Cyano-dienes, halopyridines, intermediates and a process for their preparation

This invention relates to certain cyano-dienes and halopyridines and the processes for their preparation from a protected 1,3-dialdehyde and a cyano-diene.

BACKGROUND OF THE INVENTION 
This invention relates to certain cyano-dienes and halopyridines and the 
processes for their preparation from a protected 1,3-dialdehyde and a 
cyano-diene. 
The "sulfonylurea" herbicides are an extremely potent class of herbicides 
discovered within the last few years which generally consist of a 
sulfonylurea bridge, --SO.sub.2 NHCONH--, linking two aromatic or 
heteroaromatic rings. Research directed to methods for preparing 
sulfonylurea herbicides is continually producing new processes. The search 
for improved methods for more effectively preparing such compounds and 
intermediates required for preparing such compounds continues. 
South African Patent Application 870,436 filed Jan. 21, 1987 discloses the 
use of compounds of Formula I in the preparation of pyridine 
sulfonylureas. 
##STR1## 
EP-A-237,292 published Sep. 16, 1987 discloses the use of compounds of the 
above Formula I in the preparation of pyridine sulfonylureas. 
J. Org. Chem. 41, 2066 (1976) discloses the preparation of 2-bromonicotinic 
esters according to the following procedure. 
##STR2## 
J. Org. Chem. 38, 3436 (1974) discloses the preparation of nicotinamide 
from the 2-bromonicotinic esters according to the following procedure. 
##STR3## 
Japanese Patent 80-76,863, priority date Dec. 6, 1978, discloses the 
preparation of 2-chloro- nicotinic acids according to the following 
procedure. 
##STR4## 
SUMMARY OF THE INVENTION 
A process for making intermediates useful for the preparation of 
herbicidally active sulfonylureas has been discovered as well as novel 
intermediate compounds. In accordance with the invention, the process for 
preparing a compound of formula I and its corresponding salts, 
##STR5## 
wherein 
R.sub.1 is COR.sub.2 or SO.sub.2 CH.sub.2 CH.sub.3 ; 
R.sub.2 is C.sub.1 -C.sub.3 alkyl or C.sub.1 --C.sub.2 dialkylamino; and 
X is F, Cl or Br; 
comprises reacting a compound of the Formula II with a compound of Formula 
III 
##STR6## 
wherein R is --CH.sub.3 or --CH.sub.2 CH.sub.3 and R.sub.1 is as defined 
above; in the presence of acetic anhydride, a ZnX.sub.2 catalyst where X 
is as defined above and optionally acetic acid at a temperature of 
110.degree. to 150.degree. C. to form a compound of the formula 
##STR7## 
wherein R.sub.1 and R are as defined above; and reacting in the presence 
of acetic acid at a temperature of 0.degree. to 60.degree. C. the compound 
of Formula IV with HX where X is as defined above. 
The compounds of Formula IV 
##STR8## 
wherein R and R.sub.1 are as defined; prepared by the process of the 
invention are novel and useful for preparing intermediates for the 
preparation of sulfonylurea herbicides. 
Compounds of the Formula I 
##STR9## 
wherein R.sub.1 and X are defined as above; 
provided that when R is C.sub.1 -C.sub.2 dialkylamino; 
then X is F or Br. 
and their corresponding salts prepared by the process of the invention are 
novel and useful compounds for the preparation of sulfonylurea herbicides. 
Preferred for reasons of ease of synthesis and efficiency are: 
1. The process of the invention wherein R.sub.1 is C(O)R.sub.2. 
2. The process of Preferred 1 wherein R.sub.2 is C.sub.1 -C.sub.2 
dialkylamino. 
3. The process of the invention wherein R.sub.1 is SO.sub.2 CH.sub.2 
CH.sub.3. 
4. The process of the invention wherein X is Br. 
5. The process of the invention wherein the corresponding salt of Formula I 
is the HBr salt. 
