Process for the preparation of 1,2-benzoxathiines

The present invention relates to a process for the preparation of 
8-sulfonyl-1,2-benzoxathiine derivatives. 
The 8-sulfonyl-1,2-benzoxathiine derivatives obtainable by the process of 
this invention are valuable intermediates for the preparation of 
herbicides and plant growth regulators of the class of the sulfonylureas. 
Such compounds and their biological properties are known for example from 
published European patent application EP-A-No.99 339 and No. 84810215.8. 
The preparation of compounds having the 1,2-benzoxathiine structure has 
been described in various publications: Int. J. Sulfur Chem., A, Volume 2, 
No. 4, 249-255 (1972) or EP-A-No.107 979. The procedures employed are 
poorly suited to large-scale production, as they proceed via a relatively 
large number of process steps. 
Accordingly, there is a need for a simple synthesis comprising a few 
reaction steps and permitting the production of the desired intermediates 
in good yield. 
Surprisingly, it has now been found that it is possible to prepare 
1,2-benzoxathiine derivatives of the formula I 
##STR3## 
wherein Hal is chlorine, bromine or iodine, 
R is hydrogen, halogen, nitro, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 
haloalkyl, cyano or a --X--R.sup.1, --CO--X--R.sup.2, --CO--NR.sup.3 
R.sup.4, --SO--R.sup.5 or --SO.sub.2 --R.sup.6 group, where 
R.sup.1 is C.sub.3 -C.sub.5 alkynyl, or is C.sub.1 -C.sub.4 alkyl, 
unsubstituted or substituted by halogen or C.sub.1 -C.sub.4 alkoxy, or is 
C.sub.3 -C.sub.5 alkenyl, unsubstituted or substituted by halogen or 
C.sub.1 -C.sub.4 alkoxy, 
R.sup.2 and R.sup.5 are each independently of the other C.sub.1 -C.sub.4 
alkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 alkoxyalkyl, C.sub.3 
-C.sub.5 alkenyl, C.sub.3 -C.sub.5 alkynyl, phenyl or benzyl, 
R.sup.3 and R.sup.4 are each independently of the other hydrogen, C.sub.1 
-C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 alkoxyalkyl, 
C.sub.3 -C.sub.5 alkenyl, C.sub.3 -C.sub.5 alkynyl, phenyl or benzyl, 
R.sup.6 is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 
-C.sub.4 haloalkoxy or --NR.sup.7 R.sup.8, 
R.sup.7 and R.sup.8 are each independently of the other hydrogen, C.sub.1 
-C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 alkoxyalkyl, 
C.sub.3 -C.sub.5 alkenyl, C.sub.3 -C.sub.5 alkynyl, phenyl or benzyl, and 
X is oxygen or sulfur, 
by treating a dihydrobenzofuran derivative of the formula II 
##STR4## 
with chlorosulfonic acid of the formula ClSO.sub.3 H. Within the scope of 
the present invention, halogen both by itself or as moiety of a radical 
such as haloalkyl denotes fluorine, chlorine, bromine or iodine. Fluorine 
and chlorine are preferred. Alkyl is straight chain or branched alkyl, 
e.g. methyl, ethyl, n-propyl, isopropyl or the four butyl isomers, with 
methyl, ethyl and isopropyl being preferred. Alkoxy will be generally 
understood to mean methoxy, ethoxy, n-propoxy, isopropoxy or the four 
butoxy isomers. Alkenyl is usually allyl, 2-butenyl, 3-butenyl or 
methallyl; and alkynyl is propargyl, 2-butynyl or 3-butynyl. Within the 
scope of the above definitions, alkoxyalkyl comprises: methoxymethyl, 
methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl and propoxymethyl. 
Preferred examples of haloalkyl are fluoromethyl, difluoromethyl, 
trifluoromethyl, 2,2,2-trifluoromethyl, 1,1,2,2-tetrafluoroethyl, 
perfluoroethyl, 2-chloroethyl, 2,2,2-trichloroethyl, 3,3,3-trifluoropropyl 
or 1,1,2,3,3,3-hexafluoropropyl. Haloalkyl will also be understood as 
being moiety of a haloalkoxy or haloalkylthio substituent. In the process 
of this invention there will preferably be obtained those compounds in 
which Hal is chlorine or bromine and R is hydrogen or C.sub.1 -C.sub.4 
alkyl. 
The reaction products of the formula I can be converted into herbicidal and 
plant growth regulating sulfonylurea derivatives by methods analogous to 
those known in the literature, for example by converting the sulfonyl 
chloride group into the sulfonamide group with ammonia and reacting 
resultant derivatives of the formula III 
##STR5## 
in known manner, either direct or, for example, in the form of the 
corresponding carbamate, to give a sulfonylurea. The intermediates of 
formula III can also be converted by methods known per se into further 
intermediates (of formulae IV and V) for preparing highly effective 
herbicides of the class of the sulfonylureas. 
