IODINE CATALYSED FORMATION OF l-(BENZO|D|[I,3)DIOXOL-5-YL)PROPAN-l-
ONE IN ALIPHATIC ACIDS
Field
This invention relates to a new process for making the agrochemicaMy important intermediate, I-(benzo[d][ 1,3]dioxol-5-yl)propan-1 -one by reacting 1.3-benzo dioxole with propionic anhydride in an aliphatic acid in the presence of iodine as a catalyst. The described process makes use of a mild, eco-friendly and non-toxic lewis acid and results in high purity and high yield of the desired propiophenone intermediate while eliminating the need to use an excess of reagents and eliminating the use of difficult purification techniques, such as chromatography and vacuum distillation.
Background
l-(benzo[d][l,3]dioxol-5-yl)propan-l-one is an important intermediate in the agrochemical industry, especially to make the insecticide, piperonyl butoxide. The ability for general, efficient syntheses of substituted benzodioxoles under high purity and yield with mild reaction conditions is still of continuing interest to the industry. Recent efforts have been made in the prior art for the development of novel processes to make substituted benzodioxoles using reactive propanyl species and acid catalysts. Valerio Borzatta et al., US 6342613B1; Li, Yonghong et al., CN 106632228; Zhu. Zhaofu et,al. Huaxue Yanjiu Yu Yingyong, 15(3), 417-418; 2003; Koura, Minoru et al., Bioorganic & Medicinal Chemistry Letters, 25(13), 2668-2674: 2015; Kong, Fanlei et al., CN 103788057 and Chen, Xinzhi et al., CN 102070596 have all described the preparation of benzo propanone using propionic anhydride or propionyl chloride and Lewis acids like AlCb,ZnCb,

FeCb- Valerio Borzalla el al., US6252092 and Du, Yunxing et al, CN 1907980A have describe the preparation ofbenzo propanone using propionic anhydride in the presence of 70% perchloric acid. Dauksas. V. et al.s Khimiko- Farmatsevticheskti Zhurnal, 21(5). 569-73. (1987) have described the use of propionyl chloride with a combination of Lewis acids such as SnCUand AlCh. to produce benzo propanone while Jacob et al., W09639133 have described the preparation of benzo propanone using propionic anhydride in present of iodine catalyst. But all these processes use harsh metallic reagents and/or result in poor yields of less than 50 percent, making these described processes environmentally hazardous and of marginal commercial utility. Accordingly, there exists a need to prepare l-(benzo[d][1,3]dioxol-5-yl) propan-1-one directly from easily available 1,3-benzodioxoles by direct reaction with propionic anhydride in an environmentally benign manner using a mild catalyst to affect high yield and purity in the preparation of substituted benzo propanones.
Summary of the Invention
The present invention describes a modified condensation reaction of l-(benzo[d][l,3]dioxol-5-yl)propan-l -one and propionic anhydride in the presence of iodine as a catalyst that is facile, high yielding and environmentally benign. The process for preparing l-(benzo[d][l,3]dioxol-5-yl)propan-l-one involves the addition of a slight excess as compared to 1,3-dibenzodioxole. of propionic anhydride dissolved in a solvent of propionic acid to a stirred mixture of 1,3-benzodioxole in the presence of catalytic quantities of elemental iodine. The reaction is held at reflux temperature for 20 - 25 h followed by vacuum distillation to yield l-(benzo[d][l,3]dioxol-5-yl) propan-l-one in high yield and purity. The use of a catalytic system of 2 - 4 percent weight to weight of iodine catalyst in propionic acid solvent is particularly advantageous and not described

