The present invention relates to 2,1,3-benzothiadiazole derivatives. 
The present invention provides compounds of formula I, 
##STR2## 
wherein R.sub.1, and R.sub.2 and R.sub.3, independently, are hydrogen, 
halogen, nitro, cyano, hydroxy, alkyl, alkoxy or alkylthio, wherein any 
alkyl moiety contains 1 to 4 carbon atoms. 
Halogen is fluorine, chlorine, bromine or iodine, preferably bromine or 
chlorine. Alkyl, alkoxy or alkylthio preferably has 1 or 2 carbon atoms. 
Preferably one or two radicals of R.sub.1, R.sub.2 and R.sub.3 are 
hydrogen. R.sub.1 is preferably halogen. R.sub.2 is preferably hydrogen, 
halogen or methyl. R.sub.3 is preferably hydrogen, chlorine or methyl. 
The compounds of formula I may exist in the tautomeric form of formula Ia, 
##STR3## 
wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above. 
For the sake of convenience compounds of formula I and Ia are defined 
herein as compounds of formula I. Similar considerations apply to the 
starting materials of formula II and III mentioned hereinafter. 
The present invention provides a process for the production of a compound 
of formula I as defined above, which comprises: 
reacting ethylene diamine with a compound of formula II, 
##STR4## 
wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above, and 
either A is hydrogen, and 
B, Z and X, together with the carbon atom to which they are bound, is 
cyano, or 
A and B together form a second bond between the nitrogen and carbon atom, 
and 
X and Z, independently, form a leaving group, or a tautomer thereof. 
The reaction may be conveniently effected in conventional manner for such 
reactions, e.g. as described in D.O.S. 2,322,880. 
X and Z are either the same or different and may be --S--R.sub.4, 
--NH--R.sub.4, --OR.sub.4 or --NH--NO.sub.2, wherein R.sub.4 is hydrogen 
or alkyl of 1 to 3 carbon atoms, or X and Z are identical and are, for 
example, chlorine. Preferably X is --S--CH.sub.3 and Z is NH.sub.2. 
Preferably the compound of formula II is in the form of an acid addition 
salt, e.g. the hydrogen iodide and the ethylene diamine is in the form of 
the free base. Alternatively, preferably the compound of formula II is in 
free base form and the ethylene diamine is in the form of a mono-acid 
addition salt, e.g. the tosylate. 
The reaction may conveniently be effected at a temperature between 
0.degree. and 200.degree. C., preferably between 60.degree. and 
160.degree. C. As solvents may be used alcohols with 1 to 8 carbon atoms, 
e.g. methanol, ethanol or n-pentanol, or dioxane, nitrobenzene or xylene. 
The compounds of formula I may be isolated and purified in known manner. 
Free base forms of compounds of formula I may be converted into acid 
addition salt form, e.g. the hydrochloride, hydrogen iodide, maleate, 
fumarate, methane sulphonate or tartrate, in conventional manner and vice 
versa. 
It is supposed that the above process proceeds via an intermediate of a 
compound of formula III, 
##STR5## 
wherein R.sub.1, R.sub.2, R.sub.3 and Z are as defined above, or a 
tautomer thereof, which cyclizes to form the compound of formula I. In 
another aspect the present invention provides a process for the production 
of a compound of formula I as defined above, which comprises cyclizing a 
compound of formula III, as defined above, or a tautomer thereof. 
The reaction may be effected in known manner for such cyclizations. 
Considerations as regards preferred temperatures, solvents, and preferred 
values for Z are as mentioned above. 
Preferably the compound of formula III is formed in situ from a compound of 
formula II, but may be produced from other compounds. 
The starting materials of formula II may be produced in analogous manner to 
that described in D.O.S. 2,322,880.

In the following Examples all temperatures are in degrees Centigrade and 
are uncorrected. 
EXAMPLE 1: 4-Chloro-5-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole 
A solution of 9.5 g of 
S-methyl-N-(4-chloro-2,1,3-benzothiadiazol-5-yl)-isothiouronium hydrogen 
iodide in 70 ml of methanol is treated with 1.7 ml ethylene diamine. The 
mixture is heated to boil for one hour. The solvent is subsequently 
concentrated by evaporation. The residue is treated with 10 ml of pentanol 
and heated to 150.degree. C. for one hour. The cooled mixture is treated 
with 100 ml of ether. The resultant precipitate is filtered and washed 
with a little ether. The residue is dissolved in 70 ml of methanol. The 
solution is treated with active charcoal, filtered, made alkaline with 2 N 
aqueous sodium hydroxide, diluted with 100 ml of water and reduced to half 
the volume. After the mixture is cooled the resultant precipitate is 
filtered off, washed with water and boiled with 200 ml of methanol, 
yielding on cooling the title compound; M.Pt. 232.degree.-235.degree. C. 
