MXPA99004473A - Process for the preparation of benzyl-ethers - Google Patents

Abstract

The subject of the invention is the process for the preparation of mixed ethers of general formula (I), wherein Ar represents an alicyclic, aromatic or one or more heteroatom-containing heterocyclic moiety, optionally substituted by one or more C 1-4 alkoxy, methylenedioxy, C 1-4 alkyl, halogen, C 1-4 haloalkyl or nitro-group, and/or condensed with a benzine ring, R 1 and R 2 independently mean hydrogen C 1-4 alkyl, C 1-4 haloalkyl, C 2-4 alkenyl, phenyl, substituted phenyl, C 3-6 cycloalkyl group, R 3 means C 1-6 alkyl, C 3-6 alkenyl, or C 3-6 alkynyl group, optionally substituted by one or more C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, C 1-6 haloalkyl group, or halogen atom;or a C 1-4 alkyloxy-C 1-4 alkyloxy-C 1-4 alkyl group characterized by, that the compounds of general formula (II), wherein X means hydroxy, halogen or sulphonester leaving group, are reacted in the presence of acid, Lewis acid, metal oxide or metal carbonate, with 1-3 molar equivalent of the alcohol of general formula (III), wherein the meaning of the substituent is as defined above, the resulting ether of general formula (I) is isolated, if desired, stabilized by the addition of a base and/or an anti-oxidant, and if desired the excess of the alcohol is recovered.

