Benzothiazole compounds XXVIII. Synthesis of 2-styrylbenzothiazolium salts substituted at position 3 and their biological activity

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1 Benzothiazole copounds XXVIII. ynthesis of 2-styrylbenzothiazoliu salts substituted at position 3 and their biological activity a P. CHABREČEK, a V. UTORI, b P. FOLTÍNOVÁ, C V. EKERKA, and d A. GÁPLOVKÝ 3 Departent of Organic Cheistry, Faculty of Natural ciences, Coenius University, C atislava ъ Institute of Molecular and ubcellular Biology, Coenius University, C atislava c Departent of Molecular Biology and Genetics, Faculty of Natural ciences, Coenius University, C atislava á Institute of Cheistry, Coenius University, C atislava Received 5 March tyrylbenzothiazoliu salts substituted at the position 3 were prepared by alkylation of 2-styrylbenzothiazole with ethyl iodide, diethyl sulfate, allyl broide, propargyl broide, benzyl broide, brooacetic acid, and brooacetic acid esters. Their structure was proved by UV, IR, and 'H NMR spectra. The copounds showed the activity as plant-growth regulators, and affected both the cells division of Euglena gracilis and the synthesis of chlorophyll. The antibacterial and antifungal activities were also found. Соли 2-стирилбензотиазолия, замещенные в положении 3, были получены посредством алкилирования 2-стирилбензотиазола йодистым метилом, диметилсульфатом, бромистым аллилбм, бромистым пропаргилом, бромистым бензилом, бромуксусной кислотой и эфирами бромуксусной кислоты. Их строение было доказано с помощью УФ, ИК и *Н ЯМР спектрометрии. Полученные соединения обладали свойством регулировать рост растений и влияли как на деление клеток Euglena gracilis, так и на синтез хлорофилла. Кроме того были обнаружены бактерицидная и фунгицидная активности этих соединений. Just a little attention has been paid to the synthesis of 2-styrylbenzothiazoliu salts substituted at the position 3. o far, only 2-styryl-3-rnethylbenzothiazoliu ethyl sulfate (/), iodide {II), and Perchlorate {III) have been described. The copounds 77 and /// were prepared by an anion-exchange reaction fro / [1]. Che. Papers 41 (5) (1987) 655

2 Table 1 Characterization of the synthesized benzothiazohu salts (go Copound Forula M r и 4 (са1с.)/% Hi(found)/% Yield M.p. / // /// IV v VI VII CH 3 CH 3 CH 3 CH 3 C 6 H 5 C 6 H 5 C 6 H 5 CH C I7 H I5 N I C, 6 H I4 IN C10 4 C 16 H I4 C1N BF 4 C 16 H, 4 BF 4 N C 22 H l8 N СЮ4 C 22 H I8 C1N BF 4 C 22 H 18 BF 4 N H N о x CD 70 c ч o 70 TI O r H z o то O TJ 5

3 5 Í. Table 1 (Continued) Copound R VIII СН 2 С б Н 5 IX CH = X XI СН 2 С = СН СН 2 СООН XII сн 2 со 2 сн 3 XIII сн 2 со 2 с 2 н 5 XIV CO 2 C 3 H 7 -Í XV сн 2 со 2 с 3 н 7 N0 3 Forula C 22 H, 8 N C 18 H 16 N C 18 H l4 N C 17 H 14 N0 2 C 18 H 16 N0 2 C 19 H I8 N0 2 C 2 oh2on0 2 C 2 oh 2 on0 2 K Wi(calc.)/% Wi(found)/% H N Yield M.p z N O 4 x N O n o s c z Ö x

4 Table I (Continued) Copound XVI XVII XVIII XIX XX XXI C0 2 CH = C0 2 CH2CH = C0 2 C 4 H 9 СН 2 С0 2 С 5 Н и C0 2 C 7 H l5 C0 2 C 6 H 5 Forula C l9 H l6 N0 2 C 20 H l8 NO 2 C 21 H22N0 2 C 2 2H,4N0 2 C24H 28 N0 2 C 2 4H 20 NO 2 M r С H'j(Cc ilc.)/% n'i(found)/% H N Yield % M.p. c У о x to 73 ГУ?* on С H О 2 'тз TI r H z 70 Ti O r O

