CA1097666A - Process for preparing piperonal - Google Patents

Abstract

Title of the Invention Process for Preparing Piperonal Abstract of the Disclosure A process for preparing piperonal which comprises the steps of reacting 1, 2-methylenedioxybenzene with an N-alkylformanilide and a condensing agent comprising one or more compounds selected from the group consisting of phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, sulfuryl chloride, sulfuryl bromide, phosphorus trichloride, and phosphorus pentachloride, and then hydrolyzing the resulting reaction product.

Description

~o 766~ 1 1 Background of the Invention This invention relates to a novel process for preparing piperonal.
Piperonal is the basis o-E heliotrope type perfume compositions and is widely used in perfumes for general cosmetic preparations. In addition, it is very useful as an industrial material for the production of drugs, agricultural chemicals, and the like and as a brightener for metal plating. Industrially, piperonal is now being produced mainly by isolating safrole from the essential oil of Ocotea cymbarum and oxidizing it with ozone or dichromate. In recent years, however, the tendency toward the ¦
exhaustion of natural resources from which safrole can be obtainedj has created a growing demand for stable supply oE piperonal through its industrial synthesis from petroleum chemicals.
Conventional processes for preparing piperonal can be divided into two groups: one starting with 1, 2-methylenedioxybenzene prepared from pyrocatechol and the other starting with 3, 4-dihydroxybenzaldehyde. The former is found to be more advantageous to industrial appllcatlons.
Several processes or preparing piperonal from 3, 4-dihydro-xybenzaldehyde are known.
(1) In order to prepare the starting material or 3, 4-dihydroxy- 1 benzaldehyde, a process has been proposed which involves condensing pyrocatechol with glyoxylic acid in aqueous alkali and then oxidizing the resulting dihydr~xymandelic acid ~Japanese Patent Application Disclosure No. 2,952/'75). The yield attainable with this process is at most 77%. (2) One process for preparing piperonal from 3, 4-dihydroxybenzaldehyde comprises reacting 3, 4-dihydroxybenzaldehyde with methylene chloride and alkali in a non-protic polar solvent such as dimethyl sulfoxide, and gives a 61% yield of piperonal (British Patent No. 1,097,270)~, Another process comprises reacting 3, 4-dihydroxybenzaldehyde

