MXPA99001054A - Processes for preparing indeno[1,2-e][1,3,4]oxadiazine-dicarboxylates - Google Patents

Abstract

Oxadiazines of formula (I), wherein R1 is F, Cl or fluoralkoxy and R2 is alkyl, are prepared by reacting hydrazine derivatives of formula (II) with a dialkoxymethane in the presence of a protic acid catalyst in an inert solvent under conditions which allow for the prompt removal of the alcohol by-product by distillation. The reaction can be combined with the preparation of the hydrazines derivatives (II) from the corresponding ketones and hydrazines NH2-NHR3 in the presence of the same protic acid catalyst and an inert solvent. Oxadiazines I are useful as intermediates in the preparation of arthropodicidal agents.

Description

PROCESSES FOR THE PREPARATION OF INDENOUS [1, 2- E] [1,3,4] OXADIAZINA-DICARBOXYLATES FIELD OF THE INVENTION This invention relates to processes for the preparation of intermediate compounds, particularly dicarboxylate oxadiazines of Formula I and hydrazine carboxylates of Formula II, which are useful in the preparation of oxadiazines artropodicides.

BACKGROUND OF THE INVENTION W095 / 29171 describes the preparation of arthropodicidal oxadiazines of dicarboxylate oxadiazines of Formula I and hydrazine carboxylates of Formula II. In W095 / 29171, the compounds of Formula I are prepared by the reaction, of the compounds of Formula II with a di (C 1 -C 3 alkoxy) methane in the presence of a Lewis acid, and optionally in an inert solvent. The named Lewis acids are P205, BF3, S03 (0.9 to 4.0 molar equivalent required) and REF .: 29160 tr: metal. Fluoroethanesulfonates (0.1 to 0.5 of the molar equivalent required). All solvents specifically named for this transformation sor. halogenated (dichloromethane, 1,2-dichloroethane, chlorobenzene, a, a, a-trifluorotoluene). It is understood that when a metal trifluoromethanesulfonate is used, it is preferable to continuously remove the alcohol as a by-product by distillation. In contrast, the process of the present invention allows the use of a protic acid such as sulfonic acid para-toluene in catalytic amounts, such as the molar equivalent of 0.1 in a non-halogenated solvent (for example to uene) to provide good product quality in a high chemical yield There is a need for a more efficient process for preparing oxadiazines of Formula I with the hydrazine carboxylates of Formula II, BRIEF DESCRIPTION OF THE INVENTION The present invention relates to processes for the preparation of oxadiazine dicarboxylates of Formula I which are racemic or enantomerically enriched to the chiral center * wherein R1 is F, Cl, or fluoroalkoxy of 1 to 3 carbon atoms, R2 is alkyl of 1 to 3 carbon atoms, and R3 is a protecting group such as C02CH2 (C6H5) which comprises: reacting a compound of Fó -muía II, which is racemic or enantoméricamente en-iquecido en *, cor a di (C1-C3 alkoxy) methane in the presence of a protic acid catalyst in an inert solvent, or conditions that allow the rapid removal of ^. alcohol as a secondary product by distillation. This invention further relates to processes for preparing compounds of Formula I as defined above which comprises: (a) reacting a compound of the Fó "mule III, which is racemic or enantomerically enriched in *, co. "the compound of Formula IV in the presence of a protic acid catalyst in an inorte solvent, H2NNHR3 IV to form a compound of Formula II and (b), by reacting the compound of the Fa-lamine II with a di (C? -C3 alkoxy) methane in the presence of the same protic acid catalyst and an inert solvent used in