5 Table 2 'H NMR, UV, and IR spectral data of the synthesized copounds g Copound /pp ^ax/n / II III IV v VI VII VIII IX x XI XII XIII XIV (, 11 H, Ar, CH = CH ), 4.34 (s, 3H, N CH 3 ) fl (, 11 H, Ar, CH = CH ), 4.35 (s, 3H, N CH 3 ) fl (, IIH, Ar, CH = CH ), 4.38 (s, 3H, N CH 3 ) a (, 10H, Ar, CH = CH ), 3.96 (s, 3H, N CH 3 ) fl (, 16H, Ar, CH = CH ), 5.69 (s, 2H, N- f (, 16H, Ar, CH = CH ), 5.67 (s, 2H, N f (, 16H, Ar, CH = CH ), 5.64 (s, 2H, N ) b (, 16H, Ar, CH = CH ), 5.60 (s, 2H, N- f (, IIH, Ar, CH = CH ), (, 5H, N CH = ) fl (, 11 H, Ar, CH = CH ), 6.01 (s, 2H, N ), 3.70 (s, 1H, =CH) a (, 11 H, Ar, CH = CH ), 5.99 (s, 2H, N ) (, 11 H, Ar, CH = CH ), 6.09 (s, 2H, N ), 3.78 (s, 3H, OCH 3 ) (, IIH, Ar, CH = CH ), 6.07 (s, 2H, N ), 4.20 (q, 2H, O ), 1.20 (t, 3H, CH 3 ) e (, 11 H, Ar, CH = CH ), 5.41 (s, 2H, N ), 4.80 (, 1H, OCH), 0.87 (d, 6H, (CH 3 ) 2 )* g t. IQ" 3 v(c = Q) v(c = C) d 2 ol P/c -1 č/c Z s s r 8 c z o x

6 Table 2 (Continued) Copound /pp ^ax/ n g,.lq- 3 v(c = Q) v(c = C) d 2 ol v/c ~' p/c "' ' XV (, 11H, Ar, CH = CH ), 5.45 (s, 2H, N ), 3.90 (t, 2H, O ), 1.26 (, 2H, ), 0. (t, ЗН, СН 3 ) Л о ас XVI (, 12H, Ar, CH = CH ОСН = ), 5.51 (s, 2Н, N СН 2 ), 4.71 (dd, 1Н, = СН 2 trans), 4.40 (dd, IH, = cisf XVII (, ПН, Ar, CH = CH ), 5.46 (s, 2Н, N СН 2 ), Я (, ЗН, СН = СН 2 ), 4.40 (d, 2Н, ОСН 2 f XVIII (, ПН, Ar, CH = СН 2 ), 5.43 (s, 2Н, N СН 2 ), 3.92 н (t, 2Н, ОСН 2 ), (, 7Н, СН 2 СН 3 ) У 1 XIX (, ПН, Ar, СН = СН ), 5.41 (s, 2Н, N СН 2 ), 3.90 У (t, 2Н, ОСН 2 ), (, 9Н, СН 2 СН 3 ) А XX (, ПН, Ar, СН = СН ), 5.46 (s, 2Н, N СН 2 ), 3.92 z (t, 2Н, ОСН 2 ), (, 13Н, СН 2 СН 3 ) I" XXI (, 16Н, Ar, СН = СН ), 5.41 (s, 2Н, N СН 2 ), (s, 2Н, ОСН 2 ) ь и á) In DMO-d 6 ; b) In CF 3 COOD. J о 5