- 2 -,. fj ~Q76~
, with methylene chloride in aqueous alkali under the influence of , an interphasic moving catalyst such as quaternary ammonium compound, and gives a 70 - 73~ yield of piperonal. However, the catalyst used in this process is expensive and, by nature, easily soluble in both aqueous and organic phases. Accordingly, the recovery of the catalyst is too low to make this process practicable (Japanese Patent Application Disclosure Nos.23,265t'76 ¦ and 113,967/'77). In any event, neither of these process can provide satisfactory yields based on the amount of ~he starting ¦ material. In addition, James H. Clark et al. have described still another process in which 3, 4-dihydroxybenzaldehyde is reacted i with dibromomethane in N, N-dimethylformamide under the influence ?
of an excess of potassium fluoride or cesium fluoride to give a i 1 90% yield of piperonal [Tetrahedron Letters, No. 38, pp. 3361 -3364 (1976)]. This process is of advan~age in that no strong I base is used, the reaction time is relatively short, and a high I
- I yield can be obtained. However, an expensive fluoride must be ¦
I used in .large excess as a halogen trapplng agent and cannot be I recycled because its fluorine component is stoichiometrically ,I replaced by the halogen atoms in the dihalomethane used. I
Accordingly, this process is not satisfactory for industrial I ~-applications. Moreover, when based on~the amount of pyrocatechol ¦ I
j used, the yield attainable with this process does not reach 70%. I j j Meanwhile, several processes for preparing piperonal from 1, 2-methylenedioxybenzene are~als~o known. (1) The starting materiaI or 1, 2-methylenedioxybenzene can be prepared by processes in which pyrocatechol is reacted with methylene chloride I and alkali in a non-protlc polar solvent such as dimethyl sulfone to give a 91 - 99% yield tBritish Patent No. 1,097,270 and Japanese Patent Application Disclosure Nos. 5,963/'76 and 13,773/'76). In addition, other processes which can give high ll 3 1,l lOg7666 ~ I
yields o 1, 2-methylenedioxybenzene are also available.
Accordingly, it would be of great advantage from an industrial viewpoint if piperonal could be prepared from 1, 2-methylene-dioxybenzene with good yield and high selectivity. (2) A typical 1 process or preparing piperonal from 1, 2-methylenedioxybenzene has been reported by P. P. Shorygin et al. ~J. Gen. Chem. (U.S.S.R.), 8,975 (1938)]. This is a two-step process. In the first step, Il 1, 2-methylenedioxybenzene is reacted with formalin in petroleum I benzine under the influence of hydrogen chloride gas and zinc chloride to form piperonyl chloride (with a 70 - 78% yield based !
on the amount o 1, 2-methylenedioxybenzene having reacted).
¦1l This is followed by the second step in which the piperonyl chloride is reacted with an equimolar amount of hexamine in 60%
alcohol to give a 70 - 80% yield of piperonal. By E. D. Laskina I
Il et al. [Chemical Abstracts, 57,9714 (1962)], another process has t 1 been described in which 1, 2-methelenedioxybenzene is reacted ¦ with formalin in the presence o~ a large excess of the sodium salt of m-nitrobenzenesulonic acid, hydrogen chloride, and an aluminum catalyst to give a 42.4% yield of plperonal.
However, these conventional proces$es are not entirely ~1 i I
satisfactory for industrial applications because the yield and I
particularly selectivity (that is, the yield o piperonal based ¦ on ~he amount o 1, 2-methylenedloxybenzene having reac~ed) is ¦ rather limited due to the abundant formation of tarry by-products~ l the procedure ~or reaction is complicated, and ~he large amount ,j I
of metal hydroxide formed as a by-product must be disposed of.
i ' ~ '.
Summary of the Inventlon It is, therefore, an object o this invention to provide an ,j , . .
easily practicable process for preparing piperonal from ~, 1, Z-methylenedioxybenzene with good yield and particularly high 1, ~97~
i, i selectivity based on the amount of the starting material.
As a result of intensive search for an easily practicable process which will eliminate the disadvantages of conventional processes and can give a high yield of piperonal, we have no~ !
found that piperonal can be obtained with good yield and high selectivity by reacting 1, 2-methylenedioxybenzene ~ith an i N-alkylformanilide and a condensing agent comprising ons or more compounds selected from the group consisting of phosgene, i phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, tllionyl bromide, sulfuryl chloride, sulfuryl bromide, phosphorus ¦
¦ trichloride, and phosphorus pentachloride, and then hydrolyzing the resulting reaction product. That is, this invention is based ! on the discovery that N-alkylformanilides can formylate , 1, 2-methylenedioxybenzene to p~roduce piperonal with good yield j and high selectivity, as contrasted with dimethylformamide which ¦¦ is commonly used as a formylating agent in the Vilsmeier reaction j¦ but found to give only a very low yield and selectivity of piperonal. ~
By the process of the inv~ntion, the desired product or i piperonal is produced with good yield and high selectivity, as ¦~ represented by the ollowing reac~ion formula.

\N~

a) Condensing Agent (b) H20 CHO

where the condensing agent (a) comprises one or more compounds ¦
selec~ed from the group consis~ing of phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl I bromide, sulfuryl chloride, sulfuryl bromide, phosphorus I

` ` `

7~i6 trichloride, and phosphorus pentachloride.
That is, 1,2-methylenedioxybenzene ~II) is reacted with an N-alkylformanilide (I) and a condensing agent (a), such as phos~ene or phosphorus oxychloride, and the resulting reaction product is then hydrolyzed to form piperonal ~III) and an N-alkylaniline (IV).
The process of the invention is more preferably practiced by reacting an N-alkylformanilide ~I) with a condensing agent ~a), such as phosgene or phosphorus oxychloride, to form an addition product ~hereinafter referred to as "amide chloride"), reacting the amide chloride with 1, 2-methylenedioxybenzene ~II), and then hydrolyzing the resulting reaction product.
In addition, the process of the invention facilitates the recovery of the N-alkylaniline ~IV) formed along with piperonal ~III). The N-alkylaniline thus obtained may be reacted with formic acid to form an N-alkylformanilide ~I) which can then be recycled in the process of the lnvention. This also makes the process of the invention advantageous to industrial applications.
Thus, in accordance with one aspect of this invention there is provided a process for preparing piperonal which comprises the steps of reacting 1, 2-methylenedioxybenzene with an N-alkylformanilide of the general formula R~ ~ CH0 " ' ~ .
wherein R is an alkyl group having from 1 to 4 carbon atoms, and a condensing agent of at least one compound selected from the group consisting of phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, sulfuryl chloride, sulfuryl bromide, phosphorus trichloride, and phosphorus pentachloride, and then hydrolyzing the resulting reaction product.

