Process for the preparation of...

Details Process for the preparation of... Process for the preparation of...

1999-12-15

2001-09-25

Lambkin, Deborah C. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C549S023000, C560S009000

Reexamination Certificate

active

06294676

ABSTRACT:

BACKGROUND OF THE INVENTION
Dihydrobenzothiopyran compounds (thiochromans) and 4-oxo-dihydrobenzothiopyran compounds (thiochromanones) and the 4-oxime and 4-alkoxime derivatives thereof are useful intermediates in the preparation of 6-(arylcarbonyl)thiochroman herbicidal agents. Said herbicidal agents and methods for their preparation are described in U.S. Pat. Nos. 4,919,705; 5,468,722 and WO 95/13275. The 6-(arylcarbonyl)thiochromans and derivatives thereof are effective herbicidal agents at low rates of application and demonstrate selective control of noxious weeds en the presence of key economic crops such as corn and rice.
Heretofore, methods to prepare the above-said thiochroman and thiochromanone intermediates required appropriately substituted thiophenol starting materials which may be commercially unavailable and difficult to prepare. The importance of thiochroman and thiochromanone derivatives, particularly as essential intermediates in the manufacture of herbicidal 6-arylcarbonylthiochroman agents, creates a significant need in the art for alternative and effective processes for their manufacture.
SUMMARY OF THE INVENTION
The present invention provides compounds of formula
wherein
R
1
and R
2
are each independently C
1
-C
4
alkyl;
W
1
is —SCR
4
R
5
CR
6
R
7
COOH;
W
2
is H or W
1
and W
2
may together with the carbons to which they are attached form a ring in which W
1
and W
2
represent
R
3
, R
4
, R
5
, R
6
and R
7
are each independently H or C
1
-C
4
alkyl;
Z is O or NOR
8
; and
R
8
is H, C
1
-C
4
alkyl or C
1
-C
4
haloalkyl; or
when Z is NOR
8
, the stereoisomers thereof.
Also provided are a process to prepare a thioenol formula Ia compound via the condensation of Hagemann's ester and a &bgr;-mercaptopropionic acid and a process to prepare a tetrahydrobenzothiopyran formula Ib compound by the cyclodehydration of the formula Ia thioenol.
Further provided is the use of the formula I compounds of the invention as intermediates in the manufacture of herbicidal 6-(pyrazol-4-yl)carbonyl-dihydrobenzothiopyran, 4-oxime and 4-alkoxime compounds and in the preparation of dihydrobenzothiopyran intermediates therefor.
Still further provided is a process for the purification and isolation of compounds of formula Ib wherein Z is O.
DETAILED DESCRIPTION OF THE INVENTION
Preferred compounds of formula I are those compounds wherein R
3
, R
4
, R
5
, R
6
and R
7
are H. Also preferred are compounds of formula I wherein R
1
is methyl or ethyl. Further, compounds of formula Ib wherein Z is NOR
8
and R
9
is H or methyl are preferred.
The term haloalkyl as used in the specification and claims designates an alkyl group C
m
H
2m+1
which may be substituted with 1 to 2m+1 halogen atoms which may be he same or different. The term halogen designates Cl, Br, I or F.
The compounds of the invention of formula Ib wherein Z is NOR
9
(Ib2) include the E and Z stereoisomers shown below.
Compounds of the invention exemplary of formula Ia include: ethyl 4-&bgr;-carboxyethylthio-2-methyl-1,3-cyclohexadiene-1-carboxylate; methyl 4-&bgr;-carboxyethylthio-2-methyl-1,3-cyclohexadiene-1-carboxylate; ethyl 4-&bgr;-carboxyethylthio-2-ethyl-1,3-cyclohexadiene-1-carboxylate; methyl 4-&bgr;-carboxyethylthio-2-ethyl-1,3-cyclohexadlene-1-carboxylate; and the like.
Compounds of the invention exemplary of formula Ib include: ethyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate; ethyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate, 4-oxime; ethyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate, 4-(0-methyloxime); methyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate; methyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate, 4-oxime; methyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate, 4-O-methyloxime; and the like.