Description

PROCESS FOR THE PREPARATION OF BENCIESTERS DESCRIPTION OF THE INVENTION The invention relates to the process for the preparation of mixed ethers of the general formula 1, wherein Ar represents an alicyclic, aromatic, or one or more heteroatom portion, which is optionally substituted with one or more groups of C 1 -4 alkoxy, methylenedioxy, C 1 -halogen alkyl, haloalkyl C? -, 0 nitro, and / or is condensed with a benzene ring, R1 and R2 independently represent hydrogen, C? - alkyl, C? _ Haloalkyl, C4 alkenyl, phenyl, substituted phenyl or C3-6 cycloalkyl, R3 represents the C3-6 alkynyl group, optionally substituted with one or more C6-6 alkyl, C3-6 alkenyl, C3-6 alkynyl groups; haloalkyl C6-6 or a halogen atom; or a group of alkyl (C? -4) oxy-alky1 (C? -4) oxy to which (C? -4), under acidic conditions, by the reaction of the compounds of the general formula II, in where X represents hydroxy, halogen or a leaving group of sulphonic ester, with compounds of general formula III, wherein R 3 has the same meaning as indicated above. In the term Ar the aromatic group is preferably a phenyl or naphthyl group, Ar as a hemocyclic moiety may contain one or more heteroatoms of 0, S, N, and may preferentially represent a benzodioxol-, benz-hatexano-, portions. 2 -benzo fur ano-, 7 -benzo fur ano -. The alicyclic group may be preferably condensed with a benzene ring, this may represent a group of indane or 1, 2, 3, 4-t e rahydronaphthyl. The carboximide group may preferably represent a portion of f t to the imide. The aromatic, heterocyclic, and alicyclic Ar groups may be substituted with a group of C 4 -4 alkoxy, methylenedioxy, C 1 - alkyl, halogen, C 4 -4 haloalkyl, or nitro. The ethers of the general formula I are potential starting materials or active ingredients of a variety of chemicals. Several representatives of these compounds are synergistic ar t ropodi cides with outstanding activity (Hungarian patent application No. 3318/95). Except for the synergistic compound of methylenedioxy (MDP) having a saturated side chain (such as PBO, ie 5- [2- (2-butoxyethoxy) ethoxy ethyl] -6-propyl-l, 3-benzodioxole), which is known, the compounds are new, despite their simple structures. Its preparation and moderately expensive synthesis are of great interest due to the significant importance of these ingredients. The ethers mentioned above can be prepared according to known general methods of the synthesis of ethers (Gy Matolcsy, M. Nadasdy, V. Andris a, "Pesticide Chemistry", Akadémia (1988), Hungarian patent applications No. 3318/95 ). These methods consist essentially of reacting the alkaline salt of the alcohol component with the partner, following the rules of the nucleic acid substitution. The partner contains a leaving group which is usually halogen, preferably a bromine atom. The reaction can be carried out in two ways, depending on which part of the molecule is the physical core partner. Due to the high reactivity of the benzyl halides, in practice the alkoxide of the side chain is usually reacted with benzyl bromide. However, this method has limitations when, for some reason in particular, the alkoxide is difficult to prepare. In these cases, the reverse method is used, from which poorer reactions are usually obtained. This type of ether preparation is known in organic chemistry as the classical Williamson synthesis (B.P Mundy, M.G. Ellerd, "Yam Reactions and Reagents in Oxganic Synthesis", Wiley (1988)). However, the reaction has some disadvantages. The formation of alkoxide is expensive for the industry, since it requires expensive reagents and refined technology with guaranteed anhydrous conditions or with a drying step (Hungarian patent applications No. 180500 and 190842). For the preparation of the halide or the partner containing the leaving group, a separate step is required and the use of reagents which are also expensive. When the alpha carbon atom contains additional substituents (R1 and / or R2 is / are different from hydrogen) the preparation of the activated derivative is difficult., for example halogenated, because the product is prone to undergo an elimination reaction or secondary reactions such as, for example, electrophilic aromatic substitution. The performance of the coupling reaction depends markedly on the reactivity of the partner and the resulting product must be purified further. Other methods for preparing ethers in general are also known. The oldest and best known of these methods is the dimerization of alcohols catalyzed by acids (Ho Weyl, 6/3, pages 11 to 19). As described in the literature, the reaction is usually carried out at high temperatures and continuously stirring the product of the reaction mixture to avoid decomposition. The oxonium cation that is formed due to the action of the acid can easily participate in transposition reactions or can be stabilized by the elimination in β of the hydrogen atom of the neighboring carbon atom, thus obtaining the appropriate olefin. This causes the formation of a considerable amount of decomposition products, to which is added the fact that the water formed during the reaction slows down the process. Consequently, it can be said that the performance of the reaction (yield, purity) is low. Therefore, it is understandable that this method can not be taken into account when planning a synthesis. Rather, it is considered a secondary reaction of the acid catalyzed process (Chem. Pharm. Bull., 31, page 3024, (1983)). In order to eliminate the disadvantages in the case of the dibenzyl ethers, the dimerization method induced by me t i 1 sui phoxide was carried out (J. Org. Chem., 42, page 2012, (1977)). However, this method can not be used on an industrial scale due to the reagents and high temperatures (175 ° C) used. The discovery that, in addition to the fact that ether formation can be catalyzed by Lewis acids, the reaction with zinc (II) chloride in dichloroethane can be carried out under relatively mild conditions (J. Org. Chem., 52, page 3917, (1987)). However, the method was satisfactory only for dimerization and intramolecular cyclization reactions. For mixed ethers, the reaction quality as well as the quality and yield of the product are low. When alcohol (p-me t-oxybenzyl-1-benzyl) is used, which contains an aromatic substituent, low yields are obtained due to polymerization; again the mixed ether of unsaturated chain (a-methylbenzyl-allyl ether) can only be obtained - contrary to its saturated analogue - with low yields due to dimerization. In a published version of the reaction, the benzyl halide was reacted with the nucleophilic reagent in the presence of zinc oxide (Te tr ahedron, 38, page 1843, (1982)), but the applicability of this reaction is unknown. the compounds of the general formula I. The formation of the ether catalyzed by acids is carried out through an appropriate cationic intermediate. The stability of the substituted 1-phenylethyl carbocations in the ring and their reaction with nucleophilic reagents in a model system of trifluoroethanol / water = 1/1 (J. Am; Chem. Soc., 106, page 1361, (1984); 106, page 1373 (1984)). However, in both references there are no examples on the preparation of compounds of general formula I, nor is there any mention of their synthesis, in particular, on the reaction medium. (polarity, solvation) which - As indicated in the two mentioned references - has a very important role in the reaction, since small modifications can alter the balance so sensitive. The authors of both references cited above have published in later theoretical works that the ethers of the type similar to those of the general formula I are surprisingly sensitive to acids, while other ethers are not. The formation of the ether -transcurs by means of a reversible reaction, which increases the possibility of secondary product formation, damaging the purity and the yield of the product. As reported in the published literature, a 1 cox i to coho 1 is such as ethylene glycol monomethyl ether have a low reactivity, while unsaturated alcohols such as propargyl alcohol have a medium reactivity and much lower than that of simple alcohols and saturated such as methanol, ethanol and butanol, which react immediately. Substituents of the aromatic ring that are electron acceptors increase the equilibrium constant of ether formation, while the electron donor substituents decrease it. The increase in the water / tri-fluoroethanol ratio produces an unfavorable effect on the direct formation of the ether. The production of ethers is an extremely difficult task for the industry, not only because of expensive reagents and possible side reactions, but also because both the starting alcohols and the resulting ethers easily form peroxides and are potential explosives. In addition, the alkynyl compounds are very sensitive to heat due to the triple bond. A large-scale production without risks (1000 t / year) is possible only if the reaction can be carried out under mild conditions and if the final product, which is usually a liquid, does not require "_cLe- - a purification or subsequent distillation . - In view of the above we have investigated in detail the possibilities of preparing asymmetric ethers of the general formula I. The method that we have developed based on our experimental results is essentially based on the mixed ethers of the general formula I, where the meaning of the substituents is the same as that described above, can conveniently be prepared by reaction of compounds of the general formula II, wherein X represents hydroxy, halogen or a leaving group of sulfonyester, with 1 to 3 molar equivalents of an alcohol of the general formula III, wherein the substituents have the meaning indicated above, in the presence of an acid, a Lewis acid, a metal oxide or a metal carbonate. The resulting ether of the general formula I is isolated, the excess alcohol is recovered and, if desired, the product is stabilized by the addition of a base and / or an antioxidant. In the general formulas I, II and III the residues Ar, R1, R2 and R3 have the same meanings as those indicated above. As the acid, it is preferred to use 0.01 to 3 molar equivalents of a strong mineral acid or a strong organic acid, preferably of hydrochloric acid, sulfuric acid, perchlohyric acid or of an aromatic sulfonic acid. The reaction is carried out in the salt solution, preferably in the solution of sodium chloride, calcium chloride, magnesium chloride, zinc chloride, preferably in a 10% w / w aqueous solution of the acid, preferably saturated with the inorganic salt, and at a temperature of (-20) to (+ 30 ° C). As the Lewis acid, it is preferred to use 0.01 to 3 molar equivalents of zinc (II) chloride or an aromatic sulfonic acid, preferably benzenesulfonic acid or para-t or sui-fonic acid. The reaction is carried out in a non-polar aprotic solvent and at a temperature comprised between -30 and + 40 ° C. As the metal oxide, it is preferred to use 0.01 to 3 molar equivalents of zinc oxide, while zinc carbonate is preferred as the metal carbonate and the reaction is carried out in the absence of solvent or in the presence of a non-polar aprotic solvent. Among the organic solvents, halogenated solvents are preferred, dichloroethane being the best. In this case, a Lewis acid can also be used. As indicated in the literature, zinc (II) chloride has not given good results for the preparation of structures similar to those of the compounds of general formula I, since low yields and contaminated products were obtained (J. Org. Chem. , 52, page 3917, (1987)), however, in the optimized system of the invention a good yield and a product with an appropriate purity were obtained. In the same way, the reaction was also optimal when using zinc oxide. In this case, the zinc halide side products did not cause any polymerization. Neither conditions nor anhydrous solvents are needed for the reaction. The water that forms during the reaction does not prevent the completion of the reaction because it binds to the catalyst. The resulting emulsion or suspension can be separated simply by precipitation or filtration and be reused after its treatment. The use of water as a solvent is usually very convenient in the industry. This statement is surprising not only because it was not taken into practice previously but also because the formation of the ethers - an equilibrium reaction - was considered to be repressed in an aqueous medium (J. Am. Chem., 107, page 1340 (J. 1985)). Contrary to that described in the literature, the method could be used satisfactorily even for the preparation of benzyl alkynyl ethers with electron donor substituents (hydroxy, methoxy, ethoxy, methylenedioxy group). Benzyl ethers containing phenolic hydroxyl groups can also be synthesized directly and selectively despite containing more than one nucleophilic center. It is convenient to increase the polarity of the medium. Consequently, it is convenient to use auxiliary materials, preferably several salts. If the appropriate parameters are selected, the reaction can be directed towards the formation of the product. It suffices to use a catalytic amount of acid of 1 to 2 mol%. The reaction is rapid even at low temperatures and thus unwanted side reactions can be avoided. The alcohol is preferably used in excess, which makes it possible to significantly shorten the reaction time. The product can be isolated from the reaction mixture simply by sedimentation and the electrolyte can be used again. The starting alcohol that is recovered from the process can also be used again. In this way the procedure is practically quantitative for both components. The raw product obtained in the reaction is of very good quality. Its purity reaches the values of 93 to 95%. Of course it can be further purified by distillation or, if possible, by crystallization, but it can also be used directly. To increase its stability and avoid its acid hydrolysis, it is advisable to wash the product until neutrality and bring it to the alkaline pH region with a buffer. To avoid any type of risk it is recommended to add antioxidants of various types.

As the antioxidant it is preferred to employ, for example, TMQ, BHT, hydroquinone, hydroquinone monomethyl ether, 2,2,6,6-tetramethyl-4-piperidinol N-oxide. The non-limiting examples listed below serve to demonstrate our procedure, without the intention that it be in a co-operative manner.

