Synthesis and Biological Activity of 3-(2-Furanyl)-6-Aryl-1,2,4-Triazolo[3,4-b]-1,3,4 –Thiadiazoles

3-(2-Furanyl)-4-amino-5-mercapto-1,2,4-triazole (1) was prepared from 2-furoic acid through a multi-step reaction sequence. Compound 1 reacted with aromatic acids in the presence of phosphorus oxychloride to give 3-(2-furanyl)-6-aryl-1,2,4- triazolo[3,4-b]-1,3,4-thiadiazoles (2). The structures of all the newly synthesized compounds have been confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectra. The bioassay indicated most of the title compounds possess significant growth promoting effects on mung bean radicles.


Synthetic route and improvement of synthetic methods
The synthetic route used is shown in Scheme 1. 2-Furoic hydrazide is a needle-like crystalline compound, but often exists in form liquid when prepared according to literature methods. Sometimes the crystals only appear after standing for up to three months. The liquid form of 2-furoic hydrazide was reacted with carbon disulphide and potassium hydroxide in ethanol, successfully giving potassium furoic hydrazide dithioformate. experiments, in that the reaction mixture was gradually poured onto crushed ice with stirring, some solid potassium carbonate and then the appropriate amount of solid potassium hydroxide was added till the pH value was 8. The separated solid after standing overnight was filtered and thoroughly washed with cold water. Little product is lost because of its insolubility in water. This is a simple and convenient method of removing excess phosphorus oxychloride.

IR spectra of the title compounds
In the IR spectrum of compound 1 there are absorption bands at 3335, 3269 cm -1 due to the N-H stretching vibration, 1634, 1523, 1494, 1467, 1420 cm -1 due to furan and triazole ring skeleton vibrations, and 1109 cm -1 due to the C-O-C stretching vibration of the furan ring. Of course, the bands at 3335, 3269 cm -1 had disappeared in the IR spectra of compounds 2a-r. Furthermore, the strongest band in the IR of compound 1 is at 1457cm -1 , while in the IR of compounds 2a-r it appears at around 1470 cm -1 . The peaks at 1634 and 1109 cm -1 are also shifted to 1620 and 1125 cm -1 , respectively. The C-S-C bending vibration bands of compounds 2a-r are observed around 700 cm -1 .

C-NMR spectra of the title compounds
The δ values of the C-2 and C-3 carbons of the furan are 142.6 and 109.6, respectively. In the 13 C-NMR spectrum of the intermediate compound 1, there are peaks at 142.84, 139.91, 113.99 and 111.89 ppm, which can be attributed to 2, 5, 4 and 3 position carbons of the furan ring, respectively; the two triazole carbons have δ values of 166.56 and 145.22. In the 13 C-NMR spectra of the title compounds, the C-4 and C-3 carbons still have δ values at 111 and 112 or so, while the chemical shifts of the C-2 and C-5 carbons vary between 135 and 145. When an active methylene group is attached to 6 position of the triazolothiadiazoles, the δ values of benzyl and 1-naphthylmethyl methylene carbons are 37.30 and 34.95 respectively, which is different from the quantitative order seen in the 1 H-NMR.

Mass spectra
All the title compounds display molecular ion peaks. In the mass spectrum of a representative compound such as 2r the molecular ion peak is also the base peak. This is probably because both substituted benzene and furan ring form a well conjugated system with the triazolothiadiazole, which makes the molecular ion especially stable. The peak at m/z 151, i.e. 3-(2-furyl)-4-amino-1,2,4-triazole, is very strong, its intensity being second only to the base peak.

Biological Activity
The effect of the title compounds on sprouting of mung bean seeds has been investigated. After treating with culture solution of 10.0µgL -3 of the title compounds for 48 hours, the lengths of mung bean radicles with reference of distilled water, the growth promoting percentage has been calculated. The data of biological activity test are presented in Table 1. From the data it can be seen that 2h, 2l, 2o increase mung bean sprout growth by 40% at 10 •g·L -3 . Even those compounds which inhibit mung bean sprout growth at 10 •g·L -3 can show promoting effect at lower concentrations.

General
All melting points were determined on an XT-4A apparatus and are uncorrected. The IR spectra (KBr disks) were taken on a Bruker Quinox 55 spectrophotometer. The 1 H-NMR and 13 C-NMR spectra were measured on a Bruker Advance 300 spectrometer for DMSO-d 6 solutions using TMS as internal reference. The mass spectra were recorded on an HP 5988 spectrometer. Elemental analyses were carried out with a CE 1112 elemental analyzer. All the reagents used were AR grade. -4-amino-5-mercapto-1,2,4-triazole (1).