~76~6 In accordance with another aspect of this invention there is provided a process for prepaFing piperonal which comprises the steps of reacting an N-alkylformanilide of the general formula R CHO
N

~.' wherein R is an alkyl group having from 1 to 4 carbon atoms, with a condensing agent of at least one compound selected from the group consisting of phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, sulfuryl chloride,and sulfuryl bromide, a~ a te~perature in the range of -40 to 100C to form a reaction mixture containing an .10 amide chloride, adding the reaction mixture to 1~ 2-methylene-dioxybenz~ne or a mixture o~ 1, 2-methylenedioxybenzene and an inert organic solvent to react said amide chloride with said 1, 2-me~hylenedioxybenzene at a temperature in the range of 50 to 120C, and then hydroly~
~ ~ .- - .
ing the resulting reaction product. . ~ :
DetailPd Descripti n Oe ~he In~Ont~CA
The N-alkylformanilides ~which can be used in the practice of the invention are represented by the general formula -6a-~0~66~ i I

R ,,CHO
~ (I) where R is an alkyl group having from 1 to 4 carbon atoms.
~! Typical examples o these compounds are N-methylformanilide, Il N-ethylformanilide, N-isopropylformanilide, N-~_-propyl)forma- I t I nilide, N-(_-butyl~formanillde, N-isobutylformanilide, ~j N-(sec-butyl)formanilide, and N-(tert-butyl)formanilide. Among them, N-methylformanilide and N-ethylformanilide are most Il preferred. 1, 2-Methylenedioxybenzene may be used in any desired 1, ¦ proportion. From a practical viewpoint, however, it is desirable to use from 0.1 to 15 moles and preferably from 0.3 to 10 moles of i 1, 2-methylenedioxybenzene per mole of the N~alkylformanilide.
II It is also desirable to use from 0.3 to 5 moles and preferably ¦~ from O.7 to 2 moles of a condensing agent, such as phosgene or~
¦ phosphorus oxychloride, per mole of the N-alkylformanilide.
¦ The invention will be better understood from the following detailed description of preferred embodiments thereof.
¦~ In one preferred embodiment of the invention, an -I I ¦~N-alkylformanilide is reacted with a condensing agent, such as ¦ phosgene or phosphorus oxychloride,to~form~lan addition product ~1 ~ , which is¦hereinafter referred to asl"amide chloride". This amide chlorlde is added to 1, 2-methylenedloxyb~enzene kept at the reactlon temperature. After the r~eaction mixture is allowed to , i stand9~the resulting reacti~on product is~hydrolyzed. More ¦ !
¦ specifically, a condenslng agent, such as`phosgene or phosphorus oxychloride, is introduced~into an N-alkylformanilide with effectlve stirring to form an amide chloride. This amide chloride is an intermediate product which serves to introduce an aldehyde group~into the molecule of 1, 2-methylenedioxybenzene.
Althoueh the above-described reaction may be carried out in the , 7 t ,, , i `.
.i . ~