EXAMPLES 1.) 1- [1- (But-2-ynyloxy) ethyl] -3-hydroxy-4-methoxybenzene A.) 1.7 g (10.7 mmol) of l- (3-hydroxy-4-methyl-oxy-phenol-1) and anol are dissolved in 1.4 g of 2-butynol and to this solution are added 1.5 my solution 1% HCl-50% CaCl2 with stirring and at room temperature.

The mixture is stirred at this temperature overnight. The reaction is followed by TLC (thin layer chromatography, eluent: n-hexane-ethyl acetate 7: 3, Rf = 0.19). Diethyl ether is added to the reaction mixture until the oily organic phase is dissolved. The mixture is then neutralized with 1M NaOH, the two phases are separated, the aqueous phase is extracted twice with ether, the organic phases are combined and washed first with water and then with saturated sodium chloride solution, dried over MgSO4, they filter and evaporate. Yield: 2.08 g (941) of viscous and colorless oil. CG (CP 9000, CP-SIL-5CBm 60m x 0.53mm, 5ml / min N2FID, 250 ° C): tR = 4.44 min, > 93% IR (CHC13, cm1) v: 3601, 3541, 2972, 2924, 2857, 1728, 1615, 1596, 1507, 1457, 1443, 1372, 1308, 1288, 1271, 1235, 1164, 1132, 1110, 1084, 1043, 1030, 1004, 934, 877, 841, 808, 644, 611. XH-NMR (200 MHz, CDCl3) d: 1.44 (3H, d, J = 6.4 Hz, CH-CH3), 1.84 (3H, t, J = 2.2 Hz, = C-CH3), 3.81 and 4.01 (2H, ABX3, JAB = 15 0 Hz, JAX ^ JBX-2.34 Hz, C = CH20), 3.87 (3H, s, OCH3), 4.52 (2H, q , J = 6.4 Hz, Ar-CHO), 5.80 (1H, OH), 6.82 (2H, d, J = 1.12 Hz, 5, 6-CH aromatic), 6.91 (1H, t, CH aroma ti eos) . 13C-NMR (50MHZ, CDCl3) d: 3.56 (= C-CH3), 23.65 (CH-CH3), 55.84 (OCH3), 55.89 (= C-CH20), 75.35 (= C-CH2), 76.06 (Ar- CH3), 81.89 (= C-CH3), 110.47 (C-2), 112.66 (C-5), 118.08 (C-6), 135.93 (Cl), 145.65 (C-4), 146.08 (C-3) . B.) The procedure described in the previous example is carried out, but with the proviso that zinc chloride solution (II) is used instead of a calcium chloride solution. The resulting product is identical to the product obtained in the previous example. 2. 1- [1- (But-2-ynyloxy) ethyl] -3, -dimethoxybenzene / l- (3 ',' -dimethoxyphenyl) ethylbut-2-ynyl ether / A.) Preparation for the process: With stirring 125 g of the calcium chloride dihydrate are dissolved in 250 ml of water. Based on its density (d = 1.33 g / ml), this solution is approximately equivalent to a 35% w / w calcium chloride solution. If necessary, the solution is filtered. In a volumetric flask, 7.6 ml (9.0 g) of hydrochloric acid are diluted with the previous solution, bringing them to a volume of 250 ml.