The starting material is obtained as follows: A solution of 6 g ammonium 
thiocyanate in 200 ml acetone is treated with 7 ml benzoyl chloride and 
stirred for 10 minutes. To this solution 6 g of 
4-chloro-5-amino-2,1,3-benzothiadiazole in 200 ml of methanol is added. 
The mixture is boiled for 2 hours and cooled yielding 
N-benzoyl-N'-(4-chloro-2,1,3-benzothiadiazol-5-yl)thiourea (M.Pt. 
220.degree.-222.degree. from methanol). The precipitate was filtered off 
and quickly heated to reflux with 100 ml of a 2 N aqueous solution of 
sodium hydroxide. 
After 5 minutes the solution is cooled, filtered and made weakly acid with 
acetic acid. The formed precipitate is filtered off, washed with water, 
boiled with a little methanol, and washed with ether. The resulting 
N-(4-chloro-2,1,3-benzothiadiazol-5-yl)thiourea (M.Pt. 
210.degree.-213.degree.) is boiled in 100 ml of methanol with 5 g methyl 
iodide for 1 hour. The mixture is then evaporated to dryness to yield 
crude S-methyl-N-(4-chloro-2,1,3-benzothiadiazol-5-yl)thiouronium iodide 
(M.Pt. 175.degree.-179.degree. C. from methanol), which is used directly 
in the next step. 
EXAMPLE 2 
In analogous manner to Example 1 the following compounds may be produced. 
(a) 5-(2-Imidazolin-2-yl-amino)-2,1,3-benzothiadiazole, M.Pt. 
200.degree.-201.degree. C. 
(b) 4-Bromo-5-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole, M.Pt. 
234.degree.-236.degree. C. 
EXAMPLE 3 
In analogous manner to that described in Example 1 there are prepared the 
following compounds of formula I, wherein: 
______________________________________ 
R.sub.1 R.sub.2 R.sub.3 
______________________________________ 
(a) NO.sub.2 Cl Cl 
(b) Cl CN Cl 
(c) Cl OH Cl 
(d) Cl CH.sub.3 S Cl 
(e) Cl CH.sub.3 O Cl 
(f) Cl Cl CH.sub.3 
______________________________________ 
The compounds of formula I are useful because they exhibit pharmacological 
activity in animals. In particular, the compounds exhibit anti-rigor 
activity, e.g. for the treatment of rigor, as indicated by an inhibition 
of the rigor induced by Thalamonal in rats on i.v. administration of from 
about 0.001 to about 0.1 mg/kg in the test described in the 
above-mentioned D.O.S. 
For the above-mentioned use the dosage will, of course, vary depending on 
the compound employed, mode of administration and therapy desired. 
However, in general, satisfactory results are obtained when administered 
at a daily dosage of from 0.001 mg to about 50 mg per kg animal body 
weight, conveniently given in divided doses 2 to 4 times a day or in 
sustained release form. For the larger mammal, the total daily dosage is 
in the range from about 10 to about 500 mg, and dosage forms suitable for 
oral administration comprise from about 2 mg to about 250 mg of the 
compounds admixed with a solid or liquid pharmaceutical carrier or 
diluent. 
Additionally the compounds are useful as myotonolytics, e.g. for the 
treatment of spastic conditions, and as muscle relaxants, as indicated in 
standard tests; e.g. in rabbits on i.v. administration of from 0.001 to 
0.1 mg/kg animal body weight a significant muscle relaxing effect is 
observed in accordance with the method of Teschendorf et al Arch. Exp. 
Pharmacol. 266, 467-468 (1970). 
For the above-mentioned use the dosage will, of course, vary depending on 
the compound employed, mode of administration and therapy desired. 
However, in general, satisfactory results are obtained when administered 
at a daily dosage of from 0.0002 mg to about 1 mg per kg animal body 
weight, conveniently given in divided doses 2 to 4 times a day or in 
sustained release form. For the larger mammal, the total daily dosage is 
in the range from about 0.01 to about 10 mg, e.g. 0.1 and 6, preferably 
between 0.15 and 3 mg. Dosage forms suitable for oral administration 
conveniently comprise from about 0.0025 mg to about 5 mg of the compounds 
admixed with a solid or liquid pharmaceutical carrier or diluent. 
The compounds of Examples 1, 2a and 2b exhibit especially interesting 
activity. 
The compounds of formula I may be administered in pharmaceutically 
acceptable acid addition salt form. Such acid addition salt forms exhibit 
the same order of activity as the free base forms and are readily prepared 
in conventional manner. The present invention also provides a 
pharmaceutical composition comprising a compound of formula I, in free 
base form or in pharmaceutically acceptable acid addition salt form, in 
association with a pharmaceutical carrier or diluent. Such compositions 
may be in the form of, for example, a solution or a tablet.