7 BENZOTHIAZOLE COMPOUND. XXVIII The present paper is linked up with our previous results on benzothiazoliu salts research [2]. Our intention was to carry out various alkylations of 2-styrylbenzothiazole and thus to prepare 2-styryl-3-R-benzothiazoliu salts, to characterize the by spectral ethods and to exaine their activity as plant- -growth regulators, in cells division and synthesis of chlorophyll of Euglena gracilis as well as in antibacterial and antifungal areas. Concerning the activity tests, we expected the influence of both the character of a substituent at the position 3 (especially the nature of an ester group) and the character of a counterion. 2-tyrylbenzothiazole was prepared in 95 % yield by condensation of 2- -ethylbenzothiazole with benzaldehyde according to Dryanskďs procedure [3]. Its alkylation with alkyl halides, brooacetic acid esters, and diethyl sulfate led to 2-styryl-3-R-benzothiazoliu salts listed in Table 1. Reactions with ethyl iodide and diethyl sulfate were perfored in dry acetone at reflux teperature. The rest of alkylations was carried out in dry acetonitrile at C (bath teperature). A higher teperature caused foration of black, not identified oily aterial. In order to learn ore deeply the role of an anion in biological activity, the anions of 2-styrylbenzothiazoliu broide and iodide were replaced by C1CV, BF^, N0 3-, and CH3O7. The synthesized derivatives of benzothiazoliu salts exhibit the characteristic absorption in UV region between 372 n and 382 n (Table 2). The exceptions are copounds / and X with A^ at considerably lower wavelengths. In case of the derivative / a plausible explanation lies in a different polarizability (and the solvation related to it) of the anion CF^CV. Electron-donating effect of the propargyl group is responsible for the observed trend in case of the derivative X. The dependence of wavenubers of bands belonging to v(c = 0) vibrations on the alkoxy group (copounds XI XXI) follows alost exactly the sae pattern described for the chloroacetic acid esters [4], however, the dependence on the inductive effect is not linear. The wavenubers of v(c = C) vibration bands do not change significantly their positions either, when the R is changed, except for the derivative X. The position of v(c = C) vibration at a uch higher wavenuber than in the rest of derivatives is a consequence of a large inductive effect of the propargyl group (a* = 0.76) [5]. The influence of a counterion on the position of this band is negligible. In UV spectra taken in protic and aprotic solvents (H 2 0, CH 3 CN) a rearkable change of olar absorption coefficients occurs. In 'H NMR spectra recorded at various concentrations of our salts (c = 10" 1 10~ 3 old~ 3 ) one can observe that cheical shift of alkyl groups protons is concentration-depen- + dent; e.g. the cheical shift of ethylene protons N in 2-styryl-3- -ethoxycarbonylethylbenzothiazoliu broide (XIII) ranges fro / = = 5 2 Hz depending on the concentration. This fact points to the capabil- Che. Papers 41 (5) (1987) 661

8 Table 3 Effect of the synthesized copounds on Euglena gracilis ( 1 1 s I copound. / II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XX XXI 400 3/0/63 32/0/68 4/0/38 5/0/31 4/0/30 6/0/30 6/0/ /0/70 16/0/48 15/0/42 32/0/46 35/0/45 30/0/38 31/0/36 30/0/46 Cells / Mutants / Chlorophyll % / % /(ug c" 3 ) 2/6/8 2/0/13 3/0/13 3/0/15 7/0/16 2/0/8 10/5/26 86/0/85 /0/70 56/0/71 65/0/72 65/0/70 49/0/49 16/0/13 /0/ 62/0/70 / % 10 13/2/26 16/0/26 17/0/28 6/0/7 42/0/36 38/0/40 24/0/26 35/2/65 24/2/36 3/0/13 89/0/90 68/0/79 74/0/84 86/0/83 86/0/80 78/0/69 21/0/46 76/0/70 86/0/ /0/38 23/0/54 23/0/56 23/0/36 52/0/48 54/0/55 35/0/40 56/0/78 63/0/48 26/0/30 99/0/96 86/0/90 86/0/96 90/0/96 93/0/94 86/0/88 56/0/68 86/0/89 96/0/ /0/73 68/0/80 65/0/82 68/0/70 76/0/70 74/0/72 75/0/69 76/0/83 70/0/70 56/0/70 100/0/100 98/0/ /0/ /0/ /0/100 93/0/96 73/0/80 100/0/ /0/ /0/86 100/0/99 99/0/98 98/0/89 99/0/97 95/0/99 97/0/95 95/0/96 90/0/86 88/0/83 100/0/ /0/ /0/ /0/ /0/ /0/100 86/0/93 100/0/ /0/ С 3 70 О о то v 5