step (a) under conditions which allow the rapid removal of alcohol as a byproduct through the removal of alcohol. In previous recitations, the term "Ci-C3 fluoroalkoxy" refers to methoxy, ethoxy, n-propoxy and iso-propoxy which may be partially or completely substituted by fluorine atoms. Loi) examples of "fluoroalkoxy" include CF30 and CF3CH20: DETAILED DESCRIPTION OF THE INVENTION The compounds of Formula I can be propagated by the process of this invention comprising the process variations as described below. Preferred compounds of Formula I sor. those in which R1 is F, Cl, CF30 or CF3CH20, (e. "Cl most preferred form) and R2 is CH3." Any protic acid can be used in the process of this invention as a catalyst. suitable include mineral acids such as "their furic acid and sulfonic acids such as their aromatic, aliphatic, and polymeric phonic acids. Preferred for reasons of greater commercial utility and / or ease of practice in the process of preparing compounds of Formula I are:; protic acids which do not distil to each other in any significant degree with alcohol as a secondary product and which do not react with dialkoxymethane to form products that could be mutually distilled with alcohol as a secondary product. The acids reported are those that are catalyzed both in the reaction of the compounds of Formula III with compounds of Formula IV, to give Fólia II compounds, and the conversion of Formula II compounds to compounds of Formula I Examples of these preferred acids are para-to-uenesulfonic acid, mixtures of isomeric to uene sulfonic acids, ber.cenosulfonic acid, naphthalenesulfonic acids, ac. two xylene sulfonic acids, methanesulfonic acid, sulfuric acid, and camphor sulfonic acids. The:; more preferred are para-to-sulfonated acids and mixtures of isomeric to-sulfonic acids. While stoichiometric or larger amounts of protic acid may be employed, a catalytic amount of protic acid is proffered for reasons of greater commercial utility and / or ease of practice in the process, to prepare amounts of Formula I of any of the compounds of Formula II, or compounds of Formula III, that an amount of the catalytic acid that is employed. It is used more preferably than a total of between 0.01 and 0.20 molar equivalent of protic acid, relative to the compound of Formula II or Formula III. The process in which 0.01 and 0.20 molar equivalent of protic acid are used is used even more preferably. In general, the use of 0.05 to 0.10 molar equivalent of protic acid allows useful reaction rates while minimizing the use of acid and the generation of waste. The solvent used in the process of this invention can be any inert solvent that when combined with the reagents used in the process of the present invention forms a reaction mixture of which the alcohol produced as a by-product in the process of this invention as it would be ethanol, it can be readily separated by distillation. Depending on the :; Specific reaction conditions, alcohol can be removed as: (a) alcohol; (b) an azootrope or mixture of the alcohol and di (C? -C3 alkoxy) methane; (c) an azeotrope or a mixture of the alcohol and the solvent; or (d) an azeotrope or mixture of. alcohol, di (C? -C3 alkoxy) methane and solvent. Preferred for ease of operation, cost, toxicity and environmental reasons are non-oiled solvents such as aromatic and aliphatic hydrocarbons and alkyl nitriles. Most preferably, they are aliphatic and aromatic carbides and alkyl nitrates with boiling points of 80 and 150 ° C. More preferred are toluene, xylene, heptane and acetonitrile.