The compounds of the invention preferred for their efficiency and ease of 
synthesis are: 
6. The compounds of Formula IV wherein R.sub.1 is C(O)R.sub.2. 
7. The compounds of Preferred 6 wherein R.sub.2 is C.sub.1 -C.sub.2 
dialkylamino. 
8. The compounds of Formula IV wherein R.sub.1 is SO.sub.2 CH.sub.2 
CH.sub.3. 
9. The compounds of Formula I wherein R.sub.1 is CON(CH.sub.3).sub.2 and X 
is F or Br. 
10. The compounds of Formula I wherein R.sub.1 is SO.sub.2 CH.sub.2 
CH.sub.3. 
11. The corresponding HBr salt of compounds of Preferred 9. 
12. The corresponding HBr salt of compounds of Preferred 10. 
The process of the invention can generally be carried out by reacting 1.0 
to 3 moles of Compound II, preferably 1.2 to 1.5 moles, per mole of 
Compound III in the presence of with 1-5 moles of acetic anhydride, 
preferably 1.5-2.5 moles. Acetic acid can be advantageously used but is 
not required. Lower temperatures can be used with acetic acid. ZnX.sub.2, 
the catalyst, can be used in amounts of 0.5-2% by weight based on Compound 
II. The temperature for the reaction may be generally 
110.degree.-150.degree. C., preferably 120.degree.-130.degree. C.: the 
yield of Compound II will vary depending on the condition but yields of 
85-90% are achievable. 
The second step for the process involving the reaction of Compound IV with 
HX can generally be carried out with 0.5-8 moles of HX, preferably 2-4 
moles of HX. The amount of acetic acid required is generally from 0.2 to 1 
liter per mole of reactant, preferably 0.4 to 0.6 liter. The temperature 
may range from 0.degree.-60.degree. C., preferably 10.degree.-30.degree. 
C. 
By C.sub.1 -C.sub.2 dialkylamino is meant dimethylamino and diethylamino. 
DETAILED DESCRIPTION OF THE INVENTION 
More specifically, the process of this invention may be carried out by 
reacting 1.2 to 1.5 moles of a malonodialdehyde bis(acetal) with one mole 
of a substituted acetonitrile and 1-5 moles of acetic anhydride in acetic 
acid containing 0.5-2% of a catalytic amount of zinc chloride or zinc 
bromide. Alternatively, the reaction can be carried out in the absence of 
acetic acid. The reaction mixture is heated to 110.degree.-150.degree. C. 
and then distilled overhead until analysis of the pot contents shows a 
disappearance of starting materials and the formation of Compound IV, 
which is a mixture of geometric isomers. Compound IV can be isolated by 
distillation or crystallization. In the next step, it is treated with 0.5 
to 8 equivalents of HF, HCl or HBr in acetic acid (200-1000ml/mole) at 
0.degree.-60.degree. C. to undergo the cyclization reaction to yield 
Compound I. Alternatively, Compound IV can be directly cyclized to 
Compound I without isolation. To help facilitate the isolation of Compound 
I, excess acid such as HBr may be added to the reaction mixture. The 
resulting crystalline salt of Compound I can then be separated from the 
reaction mixture by such means as filtration. The salt of Compound I can 
be used directly in the preparation of sulfonylurea herbicides. The salt 
of Compound I can also be neutralized with base to liberate Compound I.

The following Examples further illustrate the invention: 
EXAMPLE 1 
Preparation of 2-cyano-5-methoxy-N, N-dimethyl-2,4-pentadienamide 
To a 250 ml 3-necked R.B. flask was charged 50 g malonodialdehyde 
bis(dimethylacetal), 22.5 g N,N-dimethyl-2-cyanoacetamide, 60 g acetic 
anhydride, 0.5 g zinc chloride and 100 ml acetic acid. It was heated to 
reflux to distill off low boilers until the pot temperature reached 
125.degree. C. and head reached 110.degree. C. and a total of 60 ml 
distillate was collected. GC analysis of the pot content showed 
disappearance of N,N-dimethyl-2-cyanoacetamide. The reaction mixture was 
filtered to remove zinc catalyst and then rotovapped. The pot residue was 
crystallized from a methanol in dry ice-acetone bath to afford 16 g 
(44.3%) of the title compound. 