in ihe literature.
It is of significant note and importance that the use of propionic anhydride as both the solvent and reactant with any quantities of iodine catalyst as described in W09639133A1 leads to only half the yield and significantly poorer purity of the desired l-(benzo[d][l.3]dioxol-5-yl)propan-l-one.
Detailed Description of the Invention
Before describing the present invention in detail, it is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.
In accordance with the present invention, there is provided a process to produce, in a highly environmentally benign and cost effective manner, the agrochemical insecticide piperonyl butoxide by improving the yield and purity of the key intermediate, l-(benzo[d][l,3]dioxol-5-yl)propan-l-one.
In one embodiment of the present invention, a process is described for the preparation of I-(benzo[d][l,3]dioxol-5-yl)propan-l-one by reacting 1.0 equivalent of 1,3-benzodioxole with 1.15 equivalent of propionic anhydride dissolved in propionic acid containing 2 percent weight to weight of Iodine to 1,3-benzodioxole, at 150 °C for 20 - 25 h. Vacuum distillation of the reaction mixture at 0.1 mm/Hg vacuum allows for separation of the solvent at 60 °C, followed by the isolation ofa pale brown liquid at 100-125 °C corresponding to the desired l-(benzo[d][l,3]dioxol-5-yl)propan-l-one product directly at 80% yield and 94% purity by gas chromatography.

It will be clear to those skilled in the art that modifications can be made to the process described herein without departing from the inventive concept set forth in our claims below.
Example I
Preparation of 1 -(benzoTdin .31dioxol-5-Yl)propan-1 -one
A stirred mixture of 1,3-benzodioxole (I22g. 1.0 mole) , propionic anhydride (150g, 1.15 mole) in 183 ml of propionic acid and 1.2g elemental iodine (2 percent weight to weight of I to 1,3-benzodioxole) was held at reflux temperature with a heating mantle for 20 hr. The reaction mass was monitored for completion using a gas chromatograph. After the maximum conversion of reaction, the reaction was cooled to room temperature. The reaction mass was subjected to vacuum distillation, at 65°C under a reduced pressure of 0.1 mmHg to remove propionic acid and other volatile compounds. Follow on fraction distillation at a temperature between 100-I25°C and vacuum ofO.i mmHg yielded a pale brown liquid which was identified as 1-(benzo[d][1.3]dioxol-5-yl)propan-l-one and with a weight of 137.1 g corresponding to 77% yield and 94% purity by gas chromatography.
Example 2
Preparation of Nfbenzofd^l.31dioxol-5-vnpropan-l-one using the process described in
WQ9639133A1.
A stirred mixture of 39 g 1,3-benzodioxole, 48 g propionic anhydride and 1.54 g elemental iodine
was held at reflux temperature with a heating mantle for 3.5 h. The crude reaction mixture was
heated to 65°C and 14 mmHg to remove to remove all volatiles resulting in 42 g of a heavy black
oil. The crude black oil was distilled at 0.1 mm/Hg. At 60°C a large quantity of clear colorless

liquid distilled over. Between 100-125 °C a pale brown fraction distilled over, whose identity was confirmed as l-(benzo[d][l,3]dioxol-5-yl)propan-l-one and whose weight was determined to be 28g, corresponding to 49% yield and 87% purity by gas chromatography. This 1-(benzo[d][l ,3]dioxol-5-yl)propan-l-one requires further purification when used in the preparation of commercial piperonyl butoxide as described in Example 3.
Example 3
Preparation of piperonyl butoxide
Step I: Preparation of Safrole alcohol
356 gram (2 mole) of l-(benzo[d][1.3]dioxol-5-yl)propan-l-one and 800 gram of methanol with < 5% water content was mixed together. The reaction mass was stirred and 30.4 gram (0.80 mole) of sodium borohydride was added over 1-1.5 hour. The colour of the reaction mass changed from dark red to pale brown. Exothermicity from 30 - 50°C was observed with brisk effervescence during the addition of the sodium borohydride. The reaction mass was heated for 2 hours at 50-52°C. After completion, the methanol was distilled off. The remaining crude liquid was added to water and then followed by extracted with ethylene dichloride. Removal of the ethylene dichloride resulted in 346 g of safrole alcohol (yield 95.5%).
Step 2: Preparation of Dihydrosafrole
1080 ml of isopropyl alcohol. 270 grams (1.5 moles; ) of safrole alcohol and 40.5 grams catalyst Raney nickel (15% wet basis) was mixed together and added into a autoclave. The mass was heated to 50°C and hydrogen gas was continuously purged into the autoclave and the reaction mass was slowly heated to 90°C over a period of 15 - 30 minutes, and thus maintained for 16 -18 hours. After completion, the reaction mass was filtered and washed with 100 ml of isopropyl alcohol and the filtrate was distilled to yield 234 gram of dihydrosafrole with an yield of 95%.
Step 3: Preparation of Chloromethyl dihydrosafrole
283 gram of concentrated hydrochloric acid (31%) and 125 ml of water was charged to a