Proces o: To a vigorously stirred mixture of 500.0 g of 1-coate alcohol and 192.3 g of 2-butyn-1-ol is added a mixture composed of 250 ml of the solution of calcium chloride - hydrochloric acid and 192.3 g of 2-butin-1-ol are rapidly added. The reaction is monitored by GC and TLC analysis. After 6 hours the approximate amount of product is 92-93%, as demonstrated by the CG, while the quantity of the starting materials is less than 2%. Then, while stirring, the reaction mixture is diluted with 500 ml of ether and neutralized with 1M sodium hydroxide solution. The aqueous phase is then separated and extracted with 2 × 100 ml of ether. The combined organic phase is washed with saturated sodium chloride solution (it must be checked that the pH of the aqueous phase is neutral) and dried. The solution is evaporated at atmospheric pressure. Excess butinol is removed by vacuum distillation. The 182 g of recovered butinol can be reused once its purity has been evaluated (CG, refractive index). Product: 650 g of colorless oil. Purity: 93% by direct integration, with an internal octacosan 95% standard, yield: 94%, nD20 1.5280. IR (CHC13 cm_1) v: 2976, 2855, 2837, 1605, 1595, 1514, 1465, 1419, 1371, 1353, 1311, 1260, 1164, 1141, 1086, 1027, 864 ^ -RM (200MHz, CDC13) d: 1.46 (3H, d, J = 6.5 Hz, CH- CH3), 1.85 (3H, t, J = 2.3 Hz, = C-CH3), 3.83 and 4.01 (2H, HZ, sC-CH2-0), 3.87 and 3.89 (6H in total, each s, 0-CH3), 4.55 (2H, q, J = 6.5 Hz, Ar-CH-0), 6.80-6.89 (3H, m, aromatics). 13 C-NMR (50 MHz, CDCl 3) d: 3.61 (= C-CH 3), 23.76 (CH-CH 3), 55.87 (O-CH 3) 55.96 (= C-CH 2-0), 75.36 (= C-CH 2), 76.40 (Ar-CH-O), 81.91 (= C-CH3), 109.06 (C-2), 110.86 (C-5), 118.94 (C-6), 135.30 (Cl), 148.52 (C-3) ), 149.19 (C-4). B.) In a ball provided with a magnetic stirrer, condenser and a drying tube filled with calcium chloride, the alcohol is introduced into the lectern (8.72 g, 0.0478 mol) and the 2-butin-l-ol (4.36 g). , 0.0623 mol), which are then dissolved in 100 ml of chlorine and water. The zinc (II) chloride (1.97 g, 0.0145 mol) is added to the mixture with stirring at room temperature. The reaction is accompanied by a characteristic color change. After two hours of reaction, the formed aqueous phase is separated, the organic phase is washed with 3x30 ml of saturated sodium chloride solution, dried and evaporated. With the help of a vacuum pump, the crude product (12.1 g) is distilled in vacuo. Yield: 9.2 g (0.0393 mol, 82.2%). CG (with internal standard) 98.2%. The material is identical to the compound obtained with the above method. 3 1- [1- (But-3-ynyloxy) ethyl] -3,4-dimethoxybenzene 3.0 g (0.0164 mol) of alcohol a-me ti 1 see atri 1 and 2.3 g are introduced into a ball fitted with an agitator. (0.0329 mol) of 3-butin-1-ol, and 1.5 ml of the 50% w / v solution of calcium chloride - 1% w / w hydrochloric acid are rapidly added to the mixture. The mixture is stirred at room temperature overnight. It is then diluted with ether and neutralized with a few drops of 1M sodium hydroxide solution. Both phases are separated and the aqueous phase is exhaustively extracted with ether. The combined organic phase is washed with saturated sodium chloride solution, dried and evaporated. Yield: 3.5 g (93%). 92% purity. IR (CHC13, cm "1) v: 3307.3027, 2958, 2933, 2869, 2838, 2120, 1607, 1595, 1509, 1465, 1443, 1259, 1163, 1142, 1098, 1027, 861. 1 H-NMR ( 200 MHz, CDCl3) d: 1.45 (3H, d J = 6.5 Hz, CH- CH3), 1.96 (1H, t, J = 2.7 Hz, = CH), 2.44 (2H, td, J = 7, 2.7 Hz, CH2 C =), 3.43 (2H, t, = 7 Hz), 3.87 and 3.89 (6H in total, each s, O-CH3), 4.38 (2H, q, J = 6.5 Hz, Ar- CHO,) 6.83 (2H, d, aromatics), 6.90 (1H, s, aromatic). 13 C-NMR (50 MHz, CDCl 3) d: 19.95 (OCH 2 -CH 2), 24.0 (CH-CH 3), 55.77 and 55.82 (OCH 3), 66.33 (OCH2-CH2), 69.09 (= CH), 77.87 (Ar-CH-CH3), 81.43 OC-CHz), 108.87 (C-2), 110.81 (C-5), 118.49 (C-6), 136.12 Cl), 148.34 (C-3), 149.12 (C-4). 1- . { 1- [(Z) -3-chloro-but-2-onyloxy] ethyl} -3,4-Dimethoxybenzene 4.27 g (0.02345 mole) of alcohol are added to a trimetabolic alcohol and 5.0 g (0.0469 mole) of 2-chlorobut-2-en- l-ol (consisting mainly of the geometric Z isomer), and 5.0 ml of the 50% w / v solution of calcium chloride - l% w / w hydrochloric acid is added to the mixture rapidly. The mixture is stirred at room temperature overnight. It is then diluted with ether and neutralized with a few drops of 1M sodium hydroxide solution. Both phases are separated and the aqueous phase is exhaustively extracted with ether. The combined organic phases are washed with saturated sodium chloride solution, dried and evaporated. 5.7 g of a colorless oil are obtained. Performance: 90%. Purity (CG): approximately 88.5%. CG (CP 9000, CP-SIL-5CB 60 mx 0.53 mm, 5ml / min N2, FID, 250 ° C): IR (CHC13, cm "') v: 2973, 2931, 2862, 2839, 1659, 1606, 1595 , 1511, 1465, 1443, 1261, 1164, 1141, 1093, 1028 1 H-NMR (200 MHz, CDCl 3) d: 1.43 (3 H, d J = 6.5 Hz, CH-CH 3), 1.97 (3 H, t, J = 0.5 Hz, = CC-1-CH3), 3.80 (2H, m, OCH2), 3.87 and 3.89 (6H in total, each s, OCH3), 4.38 (2H, q, J = 6.5 Hz, Ar- CHO, 5.78 (1H, m, CH = CC1), 6.83 (2H, d, Ar), 6.87 (1H, d, Ar). 13C-NMR (50MHz, CDCl3) d: 21.23 (= CC1-CH3), 24.08 (CH - CH3), 55.84 (OCH3), 64.10 (OCH2), 77.05 (Ar-CHO), 108.92 (C-2), 110.91 (C-5), 118.74 (C-6), 124.43 (CH-CC1), 134.0 (CH = CC1), 135.89 (Cl), 148.49 and 149.23 (C-3 Y (C-4). . ) 1- [1- (But-2-ynyloxy) ethyl] -3-methoxy-4-hydroxybenzene. 4.0 g) 2.6 mmoles) of ethyl alcohol - (3-methyl-4-hydroxy-1-ethyl) in 4.0 g of 2-butinol are dissolved and 8.0 ml of the 50% calcium chloride solution are added to this solution. / v - 1% w / w hydrochloric acid with stirring and at room temperature overnight. The reaction is followed by TLC (thin layer chromatography, eluent: n-hexane-ethyl acetate 7: 3, Rf = 0.55). Ether is added to the reaction mixture until the oily organic phase is dissolved. The mixture is then neutralized with 1M NaOH solution, the two phases are separated, the aqueous phase is extracted twice with ether, the organic phases are combined, washed first with water and then with saturated sodium chloride solution, dried over MgSO4, filter and evaporate. Yield: 4.8 g (92.0%) of viscous oil.

CG (CP 9000 CP-SIL-5CB 60 m x 0.53 mia. 5ml / min N2 FID, 250 ° C) t, 4.3 min, > 93% IR (CHC13, cm "') v: 3668, 3540, 2973, 2923, 2858, 2424, 2376, 2233, 1729, 1610, 1512, 1465, 1453, 1433, 1372, 1344, 1320, 1268, 1235, 1186, 1162, 1128, 1111, 1082, 1036, 1005, 970, 913, 886, 859, 822, 698, 645, 598. ^ -RMN (200 MHz, CDCl3) d: 1.45 (3H, d, J = 6.5Hz , CH- CH3), 1.84 (3H, t, J = 2.2Hz = C-CH3), 3.82 and 4.01 (2H, ABX3, JAB = 15.0 Hz, JAX = JBX = 2.3Hz, = C-CH20), 3.88 ( 3H, s, OCH3), 4.53 (2H, q, J = 6.5 Hz, Ar-CHO), 6.76-6.89 (3H, m, flavorings) 13C-NMR (50 MHZ, CDCl3) d: 3.57 (= C -CH3), 23.76 (CH-CH3), 55.83 (OCH3), 55.89 (= C-CH20), 75.35 (= C-CH2), 76.40 (Ar-CH-CH3), 81.91 (= C-CH3), 108.39 (C-2), 114.03 (C-5), 119.73 (C-6), 134.60 (Cl), 145.15 (C-4), 146.75 (C-3). 3,4-Dimethoxy-1- [1- (pent-3-ynyloxy) ethyl] benzene 1.5 g (8.23 mmoles) of alcohol is added to a ball fitted with an agitator. g (16.46 mmoles) of 3-pentin-1-ol, and 3.0 ml of the 50% w / v solution of calcium chloride-1% w / w hydrochloric acid is added rapidly to the mixture. The mixture is stirred at room temperature overnight. It is then diluted with ether and neutralized with a few drops of 1M sodium hydroxide solution. Both phases are separated and the aqueous phase is exhaustively extracted with ether. The combined organic phases are washed with saturated sodium chloride solution, dried and evaporated. Yield: 1.9 g (93%). CG (CP 9000, CP-SIL-5CB, 60 x 0.53 mm, 5ml / min N2, FID, 250 ° C) tR = 5.0 min, appro priately 93.2%. IR (CHC13, cm-1) v: 2995, 2974, 2957, 2864, 2838, 1607, 1595, 1510, 1465, 1260, 1163, 1142, 1098, 1027.