9 BENZOTHIAZOLE COMPOUND. XXVIII ity of the prepared copounds to for aggregates to a degree controlled by a solvating ability of the ediu. uch aggregates have been described for tetraalkylaoniu salts [6 8]. In contrast with chloroacetic acid esters [4], it sees probable that the observed sensitivity of wavenubers v(c = O) of the benzothiazoliu salts to the nature of alkoxy group accounts not only for the inductive effect of a substituent but also for weak, nonbonding interactions fored as a result of the aggregation of olecules. These effects will be a topic of our further, ore detailed investigation. The biological activity of the copounds under study was exained on a odel organis of Euglena gracilis', their antibacterial and antifungal properties and also effect on the growth of the root syste of vetch were also tested. Unicelled organis Euglena gracilis can live as an autotroph, heterotroph or ixotroph. Cheicals can affect either the growth of Euglena gracilis culture or can interfere with the cell chloroplast organelle. tudying both fors of action, it was found out that all the tested copounds have an effect on the cells division of Euglena gracilis and the synthesis of chlorophyll as well. The results sued up in Table 3 clearly deonstrate the inhibition activity at higher concentrations on both processes. Lower concentrations have either no effect or soe copounds slightly stiulate both processes. oe relationships between the cheical structure and the activity can be drawn fro these results. The copounds / X bearing ethyl, allyl, propargyl or benzyl group at the position 3 are relatively powerful inhibitors. Concentration of 100 ig/c 3 is 100 % lethal and even the concentration of 0.1 ig/c 3 slightly inhibits both processes. The copounds XI XVIII and XXI, to the contrary, are less toxic for Euglena gracilis, nay, stiulate the cells division and the synthesis of chlorophyll at concentrations of 0.1 lug/c 3. Higher sublethal concentrations of the copounds / Xhave the significant inhibitory effect on chlorophyll. After the inhibitor had been reoved by washing up and the cells had been inoculated on a heterotrophic ediu, 100 % green population was developed. In the case of copounds /, VIII, and IX also white colonies were present, though in aounts not exceeding 6 % of the total nuber of colonies. Tests on the antibacterial activity resulted in finding out that the copounds are preferentially active against gra-positive strains. As Table 4 shows, they are ost effective against taphylococcus aureus sensitive to antibiotics and also against taphylococcus aureus resistant to penicillin and apicillin. There is a inute or no activity at all against gra-negative strains. Escherichia coli and Pseudoonas aeruginosa were inhibited neither by the highest concentration tested ( ng/c 3 ) nor under conditions of the dilution test. The higher activity against gra-positive bacterial strains has also been found in other classes of benzothiazoliu salts reported earlier [9]. The antifungal activities (Table 5) are Che. Papers 41 (5) (1987) 663

10 P. CHABREČEK, V. UTORI, P. FOLTÍNOVÁ, V. EKERKA, A. GÁPLOVKÝ Table 4 Antibacterial activity of the synthesized copounds Miniu inhibitory concentration Copound ^/ disc / II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XX XXI 1 taphylococcus aureus 29/58; 2. taphylococcus aureus 2560; 3. Bacillus subtilis 18/66; 4. Escherichia coli 326/71; 5. Pseudoonas aeruginosa interesting, too. The ost sensitive strain to the prepared copounds, Candida pseudotropicalis (yeast), is inhibited by copounds / X even at 0.1 ig/c 3 concentration. The least sensitive strain is Chaetoiu globbosu, while fungistatical effect against Microsporu gypseu was observed at the concentration of 5 ig/c 3. Also the rest of copounds exhibits relatively satisfactory activity against the yeast strain. The growth-regulation tests were carried out on seeds of vetch (Vicia sativa, var. Fatia). The extension of roots in length is one of the iportant features of plants. The tested derivatives, concerning their structure and concentrations applied, affected the growth of priary vetch roots in length to a various degree. Ten derivatives caused the inhibitory effect in a wide range of concentrations (10~ 3 10" 13 old~ 3 ) with the axiu of inhibition at с = 10" 3 old~ 3. The inhibition of roots growth at this concentration varied fro 5.97% up to 53.76% (Table 6). The additional nine derivatives showed 664 Che. Papers 41 (5) (1987)