2 L flask. 72 gram of paraformaldehyde was added to the above acid solution and heated to 60 -65°C under stirring. The reaction was maintained at 65°C for a further 15 minutes until all the paraformaldehyde was dissolved and a clear solution was obtained. The reaction mass was cooled to 30°C and 660 ml of hexane was added while continuing to cool to 20°C. 164 gram of dihydrosafrole (I mole) was added at 20°C over a period of 5-10 minutes. 137.3 gram of phosphorus trichloride (1 mole) was slowly added dropwise during a period of 6 to 7 hours at 17 - 20°C. The reaction was further held for 8 - 10 hours at 18 -20°C. The hexane was then distilled off to get 203 gram of chloromethyl dihydrosafrole with an yield of 95%.
Step 4: Preparation of Piperonyl butoxide
532 gram of chloromethyl dihydrosafrole (2.5 mole). 2130 ml of Toluene and 410 gram (2.52 mole) of diethylene glycol monobutyl ether (butyl carbitol) was added into a 5 litre flask. 106.2 gram of sodium hydroxide (2.65 mole) was added and the mixture heated to reflux temperature while removing the water of reaction azeotropically. The heating was continued at 110-1 15°C for a period of 5 - 6 hours, until no more water separated out. The organic layer was separated and toluene distilled off under vacuum, followed by the fractional distillation of piperonyl butoxide to yield 840 gram, corresponding to a 99.0% yield. Example 4:
Preparation of l-(benzo[diri.31dioxol-5-yl)propan-l-one as per example with propionic
anhydride with DMSO
A stirred mixture of 1,3-benzodioxole (I22.12g. 1.0 mole) and propionic anhydride (149.6g. 1.15 mole) in 183g of propionic acid containing 12.2gof DMSO and 2% elemental iodine (2.4g) was heated to 134°C and cooked for 31 hr. There was 3% conversion observed by gas chromatograph. Example 5: Preparation of l-(benzo[d][K31dioxo]-5-yl)propan-l-one as per example with propionic
anhydride with DMF
A stirred mixture of 1,3-benzodioxole (I22.12g. 1.0 mole) and propionic anhydride (I49.6g, 1.15 mole) in I83g of propionic acid containing 12.2g of DMF and 2% elemental iodine

(2.4g) was healed to 134°C and cooked for 30 hr. There was 8.1% conversion observed by gas chromatograph.
Example 6:
Preparation of l-fbenzordirioldioxol-S-vDpropan-l-one as per example with propionic
anhydride with EDC
A stirred mixture of 1.3-benzodioxole (122.l2g. 1.0 mole) of propionic anhydride (149.6g= 1.15 mole) in I50g of EDC and 2% elemental iodine (2.4g) was heated to 80°C and maintained for 30 hr. until no further change was observed on gas chromatography. There was observed a maximum of 40% conversion to the desired l-(benzo[d][].3]dioxol-5-yl) propan-1-one.
Example 7:
Preparation of Ufbenzofdlfl.31dioxol-5-yl)propan-l-one as per example with propionic
anhydride with acetic acid.
A stirred mixture of 1,3-benzodioxole (122.12g, 1.0 mole) of propionic anhydride (149.6g. 1.15 mole) in 200g of acetic acid and 2% elemental iodine (2.4g) was heated to 135°C and maintained for 31 hr. until no further change was observed on gas chromatography. There was observed a maximum of 47.7% conversion to the desired l-(benzo[d][l,3]dioxol-5-yl) propan-1-one. Example 8:
Preparation of U(benzordiri.31dioxol-5-yl)propan-l-one as per example with propionic
anhydride with monochloroacetic acid.
A stirred mixture of 1,3-benzodioxole (122.12g, 1.0 mole) of propionic anhydride (149.6g: 1.15 mole) in 200g of monochloroacetic acid and 2% elemental iodine (2.4g) was heated to I40°C and maintained for 10 hr, until no further change was observed on gas chromatography. There was observed a maximum of 41% conversion to the desired !-(benzo[d][l,3]dioxo1-5-yl) propan-1-one. Example 9:

