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ANALYTICAL CHEMISTRY, VOL. 50, NO. 11, SEPTEMBER 1978
N-Methylimidazole as a Catalyst for Analytical Acetylations of Hydr~xyCompounds Kenneth A. Connors" and Nivedita K. Pandit School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53706
N-Methylimidazole is an effective catalyst of analytical acylations by acetic anhydride, having a catalyiic activity about 4 X lo2 times greater than pyridine. The conventional titrimetric determination was carried out using N-methylimidarole as the catalyst and dirnethylformamide as the solvent. Typical reaction times for primary and secondary alcohols were 7 to 10 min at 45 'C. Rate constants for the acetylation of some aicohols were determined. Imidazole was found to inhibit the catalysis by N-methylimidarole, The mechanisms of these phenomena are discussed.
Pyridine-catalyzed acylation is a standard method for the analysis of amino and hydroxy groups (1-4). The mechanism involves nucleophilic catalysis with the formation of the aeglpSTidinium ion as an intermediate ( 5 ) . Although pyridine is 6n effective catalyst in such acylations, it is not the ideal reagent for this purpose. T h e reactions are relatively slow, typical reaction times being 0.5-1 h at reflux temperatures. In addition, the noxious odor of pyridine may require the use of a fume hood. Several catalysts have been proposed as substitutes for pyridine. Schenk et al. (6) studied various tertiary amines as catalysts for the acetylation of cyclohexanol with acetic anhydride, m d found triethylenediamine to be about 50 times more effective than pyridine. This compound is also superior to pyridine in catalyzing the acylation of alcohols with the acid chloride of the 2,4-dinitrophenylhydrazoneof pyruvic acid (7). Imidazole has been reported to catalyze acylations by pyromellitic dianhydride (8). Steglich and Hofle (9, 10) have found that 4-dimethylaminopyridine (DMAP) is superior to pyridine as a catalyst for some synthetic acylations. In this laboratory ( 1 I ) , DMAP has been applied to the titrimetic determination of alcohols. Subsequently, DMAP was used to catalyze derivatizations of alcohols prior to gas chromatographic separation (12). Although DMAP is much more powerful than pyridine as a catalyst (by a factor of about lo4), pyridine has still been retained in the DMAP system as a solvent and proton scavenger (12). Side reactions, made evident through the rapid discoloration of the reaction mixture, limit the concentration of DMAP that can be used in a titrimetric determination. .Jencks and Carriuolo (13)studied the catalysis of some acyl transfer reactions and found that both imidazole and N methylimidazole (NMIM) catalyzed these reactions. Based on their results, and on arguments that will be presented in the Discussion section, we felt that NMIM would be an effective catalyst for analytical acylations, and might be superior to catalysts presently in use. This paper describes the application of NMIM to the titrimetric determination of hydroxy compounds by acetylation with acetic anhydride.
EXPERIMENTAL Apparatus. The reaction temperature was maintained at 45 = 0.1 "C 1.is:iig c thermostatic bath with a heater and circulator (E. H. Sargent and Co.). The titration end points were checked 0003-2700/78/0350-1542$01 O O i O
using an Orion model 801 digital pH meter. Materials. N-Methylimidazole (NMIM)(Aldrich Chemical Company) was used directly. All reagent solutions were made with reagent grade materials. The alcohols used were AR grade. N,N-Dimethylformamide (DMF) (9970, Aldrich Chemical Company) was used as the solvent. Reagent Solution. Reagent grade acetic anhydride (Ac,O), 15 mL, was diluted to 50 mL with DMF. Analytical Procedure. A DMF solution, 4.0 mL, containing 2 to 3 mequiv of a hydroxy compound was pipeted into a 125-mL glass-stoppered conical flask. NMIM, 4 mL, followed by 4.0 mL of the Ac10 reagent solution, was added, and the solution was well mixed. The flask was maintained at 45 OC for 7-10 min. Af'ter this time, 20 mL of distilled water was added to the flask, and the contents were allowed to cool to room temperature. If the mixture was not homogeneous, 20 mL of absolute ethanol was then added. Four drops of a 0.2% thymolphthalein solution in absolute ethanol were added and the solution was titrated with standard 0.5 M sodium hydroxide solution to a blue color. A blank determination was carried out, replacing the sample with 4 mL of DMF, and maintaining at 45 "C for 3 min to minimize discoloration. Kinetic Procedure. NMIM, DMF, and solutions of AcpOand of a hydroxy compound in DMF were equilibrated at 45 "C. Appropriate volumes of NMIM, the Ac20 solution, and the sample solution were added to a 125-mL glass-stoppered conical flask and were well mixed. The flasks were maintained at 45 "C. A t known times, 5.0-mL samples of the reaction mixture were withdrawn, discharged into 20 mL of distilled water, and allowed to cool to room temperature. If the mixture was not homogeneous, 20 mL of absolute ethanol was added. The solutions were then titrated with standard 0.5 M sodium hydroxide solution using four drops of 0.2% thymolphthalein as indicator.
