Benzothiazole Derivatives. 48. Synthesis of 3-Alkoxycarbonylmethyl-6-bromo-2-benzothiazolones and 3-Alkoxycarbonylmethyl-6-nitro-2-benzothiazolones as Potential Plant Growth Regulators

Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina,SK - 842 15 Bratislava, Slovakia.*Author to whom correspondence should be addressed.Received: 17 March 1998 / Accepted: 8 March 1999 / Published: 26 March 1999Abstract: 3-Alkoxycarbonylmethyl-6-bromo- and 3-alkoxycarbonylmethyl-6-nitro-2-benzo-thiazolones were synthesized by reaction of alkylesters of halogenoacetic acids with 6-bromo-2-benzothiazolones and 6-nitro-2-benzothiazolones respectively. The compoundswere tested for plant growth stimulating activity on wheat ( Triticum aestivum ). The bromoderivatives manifested 25.4 % average stimulating activity in comparison with the control.The stimulation activity of the nitro derivatives was not significant. Optimal structures of thecompounds were obtained by a MMPI method, atomic charges and dipole moments werecalculated by a semiempirical AM1 method. On the basis of molecular electrostatic potentialit has been found that the biological activity of synthesized compounds depends on chargedistribution in the molecules.Keywords: 3-Alkoxycarbonylmethyl-6-bromo-2-benzothiazolones, 3-alkoxycarbonyl-methyl-6-nitro-2-benzothiazolones, plant growth regulators, AM1 calculations, lipophilicity.

The compound after application does not cumulate and leave undesirable residues in the soil.It stimulates germination and sprouting, it helps to promote a richer crop, quickens ripening of the crop and improves its quality.It heightens the resistance of products against diseases caused by fungi.In the case of vegetative propagation, it stimulates the formation of the callus and root system and improves the yield of gardening products as well.
Many 4-chloro-3-alkoxycarbonylmethyl-2-benzothiazolones in tests on wheat (Triticum aestivum L.) showed significantly higher stimulating activity than the corresponding derivatives unsubstituted at position 4, which means that the substitution at position 4 by chlorine heightens stimulating efficiency.It can be supposed that other than charge distribution in the molecule, the possible intramolecular donoracceptor interaction between chlorine atom and the methylene or carbonyl group can also influence efficiency by means of raising lipophilicity [13][14][15][16].This hypothesis will be subjected to further study.

Results and Discussion
To gain further proof in favour of this hypothesis, 13 new 3-alkoxycarbonylmethyl-6-bromo-2benzothiazolones and 9 new 3-alkoxymethyl-6-nitro-2-benzothiazolones were synthesized (Scheme 1) and tested for stimulating activity on wheat (Triticum aestivum) (Table 1).The average stimulating activity in comparison to the control was 25.43 % for the bromo derivatives and only 5.53% for the nitro derivatives, which is near to the range of experimental error.The synthesized compounds were studied from the viewpoint of influence of bromo and nitro substituents upon their plant growth stimulating activity.
Optimal structures of the compounds were obtained by the method MMPI [20].Atomic charges and dipole moments of the optimal structures were calculated by the semiempirical AM1 method [21] with standard parametrization (Table 2).The theoretical values of logP were gained by Crippen's method [22].The value of Fisher -Snedecor test for parameters significant at 99.5 % level.e ) Number of compounds used in correlation.
The above data was correlated with the stimulation expressed as the percentage increase of growth caused by the tested compounds in comparison to the control (Table 1).
A low correlation coefficient resulted (0.556), which means that lipophilicity probably did not influence the studied stimulating efficiency of the synthesized compounds.Correlation of the charge distribution on the carbon atom at position 6, as well as of dipole moments obtained by quantum chemical methods have given statistically significant correlations (Table 3).
It has been concluded from the values of F-tests that the statistical significance of all regression equations is higher than 99.5 %.The results show that the biological activity of these compounds depends on the charge distribution in the molecules which also can be characterised by the distribution of the molecular electrostatic potential on the van der Waals surface of the molecule (Figure1 and Figure 2).
Due to the influence of the substituent at position 6, an essential change occurs in the distribution of the negative charge in the molecule.In the case of a nitro group the electrons are drawn off from the aromatic ring and so two divided centres of negative charge are created (red area in Figure 1).In the case of a bromo substituent at position 6 there is only one centre of negative charge in the molecule (Figure 2).These results enable the prediction, from dipole moment values, of the influence of other substituents at position 6 on the studied biological efficiency of this type of compounds.The presence of a NO 2 group causes a decrease of stimulating activity from a significant to an insignificant level.
Plant growth regulating activity has been tested on wheat (Triticum aestivum L) by measuring the primary roots according to [23].The values have been compared with the primary root lengths obtained for the control as well as with values obtained for the standards 2-indolylacetic acid (IAA) and 2,4dichlorophenoxyacetic acid (2, 4-D) in concentration 1.10 -5 mol dm -3 (Table 1).6-Bromo-2-benzothiazolone (2.30 g, 0.01 mol), triethylamine (0.01 g, 0.01 mol) and chloroacetic acid alkylester (0.015 mol) were added to acetone (15 cm 3 ).After 3 h reflux the cooled reaction mixture was poured out onto crushed ice, the crystalline product was filtered off, dried at room temperature and crystallized from the solvent given in Table 4.

Table 1 .
Growth regulation activity of the synthesized compounds tested on Triticum aestivum L. (concentration of the compounds is 10 -5 mol dm -3 ).

Table 2 .
Calculated atomic charges and dipole moments by AM1 method and theoretical values log P.

Table 3 .
Correlation analysis for experimental and theoretical data.
a ) Standard deviation of the slope.b ) Correlation coefficient.c ) Standard deviation of the correlation.d )