66~
,.
absence of any solvent, it is preferred to use l, 2-methylene-dioxybenzene or an inert organic solvent as the solvent for reaction. When no solvent is used, the resulting amide chloride may be utilized either as it is or as a solution in l, 2-methylenel-dioxybenzene or an inert organic solvent. The amide chloride or ll a solution thereof is kept in that temperature range which allows ' I it to remain in solution, and then continuously or intermittently added with effective stirring to l, 2-methylenedioxybenzene (or a mixture of l, 2-methylenedioxybenzene and an inert organic i solvent) heated previously to a -temperature at which it reacts with the amide chloride. Thus, the reaction of l, 2-methylene- ¦
dioxybenzene with the amide chloride can be preferentially accomplished while the reaction between amide chloride molecules is suppressed. Thereafter, the resulting reaction product is il hydrolyzed to obtain the desired final product or piperonal.
In this embodiment, the reaction for synthesis of an amide ! chloride is characterized as follows:
No particular limitation is imposed on the reaction i temperature, so long as it is lower than the leveI at which l decomposit1on or polymerization takes place. However, for the I purpose of suppressing the react1on between molecules of the amide~
ch1Or1de formed, lt is desirable to use those ~emperatures which !
lie in the range of -40to 100C and preferably -20to 70C and ¦
! allow the reacting mass to remain in~solution~
(2) A condensing agent, such as phosgene or phosphorus oxychlor- ¦
ide, is desirably introduced over a period of time as short as possible, but may be~introduced over a long period of time if lower temperaturels are used. Practically, it may vary from 5 minutes to~l5 hours and preferably from lO minutes to 5 hours.
¦ (3) The reaction is usualLy carried out under atmospheric pressure, though subatmospheric and super-atmospheric pressures ~oq7666 may be used. ~4) However, when the condensing agent comprises : thionyl chloride, thionyl bromide, sulfuryl chloride, or sulfuryl bromide, the reaction ~ith an N-alkylformanilide is desirably ~l ¦
carried out under reduced pressure, particularly under a l ¦
pressure in the range of 20 to 400 mmHg, and at a temperature in ! the range of 0 to 80C and preferably 40 to 60C. Moreover, it I is preferred to carry out the reaction in the absence of any solvent, though 1, 2-methylenedioxybenzene and/or inert organic solvent may be used as the solvent for reaction.
The amide chloride thus obtalned or a solution ~hereof is kept at a temperature in the range of -40 to 60C and preferably -20 to 50C.
The reaction of the amide chloride with 1, 2-methylenedioxy-benzene is carried out by adding the amide chloride or a solution ¦i thereof to 1, 2-methylenedioxybenzene at a temperature in the range of 50 to 120C and preferably 60 to 100C over a period ¦¦ of time varying from 5 minutes to 15 hours and preferably from 10 minutes to 10 hours and then heating the reaction mixture at that temperature for a period of~tlme varylng from 5 minutes to 10 hours and preferably from 10 minuteslto 3 hours. The resulting reactlon~product may be hydrolyzed, elther directly or after coollng to~room tempe~rature~, to~form plperonal.
In~another preferred embodiment of the lnvention, an ¦
I N-alkylformanil~ide, l, 2-methylenedioxybenzene, and a condensing ¦
j agen*, such as phosgene or phosphorus oxychloride, are charged into a sinigle reactor and allowed to react. More specifically, a mixture of an N-alkylformanillde~and l, 2-methylenedioxybenzene 1 ¦
and,~lf desLred, an ine~rt organic ~solvent is formed. Then a condensing agent, such as phosgene or phosphorus o~ychloride, is added to this m~xture wi~h efective stlrring and allowed to react. In this embodiment, it is possible to add the condensing i 9 ~ ' " .
-~7~

agent and carry out the reaction at an identical temperature in the range of 50 to 100C and preferably 60 to 80C. However, in view o:E the yield of piperonal and the recovery of the N-alkylaniline formed as a by-product, the condensing agent is desirably added at a temperature in the range of -40 to 100C and preferably -20 to 70C so as to form preferentially the amide chloride which is the addition product of the N-alkylformanilide with the condensing agent and, thereafter, the main reaction is carried out at a temperature in the range of 500 to 1100C and preferably 60 to 110C. The reaction time may vary from 1 to 30 hours and preferably from 2 to 15 hours, including the ~ime required for addition of the condensing agent which may vary from 5 minutes to 15 hours and preferably from 10 minutes to 10 hours.
The reaction is usually carried out under atmospheric pressure, though subatmospheric and super-atmospheric pressures may be used.
However, when the condensing agent comprises thionyl chloride, thionyl bromide, sulfuryl chloride~ or sulfuryl bromide, the reaction is desirably carried out under reduced pressure, particularly under a pressure in the range of 20 to 400 mmHg. l In either of the above-des~crlbed embodiments, the resulting ¦
reaction~product~may be treated by conventional procedure. For j ~-example, the reactlon product is poured with~effectlve s`tlrring 1, into water kept at a temperature in the range of~0 to 100C and pre-ferably~Oa to 80~C, and ~hereby hydrolyzed to Eorm the desired final product or piperonal and an N-alkylaniline which can be recycled. The resulting mixture is directly extracted with a solvent such as benzene, toluene, chloroform, carbon tetrachloride dichloroe~hylene,~ and the like. The remaining aqueous phase is ! -neutralized with alkali and the N-alkylaniline thus liberated is extracted with a solvent as descrlbed above. Each of the extractsli is distilled under reduced pressure by conventional procedure to 1l -. .