'H-NMR (200 MHz, CDCl 3) d: 1.44 (3 H, dJ = 6.4 Hz, CH-CH 3), 1.75 (3 H, t, J = 2.5 Hz, CH 3 -C =), 2.37 (2 H, m, CH 2 - C =), 3.38 (2H, t, J = 7.2 Hz), 3.87 and 3.89 (6H in total, each s, OCH3), 4.38 (2H, q, J = 6.4Hz, Ar-CHO), 6.83 ( 2H, d, aromatics), 6.90 (1H, s, aromatic). at 3 C - NMR (5 0 MH z, C D C 1 3) d: 3. 4 2 (C H 3 - C =), 2 0. 2 7 OCH2- CH2), 24.07 (CH-CH3), 55.78 and 55.85 (OCH3), 67.04 (OCH2-CH2), 75.93 and 77.78 (Ar-CH-CH3, C = C two superimposed signals), 108.92 (C- 2), 110.83 (C-5), 118.52 (C-6), 136.34 (Cl), 148.33 (C-3), 149.13 (C-4). 7.) 1- [1- (3-butyn-2-yloxy) -ethyl] -3, -dimethobenzene In a ball provided with a stirrer ~ 3.0 g (0.0164 mol) of alcohol crne ti 1 is introduced see co and 3.46 g (0.0493 mol) of 3-butin-2-ol, and 1.5 ml of the 50% w / v solution of calcium chloride - l% w / w hydrochloric acid is added to the mixture rapidly. The mixture is stirred at room temperature overnight. It is then diluted with 10 ml of ether and neutralized with a few drops of 1M sodium hydroxide solution. Both phases are separated and the aqueous phase is exhaustively extracted with ether. The combined organic phases are washed with saturated sodium chloride solution, dried and evaporated. The residue is purified by column chromatography (eluent: hexane-ethyl acetate 4: 1, R £ = 0.41 and 0.36). The two t eryomeric days (treo-erythro) were partially separated: less polar (more abundant) isomer, 1.9 g, mixture 60-40 0.76 g, isomer ß plus polar 0.32 g. Ratio of both isomers, calculated on the basis of the isolated amounts: 3.7: 1 approx imadamente.

Yield: 2.98 g (0.0127 mol, 77.6%). CG (CP 9000, CP-SIL-5CB, 60 m x 0.53 mm, 5ml / min N2, FID, 250 ° C): isomer a: tR = 3.4 min, approximately 97. 27%, ß-isomer: tR = 3.58 min, approximately 94.26%.

Isomer oc IR (CHCl3, c? "') V: 3306, 2981, 2934, 2838, 1608, 1595, 1509, 1465, 1464, 1260, 1168, 1141, 1098, 1048, 963, 910, 860, 635.

XH-NMR (200MHz, CDCl3) d: 1.39 (3H, d, J = 6.6Hz, = CCH-CH3), 1.46 (3H, d, J = 6.5 Hz, Ar-CH CH3), 2.41 (1H, d, J = 2 Hz, = CH), 3.87 and 3.89 (6H in total, each s, OCH3), 3.89 (1H, qd, J = 2, 6.6 Hz, = CCH), 4.75 (2H, q, J = 6.5 Hz, Ar-CH-CH3), 6.80-6.89 (3H, m, ar omá ti co s). "C-NMR (50 MHz, CDCl 3) d: 22.19 (== CCH-CHj), 24.15 (Ar-CH-CH3), 55.82 (OCH3), 61.78 (= CCHO), 72.44 and 75.17 (= CH and Ar- CHO), 84.11 (= CCH), 109.06 (C-2), 110.89 (C-5), 118.94 (C-6), 135.50 (Cl), 148.49 (C-3), 149.14 (C-4).

