DESC:FIELD OF THE INVENTION
[0001] The present disclosure pertains to technical field of synthesis of organic compounds. In particular, the present disclosure pertains to an improved and efficient process for preparing substituted or unsubstituted aryl aldehydes from substituted or unsubstituted aryl alkanes or alkenes.

BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Substituted or unsubstituted aryl aldehydes are useful compounds and widely used in perfume industry, as raw material for active pharmaceutical ingredients, as soap additives, as food additives, for metal electroplating and also as chemical intermediates for synthesizing different chemicals.
[0004] It is known in the art that substituted or unsubstituted aryl aldehydes can be prepared by a number of methods, one process being the oxidation of substituted or unsubstituted aryl alkanes or alkenes with manganese dioxide, water and sulfuric acid. These aldehydes can also be prepared through the oxidation of substituted or unsubstituted benzyl alcohol, followed by methylation. Of course, many other ways to prepare these aldehydes are known; however, those mentioned are exemplary of the prior art.
[0005] For oxidation of substituted or unsubstituted aryl alkanes using manganese dioxide in liquid phase system, numerous methods have been proposed in the prior art. German patents DE101221, DE107722 and DE175295 have disclosed such oxidation of different compounds.
[0006] US Patent US3985809 discloses preparation of aromatic aldehydes and acids, and is more specifically concerned with the preparation of anisaldehyde utilizing a manganic salt to oxidize either methoxytoluene or the benzyl or toluene sulfonic ester of p-cresol whereby under carefully controlled conditions there is obtained a minimum of tars, a minimum of aromatic acids and a minimum utilization of the methoxytoluene for conversion to anisaldehyde.
[0007] Japanese Patent JPS5716829 discloses preparation of 4-substituted aryl aldehydes useful as an intermediate for drugs, perfume, etc. in high selectivity, by oxidizing a 4-substituted toluene with O2 in liquid phase in dimethylsulfoxide using vanadium pentoxide and/or manganese dioxide as a catalyst and a bromine compound.
[0008] Patents US1302273 discloses the process of directly oxidizing hydrocarbons or compounds containing the methyl group to aldehydes by the use of manganese dioxide as an oxidizing agent in connection with a catalytic material consisting either of ferric, copper or cerium sulfate.
[0009] Patent US2450877 discloses synthesis of 3-t-butyl-4-alkoxy benzaldehydes from 3-t-butyl-4methoxy toluene by using manganese dioxide and sulfuric acid. FR320621 also discloses a process for preparing sulfonated aromatic aldehyde comprising oxidizing the sulfonic derivatives of benzene homologues (toluene, xylene, etc.) by means of manganese dioxide in the presence of fuming sulfuric acid.
[00010] Bull. Chem. Soc. Jp., 61,1035-1037(1988) discloses liquid phase oxidation of 3,4,5-trimethoxytoluene to 3,4,5-trimethoxybenzaldehyde using Co(OAc)2-Mn(OAc)2 mixture as catalyst in an autoclave under 3atm oxygen pressure. Cat. Lett., 97(3-4), 119-123(2004) discloses the beneficial effect of manganese dioxide on the oxidation of organic compounds by potassium permanganate.
[00011] Other methods for such oxidation reactions are, but not least, (i) Vapor-phase catalytic oxidation; (ii) Electrochemical oxidation and (iii) oxidation using different other metal catalysts or combinations of different catalysts.
[00012] Vapor-phase catalytic oxidation is reported in patents EP0228275, US4054607, US4885412, US5059716, US3946067 and many other literature references like Ind. & Engg. Chem., 28(3), 319-323(1936) and Ind. & Engg. Chem., 33(7), 891-897(1941).
[00013] Electrochemical oxidation is reported in GB2164935 and Electrochimica Acta.,39(4),497-499 (1994) and different other metal catalysts and combinations of different catalysts are reported in patents like US4339607, US4639298, US6743952, US7411099, US7453013, EP0459729 and many other literature references like Ind. J. Chem.Tech., 4(5),256-258(1997), Tetrahedron, 60(50), 11415-11420(2004) and Tetrahedron, 53, 2989-2992(2012).
[00014] In view of the prior art references, it has been found that all over the globe, a lot of work has been done by different scientists in search of industrially efficient and economic process for the preparation of such substituted or unsubstituted aryl aldehydes.
[00015] In all the processes for preparing substituted or unsubstituted aryl aldehydes known to the applicant, at least one disadvantage exists. Typical disadvantages are their relatively high costs and/or the presence of an excessive amount of impurities in the final product. Further, the known methods are invariably unsatisfactory because they have drawbacks of their own, such as;
i) Low yield and low selectivity,
ii) Use of hazardous reagents/solvents,
iii) Handling of gas in vapor-phase system,
iv) Elevated process temperatures,
v) Problems of disposal of waste,
vi) Environmentally non-friendly and
vii) No control on excess oxidation forming respective acid derivative.
[00016] Accordingly, there exists a need in the art for an improved process for the production of substituted or unsubstituted aryl aldehydes, which is simple, economic, highly efficient, environment friendly and industrially viable.
[00017] The present invention satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior art.
[00018] Furthermore, the present inventors have intensively studied based on above mentioned findings and tried to complete the present invention more closely to green chemistry.