,, .

. . , 7~ ~
obtain unreacted 1, 2-methylenedioxybenzene, the desired final product or piperonal, unreacted N-alkylformanilide, and the by-product or N-alkylanilinc~ The crude piperonal obtained by distillation may be recrystallized from alcohol by conventional procedure to yield high-purity piperonal suitable for use in perfume compositions. The above-described hydrolysis may also be carried out by pouring the reaction product into an alkaline solution In view of the yield and se]ectivity of piperonal and the recovery of the by-product or N-alkylaniline, the most preferred -¦
embodiment of the invention is such that phosgene or phosphorus ¦
oxychloride ;s used as the condensing agent and the main reaction !
is carried out while the reaction between molecules of the amide chloride which is the addition product of the N-alkylformanilide with the condensing agent is suppressed. l The condensing agents which can be used in the practice o~ ¦
the invention include phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, sulfuryl chloride,~
sulfuryl bromide, phosphorus trichloride, and phosphorus pentachloride. Prom the vlewpoint of yield and selectivity of ~
piperonal, it is desirable to use phosgene or phosphorus oxychlo-ride. In industrial applications, however~ phosgene is preferred to phosphorus oxychloride. The reasons for~thlS ale that the weight of phosphorus oxychloride required in the practice of the !
invention lS about 1.5 times as great as that of phosgene because the inventlon involves an equimolar reaction, that ~phosphorus oxychloride gives a slower reaction rate and a lower yield than phosgene, that phosphorus oxychloride requires about `
2.5 times as much~alkali as phosgene for the purpose o neutrali-zing the acid formed during hydrolysis, and that phosphorus ,! ! , 1 oxychloride necessitates the disposal of waste water containing - ~

. .

I
76~i6 phosphorus Compounds. I
If desired, inert organic solvents may be used in the practice of the invention. Typical examples of these solvents are benzene, chlorobenzene, -dichlobenzene, chloroform, carbon tetTachloride, methylene chloride, and 1, 2-dichloroethane.
In order to further illustrate this invention, the following examples are given.
Example_l Into a mixture of 97.6g (0.80 mole) of 1, 2~methylenedioxy-benzene and 108g (0.80 mole) of N-methylformanilide was introduced 87.1g (0.88 mole) of phosgene at 50C over a l-hour period. Then,i the mixture was cooled to 15C. On the other hand, 29.3g (0.24 1 ¦
mole) of 1, 2-methylenedioxybenzene was charged into another reactor and kept at 9~C. The above mixture was added to this reactor over a 5-hour period. After completion of the addition, I
the reaction mixture was kept at 90~C for 30 minutes, poured into ice water, and allowed to stand for 1 hour. Then~ the resulting I
mixture was extracted with toluene. By vacuum distillation, the l I
toluene was removed and the distillate at 84 - 85C/30 mmHg was ¦
then collected to recover 63.4g (0~.52 mole) of unreacted 1, 2-methylenedioxybenzene. Sabsequently, the dlst~llate at 131-134C~
/10 mmHg was collected to obtain 76.8g (0.512 mole) of plperonal !
having a purity of 99~.5%. The yield (expre~ssed in terms of mole I i percentage based on the amount of N-me~thylformanilide usedj and ¦
selectivlty (expressed in terms of mole percentage based on the amount of 1, 2-methylenedioxybenzene having reacted) of piperonal were 64.0% and 98.5%, respectively. This product had a melting point of 37C.
The results of analysis of the product by gas chromatography~
NMR spectroscopy, mass spectrometry, and IR spectroscopy were in complete agreement with those of an authentic sample.