Preparation of l-fbenzofdlf 1.31dioxol-5-yl)propan-l-one as per example with propionic
anhydride with dichloroacetic acid.
A stirred mixture of !.3-benzodioxole (122.12g, 1.0 mole) of propionic anhydride (149.6g, 1.15 mole) in 200g of dichloroacetic acid and 2% elemental iodine (2.4g) was heated to 140°C and maintained for 10 hr, until no further change was observed on gas chromatography. There was observed a maximum of 54% conversion to the desired i-(benzo[d][l ,3]dioxol-5-yl) propan-l-one.
Example 10:
Preparation of l-(benzo|"d1[1.3]dioxol-5-vOpropan-l-one as per example with propionic
anhydride with trichloroacetic acid.
A stirred mixture of l.3-benzodioxole(122.12g, 1.0 mole) of propionic anhydride (149.6g, 1.15 mole) in 200g of trichloroacetic acid and 2% elemental iodine (2.4g) was heated to I40°C and . maintained for 10 hr; until no further change was observed on gas chromatography. There was observed a maximum of 71% conversion to the desired l-(benzo[d][1.3]dioxol-5-yl) propan-1-one.
Example 1 ]:
Preparation of l-fbenzofd1[K31dioxol-5-yl)propan-l-one as per example with propionic
anhydride with monofluoroacetic acid.
A stirred mixture of 1,3-benzodioxole (122.12g, 1.0 mole) of propionic anhydride (149.6g, 1.15 mole) in 200ml of monofluoroacetic acid and 2% elemental iodine (2.4g) was heated to 150°C and maintained for 10 hr, until no further change was observed on gas chromatography. There was observed a maximum of 60% conversion to the desired 1-(benzo[d][i.3]dioxo!-5-yl) propan-1-one.

Example 12:
Preparation of l-(benzoj~dH~l.3"ldioxol-5-v0propan-l-one as per example with propionic
anhydride with difluoroacetic acid.
A stirred mixture of 1,3-benzodioxole (122.12g, 1.0 mole) of propionic anhydride (I49.6g, 1.15 mole) in 200ml of difluoroacetic acid and 2% elemental iodine (2.4g) was heated to I35°C and maintained for 10 hr, until no further change was observed on gas chromatography. There was observed a maximum of 65% conversion to the desired l-(benzo[d][l,3]dioxol-5-yl) propan-1 -one.
Example 13:
Preparation of l-(ben2ordiri.31dioxol-5-yl)propan-l-one as per example with propionic
anhydride with trifluoroacetic acid.
A stirred mixture of 1,3-benzodioxole (122.l2g, 1.0 mole) of propionic anhydride (149.6g, 1.15 mole) in 200ml of trifluoroacetic acid and 2% elemental iodine (2.4g) was heated to 135°C and maintained for 10 hr, until no further change was observed on gas chromatography. There was observed a maximum of 69.4% conversion lo the desired 1 -(benzo[d][ 1,3]dioxol-5-yl) propan-l-one. Example 14:
Preparation of l-(benzordin.31dioxol-5-yl)propan-l-onc as per example with propionic
anhydride with propionyl chloride.
A stirred mixture of 1.3-benzodioxole (122.12g, 1.0 mole) of propionic anhydride (149.6g, 1.15 mole) in 278g of propionyl chloride and 2% elemental iodine (2.4g) was heated to 105°C and maintained for 12 hr, until no further change was observed on gas chromatography. There was observed a maximum of 37.2% conversion to the desired l-(benzo[d][l,3]dioxol-5-yl) propan-1-one.