OBJECTS OF THE INVENTION
[00019] An object of this disclosure, therefore, is to provide a method for the production of substituted or unsubstituted aryl aldehyde of high purity with high yield.
[00020] A further object of the present disclosure is to provide a process for preparing substituted or unsubstituted aryl aldehydes which involves effective degree of required oxidation resulting in competitive high yield of the said aldehydes with optimum purity at commercial scale.
[00021] Another object of this disclosure is to provide a method for the production of 4-methoxybenzaldehyde of high purity and high yield by the liquid-phase catalytic oxidation of 4-methoxy toluene.
[00022] Another object of the present disclosure is to provide a process for preparing substituted or unsubstituted aryl aldehydes which is simple, safe, cost effective, time saving, having convenient operational steps at commercial scale and environment friendly.
[00023] Yet, another object of the present disclosure is to provide a process for preparing substituted or unsubstituted aryl aldehydes in mild reaction condition without any adverse effect on yield, purity & stability of final compound.

SUMMARY OF THE INVENTION
[00024] In an aspect of the present disclosure, there is provided a process for preparation of substituted or unsubstituted aryl aldehydes, represented by Formula (I), the process can include oxidation of substituted or unsubstituted aryl alkanes or alkenes, represented by Formula (II), in a medium comprising at least one oxidizing agent, a solvent system, and optionally in the presence of a mineral acid.
[00025] In another aspect of the present disclosure, substituted or unsubstituted aryl aldehydes can be produced by oxidizing substituted or unsubstituted aryl alkanes or alkenes with manganese dioxide in a solvent system.
[00026] In yet another aspect of the present disclosure, the solvent system can be a biphasic solvent system that can include water as the first solvent and a water-immiscible substance as the second solvent. In an aspect, the water-immiscible solvent can be a halogenated or aromatic hydrocarbon. Examples of water-immiscible solvent can include, but not limited to 1,2-dichloroethane, chloroform, chlorobenzene, trichloro ethylene, carbon tetrachloride, methylene chloride, tetrachloro ethylene, 1,1,1-trichloroethane, n-propylbromide, toluene, xylene, and mixture thereof.
[00027] In another aspect of the present disclosure, substituted or unsubstituted aryl alkanes or alkenes can be oxidized with an oxidizing agent in a biphasic solvent system in presence of a mineral acid such as sulfuric acid.

DETAILED DESCRIPTION OF THE INVENTION
[00028] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[00029] The present disclosure relates to a process for the preparation of substituted or unsubstituted aryl aldehydes, represented by Formula (I). The process can include the steps of oxidation of substituted or unsubstituted aryl alkanes or alkenes, represented by Formula (II) in a medium comprising at least one oxidizing agent, a solvent system, and optionally in the presence of mineral acid (Scheme-1).