Isomer ß IR (CHC1-3, cm "!) V: 3307, 2975, 2935, 2838, 1607, 1595, 1511, 1466, 1454, 1261, 1165, 1142, 1094, 1041, 961, 910, 862, 638. XH-NMR (200 MHz, CDCl3) d: 1.44 (6H, d, J = 6.5Hz, = CCH-CH3 and Ar-CH-CH3), 2.355 (1H, d, J = 2 Hz, = CH), 3.87 and 3.89 (6H in total, each s, OCH3), 4.23 (1H, qd, J = 2, 6.5 Hz, = CCH), 4.66 (2H, q, J = 6.5 Hz, Ar-CH-CH3), 6.79 - 6.96 (3H, m, aromatics). 13 C-NMR (50 MHz, CDC13) d: 21, 83 (= CCH-CH 3), 22.64 (Ar-CH CH 3), 55.79 and 55.86 (OCH 3), 62.53 (= C-CHO), 72.26 and 75.10 (= CH and ArCHO), 84.40 (sC-CH), 109.43 (C-2), 110.79 (C-5), 118.51 (C-6), 136.19 (C-1), 148.33 (C-3), 148.96 (C-4). 8.) 1- [1- (Prop-2-enyloxy) ethyl] -3,4-dimethoxybenzene (1- (3 ', 4'-dimethoxy-enyl) ethyl-allyl ether) In a balloon provided with a stirrer, 3.0 is introduced. g (0.0164 mol) of ethyl alcohol and 1.9 g of allyl alcohol, and 1.5 ml of the solution of 50% w / v of calcium chloride - l% w / w of hydrochloric acid are rapidly added to the mixture. The mixture is stirred at room temperature overnight. It is then diluted with ether and neutralized with a few drops of 1M sodium hydroxide solution. Both phases are separated and the aqueous phase is exhaustively extracted with ether. The combined organic phases are washed with saturated sodium chloride solution, dried and supported. Performance: 3.0 g (82.4"). CG (CP 9-000, CP-SIL-5CB, 60 x 0.53 mm, 5ml / min N2, FID, 250 ° C): tR = 3.4 minutes, approximately 90.3%. IR (CHC13, cm "1) v: 3079, 2996, 2973, 2933, 2860, 2838, 1607, 1595, 1510, 1465, 1443, 1419, 1311, 1260, 1164, 1141, 1089, 1027, 996, 928, 860. XH-NMR (200 MHz, CDCl3) d: 1.45 (3H, d, J = 6.4 H z, CH3), 3.83 AB mid (2H, ABdt, JAB = 12.7 Hz, J = 1.3, 6.0 Hz, OCH2CH =), 3.89 and 3.87 (6H in total, each s, CH30), 4.41 (2H, q, J = 6.4 Hz, CH- 0), 5.11-5.29 (2H, m), 5.81-6.0 (lH, m ), 6.83 (2H, s), 6.89 (1H, s) 13 C-NMR (50 MHZ, CDCl 3) d: 24.0 (CH-CH 3), 55.77 (OCH 3), 69.17 (OCH 2 =), 108.94 (C-2) , 110.82 (C-5), 116.58 (CH- = CH2), 118.58 (C-6), 135.0 (Cl), 136.26 (CH = CH2), 148.29 and 149.11 (C-3 'and C-4). .) 1- [1- (But-2-ynyloxy) ethyl] naphthalene / l- (1-naphthyl) ethyl but-2-ynyl ether / In a ball fitted with a magnetic stirrer, condenser and a chloride-filled drying tube of calcium is introduced cc-me ti 1 - 1 -naf ti 1-methanol (0.86 g, 5 mmoles) and 2-butin-l-ol (0.7 g, 10 mmoles), which are then dissolved in 15 ml of di chloroethane The zinc chloride (II) ( 0.68 g, 5 mmol) is added to the mixture with stirring at room temperature. The reaction is accompanied by a characteristic color change. After 24 hours of reaction, the organic phase is washed with 3 × 5 ml of saturated sodium chloride solution, dried and evaporated. The crude product (1.2 g) is purified by column chromatography. Yield: 0.8 g (3.57 mmol, 71%). CG 95%. IR (CHClj, cm "1) v: 3052, 2977, 2921, 2856, 1596, 1509, 1444, 1371, 1095, 1078. 1 H-NMR (200 MHz, CDCl 3) d: 1.67 (3H, d, J = 6.5 Hz, CH3- CH), 1.87 (3H, t, J = 2.3 Hz, = C-CH3), 2.96 and 4.15 (2H in total, ABX, JAB = 15.0Hz, JAX = JBX = 2.3Hz, OCH2-C = C), 5.40 (1H, q, J = 6.5 Hz, C? 0H7-CH- 0), 7.51 (3H, m) 7.61 (1H, d, J = 6.8 Hz), 7.79 (1H, d, J = 8.1 Hz), 7.89 (1H, dd, J = 7.9, 1.8 Hz), 8.22 (1H, d, J = 8.1 Hz) 13C-NMR (50MHZ, CDCl3) d: 3.64 (C = C-CH3), 22.96 ( CH3- CH), 56.37 (0-CH2-C = C), 74.29 (CH3-, CH), 75.36 and 82.14 (C = C), 123.26 (C-8), 123.52, 125.50, 125.85, 127.92, 128.83, 130.78 (C- a), 133 C-4a 138.42 Cl) 10 General procedure for the preparation of but-2-inyl benzyl ethers 10 mmoles of the benzyl alcohol indicated below and 1.2 g are introduced into a ball fitted with a stirrer ( 20 mmoles) of 2-but in 1-or 1, and 1.5 ml of the 50% w / v solution of calcium chloride-1% w / w hydrochloric acid is added to the mixture rapidly. stir at room temperature overnight, the reaction is monitored by TLC. The mixture is then diluted with ether and neutralized with a few drops of 1M sodium hydroxide solution. Both phases are separated and the aqueous phase is exhaustively extracted with ether. The combined organic phases are washed with saturated sodium chloride solution, dried and evaporated. The product obtained is purified by column chromatography. a) Starting benzyl alcohol: 3,4-dimethoxybenzyl alcohol Product: 3,4-dimethoxybenzyl 1 but-2- inyl ether Rendimi ent o: 85% Purity (CG): 94% IR (CHC13, cm ")) v : 3025, 3000, 2956, 2937, 2921, 2855, 2839, 1607, 1595, 1512, 1466, 1443, 1420, 1158, 1140, 1070, 1028. ^ -RMN (200 MHz, CDCl3) d 1.84 3H, t, J = 2.3Hz, C = C-CH3), 3 3 and 3.85 (6H in total, CH30), 4.08 (2H, q, J = 2.3 Hz, OCH2C = C-), 4.48 (2H, s, ari 1 - CH ), 6.77-6.88 (3H,, aryl). 13 C-NMR (50 MHZ, CDCl 3) b 3.45 (C = C-CH 3), 55.67 and 55.71 (CH 3 O), 57.31 (0 CH 2 C = C-), 71.22 (aryl-CH 2), 75.0 (C = C-CH 3) , 82.42 (C = C-CH3), 110.76 (C-2), 111.23 (C-5), 120.54 (C-6), 130.05 (Cl), 148.58 (C-4), 148.88 (C-3). b. ) Starting benzyl alcohol: (3,4-dimethoxyf eni 1) dimethylcarbinol Product 1- (3,4-dimethoxyphenyl) -1- methylethyl 2- (but-2-inyl) er er Rendimi ent o 85 -6 Purity (CG) 94% Benzyl alcohol: 1 - [1 -hydrox ipropi 1] 3, 4-dimethoxybenzene Product 1- [1- (2-butynyloxy) -propyl] -3,4-dimethoxybenzene Rendimi 87% Purity (CG) CP 9000, CP-SIL-5CB, 60 m x 0.53μm, 5ml / minN2:, FID, 220 ° C tR = 13.0 min, > 951 IR (CHC13, cm) v 2999, 2959, 2935, 2875, 2856, 2839, 2240, 1608, 1595, 1513, 1465, 1261, 1234, 1162, 1142, 1061, 1028.? -RMN (200 MHZ, CDCl3) d 0.84 (3H, t, J = 7.4 Hz, CH2CH3), 1.65 and 1.83 (2H in total, each m, CH2CH3), 1.82 (3H, t, J = 2.3 Hz, C = C-CH3), 3.84 and 3.86 (6H in total, s, CH30), 3.78, and 3.99 (2H in total, ABX3, JAB = 15.0 Hz, JAX = JB = 2.3 Hz, 0CH2), 4.22 (1H, t, J = 6.8 Hz, CH-O ), 6.80-6.83 (3H, m, aromatics) (at 1.22 (t), 2.01 (s) and 4.08 (q) ppm (signs can be seen to ethyl acetate.) 13 C-NMR (50MHZ, CDC13) 3.55 (C = C-CH3), 10.23 (CH2CH3), 30.58 (CH2CH3), 55.77 (OCH3), 56.03 (OCH), 75.41 (C = C-CH3), 81.71 (C = C-CH3), 82.24 (CH-) O), 109.34, 110.64 (C-2, C-5), 119.63 (C-6), 133.95 (C-1), 148.44 and 149.09 (C-3, C-4). : 1 - [1 -hi dr ox i - 2 - methylpro-pil] -3,4-dimethoxybenzene Product: 1 - [1 - (2-b tini 1 oxy) -2-methylProPil] -3,4- dimethoxybenzene Performance : 85% Purity (CG) : CP 9000, CP-SIL-5CB, 60m x 0.53μm, 5ml / minN2, FID, 220 ° C tR = 14.0.0 min, > 91% IR (CHC13, cm "1) v: 3029, 2995, 2958, 2937, 2871, 2857, 2839, 2238, 1606, 1595, 1510, 1466, 1443, 1420, 1263, 1238, 1157, 1142, 1062, 1028. ! H-NMR (400 MHz, CDCl3) d: 0.65 and 0.97 (6H in total, each d, J = 6.8 Hz, CH (CH3) 2), 1.77 (3H, t, J = 2.3 Hz, C = C -CH3), 1.87 (1H, m, CH (CH3) 2), 3.80 and 3.81 (6H in total, every 3.95 (2H in total, ABX3, JAB = 15.OHz, JAX = JBX = 2.3Hz, OCH2) , 3.90 (1H, d, J = 8.1Hz, CH-O), 6.68-6.78 (3H, m, aromatics) 13C-NMR (50 MHZ, CDC1: 3.39 (C = C-CH3), 18.87 and (CH ( CH3) 2 /) 55.61 (OCH., 56.11 (OCH2), 75.44 (C = C-CH3), 81.37 (C = C-CH3), 86.25 (CH-O), 109.76 (C-5), 110.32 (C -2, 120.19 (C-6), 132.91 (Cl), 148.24 (C-4) and 148.80 (C-3) e.) Starting benzylic alcohol: 5- [1 -hydroxie ti 1] - 1, 3 - benxodioxo 1 Product: 5- [1- (2-Butynyloxy) ethyl- 1,3-benzodioxol Yield: 84% Purity (GC): 94% IR (CHC13, cm "1) v 2979, 2921, 2882, 1609, 1502, 1486, 1441, 1079, 1041, 941. '"H-NMR (400 MHz, CDC13) d 1.41 (3H, d, J = 6 .5 Hz, CHCHj), 1.83 (3H, t, J = 2.3 Hz, C = C-CH3), 3.80 and 3.99 (2H in total, ABX3, OCH2), 4.51 (1H, q, J = 6.5 Hz, CHCH3 ), 5.92 (2H, AB, OCH20), 6.74 (2H, AB, H-6, H-7), 6.83 (1H, s, H-4). 13 C-NMR (100 MHz, CDC13) d: 3.50 (C = C-CH3), 23.67 (CHCH3), 55.80 (OCH2), 75.18 (C = C-CH3), 76.16 (CH-O), 81.93 (C = C-CH3), 100.84 (OCH20), 106.47, 107.88 (C-4, 7), 119.90 (C-6), 136.63 (C-5), 146.94 and 147.77 (C-3a, 7a) Benzyl starting alcohol: 1 - [1 -hydroxie ti 1] - 3, 4 • diethoxybenzene Yield: 1- [1- (2-butynyloxy) ethyl] -3,4-diethoxybenzene Yield: 86% Purity (GC): 93 % g) Benzyl alcohol with a partial ring: 1 - [1 -hi dr oxy-1] -3,4-dimethoxy-6-propylbenzene Product: 1- [1- (2-butynyloxy) ethyl] -3,4-dimethoxy -6-Pronilbenzene Rendimi ent o: 73% Purity (CG): CP 9000, CP-SIL-5CB, 60m x0.53mm, 5ml / min N2, FID, 250 ° C, tR = 6.7 min. , kb 95.4%. IR (CHC13, cm) v 2961, 2933, 2873, 2331, 1610, 1511, 1466, 1261, 1132, 1098, 1047. H-NMR (400 MHz, CDCl 3) d 0.96 (3H, t, J = 7.3 Hz, CH3), 1.41 (3H, d, J = 6.4 Hz, CH3CHO), 1.58 (2H, sextet, J = 7.4 Hz, CH2-CH3), 1.81 (3H, t, J = 2.5 Hz, CH3-C =), 2.54 (2H, m, CH2-Ar), 3.78, and 3.98 (2H, ABX3, JB = 15.0 Hz, JAX = 3.83 (6H, s, OCH3), 4.86 (H, q, J = 6.5 Hz, Ar- CHO) , 6.60 and 6.91 (2H, s, aryl) .13 C-NMR (100 MHZ, CDCl3) d 3.46 (= C-CH3), 14.05 (CH3), 23.70 and 24.97 (CH2-CH3 and CH3CHOH), 34.03 aryl- CH2), 55.62, 55.69 and 55.80 (0CH3y = C-CH20), 71.60 (Ar-CH-CH3), 75.46 (= C-CH2), 81.84 (= C-CH3), 108.45, 112.32 (C-2, C - 5), 132.29, 132.33 (C-6, Cl), 147.60, 147.79 (C-4, C-3). 11.) 5- [(2-Butynyloxy) methyl] -1,3-benzodioxole In a ball fitted with a magnetic stirrer, condenser and drying tube filled with calcium chloride, 3.0 g (13.95 mmoles) of piperonyl bromide is introduced, 2.0 g (27.9 mmoles) of 2-butin-1-ol and 50 ml of di chlorite. After adding the zinc (II) oxide (1.1 g, 13.5 mmol), the suspension is stirred for 1 hour at room temperature. The reaction is accompanied by a characteristic color change. Then the mixture is filtered and the filtrate is evaporated. The residual oil is dissolved in 50 ml of ether, washed with 2x10 ml of water, dried and evaporated. Yield: 2.3 g (11.2 mmol, 80.7%). CG 82%.