RESULTS Figure 1 shows the time course for acetylation of isopropyl alcohol in a NMIM/Ac,OjDMF system a t various concentrations of NMIM. A comparative study with pyridine instead of NMIM was also carried out. The catalytic superiority of NMIM is clearly demonstrated in the figure. No reaction was observed in the absence of any catalyst over a 60-min time period. An estimate of the relative catalytic efficiencies of NMIM and pyridine was obtained as follows. The rates of acetylation in the two systems are expected to be described by Equations 1 and 2. V1 = ~,,,,[NMIM][ROH][AC,O] = ~'NMIM[ROHI[ACZOI (1)
V, = ~,,,[PYR][ROH][AC,O] = ~ ' , , , [ R O H ] [ A C ~ O ] ( 2 ) From the titrimetric data, apparent second-order rate constants a t essentially constant catalyst concentration could be obtained. T h e plots followed second-order kinetics over approximately 9570 of the reaction. For the reaction with isopropyl alcohol a t 45 "C, these estimates were obtained: M-2 s-l. Therefore, hmfm = 7.6 X M-2s-l; k,,= = 2.1 X NMIM is about 4 X lo2times more effective as a catalyst than is pyridine in this reaction. Table I lists rate constants obtained by the same method for the NMIM-catalyzed acetylation of several hydroxy compounds. The rates of 1978 American Chemical Society
ANALYTICAL CHEMISTRY, VOL. 50, NO. 11, SEPTEMBER 1978
60
71
40
-I/P
2o
I
C
1543
0
8 t (mn)
4
t (mid
8
I6
Figure 1. Time course for the acetylation of isopropyl alcohol at 45 "C in 0.8 M Ac,O. The catalyst concentrations were: Curve A , 4.7 M NMIM; B, 2.5 M NMIM; and C, 4.4M pyridine
Figure 2. Time course for the NMIM-catslyzed acetylation of isopropyl alcohol at 45 "C in the presence and absence of imidazole. Concentration of NMIM is 2.5 M. Imidazole, at a concentration of 0.15 M, is present in the slower reaction and is ,absent from the faster reaction
Table I. Rate Constants for the NMIM-Catalyzed Acetylation of Some Hydroxy Compounds h x 102/M-2 s-l hydroxy compound terf-butyl alcohol 0.0012 isopropyl alcohol 0.76 sec-butyl alcohol 0.35 n-propyl alcohol 4.80 n-butyl alcohol 4.00 isobutyl alcohol 3.90 n-amyl alcohol 3.64 phenol 11.10 a In DMF solution at 45 "C.
Figure 2 shows the effect of imidazole on the NMIMcatalyzed acetylation of isopropyl alcohol a t 45 "C. It can be seen that imidazole decreases the rate of this reaction.
a
Table 11. Analytical Results of NMIM-Catalyzed Acetylation of Some Hydroxy Compounds mean recovery, std dev, sample compound %a % phenol 99.4 0.36 isopropyl alcohol 99.6 0.40 n-propyl alcohol 99.9 0.26 n-butyl alcohol 99.6 0.06 isobutyl alcohol 99.6 0.40 sec-butyl alcohol 99.8 0.32 n-amyl alcohol 99.5 0.45 1,2-propanediol 99.P 0.17 ethylene glycol 100.0b 0.10 Mean of three determinations. Both hydroxy groups acetylated. acetylation are in the order phenol > primary alcohols > secondary > tertiary. Table I1 gives analytical results by the NMIM-catalyzed acetylation method. The accuracy and precision of the method are comparable with those of other acylation procedures. The attempted determination of tert-butyl alcohol yielded 36% acetylation in a 40-min reaction time. A yellow color, which progressively darkens with time, is observed in the blank and limits t h e accuracy of the visual end-point detection. Possibly the catalyst promotes Cacylation of AczO in a Perkin-type reaction. However, we have observed no significant alteration in the consumption of sodium hydroxide solution by the blank due to the discoloration. Hence, to improve end-point detection in the blank, we recommend that the blank be maintained a t 45 "C for 3 instead of 7 min. Very little or no discoloration is observed in the sample solution. Thymolphthalein is preferred to phenolphthalein as the indicator because potentiometric titration showed that the thymolphthalein end point coincided better with the potentiometric end point.