11 BENZOTHIAZOLE COMPOUND. XXVIII Table 5 Antifungal activity of 2-styryl-3-R-benzothiazoliu salts Fungicidal/statical concentration Copound l Q I II III IV V VI VII VIII IX X XI XII XIII XIV XVI XVII XXI /5 /5 /5 /5 /5 /5 /5 /5 25/5 25/5 / / / / /5 / 400/ / / /5 /5 / / / / /5 /5 / 400/ 400/ 400/ / 400/ 400/ 400/ 400/ / / / 400/ 400/ 400/ / / 400/ 400/ 400/ 400/ 400/ 400/ 400/ 10/1 /10 /10 /10 /10 /10 / / 1. Microsporwn gypseu; 2. Penicilliu funiculosu; 3. Chaetoiu globboswn; 4. Candida pseudotropicalis. also an inferior stiulation activity due to low concentrations. The ost effective derivative of the presented benzothiazoliu salts is 2-styryl-3-propoxycarbonylethylbenzothiazoliu broide {XV). This copound stiulates the growth within the range of concentrations of 10~ 7 10" n old" 3 with the axiu of % at с = 10~ n old~ 3, and acts as an inhibitor in the range of с = 10" 3 10~ 4 old~ 3, with the axiu of inhibition being 53.03% at с = 10" 3 old" 3. Table 7 presents the values obtained in the stiulation area as well as the levels of significance. The tests did not prove any positive correlation between the cheical structure of the studied copounds and the stiulation/inhibition activity on the plant growth. For instance, the copound XI displays a inute activity in both areas. Replaceent of hydrogen in the carboxyl group for ethyl {XII) or ethyl {XIII) increases the inhibitory effect enorously. Allyl group {XVII) deonstrates the inhibitory effect in the whole scale of concentrations. Propyl group {XV) has the excellent stiulatory and inhibitory effect, while heptyl group {XX) represents approxiately % of Che. Papers 41 (5) (1987) 665

12 P. CHABREČEK, V. UTORI, P. FOLTÍNOVÁ, V. EKERKA, A. GÁPLOVKÝ Table 6 Growth-regulation activity of the synthesized copounds on vetch Copound tiulation % с ol d -3 Inhibition % с ol d -3 I II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XX XXI IAA 2,4-D CCC ю- 7 io- 9 io- 7 IO" 13 IO" 13 IO" 11 IO" 9 IO" 9 IO" 5 IO" 12 IO" " 3 IO" 6 IO" 5 tiulation and inhibition were deterined in respect to a control experient perfored with distilled water. the propyl derivative (XV) activity. One can state unabiguously that the replaceent of I" for QO^~ or BF^ shifts the activity towards the inhibition area in the whole concentration scale. Experiental Melting points were deterined on a Kofler hot-stage apparatus and the analytical data of the synthesized copounds are presented in Table 1. IR spectra (Table 2) were easured in nujol on a Perkin Eler 180 instruent calibrated with the standard spectru of polystyrene. The wavenubers were read with the accuracy of ± 2 c" 1. UV spectra were taken on a Perkin Eler 4 spectroeter in acetonitrile 666 Che. Papers 41 (5) (1987)

BENZOTHIAZOLE COMPOUND. XXVIII Table 7 tiulation activity of 2-styryl-3-propoxycarbonylethylbenzothiazoliu broide (XV) с Length of roots tiulation t ol d 3 % x s(x) С 24.95 ±0.47 KT 11 29.07 ±0.36 16.