IR (CHCl3, cm-1) v: 2997, 2946, 2921, 2888, 2376, 1609, 1503, 1491, 1445, 1251, 1099, 1070, 1042, 937, 865, 810 2H-NMR (400 MHz, CDCl3) d: 1.87 (3H, t, J = 2.3 Hz, Me), 4.10 (2H, q, J-2.3 Hz, 0-CH2-C =), 4.47 (2H, s, 0-CH2-Ar), 5.94 ( 2H, s, 0- CH2-0), 6.76 (1H, d, J = 8 Hz, H-7), 6.81 (1H, dd, J = 8.15 Hz, H-6), 6.86 (1H, J = 1 .5 Hz, H-4). 13 C-NMR (100 MHz, CDC13) d: 3.52 (Me) 57.29 (0-CH2-C =), 71.15 (O-CH.-Ar), 82.54 (CH3-C =), 100.9 (C-2), 107.95, 108.71 (C-4, 7), 121.66 (C-6), 131.39 (C-5), 147.15, 147.66 (C3a, C-7a). 12.) 1- [(2-Butynyloxy) methy1] naphthalene In a ball fitted with a magnetic stirrer, condenser and a drying tube filled with calcium chloride, the brometome Ina phtha 1 ene 1.0 4.52 mmol) is introduced. -but in- 1-ol 0.63 g, mmoles) and 10 ml of di-oroethylene. After adding the zinc oxide (II) (4.0 g, 4.52 mmol), the suspension is stirred for 1 hour at room temperature and then heated to reflux for 1 hour. The reaction is accompanied by a characteristic color change. Then the mixture is filtered and the filtrate is evaporated. The residual oil is dissolved in 15 ml of ether, washed with 2 × 50 ml of water, dried and evaporated. The product is purified by column chromatography. Purity (CG) 95 ?. IR (CHC13, c -1) v: 3044, 3001, 2945, 2920, 2854,1598, 1509, 1356, 1166, 1086, 1067 1 H-NMR (400 MHz, CDCl 3) d: 1.93 (3H, t, J = 2.3 Hz, C = C- CH3), 4.22 (2H, q, J = 2.1 Hz, 0-CH2-C = C), 5.06 (2H, s, C10H7-CH2-0), 7.45 (1H, t, J = 8 Hz), 7.53 (3H, m), 7.84 (1H, d, J = 8.1 Hz), 7.88 (3H, m), 7.88 (lH, d, J = 7.7 Hz), 8.19 (1H, d, J = 8.2 Hz). 13C-NMR (100 MHz, CDC13) d: 3.6 (C = C-CH3), 57.71 (0-CH2-C = C), 69.72 (C10H7-CH2-0), 75.10 (0-CH2_C = C), 82.76 (0-CH2-C = C), 124.03, 125.10, 125.72, 126.19, 126.85, 128.43, 128.72, 131.79 (C-8a), 133.06, 133.70. 13 5- [2- (2-Butoxyethoxy) ethoxymethyl] -6-propyl-l, 3-benzodioxole, PBO a. ) 2.98 g (14.02 mmoles) of 5-c 1 ormethyl Idihidr osaphol, 2.72 g (16.82 g) are introduced into a ball fitted with a magnetic stirrer, condenser and drying tube filled with calcium chloride. mmoles) of diethylene glycol monobutyl ether and 20 ml of di chloro ethane. After adding zinc (II) oxide (1.22 g, 15. 0 mmol), the suspension is stirred for 24 hours at room temperature. The reaction is followed by TLC and After the starting benzyl chloride has disappeared, the mixture is filtered and the filtrate is evaporated. The residual oil is dissolved in 25 ml of ether, washed with 2 × 50 ml of water, dried and evaporated. The product is vacuum distilled, P. eb. : 180 ° C / lHgmm. The material is identical to the commercial PBO. Yield: 4.0 g (90%). Purity (CG) 98%. b. ) 2.12 g (10.0 mmol) of 5-chlorohene ti Idihidros afrol and 2.42 g (15.0 mmol) are introduced into a balloon provided with a magnetic stirrer, condenser and a drying tube filled with calcium chloride. diethylene glycol monobutyl ether. After adding 0.97 g (15.0 mmoles) of zinc oxide (II), the suspension is stirred for 12 hours at room temperature. The reaction is followed by TLC and after the starting benzyl chloride is dissolved, the mixture is diluted with diethyl ether, filtered, the filtrate is washed with 2 × 50 ml of water, dried and evaporated. The product is vacuum distilled, P. eb. : 180 ° C / lHgmm. The material is identical to the commercial PBO. Yield: 2.8g (91%). Purity (CG) 98%.

