C21H~sN,0S, 11.70
11.89
26.79
26.25
96.5 61.3 97.5
227d 213-215' 199-201'
C igHz,N,Sa CiiHmNA CigHnNIOS,
12.83 13.71 12.43
12.30 13.98 12.25
...
.. . ..
... ... ...
88.2 99.5 76.0 54.0
197-199' 180-182' 144-146 185-187'
CziH2~NaSa CmH3zNk3a CaHzINaOS3 C2iHz8NIS4
12.06
12.27
27.60 26.03 22.87 27.60
27.36 25.82 23.08 26.95
...
13.32 12.06
...
13.39 12.12
...
,
...
Recrystallization from ethyl alcohol and acetone. * Recrystallization from acetone. e Recrystallization from ethyl alcohol and chloroform. Recrystallization from chloroform and ethyl acetate. Recrystallization from chloroform and ethyl ether.
VOL. 8, N o . 3,JULY 1963
449
Table Ill. 5-[6-( 1,4-Dihydro-2-Thioxo-4,4,6-Trimethylpyrimidin- 1-yl) Benzothiazol-2-yl] 0 (or S')-Alkyl Thiol (or Dithiol) Carbonates
C hloroformate or Chlorothioformate
Yield Crude, 70
M.P., "C.
Empirical Formula
s, 70
N, 70 Calcd. Found
Calcd.
Found
CliHiSN30&
10.68
10.02
24.44
24.49
120-122"
C16HiiN302S3
11.07
11.26
25.35
25.00
83.8
156-158"
CiaHziN30zS3
10.31
9.78
...
...
ClC(0)OCsHii
45.9
142-144"
CzoHzN302S3
9.65
9.95
22.08
21.79
CHz=CHCHz-
ClC(O)OCHzCH=CHz
14.9
133
CiaHi9N302S3
10.36
10.58
S
CH3-
C1C (0)SCHj
93.0
146-148
CxHiiN30S4
10.62
10.67
... ...
.. ..
S
C2Hs-
ClC(O)SC?H,
90.5
135-137"
CijH~N30S4
10.26
10.63
31.31
30.75
No.
X
R
XXXIII
0
C2H5-
C1C (O)OCzH,
86.2
127-129"
XXXIV
0
CH3-
ClC(O)OCH,
79.2
xxxv
0
(CHs),CH-
ClC (O)OCH(CH3)z
XXXVI
0
CsHn-
XXXVII
0
XXXVIII XXXIX
Recrystallization from ethyl alcohol.
Table IV. Sulfenamides
No. XL XLI XLII
R Hexamethylenimino Morpholinyl 2,6-Dimethylmorpholinyl
Amine Hexamethylenimine Morpholine cis- and truns2,6-Dimethylmorpholine
Mole Ratio Amine to
Yield Crude,
170-173"
Empirical Formula C*oHxN&
N, 70 Calcd. Found 13.56 13.38
168-170" 123-125"
CnHnNIOS3 CzoHxNIOS3
13.78 12.89
70
M.P., OC.
1.5:l
93.5
3:l 3: 1
77.0 98.0
J
13.70 12.59
s, 70 Calcd. 22.98
Found 22.66
23.60
23.75
...
...
'Melting point with decomposition. Recrystallization from ethyl alcohol.
LITERATURE CITED Eng. Chem. 13, 1034 (1921). (1) Bedford, C.W., Sebrell, L.B., Id. (2) Bruni, G., Romani, B., Giorn. chem. i d . aPPlicUtU 3, 196 (1921). (3) Cooper, R.H., D'Amico, J.J. (to Monsanto Chemical CO.1 U S . Patent 2,807,620 (September 24,1956). (4) D'Amico, J.J., Harman, M.W., Cooper, R.H., J . A m . Chem. SOC. 79,5270 (1957). (To Monsanto Chemical Co.) U S . Patent 2,871,239 (January 27, 1959).
450
( 5 ) Harman, M.W., Ind. Eng. Chem. 29, 205 (1937). (To Monsanto Chemical Co.) U S . Patent 2,191,656 (February 27, 1940). m &.~. 20, ~ 1788 , (1887). (6) ~ ~ f A.w., (7) Horstter, W.P., (to United States Rubber Co.) U.S. Patent 2,234,848 (March 11,1941). (8) Mathes, R.A., Stewart, F.D., Swedish, F., J . Am. C k m . SOC. 70, 1452 (1948). (9) Sayre, R., J . ~ mC k. m . Soc. 77,6689 (1955). RECEIVEDfor review May 31, 1962. Accepted March 22, 1963.
JOURNAL OF CHEMICAL AND ENGINEERING DATA