NMR(DMSO-d6): 2.95 (6H,s), 3.80 (3H,s), 6.85 (1H, t), 7.65 (1H, dd), 
m/e=180 (theoretical 180) 
EXAMPLE 2 
Preparation of 2-chloro-N,N-dimethyl-3-pyridine-pentadienamide 
To a 250 ml 3-necked R.B. flask was charged 16 g of Compound IV from 
Example 1 and 150 ml acetic acid. At ambient temperature, 15 g gaseous HCl 
was fed into the mixture over 20 minutes. The resulting solution was 
allowed to stand overnight and was then rotovapped. The residue was 
diluted with 500 ml water and extracted 3 times with 500 ml chloroform. 
The combined chloroform was dried with anhydrous MgSO.sub.4, filtered, 
rotovapped and then distilled to produce 5.5 g (30%) of the title compound 
which was identical to an authentic sample by GC, NMR and MS. 
EXAMPLE 3 
Preparation of 2-chloro-N,N-dimethyl-3-pyridine-carboxamide (without 
isolating the intermediate) 
To a 250 ml 3-necked flask was charged 40 g malonodialdehyde 
bis(dimethylacetal), 22.5 g N,N-dimethyl-2-cyanoacetamide, 60 g acetic 
anhydride, 0.5 g zinc chloride and 100 ml acetic acid. The mixture was 
heated to reflux to distill off 60 ml of byproducts and then cooled to 
ambient temperature. The mixture was diluted with 100 ml acetic acid, 
charged with 60 g gaseous HCl and was allowed to stand overnight. It was 
rotovapped to remove all solvents and then diluted with water and 
extracted 3 times with 500 ml chloroform. After drying the chloroform 
solution with anhydrous MgSO.sub.4 and filtering, the filtrate was 
rotovapped to afford 14.5 g (39%) of the title compound which was 
identical to an authentic sample by GC, NMR.sub.1 and MS. 
EXAMPLE 4 
Preparation of 2-Bromo-3-(ethylsulfonyl)pyridine 
A mixture of 12.3 g (0.075 mole) malonodialdehyde bis(dimethylacetal), 25 
ml (0.25 mole) acetic anhydride, and 0.08 g zinc chloride was treated at 
91.degree. C. for 25 minutes. Cyanomethyl ethylsulfone (6.7 g, 0.050 mole) 
was added and the mixture was heated at reflux (95.degree.-109.degree. C.) 
for 16 hours. 
The reaction mixture was cooled to 16.degree. C., and 10 ml of 30% 
hydrobromic acid in acetic acid was added. An additional 6.5 g of hydrogen 
bromide gas was added at 15.degree.-20.degree. C. After one hour, the 
reaction was quenched with 100 ml of ice water. After neutralizing with 
sodium hydroxide, the mass was extracted twice with methylene chloride, 
washed with water, dried with magnesium sulfate, filtered, and the solvent 
evaporated to leave 7.2 g of an oil. 
H-NMR.sub.1 (CDCl.sub.3): .delta.=8.58 (m, 1H); 8.45 (m, 1H); 7.53 (m, 1H); 
3.55 (q, 1H); 1.30 (t, 2H, J=0.04). 
A sample prepared similarly and recrystallized from ethyl acetate melted at 
78.degree.-79.degree. C. 
Elemental analysis calc. for C.sub.7 H.sub.8 BrNO.sub.2 S. 
Calculated: C, 33.61; H, 3.22; Br, 31.95; N, 5.60; S, 12.82. 