, f , 3L~997~;~6 The aqueous phase remaining after the above-described extraction with toluene was alkalified by addition of sodium hydroxide and then extracted with toluene.
I By vacuum distillation, the toluene was removed and the I distillate at 111 - 113C/50 mmHg was then collected to recover I 64.5g ~0.603 mole) of N-methylaniline. Its recovery was 75.4%.
Subsequently, the distillate at 151 - 153C/50 mmHg was collected to recover 6.7g (0.050 mole) of N-methylformanilide. Its recovery was 6.3%. The N-methylaniline thus Tecovered could be reacted with formic acid to form N-methylformanilide.
Example 2 Into a mixture of 97.7g (0.80 mole) of 1, 2-methylenedioxy-,I benzene and 108g (0.80 mole) of N-methylformanilide was introduced 80.0g (0.81 mole) of phosgene at 50C over a l-hour period. Then, Il the reaction mixture was heated at 70C for 5 hours, poured into ¦, ice water, and allowed to stand for 1 hour. Thereafter, the resulting mixture was treated in the same manner as in Example 1 to obtain 48.0g (0.393 mole) of 1, 2-methylenedioxybenzene and 58.9g~ (0.392 mole)~ of piperonal. The yield and $electivity of piperonal were 49.0% and 96.3%, respectively. The recoveries of N-methylaniline and N-methylformanilide were 64.2% and 2.3%, , I-respectlvely. ;
Control 1 The precedure of Example 2 was repeated,`~except that 58.5g , (0.80 mole) of dimethylformamide was used in place of the N-methyl-Eormanilide. As a result, the conversion of`l, 2-methyl- !
enedloxybenzene was 2.5%. The yield and selectivity of piperonal ¦
P were 0.4% and 16.2%,~respectively.
I Control~2 I The precedure of Example 2 was repeated, except that 58.5g (0.80 mole) of dimethylformamide was used in place of the ~97~

N-methylformanilide and that the phosgene was introduced at j ¦
85 - 90C over a 40-minute period and the reaction mixture was then heated at 90C for 7.5 hours. As a result, the conversion I i of 1~ 2-methylenedioxybenzene was 12.5%. The yield and selecti-viky of piperonal wer0 4.1% and 33%, respectively. ¦
Example 3 ¦
The procedure of Example 1 was repeated, except thatphosphorus oxychloride was used in place of the phosgene. The results obtained are summarized in Table I.
Example 4 The procedure of Example 2 was repeated, except that N-ethylformanilide was used in place of the N-methylformanilide and that the phosgene was introduced at 60C instead of 50C.
The results obtained are summarized ln Table I.
Example 5 -The procedure of Example 1 was repeated, except thàt N-iso-propylformanilide l~as used in piace of the N-methylformanilide anc that 1, 2-dichloroethane was used as the solvent for reaction in an amount equal to that of the N-isopropyl~ormanilide and as the l I
solvent fol extraction in place of the toluene. The results ¦
obtalned are summa;riæed in Table I.
Example~6 The procedure of ~xample~5 was repeated, except that N-(n-butyl)formanilide was used in place of the N-lsopropylform- I
anilide. The results obtalned are summar~zed in Table I.

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~a7~;66 Example 7 The procedure of Example 1 was repeated, except that I phosphorus oxybromide was used in place of the phosgene. The I results obtained are summarized in Table II.
~ Example 8 ~ _ ' lhe procedure of Example 2 was repeated, except that the phosgene was introduced at 70C over a O.S-hour period, and, subsequently, the reaction mixture was`kept at that temperature for 3 hours. The results obtained are summarized in Table II.
Example 9 i The procedure of Example 2 was repeated, except that thionyl¦
chloride was used in place of the phosgene and that the reaction was carried out under a reduced pressure of 60 - 80 mmHg. The results obtained are summarised in Table II.
Example lO ¦
To 108g (0.80 mole) of N-methylformanilide cooled in an ice-water bath, 95.2g tO.80 mole)of thionyl chloride was added drop by drop with stirring. After completion of the addition, the mixture was allowed to stand at room temperature for 2 hours and then heated at 40 - 50C for 1 hour under a reduced pressure of I
60 - 80 mmHg. To the resulting yellow mlxture,-97.6gl~0.80 mole)¦
of 1, 2-methylenedloxybenzene was added and kept at 15C. l Thereafter, the reaction with 1, 2-methylenedioxybenzene was ¦
carried out in the same manner as in Example `1 ? The results I
obtained~are summarized in Table II.
Example 11 To the yellow mixture obtained according to the procedure o-f Example 10, 15g o-f o-dlchlorobenzene ~as added in place of the 1, 2-methylenedioxybenzene. Thereafter, the reaction with 1, 2-methylenedioxybenzene was carried out in the same manner as in-Example 1, except that 1~2g ~1.0 mole) of 1, 2-methylene-'~