[00030] In an embodiment, R can be branched or linear alkyl or alkene group having C1-C4 carbon atoms; R' can be independently a hydrogen, halogen, nitro or alkoxy group having C1-C3 carbon atoms, and X can be O or S.
[00031] In an embodiment of the present disclosure, substituted or unsubstituted aryl aldehydes of Formula (I) can be produced by oxidizing substituted or unsubstituted aryl alkanes or alkenes of Formula (II) with manganese dioxide as an oxidizing agent in a solvent system.
[00032] In a preferred embodiment, substituted or unsubstituted aryl alkanes or alkenes of Formula (II) can be oxidized in the presence of an oxidizing agent in a solvent system in presence of a mineral acid such as sulfuric acid to produce substituted or unsubstituted aryl aldehydes of Formula (I).
[00033] In an embodiment of the present disclosure, the solvent system can be a biphasic solvent system that can include water as the first solvent and a water-immiscible second solvent.
[00034] In an embodiment of the present disclosure, the water-immiscible solvent can be a halogenated or an aromatic hydrocarbon. Examples can include, but are not limited to 1,2-dichloroethane, chloroform, chlorobenzene, trichloro ethylene, carbon tetrachloride, methylene chloride, tetrachloro ethylene, 1,1,1-trichloroethane, n-propylbromide, toluene, xylene and mixture thereof.
[00035] In a preferred embodiment of the present disclosure, the water-immiscible solvent is toluene or 1,2-dichloroethane.
[00036] In a more preferred embodiment of the present disclosure, the water -immiscible solvent is 1,2-dichloroethane.
[00037] In a preferred embodiment, R' is independently a hydrogen, X is oxygen and R is methyl group.
[00038] In a preferred embodiment, compound of Formula (I) is 4-methoxy benzaldehyde and compound of Formula (II) is 4-methoxytoluene.
[00039] In a specific embodiment of the present disclosure, the process can be used to produce 4-methoxybenzaldehyde by liquid-phase catalytic oxidation of 4-methoxytoluene, which enables 4-methoxybenzaldehyde to be produced with high purity, high yield and having less amount of impurities.
[00040] For the purposes of implementing a cost effective and industrially efficient process for the synthesis of substituted or unsubstituted aryl aldehydes of Formula (I) with good yield and high purity of the final product, particular attention is to be given to the starting materials, solvents and reagents as well as to the reaction conditions of the steps of the synthesis.
[00041] In an embodiment of the present disclosure, there is provided a process for the synthesis of compound of formula (I), wherein the process can include the steps of:
(a) contacting an oxidizing agent, a first solvent, compound of formula (II), and a second solvent in a reaction vessel to obtain a reaction mixture, wherein said contacting is carried out at temperature range of 20-35°C and each contacting step is for varying periods of time;
(b) contacting the reaction mixture of step (a) with sulphuric acid at elevated temperature;
(c) stirring the reaction mixture of step (b) and monitoring the reaction for depletion of compound of formula (II);
(d) adjusting the temperature of the reaction mixture to a range of 25-30°C;
(e) separating the layers and extracting the aqueous layer at least once with at least one second solvent;
(f) pooling the organic layers to obtain a mother liquor;
(g) washing the mother liquor with water and with a caustic solution; and
(h) concentrating the washed mother liquor to obtain a compound of formula (I) by fractional distillation.
[00042] In an embodiment of the present disclosure, in step (b) of said process, the elevated temperature is in the range of 70-80°C.
[00043] In an embodiment of the present disclosure, step (c) of the said process can be optionally carried out at a temperature in the range of 75-85°C to speed up the reaction.
[00044] In an embodiment of the present disclosure, in step (a) of the said process, oxidizing agent, first solvent, compound of formula (II), and a second solvent are contacted individually in a sequential manner or contacted in varying combinations sequentially.
[00045] In an embodiment of the present disclosure, the oxidation agent used in step (a) can be either in solid powder form or as an aqueous solution.
[00046] In a preferred embodiment, the oxidizing agent used in step (a) is manganese dioxide.
[00047] In an embodiment of the present disclosure, the first solvent used in step (a) is water.
[00048] In one embodiment of the present disclosure, the second solvent used in step (e) can be a halogenated or aromatic hydrocarbon, including, but not limited to 1,2-dichloroethane, chloroform, chlorobenzene, trichloro ethylene, carbon tetrachloride, methylene chloride, tetrachloro ethylene, 1,1,1-trichloroethane, n-propylbromide, toluene, xylene and mixtures thereof, more preferably 1,2-dichloroethane.
[00049] In another embodiment of the present disclosure, the weight ratio of the second solvent to the compound of formula (II) in step (a) can be in the range from 2:1 to 4:1 preferably 3:1.
[00050] In yet another embodiment of the present disclosure, the oxidizing agent to compound of formula (II) molar ratio in reaction mixture is in the range of 2.2:1 to 2.5:1, preferably 2.3:1.
[00051] In another embodiment of the present disclosure, the oxidation of compound of formula (II), i.e. step (a) to step (c) can be carried out in a biphasic solvent system that comprises water as the first solvent and a halogenated or aromatic hydrocarbon as the second solvent.
[00052] In another embodiment of the present disclosure, the sequence of contacting of compound of formula (II), solvent, and oxidation agent as mentioned herein can be interchanged according to the suitability of the reaction conditions.
[00053] In another preferred embodiment, after completion of the reaction, unreacted starting compound of formula (II) is isolated and recycled.
[00054] In an embodiment of the present disclosure, yield of compound of formula (I) is in the range of 84-93%, preferably >90%, with respect to the starting amount of the compound of formula (II).
[00055] In an embodiment of the present disclosure, purity of compound of formula (I) is at least 98% preferably >99%. Purity can be determined by GC for example, or other methods known in the art.
[00056] Additional embodiments and advantages to the present invention will be readily apparent to one of skill in the art, based on the disclosure provided herein.
[00057] Generally, the process is carried out in the presence of a solvent in which the substituted or unsubstituted aryl aldehydes are at least partially soluble. Thus, in the case of 4-methoxytoluene, water and 1,2-dichloroethane may for example be used.
[00058] It will be appreciated that the process of the invention may be used to prepare hitherto undescribed substituted or unsubstituted aryl aldehyde analogues accordingly form a further aspect of this invention.
[00059] The invention will now be described by reference to the following non-limiting Examples in which all parts, ratios and percentages are by weight unless otherwise stated.