Found: C, 33.87; H, 3.27; Br, 32.60; N, 5.64; S, 12.83. 
EXAMPLE 5 
Preparation of 2-(ethylsulfonyl)-5-methoxy-2,4-pentadienitrile 
A mixture of 57 g (.342 mole) malonodialdehyde bis(dimethylacetal), 95 ml 
(1.0 mole) acetic anhydride, and 0.5 g of zinc chloride was heated to 
95.degree. C. After heating at 90.degree.-95.degree. C., while allowing 
the methylacetate to distill off for 20 minutes, 33.2 g (0.25 mole) of 
cyanomethyl ethylsulfone was added. The reaction mass was heated to 
120.degree. C. while distilling off further amounts of methylacetate. The 
reaction was held at 120.degree. C. for 4 hours and then cooled to 25 
.degree. C. Water, 200 ml, was added, then the mass was extracted twice 
with 200 ml each of methylene chloride. The combined methylene chloride 
extracts were washed with 10% sodium carbonate and then with water. After 
drying with anhydrous magnesium sulfate and filtering, the filtrate was 
evaporated to yield 63.6 g of the desired product. The crude product was 
recrystallized from chlorobutane to yield yellow crystals, m.p. 
72.degree.-74.degree. C. 
Elemental analysis calc. for C.sub.8 H.sub.11 NO.sub.3 S. 
Calculated: C, 47.74; H, 5.51; N, 6.91; S, 15.94. 
Found: C, 47.83; H, 5.39; N, 7.18; S, 16.14. 
H-NMR.sub.1 (CDCl.sub.3): .delta.=7.70 (d, 1H); 7.38 (d, 1H); 6.04-5.98 
(dd, 1H); 3.91 (s, 3H); 3.21 (q, 2H); 1.38 (t, 3H). 
The following entries in Tables I and II may be prepared using the methods 
taught in the above examples. 
TABLE I 
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##STR10## 
R R.sub.1 Physical Data 
______________________________________ 
CH.sub.3 CON(CH.sub.3).sub.2 
NMR .delta. 2.95 (6H, s) 
CH.sub.3 CON(CH.sub.2 CH.sub.3)CH.sub.3 
CH.sub.3 CON(CH.sub.2 CH.sub.3).sub.2 
CH.sub.3 SO.sub.2 CH.sub.2 CH.sub.3 
m.p. 72-74.degree. C. 
CH.sub.2 CH.sub.3 
CON(CH.sub.3).sub.2 
CH.sub.2 CH.sub.3 
CON(CH.sub.3)CH.sub.2 CH.sub.3 
CH.sub.2 CH.sub.3 
CON(CH.sub.2 CH.sub.3).sub.2 
CH.sub.2 CH.sub.3 
SO.sub.2 CH.sub.2 CH.sub.3 
______________________________________ 
TABLE II 
______________________________________ 
##STR11## 
R.sub.1 X Physical Data 
______________________________________ 
SO.sub.2 CH.sub.2 CH.sub.3 
F 
SO.sub.2 CH.sub.2 CH.sub.3 
Cl 
SO.sub.2 CH.sub.2 CH.sub.3 
Br m.p. 78-79.degree. C. 
CON(CH.sub.3).sub.2 
F 
CON(CH.sub.3).sub.2 
Br 
CON(CH.sub.2 CH.sub.3).sub.2 
F 
CON(CH.sub.2 CH.sub.3).sub.2 
Cl 
CON(CH.sub.2 CH.sub.3).sub.2 
Br 
SO.sub.2 CH.sub.2 CH.sub.3 
F (HBr salt) 
SO.sub.2 CH.sub.2 CH.sub.3 
Cl (HCl salt) 
SO.sub.2 CH.sub.2 CH.sub.3 
Br (HBr salt) m.p. 196-198.degree. C. 
CON(CH.sub.3).sub.2 
Br (HBr salt) 
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