DISCUSSI 0N Pyridine-catalyzed acylations proceed through the formation of the acylpyridinium ion (I) as an intermediate ( 5 ) as shown in Equations 3 and 4 for the acylation of an alcohol. 0 (RC0)20
N
+
-
3
e
3'
F;!%-N/+
I
+
RCOO-
(3)
Pyridine in this system serves as a proton scavenger as well as a catalyst. A suitable replacement for pyridine, therefore, should be a nucleophilic catalyst with an effectiveness greater than pyridine but not as great as DMAP so that it can be used in high enough concentrations to serve as both the proton scavenger and the catalyst. It should also be a liquid for ease of use and so it can function as a solvent, and a fairly weak base to prevent interference with titrimetric finishes. Imidazole-catalyzed acyl transfers from reactive acyl compounds have been well studied (14-18). Letting RCOX represent such an activated acyl compound, the mechanism can be summarized as follows. 0 R8-x
A
+ N ~ N H
0
R~-,@NH
"T tart
H20
RCOO-
X-
(5)
R C - N ~ N + H+
(6)
R ~ - N + NU
u
w
+
+
?
m W
,'7
H20
RCOO-
In this scheme, water is shown as the nucleophile, but the mechanism is the same for other nucleophiles. To illustrate the meanings of the terms "fast" and "slow" in Equation 6, the second-order rate constants for the hydrolysis (at 25 "C) of N-acetylimidazolium ion (11) and of N-acetylimidazole (111) are 5 X lo-* M-I min-' and 9 X M-' min-] , respectively (18). The cation is more reactive than the neutral molecule because its leaving group is the neutral imidazole molecule, the more stable form under mild conditions. Since I1 is the intermediate via which most of the catalysis occurs, it is reasonable to expect that N-methylimidazole will also be an effective catalyst, possibly even better than im-
1544
ANALYTICAL CHEMISTRY, VOL. 50, NO. 11, SEPTEMBER 1978
T a b l e 111. R a t e s of A l k a l i n e H y d r o l y s i s of S o m e A c t i v a t e d A c e t y l Compounds relative
kOH!M;l
compound AcIm
min- ) 1.9 x i o 4
rate (1.0) 3 470
5 . 8 x 104
Ac,O
9.0 x
AcNMIM'
ref. 17
lo6
17 18
idazole, because in t h e corresponding intermediate, l-acyl3-methylimidazolium ion (IV), there is no possibility of deprotonation. 0
+ N%Mo
RC-X
i-/
-x- R e RC-N+
N-Me
u
lost
/,
Ip
rate of this reaction. Imidazole has also been observed to inhibit the rate of the pyridine-catalyzed acetylation. These observations are in accord with the above discussion. We must briefly consider the report by Kingston, Garey, and Hellwig (8) that acylation of alcohols by pyromellitic dianhydride (PMDA) is catalyzed by imidazole. This phenomenon may seem inconsistent with the arguments and observations of the present paper, but we note that PMDA is a cyclic anhydride. The product of the nucleophilic attack of imidazole on a cyclic anhydride will be an acylimidazole having a 1,2 relationship to a carboxylic acid function, as shown in Equation 10 for phthalic anhydride. 0
(7)
H20
RCOO-
This expected catalysis is in fact observed (13). Compound IV is an excellent model for the reactions of 11, and has been used to show that the imidazole catalysis proceeds through I1 (18). Table 111 compares published second-order rate constants and relative rates for the alkaline hydrolysis of acetylimidazole ( AcIm), N-acetyl-N'-methylimidazole (AcNMIM+),and AczO (17, 18). The same order of reactivity is seen with other nucleophiles. The reactivity of protonated N-acetylimidazole, AcHIm+, will be about equal to that of AcNMIM+. If acetic anhydride is reacted with imidazole, rapid quantitative formation of N-acetylimidazole occurs (17). Since the pK, of imidazole is 7 and that of N-acetylimidazole is 3.6, the neutral or basic medium required to place most of the imidazole in its reactive conjugate base form ensures that N-acetylimidazole will exist almost wholly as the neutral, relatively unreactive, species. Thus the net result is that the more reactive AczO is transformed into the less reactive AcIm (Table 111). From the point of view of the overall transfer of an acetyl group from AczO t o (for example) an alcohol, the presence of imidazole is therefore predicted to inhibit the rate. T h e situation is otherwise for N-methylimidazole, the pK, of which is also 7 (18). Now AczO is transformed into the more reactive AcNMIM+, so we predict that N-methylimidazole will catalyze acylations by acetic anhydride. T h e mechanism for the acetylation of alcohols in a NMIM/Ac20 system is therefore probably as shown in Equations 8 and 9. (CH3CO)20
+
NAN-Me
\-i
19,
CH C-NL N-Me
3 w
+
CH3COO-
(8)
ACKNOWLEDGMENT We thank Judy Batty, who made some preliminary studies in this field.