Thus, for example, a compound of the formula IV 
##STR6## 
wherein R is as defined for formula I, is obtained by dehalogenating a 
compound of formula III, in known manner, with hydrogen. 
Further, a compound of formula V 
##STR7## 
wherein R is as defined for formula I, is obtained by hydrogenating a 
compound of formula IV with hydrogen in the presence of a noble metal 
catalyst. 
The intermediates of formula IV and V can be converted into effective 
herbicides of the class of the sulfonylureas by methods analogous to those 
described for obtaining compounds of formula III. Commercially available 
chlorosulfonic acid is employed for carrying out the process of this 
invention for the preparation of compounds of formula I. At least 3 moles 
of chlorosulfonic acid are used per mole of compound of formula II. It is 
convenient to use a substantial excess, for example at least 5 moles, of 
chlorosulfonic acid per mole of compound II. In individual cases, the 
chlorosulfonic acid can be used simultaneously as reactant and as solvent. 
In general, however, the reaction is carried out in an inert solvent. 
Suitable solvents are carbon disulfide, ethyl acetate, and chlorinated 
hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 
1,2-dichloroethane, 1,2-dichloroethylene, tetrachloroethylene, 
chlorobenzene or dichlorobenzene. The preferred solvents are methylene 
chloride, 1,2-dichloroethane and chloroform. The reaction temperatures are 
normally in the range from -10.degree. to +80.degree. C., preferably from 
-10.degree. to +60.degree. C. 
In a preferred embodiment of the invention, the compounds of formula I, 
wherein Hal is chlorine or bromine and R is hydrogen or C.sub.1 -C.sub.4 
-alkyl, are prepared by reacting an appropriate compound of formula II 
with at least 3 moles of chlorosulfonic acid per mole of compound of 
formula II, in an inert solvent and in the temperature range from 
-10.degree. to +80.degree. C. 
The most preferred embodiment of the process of the invention is that in 
which the reaction is carried out in the temperature range from 
-10.degree. to +60.degree. C. in methylene chloride, 1,2-dichloroethane or 
chloroform, with at least 5 moles of chlorosulfonic acid per mole of 
compound of formula II. 
The optional conversion reactions to give compounds of the formulae III, IV 
or V are conducted under the reaction conditions conventionally employed 
for these per se known reactions. Accordingly, the compounds of formula 
III are normally obtained by treating compound I with an aqueous solution 
of ammonia under normal pressure at room temperature. The dehalogenation 
of the compound III to give the compound IV by catalytic hydrogenation is 
generally carried out at room temperature under normal pressure in an 
inert solvent and in the presence of an acid acceptor, preferably a 
tertiary amine, for example triethylamine. The catalytic hydrogenation of 
the non-aromatic double bond of the compound IV to give the compound V is 
carried out under more severe conditions: both the pressure of the 
hydrogen atmosphere and the temperature are increased (to 1 to 10 bar and 
30.degree. to 60.degree. C. respectively). Suitable hydrogenation or 
dehalogenation catalysts are: platinum or palladium in the form of 
platinum oxide, platinum black, platinum or barium sulfate, palladium 
black or palladium on carbon. The most widely used catalyst is palladium 
on carbon in commercial form as 5% palladium/carbon. 
The compounds obtainable by the process of this invention are for example 
those of formula I listed in Table 1 
TABLE 1 
______________________________________ 
##STR8## 
Compound No. Hal R 
______________________________________ 
1.1 Cl H 
1.2 Br H 
1.3 Cl 7-CH.sub.3 
1.4 Cl 5-CH.sub.3 
1.5 Cl 5-C.sub.2 H.sub.5 
1.6 Cl 7-C.sub.2 H.sub.5 
1.7 Br 7-CH.sub.3 
1.8 Br 7-C.sub.2 H.sub.5 
1.9 Br 7-C.sub.3 H.sub.7i 
1.10 Br 5-CH.sub.3 
1.11 Br 5-C.sub.2 H.sub.5 
1.12 Br 5-NO.sub.2 
1.13 Br 5-Br 
1.14 Br 5-Cl 
1.15 Br 5-CN 
______________________________________ 
The intermediates listed in Tables 2 to 4 (in the sulfonamide stage) can be 
obtained from the above compounds by optional subsequent operations for 
preparing herbicidally effective sulfonylureas. 