EXAMPLES
[00060] The present invention is further explained in the form of following examples. However it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

Example 1
[00061] In a round bottom flask (RBF), MnO2 (258.65g) and water (600g) was added and stirred at 25-30°C for 10-15min. 4-methoxytoluene (122.16g) and 1,2-dichloroethane (245g) was added and stirred for 15 min at the same temperature. The temperature of the reaction mixture was raised to 70-75°C and H2SO4 (80%, 471.60g) was added slowly over a time period of 4 hours while maintaining the temperature. Post addition of H2SO4, the temperature of the reaction mixture was raised to 80-85°C and stirred for 2 hrs. the reaction progress was monitored on gas chromatography (GC) (unreacted 4-methoxytoluene 30-35%). The reaction mass was cooled to 25-30oC and the layers were separated. The aqueous layer was extracted with 1,2-dichloroethane (122gm). The organic layers were combined and washed with water (122gm). The organic layer was washed with 5% caustic solution (122g). The organic layer was concentrated and fractionated to obtain the required product [Formula (II)] under vacuum to afford 100g, 4-methoxy benzaldehyde (GC purity 99.15%w/w; yield 90.21%). Recovered 4-methoxytoluene was 22.7g, which can be recycled in subsequent batches.

Example 2
[00062] In a RBF, MnO2 (221.67g), water (600g), and 1,2-dichloroethane (200g) were added and stirred at 25-30°C for 10-15min. The temperature of the reaction mixture was raised to 70-75°C, followed by simultaneous addition of a solution of 4-methoxytoluene (122.16g) with 1,2-dichloroethane (100g) and H2SO4 (98%, 446.88g) slowly over 5 hours. The temperature was maintained at 75°C temperature for 3 hours. The reaction progress was monitored on GC (unreacted 4-methoxytoluene 2-5%). The reaction mass was cooled to 25-30oC and layers were separated. The aqueous layer as extracted with 1,2-dichloroethane (100gm). The organic layers were combined and washed with water (200gm). The organic layer was washed with 5% NaOH solution (200g). The organic layer was concentrated and fractionated to obtain the require product under vacuum to afford 121.90g of 4-methoxy benzaldehyde (GC purity 99.44% w/w; yield 90.53%) based on consumed 4-methoxytoluene. Recovered unreacted 4-methoxytoluene was 1.34g, which can be recycled in subsequent batches.

Example 3
[00063] In a RBF, MnO2 (201.99g), water (600g), and 1,2-dichloroethane (245g) was contacted with each other and stirred at 25-30°C for 15 min. The temperature of the reaction mixture was raised to 70-75°C, and a solution of 4-methoxytoluene (122.16g) with 1,2-dichloroethane (55g) and H2SO4 (98%, 412.50g) was added simultaneously to the reaction mixture slowly in 5 hours. After addition, the temperature of the reaction mixture was maintained at 75°C temperature for 3 hours. Reaction progress was monitored on GC (unreacted 4-methoxytoluene 5-10%). The reaction mass was cooled to 25-30°C and layers are separated. The aqueous layer was extracted with 1,2-dichloroethane (100gm). The organic layers were combined and wash with water (200gm), and washed with 5% NaOH solution (200g). The organic layers were concentrated and fractionated to obtain the require product under vacuum to afford 119.92g of 4-methoxy benzaldehyde (GC purity 99.30%w/w; yield 92.13%) based on consumed 4-methoxytoluene. Recovered unreacted 4-methoxytoluene was 5.38g, which can be recycled in next batches.