The alcohol or alcohol-containing component can be distilled from the reaction mixtures using equipment and techniques known to those skilled in the art. Equipment and methods that allow efficient removal of alcohol while minimizing mu..ua distillation of di (C1-C3 alkoxy) methane and / or solvent are preferred. This can be achieved using conventional fractional distillation equipment. The reaction of the compounds of the Formula II with a di (C? -C3 alkoxy) methane is more conveniently run at the boiling point of the reaction medium at ambient pressure. The reaction temperatures need to be at least equal to the boiling point of the alcohol as a by-product (eg, ethanol) or of the alcohol containing azeotrope or mixture being removed. Preferred for reasons of greater commercial utility and / or ease in the practice of the process of preparing compounds of Formula I from the compounds of Formula II with a reaction temperature between about 40 and 50 ° C which allows the distillation of alcohol as a secondary product. More preferred would be a reaction temperature of between 60 and 130 ° C. More preferably, it is a reaction temperature of between about 80 and 120 ° C. The reaction can also be carried out at elevated or reduced pressure. The use of reduced pressure can be particularly advantageous when using higher boiling solvents. The reaction of the compounds of Formula II from compounds of Formula IV is conducted at a reaction temperature of about 40 to 120 ° C. More preferably, it is a reaction temperature of about 50 to 90 ° C. Although the reaction can be carried out at ambient pressure, the reaction can also be carried out at elevated or reduced pressure.The use of reduced pressure can be particularly advantageous when using solvents having boiling points higher than the desired reaction temperature. When compounds of Formula II are prepared from compounds of Formula III and the compound of Formula IV, it is preferable that ag, as a byproduct be removed from the reaction mixture before the combination of the me /. Reaction rate with the di (C? -C3 alkoxy) methane. In more preferred form, water as a by-product can be removed by distillation at the time it is formed. In principle, only one molar equivalent of di (C1-C3 alkoxy) methane is needed. However, di (C 1 -C 3 alkoxy) methane suffices to be used sufficiently to allow losses of di C 1 -C 3 alkoxy) ethane via mutual distillation. Any practical amount of di (C 1 -C 3 alkoxy) methane can be employed in the process of this invention and can be used as the solvent of the reaction to convert compounds of Formula II to compounds of Formula I. For reasons of economy it is preferable to use between about 1 and 20 equivalents of di (C? C3 alkoxy) methane in conjunction with an inert solvent. More preferably between about 1 and 10 equivalents of di (C 1 -C 3 alkoxy) methane may be employed, more preferably between 2 and 7 equivalents. The di (C2-C3 alkoxy) methanes are preferred because they have a boiling point more than: higher than the alcohols of 2 to 3 carbon atoms that are produced during the course of a reaction. This allows the removal of alcohol by distillation without removing large amounts of di (C2-C3 alkoxy) methane. The most preferred dietoximene is di (C2-C3 alkoxy) methane because of the low price and availability. In the reactions of compounds of formula II with a di (C? -C3 alkoxy) methane, the reactants must be combined in such a cup, that the alcohol as a byproduct is promptly and efficiently removed to prevent the formation of side reaction products which adversely In one embodiment, a slurry of the hydrazine carboxylate of Formula II containing all or part of the solvent and optionally containing all or part of the protic acid and the di (C? -) would affect the pu-eza and production of the desired product. C3 alkoxy) ethane is added over time to the mixture of the rest of the solvent, protic acid and the di (C? -C3 alkoxy) methane which has been preheated to the appropriate reaction temperature. In an alternative embodiment, the di (C? -C3 alkoxy) methane can be added to one medal of the hydrazine carboxylates of Formula II, solvent and protic acid which have been pro-heated to the reaction temperature -opied. When protic acid and di (C 1 -C 3 alkoxy) methane combined and preheated before the combination with the hydrazine carboxylate of Formula II, it is preferable to distill any alcohol produced by the reaction of the acid with the dihydrate.; C? -C3 alkoxy) methane at the same time it is formed. The present invention also relates to processes for preparing compounds of Formula I comprising: Step (a) preparing compounds of Formula II from compounds of Formula III and Step (b) reacting the compounds of Formula II with a di ( C1-C3 alkoxy) methane under conditions that "will prompt the rapid removal of alcohol as a by-product by distillation in the dor. Both steps are carried out in the presence of the same protic acid catalyst and inert solvent. Formula I can also be converted into arthropodicidal oxadiazines of Formula VII by (a) hydrogenating the compound of Formula I for forming a compound of Formula V V (b) reacting the compound of Formula V with the compound of Formula VI pa to form a compound of Formula VII having substantially the same absolute configuration as the compound of Formula I.