0 CH C-N+ I! AN-Me + R'OH + CH3COOR' + HiAN-M0
3
The reverse reaction is a p t to be favored because of this relationship. However, the reaction of the acylimidazole with a nucleophile will also be aided, much as is the hydrolysis of the closely related phthalamic acid (16),by intramolecular participation. One possibility is the intramolecular transfer of a proton to the leaving group, converting it into the reactive protonated acylimidazole. Attack by the nucleophile (such as an alcohol) might be further facilitated by the general base carboxylate. The proposal that intramolecular facilitation is to be expected in acylations by cyclic anhydrides is supported by evidence on some related reactions. It has been suggested that this intramolecular phenomenon might account for the unusual specificity patterns of hydroxy group determinations by cyclic anhydrides (19);these anhydrides acylate alcohols but not phenols. Cohen (20) later provided experimental support for an intramolecular process. Lapshin et al. (21)have studied the kinetics of acetyl halide reactions with aromatic amines in the presence of NMIM, and found that the nature of the counterion had major kinetic effects upon the rates of the N-acetyl-N'-methylimidazolium ion with the amines. Phosphorylation of alcohols using NMIM and mercuric chloride as catalysts was also reported to proceed through the formation of an intermediate, the N-phosphoryl-N'-methylimidazolium salt. This in turn reacted with the alcohols to give the alkyl dihydrogen phosphates (22). The NMIM-catalyzed acetylation reported here appears to be one of the most effective of the available anhydrideacylation methods involving nucleophilic catalysis. Reaction times are short, precision and accuracy are good, and pyridine has been removed from the system.
L
I
w
(9)
In comparing the relative effectiveness of pyridine and NMIM as catalysts, pyridine might be thought to be better since the acetylpyridinium ion is much more reactive than the N-acetyl-iV'-methylimidazolium ion ( 5 ) . However, the formation of the acetylpyridinium ion from AczO is not favored; i.e. t h e formation of this ion is the rate-determining step in the Ac20/pyridine system, whereas the reaction of the iVacetyl-N'-methylimidazolium ion with the alcohol is ratedetermining in the Ac,O/NMIM system. Hence NMIM is predicted to be superior to pyridine as a catalyst for acylations. T h e high catalytic effectiveness of DMAP is a consequence of stabilization of the corresponding acetylpyridinium ion by delocalization within the 4-dimethylaminopyridyl system. Figures 1 and 2 show that NMIM is a better catalyst than is pyridine of the acetylation, and that imidazole inhibits the
LITERATURE CITED (1) V. C. Mehlenbacher, Org. Anal. 1, 1 (1953). (2) C. L. Ogg, W. L. Porter, and C. D. Willits, Ind. Eng. Chem., Anal. E d . , 17, 394 (1945). (3) P. J. Elving and B. Warshowsky, Ind. Eng. Chem., Anal. Ed., 19, 1006
,." . . ,.