13 BENZOTHIAZOLE COMPOUND. XXVIII Table 7 tiulation activity of 2-styryl-3-propoxycarbonylethylbenzothiazoliu broide (XV) с Length of roots tiulation t ol d 3 % x s(x) С ±0.47 KT ± Ю" ± " ± P(0.05) = 2.31 Д0.01) = 3.36 С control; x arithetic ean; s(x) standard error of arithetic ean; t significance; P(0.05) level of significance; P(0.01) level of high significance. (c = 10" 4 old~ 3 ). 'H NMR spectra were easured on a Tesla 487 instruent in deuterated diethyl sulfoxide with HMDO as an internal standard. The activity tests against Euglena gracilis were perfored on the strain Z which was aintained on a heterotrophic proteozo-peptone-triptonic ediu at the teperature of (26 ± 2) C under peranent illuination. The effect of the tested copounds on the cells division of Euglena gracilis was investigated in a liquid cultivation ediu in which the specific concentration of a copound was prepared. After 120 h the following was deterined: a) the nuber of cells by a PICOCAL-P-4 instruent, b) the content of chlorophyll by Arnorťs ethod [10], c) potential inductions of white utants by inoculating on a heterotrophic ediu ipregnated with agar; the presence of green and white colonies (bleaching activity) was established after additional 10 days cultivation on light. Nondeveloped colonies indicated the lethal effect at a particular concentration. The following strains were involved in the antibacterial and antifungal activity studies: taphylococcus aureus Май 29/58 (sensitive to antibiotics), taphylococcus aureus Май 2560 (resistant to penicillin and apicillin), Bacillus subtilis B.s. 18/66, Escherichia coli E.c. 326/71 and Pseudoonas aeruginosa. The tests were accoplished by the plate- -diffusion ethod in a Mueller Hinton agar. The copounds were placed on circles of a chroatographic paper in defined concentrations. The effect was estiated in respect of the areas of the inhibition zone developed after cultivation at 37 C for 24 h. The inhibitory concentrations (MIC) given in Table 4 represent such concentrations that created still visible and easurable zone of the growth inhibition. The antifungal activity was tested against the strains of Microsporu gypseu, Penicilliu funiculosu 1818, Chaetoiu globbosu 358, and Candida pseudotropicalis С126. The effect was deterined by the test-tube dilution ethod in a abourand ediu. Che. Papers 41 (5) (1987) 667

14 P. CHABREČEK, V. UTORI, P. FOLTÍNOVÁ, V. EKERKA, A. GÁPLOVKÝ 2-tyryl-3-ethylbenzothiazoliu ethyl sulfate (I) To a solution of 2-styrylbenzothiazole (2.3 g; 0.01 ol) in 15 c 3 of anhydrous acetone, diethyl sulfate (1.8 g; ol) was added. The ixture was heated for 2 h at reflux teperature and then left to stand at roo teperature for 24 h. The crystals separated were filtered off and washed with acetone. 2-tyryl-3-ethylbenzothiazoliu iodide (II) 2-tyrylbenzothiazole (2.3 g; 0.01 ol), 15 c 3 of anhydrous acetonitrile, and ethyl iodide (2.1 g; ol) were heated at C (bath teperature) for 18h. The crystals were washed with acetone and crystallized fro a ixture of anhydrous ethanol acetone (volue ratio = 2:1). 2-tyryl-3-ethylbenzothiazoliu Perchlorate (III) and tetrafluoroborate (IV) 2-tyryl-3-ethylbenzothiazoliu iodide (II) (7.5 g; 0.02 ol) was dissolved in 30 c 3 of war (40 C) ethanol water ixture (r v = 1:1). A solution of KC10 4 (KBF 4 ) (0.04 ol) in 20 c 3 of 40 C war water was gradually added with stirring. The crystalline product was washed with water and purified by crystallization fro ethanol. 2~tyryl-3-benzylbenzothiazoliu broide (V) 2-tyrylbenzothiazole (2.3 g; 0.01 ol), 15 c 3 of anhydrous acetonitrile or diethylforaide, or a ixture of diethylforaide and acetone (/= 2:1) and benzyl broide (2.5 g; ol) were heated at C (bath teperature) for 24h. On cooling, the product usually separates in a crystal for. If not, 1 2 c 3 of the solution is placed in a test-tube, the sae volue of ether or acetone is added and the crystallization is induced by scratching the inside of the test-tube. The content of the test-tube is returned to the reaction ixture. Isolated solid is crystallized fro ethanol. Alternatively, if no crystals separate on cooling, anhydrous ether or acetone is added to the solution until turbidity occurs. 2-tyryl-3-benzylbenzothiazoliu Perchlorate (VI), tetrafluoroborate ( VII), and nitrate ( VIII) 2-tyryl-3-benzylbenzothiazoliu broide (V) (4.0g; 0.01 ol) was dissolved in 30 c 3 of 40 C war water and KC10 4 (KBF 4 or KN0 3 ) (0.02 ol) dissolved in 668 Che. Papers 41 (5) (1987)