Example 15
Preparation of l-(benzord"iri.31dioxo]-5-vOpropan-l-one as per Example with the catalyst iodine
substituted with potassium iodide
A stirred mixture of 1,3-benzodioxole (6l.0g, 0.5 mole), propionic anhydride (75g, 0.576 mole) in 91.6g of propionic acid and potassium iodine (1,23g) was heated to 150°Cand maintained for 12hr. There was no reaction observed by gas chromatography.
Example 16
Preparation of l-(benzo[dl[l.31dioxol-5-vl)propan-l-one as per Example with the catalyst iodine
substituted with bromine
A stirred mixture of 1,3-benzodioxole (30.5 g: 0.25 mole), propionic anhydride (37.5g, 0.288 mole) in 45.8g of propionic acid and bromine (1.23g) was heated to I49°C and maintained for I2hr. There was <5% conversion to the desired i -(benzofdlf 1.31dioxol-5-vDpropan-1 -one as measured by gas chromatography.
Example 17
Preparation of l-fbenzoldlf l.31dioxol-5-yl)propan-l-one as per Example with the catalyst iodine
substituted with potassium bromide
A stirred mixture of 1,3-benzodioxole (61.0g, 0.5 mole), propionic anhydride (75g, 0.576 mole) in 91.6g of propionic acid and potassium bromide (1.2g) was heated to 150°C with a heating mantle and maintained for 9hr. There was no reaction observed by gas chromatography.
Example 18

Preparation of l-(benzordin.31dioxol-5-yl)propan-l-one as per Example I but with lower amount of the iodine catalyst
A stirred mixture of 1.3-benzodioxote (61.0g: 0.5 mole, propionic anhydride (75g, 0.576 mole) in 91.6g of propionic acid and 0.6g of iodine was heated to 135°C and maintained for 15 hr, until no further change was observed on gas chromatography. There was a maximum of 44% conversion to the desired l-(benzo[d][1.3]dioxol-5-yl) propan-l-one.
Example 19
Preparation of l-(benzofd1p.31dioxol-5-vl)propan-l-one as per Example I with 2.5% iodine
catalyst versus 2% in Example 1
A stirred mixture of l33-benzodioxole (122.0g. 1.0 mole, propionic anhydride (I50g, 1.15 mole) in 222g of propionic acid and 1.5g of iodine was heated to 1 SOX and maintained for 14 hr. until no further change was observed on gas chromatography. There was a maximum of 75% conversion to the desired l-(benzo[d][t,3]dioxol-5-yl) propan-l-one.
Example 20
Preparation of l-fbenzo[d]fl.31dioxol-5-yl)propan-l-one as per Example I with 3% iodine
catalyst versus 2% in Example i
A stirred mixture of 1,3-benzodioxole (122.0g, 1.0 mole, propionic anhydride (150g, 1.15 mole) in 222g of propionic acid and 1,8g of iodine was heated to I50°C and maintained for 14 hr, until no further change was observed on gas chromatography. There was a maximum of 70% conversion to the desired l-(benzo[d][l,3]dioxol-5-yl) propan-l-one.

Example 21
Preparation of l-(benzo[d]| ].3]dioxol-5-vl)propan-l-one as per Example 1 with 4% iodine
catalyst versus 2% in Example 1
A stirred mixture of 1,3-benzodioxole (122.Og. 1.0 mole, propionic anhydride (150g, 1.15 mole)
in 222g of propionic acid and 2.4g of iodine was heated to 150°C and maintained for 14 hr. until
no further change was observed on gas chromatography. There was a maximum of 63% conversion
to the desired l-(benzo[d][l,3]dioxol-5-yl) propan-1 -one.Preparation of l-(benzo[d][!:3]dioxol-
5-yl)propan-l-one
Claims
What is claimed is:
1. A process to produce l-(benzo[d][l.,3]dioxol-5-yl)propan-l-one from 1,3-benzodioxole and propionic anhydride in an aliphatic acid solvent containing a catalytic amount of iodine.
2. A process according to claim I, wherein the solvent is preferably propionic acid or halogen substituted acetic acids.
3. A process according to claim 2. wherein the solvent is most preferably propionic acid.
4. A process according to claim I. wherein the amount of iodine catalyst is preferably between 2 - 4 % weight to weight of elemental iodine to 1,3-benzodioxole.
5. A process according to claim 1, wherein the reaction is refluxed at boiling temperature for 10 to 25 hours.
6. A process according to claim 5, wherein the reaction is preferably refluxed at boiling temperature for 16 hours.