The preparation of the compound of Formula VI is described in WO 95/29171.

Without further elaboration, it is thought that one skilled in the art using the foregoing description may use the present invention to its fullest extent. The following Examples are, then, to be construed as illustrative, and not limitative of the discovery in any way. The po-centages are by weight except for the mixture of the chromatographic solvent, which goes by volume. EXAMPLE 1 P Repair of 2- (phenylmethyl) -7-chloroindene [1, 2e] [', 3, 4] oxadiazine-2, 4 a (3H, 5H) -dicarboxylate of 4a-methyl "5 A flask of 1L, with 4 necks and round base (RBF) was equipped with an oval paddle stirrer, thermometer, liquid feeding line with FMI pump (Fluid Metering Inc.), 0 Oldershaw counting with 10 trays equipped with a caoezal of variable separation, condenser and in. for nitrogen and a blanket of heating.The system was arranged so that the temperature could be inspected in the crucible, in the trays 2, 4, 6, 8, 10, and in the distillation head. The flow of water was started through the condenser. The flask was charged with 50 mL (0.4 mol) of Aldrich diextimethane and 100 mL of toluene and heated for reflux. The temperatures of the head and the crucible were 106 and 83:, C respectively. The temperatures of the counting column at the second, fourth, eighth and tenth (from the bottom up) were 97 ° C, 93 ° C, 90 ° C, 88 ° C and 83 ° C. In a separate flask, a mixture of 1.15 g of para-butylene sulfonic acid monohydrate and 125 mL of toluene were dried by azeotropic distillation of approximately 45 L of the solvent using a Dean-Stark trap. The resulting mixture was allowed to cool to room temperature and 24.56 g (0.06 mol, 94.8% product) of phenylmethyl [5-chloro-2,3-dihydro-2-hydroxy-2- (methoxycarbonyl) -lH were added. -indeno-1-yldeno] racemic hydrazine carboxylate described in W095 / 29171 to give a thick slurry consistency. The slurry was then pumped into the mixture of diethoxymethane and toluene under reflux for 2 hours and 24 minutes and rinsed with toluene. Once the temperature in the eighth tray (counting from below) of the column dropped to 80 ° C, the separated ethanol / diethoxymethane / toluene distillate was started at such a rate as to maintain the temperature of the fourth tray between 79-83 ° C. After the addition of the slurry was completed, the distillate was collected slowly until the temperature of the tray reached 88 ° C. The separation ratio was increased and the distillation continued until the head temperature reached 11 ° C. A total of approximately 117 mL (99.0 g) of distillate was collected. The reaction mixture was allowed to cool and concentrated using a rotary evaporator; the residue was dissolved in ethyl acetate, filtered and the filtrate was concentrated using a rotary evaporator to leave 12 g of oil. The oil was formed in slurry with 75 mL of methanol and cooled in an ice bath. The crystals that formed were collected and washed with two 10 mL portions of cold methanol, and dried in a vacuum oven to give 21.0 grams (87% yield) of the product that was tested (HPLC, 4.6X250 mm 5-micron , column Zo -baxR SB-C8 and eluting at 1.5 mL / min with 60% acetonitrile / 40% water, 40 ° C, UV detector ca.ibrated at 254 nm) as 98.99% of 2- (phenylmethyl) -7 -chloroindeno [1,2e] [1, 3, 4] oxadiazine-2,4a (3H, 5H) -dicarboxylate of 4a-methyl. mp 113-123 ° C.

EXAMPLE 2 Preparation of 2- (phenylmethyl) -7-chloroindene [1, 2e] [', 3, 4] oxadiazine-2,4a (3H, 5H) -dicarboxylate of 4a-ethyl A 1L flask, with 4 necks and round base (RBF) was equipped with an overhead stirrer of oval pitch, thermometer, Dean-Stark trap, reflux condenser and a heating mantle. The reactor was charged with 45.7 g (0.183 mol), 96.3% assay of racemic methyl 5-chloro-2,3-dihydro-2-hydroxy-l-oxo-lH-indene-2-carboxylate described in WO-5/29171 , 35.1 g (0.21 mol) of 99.4% phenylmethyl hydrazine carboxylate, 3.5 g (0.018 mol) of para-toluenesulfonic acid monohydrate and 235 mL of toluene. The mixture was refluxed for 7 hours under a vacuum (~ 168 to 205 mm) sufficient to maintain the boiling point between 65 and 72 ° C. During this time, 3.4 mL of water was collected in the Dean-Stark trap, The treatment was discontinuous and the flask was returned to room temperature.When cooling to room temperature, the reflux condenser and the Dean-Stark trap were removed and exchanged for a 5 tray Oldershaw column and equipped with a variable subtraction caoezal. The bottle was then equipped with a liquid feed line with an FM pump (Fluid Metering Inc.) The system was assembled so that the temperature could be inspected in the crucible, in each tray of the Oldershaw column and in the distillation head, the circulation of the ice water through the condenser was started and the reaction mixture was refluxed, the temperatures of the crucible and the head were 113 and 110 ° C. r Specifically, the temperatures of the column (from the bottom to the bottom) were 111 ° C, 110 ° C, 110 ° C, 110 ° C, and 110 ° C respectively. Then diethoxymethane (68 L 0.54 mol) was pumped into the reaction mixture at a fi step, or for 1 hour and 6 min. Once the temperature in the fourth tray (continuing from below) of the column dropped to 80 ° C, the distillate separation of ethanol / diethoxymethane / toluene was started at such a rate as to maintain the temperature of the fourth tray between 77 -84 ° C. After the addition was complete, the distillate was collected little by little for 50 minutes until the temperature of the fourth tray reached 91 ° C. The separation cup was increased and the distillation continued until the head temperature reached 10 ° C. A total of about 104 mL (84.9 g) of distillate was collected. The reaction mixture was allowed to cool, and concentrated using a rotary evaporator, the residue was dissolved in 210 mL of methanol and cooled in an ice bath. The crystals that formed were collected, washed with three 30 mL portions of cold methanol, and dried in a vacuum oven to give 61.17 g (82% yield) of roasted product that was hardened (HPLC, 4.5X250 mm 5 microns, Zorbax SB-C8 column and the .. to 1.5 mL / min with 60% acetonitrile / 40% water, 40 ° C, UV detector calibrated at 254 nm) as 96 98% 4a-methyl 2- (phenylmet il) -7-chloroindene [1, 2e] [1, 3, 4] oxadiazine-2, 4a (3H, 5H) -dicarboxylate. p.f. 120-122 ° C.