Claims (7)

1. RE IVIND I CAC I ONE S 1. Procedure for preparing the mixed ethers of general formula I, wherein Ar represents an alicyclic, aromatic, aromatic moiety with one or more heteroatoms, which is optionally substituted by one or more groups of C 1 - alkoxy, methylenedioxy, C 4 -4 alkyl, halogen, haloalkyl C? -4, or nitro, and / or is condensed with a benzene ring, R1 and R2 independently represent hydrogen, C? - alkyl, C? _4 haloalkyl, C2_4 alkenyl, phenyl, substituted phenyl or C3_6 cycloalkyl, R3 represents the C3-6 alkynyl group, optionally substituted with one or more C6_6 alkyl, C3_6 alkenyl / C3-6 alkynyl groups? haloalkyl C? -b or a halogen atom; or a group of C 1 -oxi-alkyl-C 1 -oxi-C 1 -C 4 alkyl, characterized in that the compounds of the general formula II, wherein X represents hydroxy, halogen or a leaving group of sulphonic ester, they are reacted in the presence of Lewis acid, metal oxide or metal carbonate with 1 to 3 molar equivalents of an alcohol of the general formula III, R3-OH wherein the substituent has the meaning indicated above, the resultant ether of the general formula I is isolated, if desired, stabilized by the addition of a base and / or an antioxidant and, if desired, the excess of the alcohol .
2. 2. The process according to the rei indication 1., characterized in that 0.01-3 molar equivalent of a strong mineral or organic acid, preferably hydrochloric acid, sulfuric acid, perchloric acid or an aromatic sulfonic acid is used as the acid.
3. 3. The process according to the rei indication 1-2, characterized in that the reaction is carried out in a solution of salts, preferably in a solution of sodium chloride, calcium chloride, magnesium chloride, zinc chloride.
4. 4. The process according to the above indications 1-3, characterized in that the reaction is carried out in the aqueous solution of the acid, preferably in an aqueous solution at 10% w / w of the acid, saturated with the inorganic salt, at a temperature of ( -20) - (+30) ° C.
5. 5. The process according to claim 1, characterized in that 0.01-3 molar equivalents of zinc (II) chloride or an aromatic sulfonic acid, preferably benzenesulfonic or para-aluminum sulfonic acid are used as the Lewis acid, and the reaction is carried out in a non-polar aprotic solvent.
6. 6. The process according to claim 5, characterized in that the di-chloro or ethane is used as the non-polar aprotic solvent, and the reaction is carried out at a temperature of (-30) - (+40) ° C.
7. 7. The process according to claim 1, characterized in that 0.01-3 molar equivalents of zinc oxide are used as metal oxide, while zinc carbonate is used as the metal carbonate, and the reaction is carried out in absence of a solvent or in the presence of a non-polar aprotic solvent, preferably dichloroethane. SUMMARY The object of the present invention relates to the process for the preparation of mixed ethers of the general formula (I), wherein Ar represents an alicyclic, aromatic, or one or more heteroatom het eroc tic portion, which is found and substituted with one or more groups of C 1-4 alkoxy, methylenedioxy, C? -4 alkyl halogen, C? - haloalkyl, or nitro, and / or is fused with a benzene ring, R 1 and R 2 independently represent hydrogen, alkyl C? _, Haloalkyl C? _ / C2-4 alkenyl, phenyl, substituted phenyl or C3-6 cycloalkyl, R3 represents the group C? -6 alkyl, C3-6 alkenyl, or C3-6 alkynyl / and is one or more C? -6 alkyl, C3-6 alkenyl / C3-6 alkynyl groups? haloalkyl C i -6 or a halogen atom; or a group of alky1 (C4-4) oxy-alky1 (C4-4) oxy-alkylo (C4-4), characterized in that the compounds of the general formula (II), wherein X represents hydroxy, halogen or a leaving group of sulphonic ester, are reacted in the presence of acid, Lewis acid, metal oxide, or metal carbonate, with 1-3 molar equivalents of the alcohol of the general formula ( III), wherein the meaning of the substituent is also as defined above, the resulting ether of the general formula (I) is isolated, if desired, stabilized by the addition of a base and / or an anti oxidant. you, and if you want the excess alcohol is recovered.