l, ~
~97~6~i 1 , dioxybenzene was charged into the other reactor. The results Il obtained are summarized in Table II.
!~ Example 12 1ll The procedure of Example 10 was repeated, except that I thionyl bromide was used in place of the thionyl chloride. The ¦ results obtained are summarlzed in Iable II.
¦~ Example 13 ¦¦ The procedure of Example 10 was repeated, except that sulfuryl chloride was used in place of the thionyl chloride. The ! results obtained are summariæed in Table II.
Example 14 ¦ The procedure of Example 10 was repeated, except that ¦ N-ethylformanilide was used in place of the N-methylformanilide.
Ihe result obtained are summarized in Table II.

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Claims (13)

What is claimed is:

1. A process for preparing piperonal which comprises the steps of reacting 1, 2-methylenedioxybenzene with an N-alkylformanilide of the general formula wherein R is an alkyl group having from 1 to 4 carbon atoms, and a condensing agent of at least one compound selected from the group consisting of phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, sulfuryl chloride sulfuryl bromide, phosphorus trichloride, and phosphorus pentachloride, and then hydrolyzing the resulting reaction product.

2. A process as claimed in Claim 1 wherein said 1, 2-methylene-dioxybenzene is reacted with said N-alkylformanilide and said condensing agent in the presence of an inert organic solvent.

3. A process as claimed in Claim 1 wherein said N-alkylformanil-ide is N-methylformanilide or N-ethylformanilide.

4. A process as claimed in Claim 1 wherein said condensing agent is phosgene.

5. A process as claimed in claim 1 wherein said condensing agent is added to a mixture of said 1, 2-methylenedioxybenzene and said N-alkylformanilide at a temperature in the range of 50° to 100°C and the reaction is carried out at the same temperature at which said condensing agent is added.

6. A process as claimed in Claim 1 wherein said condensing agent is added to a mixture of said 1, 2-methylenedioxybenzene and said N-alkylformanilide at a temperature in the range of -40° to 100°C and, thereafter, the reaction is carried out at a temperature in the range of 50° to 110°C.

7. A process as claimed in Claim 1 wherein said condensing agent comprises thionyl chloride, thionyl bromide, sulfuryl chloride, or sulfuryl bromide and wherein the reaction is carried out under a reduced pressure in the range of 20 to 400 mmHg.

8. A process for preparing piperonal which comprises the steps of reacting an N-alkylformanilide of the general formula wherein R is an alkyl group having from 1 to 4 carbon atoms, with a condensing agent of at least one compound selected from the group consisting of phosgene, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, sulfuryl chloride,and sulfuryl bromide, at a temperature in the range of -40° to 100°C to form a reaction mixture containing an amide chloride, adding the reaction mixture to 1, 2-methylene-dioxybenzene or a mixture of 1, 2-methylenedioxybenzene and an inert organic solvent to react said amide chloride with said 1, 2-methylenedioxybenzene at a temperature in the range of 50° to 120°C, and then hydrolyz-ing the resulting reaction product.

9. A process as claimed in Claim 8 wherein said N-alkylformanilide is reacted with said condensing agent in the presence of 1, 2-methylenedioxybenzene or an inert organic solvent.

10. A process as claimed in Claim g wherein said inert organic solvent is benzene, chlorobenzene, o-dichlorbenzene, chloroform, carbon tetrachloride, methylene chloride, 1, 2-dichloroethane, or trichloroethylene.

11. A process as claimed in Claim 8 wherein said N-alkylformanilide is N-methylformanilide or N-ethylformanilide.

12. A process as claimed in Claim 8 wherein said condensing agent is phosgene.

13. A process as claimed in Claim 8 wherein said condensing agent comprises thionyl chloride, thionyl bromide, sulfuryl choride, or sulfuryl bromide and wherein the reaction of said N-alkylformanilide with said condensing agent is carried out in the absence of any solvent, at a temperature in the range of 0° to 80°C, and under a reduced pressure in the range of 20 to 400 mmHg.