EXAMPLE 3 Preparation of 2- (phenylmethyl) -7-chloroindene [1,2-e] - [', 3,4] oxadiazine-2,4a (3H, 5H) -dicarboxylate of 4a-methyl Step A A 2L flask, with 4 necks and round base, was equipped with: an overhead stirrer with an oval blade, thermometer, Dean-Stark trap, with "a reflux condenser, and nitrogen inlet, and heating mantle. The reactor was purged with nitrogen and charged with 583 g of toluene, 120 g (D.50 mol, 99.68% test) of 62% ee 5-chloro-2,3-di ". Idro-2-hydroxy-oxo-lH- indene-2-carboxylate, 94 13 g (0.55 mol) of 97% benzyl carbazate and 9. 65 g (0.05 mol) of 98.5% para-toluensulonic. The mixture was heated to reflux under a vacuum (approximately 184 mm) sufficient to give a boiling point of 70 ° C. After a total of 6 hours under reflux, the reaction mixture was allowed to cool to room temperature. Just before use in Step B, 131.5 g of diethoxymethane was added to the slurry.

Step B A 3L flask, with 4 necks and round base, was equipped with: an oval overhead stirrer, thermometer, Oldershaw column of 5 ba-.dejas equipped with a variable separation head, condenser, nitrogen inlet and a heating tablecloth. The system was arranged so that the temperature could be inspected in the sun, in each tray of the Oldershaw column, and in the distillation head. The circulation of ice water through the condenser was started. The flask was charged with 26.3 g (0.25 mo) of diethoxymethane from Aldrich and 580 g of toluene and heated to reflux with a boiling of ap-about 35 mL / min. The temperatures of the sun and head were 111 ° C and 102 ° C respectively. The temperatures of the column in the first, second, third, fourth and fifth trays (bottom to top) were 109 ° C, 107 ° C, 106 ° C, 104 ° C, and 102 ° C. The thick suspension of :. Step A was then dosed into the hi-live solution for 6 hours and 20 minutes and rinsed with a mixture of 50 g of toluene and 26.3 g of diethoxymethane. As the addition continued, head and column temperatures decreased. Once the temperature of the fourth tray (continuing from the bottom) of the column went down to 80 ° C, the distillate separation of ethanol / diethoxymethane / toluene was carried out at a certain rate to maintain the temperature of the fourth tray between 80 to 84 ° C. After the addition was completed, the distillate was slowly collected until the temperature in the fourth tray reached 101 ° C. Distillate separation was discontinued for 10 minutes, during which time the temperature in the fourth tray was maintained at 101 ° C. The separation was summarized at an increased rate until the head temperature reached 109 ° C. of 328 mL (249 g) of distillate was collected The reaction mixture was allowed to cool and the solvent was removed by distillation at 35 mm Hg until the temperature of the sun reached 70 ° C. Ethanol was added (360 ml). ) and the mixture was heated to reflux for 1 hour and allowed to cool.When the temperature reached 40 ° C, 30 mL of water were added and the mixture was cooled to about 0 ° C. The product was collected by filtration, a displacement wash was made with four cold 50 mL portions of ethanol, then dried on the filter to give 176.9 g (85% product) that was tested (HPLC, 4.6X250 mm 5 microns, Zorbax SB-C8 column and eluting 1. or mL / min with 60% acetonitrile / 40% water, 40Í! C, detecto r UV calibrated at 254 nm) as 96.91% of 2- (phenylmethyl) -7-chloroindene [1, 2e] [1 3, 4] oxadiazine-2, 4a (3H, 5H) -dicarboxylate of 4a-methyl, with an ee of 70%, m.p. 103-120 ° C.