Thiochroman (tetrahydrobenzothiopyran) and thiochromanone (4-oxo-tetrahydrobenzothiopyran) derivatives have heretofore been prepared by the reaction of an appropriate thiophenol substrate with an &agr;,&bgr;-unsaturated carboxylic acid, or a 3-halopropionate, followed by cyclodehydration. However, the required appropriate thiophenol starting material may be unavailable commercially and can require up to four synthetic steps to prepare.
It has now been found that thiochromanone derivatives may be prepared from the readily available Hagemann's ester of formula IV. The formula IV ester may be purchased or, alternatively, may be prepared from the easily obtainable simple starting materials of alkyl acetoacetate and formaldehyde.
Surprisingly, the formula IV ester may be condensed with a &bgr;-mercapcopropionic acid of formula V to give the thioenol formula Ia compound of the invention. The reaction is shown in flow diagram I wherein R
1
and R
2
are each independently C
1
-C
4
alkyl and R
3
, R
4
R
5
, R
6
and R
7
are each independently H or C
1
-C
4
alkyl.
The condensation may be carried out in the presence of a solvent, an acid catalyst and the azeotropic removal of water. Suitable solvents are any inert solvent capable of forming an azeotrope with water such as toluene, benzene, halobenzene, xylene or the like, preferably toluene. Suitable acid catalysts include sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, pyridinium p-toluenesulfonate, boron trifluoride, pyridinium methanesulfonate and the like, preferably pyridinium methanesulfonate or pyridinium p-toluenesulfonate. Any appropriate water separator, such as a Dean Stark trap may be used to remove the azeotroped water. Increased reaction temperature leads to increased reaction rate and drives the reaction to completion. However, excessively high temperatures may be detrimental and are not required. Preferable reaction temperatures may range from room temperature to the reflux temperature of the solvent, about 25°-200° C., more preferably about 75°-150° C.
Alternatively, the condensation illustrated in flow diagram I may be carried out in the presence of a solvent, an acid catalyst and a dehydrating agent. Suitable dehydrating agents are acetic anhydride, triethyl orthoformate, trimethyl borate, and the like, and mixtures thereof. Solvents suitable for use include toluene, benzene, halobenzene, xylene and the like, preferably toluene. Acid catalysts useful in the condensation include sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, pyridinium p-toluenesulfonate, boron trifluoride, pyridinium methanesulfonate and the like, preferably pyridinium methanesulfonate or pyridinium p-toluenesulfonate.
The formula Ia thioenol compounds of the invention may be readily converted to 4-oxo-tetrahydrobenzothiopyran compounds of formula Ib1 via a simple single cyclodehydration step as shown in flow diagram II wherein R
1
, R
2
, R
3
, R
4
, R
5
, R
6
and R
7
are as described hereinabove.
The cyclodehydration may be carried out in the presence of a solvent and a dehydrating agent and optionally in the presence of an acid catalyst. Solvents contemplated for use in the cyclodehydration reaction are any inert solvent which is relatively nonreactive towards water or any of the utilized reagents. Suitable solvents are toluene, benzene, halobenzene, xylene and the like, preferably toluene. Dehydrating reagents particularly suitable for the cyclodehydration reaction shown in flow diagram II are acetic anhydride, trifluoroacetic anhydride, phthaloyl chloride, trifluoroacetyl chloride, and the like. Acid catalysts which optionally may be present include sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, pyridinium p-toluenesulfonate, boron trifluoride, pyridinium methanesulfonate and the like, preferably methanesulfonic acid. Reaction rate is increased by increased temperatures, however excessively high temperatures may be detrimental and are to be avoided. Suitable reaction temperatures may range from 0° C. to the boiling point of the solvent.
Advantageously, the cyclodehydration of a thioenol compound of formula Ia to form a 4-oxo-tetrahydrobenzothiopyran compound of formu

Affiliated with

Also associated with

Rating

Process for the preparation of... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the preparation of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2547463