TABLE 2 
______________________________________ 
##STR9## 
Compound No. Hal R 
______________________________________ 
2.1 Cl H 
2.2 Br H 
2.3 Cl 7-CH.sub.3 
2.4 Cl 5-CH.sub.3 
2.5 Cl 5-C.sub.2 H.sub.5 
2.6 Cl 7-C.sub.2 H.sub.5 
2.7 Br 7-CH.sub.3 
2.8 Br 7-C.sub.2 H.sub.5 
2.9 Br 7-C.sub.3 H.sub.7i 
2.10 Br 5-CH.sub.3 
2.11 Br 5-C.sub.2 H.sub.5 
2.12 Br 5-NO.sub.2 
2.13 Br 5-Br 
2.14 Br 5-Cl 
2.15 Br 5-CN 
______________________________________ 
TABLE 3 
______________________________________ 
##STR10## 
Compound No. R 
______________________________________ 
3.1 H 
3.2 7-CH.sub.3 
3.3 7-C.sub.2 H.sub.5 
3.4 5-CH.sub.3 
3.5 5-C.sub.2 H.sub.5 
3.6 5-Cl 
3.7 5-CN 
3.8 7-C.sub.3 H.sub.7i 
______________________________________ 
TABLE 4 
______________________________________ 
##STR11## 
Compound No. R 
______________________________________ 
4.1 H 
4.2 7-CH.sub.3 
4.3 7-C.sub.2 H.sub.5 
4.4 5-CH.sub.3 
4.5 5-C.sub.2 H.sub.5 
4.6 5-Cl 
4.7 5-CN 
4.8 7-C.sub.3 H.sub.7i 
______________________________________

The following Examples P1 to P7 will serve to illustrate the invention in 
more detail. 
PREATORY EXAMPLES 
Example P1 
6-Bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide 
(a) 5-Bromo-2,3-dihydro-2-methylbenzo[b]furan 
A solution of 215 ml of bromine in 450 ml of methylene chloride is added 
dropwise over 21/2 hours to an ice-cooled mixture of 562.3 g of 
2,3-dihydro-2-methylbenzo[b]furan, 1600 ml of methylene chloride, 1600 ml 
of water and 352.5 g of sodium bicarbonate. After the mixture has been 
stirred for another 11/2 hours at the same temperature, the aqueous phase 
is separated and extracted with two 300 ml portions of methylene chloride. 
The combined organic phases are washed with 2.times.250 ml of water, dried 
over sodium sulfate and concentrated. After removal of all constituents 
having a boiling point below 99.degree. C. under a pressure of 8 mbar, 
there are obtained 750.7 g of 5-bromo-2,3-dihydro-2-methylbenzo[b]furan as 
residue. 
(b) 6-Bromo-2,2-dioxo-3-methyl-1,3-benzoxathiin-8-ylsulfonylchloride 
400 ml of chlorosulfonic acid are added dropwise over 20 minutes to a 
solution of 160 g of 5-bromo-2,3-dihydro-2-methylbenzo[b]furan in 460 ml 
of absolute chloroform, which solution has been cooled to -7.degree. C. 
The mixture is stirred at a temperature of 15.degree. C. for 15 minutes 
and then stirred dropwise over 35 minutes into a mixture of 1.5 kg of ice, 
1000 ml of water and 500 ml of chloroform. After this mixture has been 
stirred for 15 minutes at 0.degree. C., the organic phase is separated and 
the aqueous phase is extracted with 3.times.250 ml of chloroform. The 
combined organic extracts are washed with 150 ml of water, dried over 
sodium sulfate and concentrated, affording 180 g of 
6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl chloride as oily 
residue which can be further processed direct. 
(c) A solution of 180 g of 
6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl chloride in 500 
ml of tetrahydrofuran is added dropwise over 30 minutes to 307 ml of a 30% 
aqueous solution of ammonia. The mixture is stirred for 30 minutes at 
20.degree. C. and concentrated under reduced pressure at 45.degree. C. The 
residue is triturated with 200 ml of ether. The precipitate is isolated, 
washed with water and dried at 45.degree. C., affording 63.2 g of 
6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of m.p. 
243.degree.-245.degree. C. (recrystallisation from ethanol). 
Example P2 
6-Bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide 
(a) 6-Bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl chloride 
133 ml of chlorosulfonic acid are added dropwise at a temperature from 
40.degree. to 50.degree. C. over 30 minutes to a solution of 42.6 g of 
5-bromo-2,3-dihydro-2-methylbenzo[b]furan in 120 ml of chloroform. The 
mixture is heated to reflux for 4 hours and, after being cooled to 
0.degree. C., added dropwise over 30 minutes to a mixture of 400 g of ice, 
500 ml of water and 100 ml of chloroform. The organic phase is separated 
and the aqueous phase is extracted with 3.times.100 ml of chloroform. The 
combined organic phases are washed with water and concentrated, affording 
72.2 g of 6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl 
chloride as oily residue. 