15 BENZOTHIAZOLE COMPOUND. XXVIII 20 c 3 of water of the sae teperature was added gradually with stirring. After washing the crystals with water, they were satisfactorily pure according to the results of eleental analysis. 2-tyryl-3-allylbenzothiazoliu broide (IX) and 2-styryl- -3-propargylbenzothiazoliu broide (X) 2-tyrylbenzothiazole (2.3 g; 0.01 ol), 10c 3 of acetonitrile, and allyl broide (propargyl broide) (0.015 ol) were heated at C (bath teperature) for 20 h. After cooling, the crystalline product was washed with acetone. 2-tyryl-3-carboxyethylbenzothiazoliu broide (XI) and esters (XII XXI) 2-tyrylbenzothiazole (2.3 g; 0.01 ol), 10 c 3 of acetonitrile, and brooacetic acid (corresponding ester) (0.015 ol) were heated at C (bath teperature) for 16 h. The crystals were filtered off and ipurities were reoved by extraction with boiling anhydrous ethanol. References 1. Kiprianov, A. I. and Iľchenko, A. Yu., Zh. Obshch. Khi. 35, 498 (1965). 2. utoris, V., Halgaš, J., ekerka, V., Foltínová, P., and Gáplovský, A., Che. Zvesti 37, 653 (1983). 3. Dryanská, V. and Ivanov, С, ynthesis 1976, Perjéssy, A. and utoris, V., Acta Fac. Reru Natur. Univ. Coenianae (Chiia) 20, 71 (1974). 5. Hansch, C. and Leo, A., ubstituent Constants for Correlation Analysis in Cheistry and Biology. J. Wiley, New York, Kinart, W. J. and kulski, L., Polish J. Che. 57, 515 (1983). 7. Kinart, C. M., Kinart, W. J., and kulski, L., Polish J. Che. 58, 615 (1984). 8. Kinart, W. J. and kulski, L., Polish J. Che. 58, 173 (1984). 9. Foltínová, P., utoris, V., odoová, J., and Halgaš, J., Biológia (atislava) 38, 671 (1983). 10. Arnon, D. I., Plant Physiol. 24, 1 (1949). Translated by J. Šraga Che. Papers 41 (5) (1987) 669

Benzothiazole compounds XXVII. Alkylation and antifungal activity of some 2-R-3-(2-mercaptoethyl)benzothiazolines

Benzothiazole compounds XXVII. Alkylation and antifungal activity of some 2-R-3-(2-mercaptoethyl)benzothiazolines Benothiaole copounds XXVII. Alkylation and antifungal activity of soe 2-R-3-(2-ercaptoethyl)benothiaolines a S. MIKULÁŠEK, a V. SUTORIS, a A. PERJÉSSY, and b P. FOLTÍNOVÁ a Departent of Organic Cheistry,