Example 4
[00064] In a RBF, water (1500g), MnO2 (478.45) was contacted and stirred at 25-30oC for 15 min. 4-methoxytoluene (305.40g) and toluene (612.5g) was added to the reaction mixture and stirred for 15 min at the same temperature. The temperature of the reaction mixture was raised to 75-80°C and H2SO4 (98%, 943.20g) was added slowly drop-wise in 4 hours. After addition, the reaction mixture temperature was maintained at 80-85°C for 3 hours. Reaction progress was monitored on GC (unreacted 4-methoxytoluene 12-15%). The reaction mass was cooled to 25-30oC and the layers were separated. The aqueous layer was extracted with toluene (305g). The organic layers were combined and washed with water (305gm). Subsequently, the organic layer was washed with 5% NaOH solution (305g). The organic layer was concentrated under vacuum to afford about 252.46g of 4-methoxy benzaldehyde (GC purity 99.56%w/w; yield 84.29%) based on consumed 4-methoxytoluene. Recovered unreacted 4-methoxytoluene was 36.68g, which can be recycled in next batches.
[00065] The numerical values of various parameters given in the specification are at approximations and slightly higher or slightly lower values of these parameters fall within the ambit and the scope of the invention.
[00066] While considerable emphasis has been placed herein on the specific steps of the preferred process, it will be highly appreciated that many steps can be made and that many changes can be made in the preferred steps without departing from the principles of the invention. These and other changes in the preferred steps of the invention will be apparent to those skilled in the art from the disclosures herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.
[00067] The applicant has developed an improved process for the synthesis of substituted or unsubstituted aryl aldehydes by oxidation of substituted or unsubstituted aryl alkanes or alkenes using environment friendly and economic reaction conditions, but taking in consideration the industrial need to operate in mild conditions and with easy available and easy to handle reagents. The synthesis processes of the present disclosure has been found surprisingly to be more favorable either for purity and yield of the final product, while costing advantageous and easily available starting products and reagents are used.
,CLAIMS:1. A process for the preparation of a compound of formula (I) from a compound of formula (II),

wherein R is a branched or linear alkyl or alkene group having C1-C4 carbon atoms; R' is independently a hydrogen, halogen, nitro or alkoxy group having C1-C3 carbon atoms, and X is O or S and which comprises the steps:
a. contacting an oxidizing agent, a first solvent, compound of formula (II), and a second solvent in a reaction vessel to obtain a reaction mixture, wherein said contacting is carried out at temperature range of 20-35°C and each contacting step is for varying periods of time;
b. contacting the reaction mixture of step (a) with sulphuric acid at elevated temperature;
c. stirring the reaction mixture of step (b) and monitoring the reaction for depletion of compound of formula (II);
d. adjusting the temperature of the reaction mixture to a range of 25-30°C;
e. separating the layers and extracting the aqueous layer at least once with at least one second solvent;
f. pooling the organic layers to obtain a mother liquor;
g. washing the mother liquor with water and with a caustic solution; and
h. concentrating the washed mother liquor to obtain a compound of formula (I) by fractional distillation.
2. The process according to claim 1, wherein in step (b), elevated temperature is in the range of 70-80°C.

3. The process according to claim 1, wherein in step (c), the reaction mixture temperature is optionally in the range of 75-85°C.

4. The process according to claim 1, wherein in step (a), said oxidizing agent, a first solvent, compound of formula (II), and a second solvent are contacted individually in a sequential manner or contacted in varying combinations sequentially.

5. The process according to claim 1 to 4, wherein said oxidizing agent is manganese dioxide.

6. The process according to claim 1 to 5, wherein said oxidizing agent to compound of formula (II) molar ratio in reaction mixture is in the range of 2.2:1 to 2.5:1.

7. The process according to claim 6, wherein said oxidizing agent to compound of formula (II) molar ratio in reaction mixture is 2.3:1.

8. The process according to claim 1 to 7, wherein the process is carried out in a biphasic solvent system, wherein the first solvent is water, and the second solvent is selected from the group consisting of halogenated hydrocarbons, aromatic hydrocarbons, and combinations thereof.

9. The process according to claim 8, wherein said second solvent is selected from the group consisting of 1,2-dichloroethane, chloroform, chlorobenzene, trichloro ethylene, carbon tetrachloride, methylene chloride, tetrachloro ethylene, 1,1,1-trichloroethane, n-propylbromide, toluene, xylene, and mixtures thereof.

10. The process according to claim 1 to 9, wherein the second solvent to the compound of formula (II) weight ratio in step (a) is in the range of 2:1 to 4:1.

11. The process according to claim 10, wherein the second solvent to the compound of formula (II) weight ratio is 3:1.

12. The process according to claim 1, wherein starting compound of formula (II) is optionally isolated from organic layer obtained from step (h) by fractional distillation, and optionally recycled.

13. The process according to claim 1 to 12, wherein compound of formula (I) yield with respect to compound of formula (II) is in the range of 84% to 93% and compound of formula (I) purity is at least 98%.