11947)
(4) S Veibel, "The Determination of Hydroxy Gfoups". Academic Press, New York. N.Y.. 1972. (5) A. R.'Fersht and W. P. Jencks, J . Am. Chem. SOC.,91, 2125 (1969). (6) G. H. Schenk, P. Wines, and C. Mojzis, Anal. Chem.. 36,914 (1964). (7) D. P. Schwartz, Anal. Biochem., 36, 148 (1970). (8) E. H. M. Kingston, J. J. Garey, and W. 8 . Hellwig, Anal. Chem., 41, 86 (1969). (9) W. Steglich and G. Hofle, Angew. Chem., Int. Ed. Engl., 8, 981 (1969). (10) G. Hofle and W. Steglich, Synthesis, 620 (1972). (11) K. A. Connors and K. S. Albert, J . Pharm. Sci., 62, 845 (1973). (12) E. L. Rowe and S. M. Machkovech. J . Pharm. Sci., 66, 273 (1977). (13) W. P. Jencks and J. Carriuolo, J . B i d Chem., 234, 1972 (1959). (14) T. C. Bruice and S.J. Benkovic, "Bioorganic Mechanisms", Vol. I, W. A. Benjamin, New York, N.Y., 1966, p 46. (15) W. P Jencks, "Catalysis in Chemistry and Enzymology", McGraw-Hill, New York. N.Y., 1969, p 67.
ANALYTICAL CHEMISTRY, VOL. 50, NO. 11, SEPTEMBER 1978 (16) M. L. Bender, "Mechanisms of Homogeneous Catalysis from Protons to Proteins", Wiiey-Interscience, New York, N.Y., 1971, p 159. (17) J. F. Kirsch and W. P. Jencks, J . Am. Chem. Soc., 86, 833 (1964). (18) R. Wolfenden and W. P. Jencks, J. Am. Chem. Soc., 83, 4390 (1961). (19) K. A. Connors. "Reaction Mechanisms in Oraanic Analvtical Chemistrv". Wiley-Interscience, New York, N.Y., 1973,-pp 598-601, (20) J. L. Cohen and G. P. Fong, Anal. Chem.. 47, 313 (1975). (21) S.A. Lapshin, V. A. Dadali, Y. S. Sirnanenko, and L. M. Litrinenko, Zh. Org, Khim., 13, 586 (1977) I
1545
(22) H. Takaku, Y. Shimada, and K. Aoshinia, Chem. Pharm. Bull. Jpn., 21, 2068 (1973).
/
RECEIVED for review March 27,1978. Accepted June 29, 1978. This work was supported in part by NSF Grant No. CHE78-06603.
Vacuum Sublimation Behavior of Various Metal Chelates of 4-Anilino-3-pentene-2-one, Acetylacetone, Dithiocarbamates, Oxine and Its Derivatives, Dimethylglyoxime, Dithizone, 1-(2-Pyridylazo)-2-naphthol, and Tetraphenylporphyrin Takaharu Honjo,
Hisanori Imura, Shigeki Shima, and Toshiyasu Kiba
Department of Chemistry, Faculty of Science, Kanaza wa University, Marunouchi, Kanaza wa, Ishika wa 920, Japan
A vacuum sublimation apparatus with continuous temperalure gradient (30-320 "C) along its length (0-65 cm) is described. Samples are inserted Into the high temperature end of the sublimator and are heated for about 4 h under low pressure (1.5-3 X lo-* Torr). The metal chelates recrystallize on the walls of the glass tube, and the high temperature end of the zone is sharply defined. The sublimation-recrystallization zone temperatures are reported for metal chelates of 14 chelating reagents. The temperatures at the start of sublimation of labeled chelate compounds of six chelating reagents are also determined by using another type of a vacuum sublimator. Diethyldithiocarbamates and oxine were found to offer the greatest promise for the purification and separation of metals as their chelates by the vacuum sublimation method.
Sublimation is a very useful method for purifying analytical reagents or reference standards, separating solid mixtures into constituents, and concentrating very small traces of impurities in a solid substance (1). Recently, vacuum sublimation behavior of various metal chelates of 8-hydroxyquinoline ( 2 ) , phthalocyanine ( 3 ) ,and P-diketones with aliphatic groups (acetylacetone (4-8) and dipivaloylmethane (6)) and fluoromethyl groups (trifluoroacetylacetone ( 6 ) , hexafluoroacetylacetone ( 6 ) , benzoyltrifluoroacetone ( 7 ) , thenoyltrifluoroacetone ( 7 ) ,and monothiothenoyltrifluoroacetone (9)) has been investigated, and many metal chelates are isolated and purified with the use of the vacuum sublimation method. Radiochemical and hot-atom chemical studies on metal chelates of phthalocyanine (10) and P-diketones with acetylacetone (11, 12) and dipivaloylmethane (13-15) have also been carried out by means of the vacuum sublimation technique. T h e purpose of this study is to find suitable chelating reagents for the purification and separation of metals by sublimation, and various chelate compounds have been treated in a vacuum sublimator with a continuous temperature gradient under low pressure. Some aspects of the behavior of the chelate compounds in vacuum sublimation will also be discussed.