(b) 72.2 g of 6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl 
chloride are dissolved in 200 ml of tetrahydrofuran and the solution is 
added dropwise to 122.6 ml of a 30% aqueous solution of ammonia. The 
mixture is stirred for 30 minutes at 20.degree. C. and concentrated under 
reduced pressure at 45.degree. C. The residue is triturated with ether. 
The precipitate so obtained is isolated, washed with water and dried at 
45.degree. C., affording 44.6 g of 
6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide. 
Example P3 
2,2-Dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide 
120 g of 6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide are 
dissolved in 2.4 liters of tetrahydrofuran and the solution is 
hydrogenated with hydrogen for 40 minutes, in the presence of 41.3 g of 
triethylamine and 12.0 g of 5% on carbon catalyst, under normal pressure 
and in the temperature range from 20.degree. to 25.degree. C. The mixture 
is filtered, the filtrate is concentrated, and the residue is taken up in 
1300 ml of hot 90% aqueous ethanol. The insoluble constituents are 
separated and the solution is cooled to 0.degree. C. The precipitate is 
separated and dried, affording 70 g of 
2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of m.p. 
204.degree.-205.degree. C. 
Example P4 
3,4-Dihydro-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-yl-sulfonamide 
10.0 g of 2,2-dioxo-4-methyl-1,2-benzoxathiin-8-ylsulfonamide are dissolved 
in 200 ml of tetrahydrofuran and the solution is hydrogenated with 
hydrogen for 21/2 hours, in the presence of 2.0 g of 5% palladium on 
carbon catalyst, under a pressure of 4 bar and at a temperature of 
40.degree. C. After removal of the catalyst the solution is concentrated 
and the residue is crystallised from 120 ml of 70% aqueous ethanol, 
affording 9.0 g of 
3,4-dihydro-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of m.p. 
185.degree.-186.degree. C. 
Example P5 
N-(3,4-Dihydro-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl)-N'-(4-meth 
oxy-6-methylpyrimidin-2-yl)urea 
A mixture of 3.33 g of 
3,4-dihydro-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide, 1.84 ml 
of 1,8-diazabicyclo[5.4.0]undec-7-ene, 3.2 g of 
N-(4-methoxy-6-methylpyrimidin-2-yl)phenylcarbamate and 35 ml of absolute 
dioxan is stirred for 45 minutes at a temperature in the range from 
20.degree. to 25.degree. C. The mixture is concentrated and the oily 
residue is triturated with ether and 14 ml of 1N hydrochloric acid. The 
crystalline precipitate obtained is isolated, washed with water and dried, 
affording 4.96 g of 
N-(3,4-dihydro-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl)-N'-(4-met 
hoxy-6-methylpyrimidin-2-yl)urea of m.p. 215.degree.-218.degree. C. 
Example P6 
N-(6-Bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-yl-sulfonyl)-N'-(4'-methox 
y-6-methyl-1,3,5-triazin-2-yl)urea 
A reaction mixture of 3.54 g of 
6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide, 1.61 ml of 
1,8-diazabicyclo[5.4.0]undec-7-ene, 2.73 g of 
N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)phenylcarbamate and 35 ml of 
absolute dioxan is stirred for 11/2 hours at room temperature. The solvent 
is evaporated and the oily residue is triturated with 10 ml of 1N 
hydrochloric acid and 5 ml of water. The precipitate is isolated by 
filtration, washed with ether and dried, affording 4.84 g of 
N-(6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8ylsulfonyl)-N'-(4-methoxy- 
6-methyl-1,3,5-triazin-2-yl)urea of m.p. 196.degree.-198.degree. C. 
Example P7 
N-(2,2-Dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl)-N'-(4-methoxy-6-methyl 
-1,3,5-triazin-2-yl)urea 
A mixture of 3.3 g of 2,2-dioxo-3-methyl-1,2-benzoxathiin-8-yl sulfonamide, 
1.90 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene, 3.28 g of 
N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)phenylcarbamate in a mixture of 
25 ml of dioxan and 10 ml of acetonitrile is stirred at 20.degree. C. to 
25.degree. C. for 1 hour. The solvents are evaporated and the residue is 
triturated with a mixture of 7 ml of 2N hydrochloric acid and 10 ml of 
water and then with 20 ml of ether. The precipitate is isolated by 
filtration and dried, affording 5.14 g of 
N-(2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl)-N'-(4-methoxy-6-methy 
l-1,3,5-triazin-2-yl)urea of m.p. 203.degree.-205.degree. C.