EXPERIMENTAL Apparatus. Hitachi Vacuum Pump, Type 3VP-C3; Shimadzu Pirani Gauge, Model PM-12; Hitachi Recorder, Type 056; Yamato 0003-2700/78/0350-1545$01.OO/O
Denki Mantle Heater, Type CL; Kubota Voltage Regulator, Type 1A-100;Hitachi Voltage Stabilizer, Type FPW-4; Iwaki Shaking Machine, Type V-S; Kubota Centrifuge Machine; Hitachi-Horiba pH Meter, M-5; 323 Hitachi Recording Spectrophotometer; 239 Hitachi Digital Spectrophotometer; Kobe Kogyo NaI(T1) Well-Type Scintillation Counter, Model EA-14; and Toshiba 200 Channel Pulse Height Analyzer, Type EDS-34208A were used. Materials. Metal low. The guaranteed-grade or reagent-grade metal salts of AgNO,, A1C13.6H20,HAuC14.4H20,BeCl,, Bi(N03)3*5H20,CaCl2-2Hz0,CdCl,, CoC 12.6H20,K2Cr20j, CuS04. 5H20, (NH4)2Fe(S04)2.6H20, FeC12.6H,0, HgC12, In(NO3I3, MgS04.7H20,MnC12.4Hz0, (NH4)6hIo7024.4H20, H2M04.H20, NiC12-6H20,Pb(N03),, PdCl,, RhCl,, TeO,, U02(CH3C00)2.2Hz0, NH4V03, and ZnCl,, were dissolved in distilled water or in a slightly acidic hydrochloric or nitric acid solution to make a lo-' M aqueous solution of each metal ion. Each of the high-purity metals, such as Cd, Cu, Fe, Mn, Pb, Se, Sn, T1, and Zn, was also dissolved in a minimum amount of concentrated hydrochloric or nitric acid, heated almost to dryness, followed by diluting it with a slightly acidic solution to make each 113-' M stock solution. A s 2 0 3 was dissolved in an aqueous solution of sodium hydroxide, and the solution was neutralized with sulfiiric acid to make a lo-' M solution. The chlorides or the nitrates of the radioisotopes, @ C ,o' 59Fe,'03Hg, and 65Zn,were purchased from the Radiochemical Centre (England), and the New England Nuclear Corporation (U.S.A.). Chelating Reagents. The reagents obtained commercially were all guaranteed-grade materials. Dithizone and l-nitroso-2naphthol were purified by recrystallization from chloroform with petroleum ether, while other reagents of the reagent-grade materials were used without further purification. DDTC (sodium diethyldithiocarbarnate), PDTC (ammonium pyrrolidindithiocarbamate), oxine (8-hydroxyquinoline), dibromooxine (5,7-dibromooxine),thiooxine (8-mercaptoquinoline), dithizone (diphenyldithioPAN (1-(2-pyridylaz0)-2-naphthol), carbazone), dimethylglyoxime, MBT (2-mercaptobenzothiazole), diphenylcarbazone, and toluene-3,4-dithiol, were purchased from the Wako Junyaku Kogyo Co. Dichlorooxine (5,7-dichlorooxine), methyloxine (2-methyloxine),nioxime (1,2-cyclohexanediondioxime), a-benzildioxime, cupferron (N-nitrosophenylhydroxylamine), and N-benzoyl-N-phenylhydroxylaminewere purchased from the Tokyo Kasei Kogyo Co. Ethylxanthate (potassium ethylxanthate) and I-nitroso-2-naphtholwere obtained from the Katayama Kagaku Kogyo Co. BDTC(sodium di-n-butyldithiocarbamate) was synthesized by the method of Klapping and Van der Kerk, that is, by the reaction of di-n-butylamine with carbon disulfide in an aqueous solution of sodium hydroxide on cooling (16),and was purified by recrystidhation from chloroform. @-Ketoimine(4-anilino-3-pentene-2-one) was synthesized by the C 1978 American Chemical Society