EXAMPLE 4 P-eparation of 2- (phenylmethyl) -7-chloroindene [1,2-e] [", 3,4] oxadiazine-2,4a (3H, 5H) -dicarboxylate of 4a-methyl Step A A 2L flask, with 4 necks and round base, was equipped with: an oval paddle stirrer, thermometer, Dean-Stark trap with reflux condenser, nitrogen inlet; and a heating tablecloth. The reactor was purged with nitrogen and charged with 583 g of toluene, 120.7 g. (0 50 mol, 99.68% test) 62% ee 5-chloro-2,3-di: uidro-2-hydroxy-oxo-lH-indene-2-carboxylate, 94.13 g (0.55 mol) of 97% benzyl carbazate and 4.85 g (0 05 mol) of 99% methanesulfonic acid. The mixture was heated to reflux under a vacuum (approximately 18 mm) sufficient to give a boiling point of 70 ° C. After a total of 5.25 hours in re luxe, the reaction mixture was allowed to cool to room temperature. Just before being used in Step B, 131.5 g of diethoxymethane were added to the slurry.

Step B A 3L bottle, with 4 necks and round base, was equipped with: an oval overhead stirrer, thermometer, Oldersha 5-foot column equipped with a separable separating head, condenser, nitrogen inlet and a ma: heating tel. The system was arranged so that the temperature could be inspected in the sun, in each tray of the Oldershaw column, and in the distillation head. The circulation of ice water through the condenser was started. The flask was charged with 26.3 g (0.25 mo) of diethoxymethane from Aldrich and 580 g of toluene and heated to reflux with a boiling of about 26 mL / min. The temperatures of the sun and head were 111 ° C and 102 ° C respectively. The temperatures of the column in the first, second, third, fourth and fifth trays (bottom to top) were 108 ° C, 10 ° C, 106 ° C, 103 ° C, and 102 ° C. The thick suspension of. Step A was then measured in the boiling du-ante solution for approximately 4 hours and rinsed with a 50 gm of toluene. At the same time that the aggregate came, the temperatures of the head and the column decreased. Once the temperature of the fourth tray (continuing from the bottom) dropped to 80 ° C, the distillate separation of ethanol / diethoxymethane / toluene was carried out at a certain rate to maintain the temperature of the fourth tray between 78 at 86 ° C. After the addition was completed, the distillate was slowly collected until the temperature in the fourth bath reached 94 ° C. The separation was summarized to an increased cup until the temperature of the caoezal reached 108 ° C. A total of 306 mL (234 g) of distillate was collected. The reaction mixture was cooled and the solvent was removed by distillation at 35 mm Hg until the temperature of the crystals reached 71 ° C. Ethanol (560 ml) was added and the mixture was heated to reflux until all the precipitated solids were dissolved. The mixture was then cooled to 0 ° C. The product was collected by filtration, washed with six cold portions of 50 mL of ethanol, and dried to give 164.1 g of product 4a-methyl 2- (phenylmethyl) -7-chloroindene [1, 2 e] [1, 3, 4] oxadiazine-2, / a (3H, 5H) -dicarboxylate with a mp of 104-123 ° C.

It is noted that with regard to this date, the best method known to the applicant for carrying out the present invention is that which is clear from the present description of the invention.

Having described the invention as an ancestor, the contents of the following are claimed as property:

Claims (9)

1. A process for the preparation of a dicarboxylate oxadiazine of Formula I I which is enriched racemic 6 enantoméricamente in the chiral center. wherein: Ri is F, Cl or a fluoroalkoxy of 1 to 3 carbon atoms and R 2 is an alkyl of 1 to 3 carbon atoms, characterized in that it comprises reacting a hydrazine carboxylate of Formula II with at least one molar equivalent of a di (C 1 -C 3 alkoxy) methane in the presence of a protic acid catalyst in an inert solvent under conditions that allow the quick removal of the alcohol as a secondary product by distillation.

2. A process according to claim 1, characterized in that Ri is Cl and R2"is CH3.

3. A process in accordance with claim 1, characterized in that a protic acid is selected from p-to-uenesulfonic acid, mixtures of isomeric isosulfonic acids, beuzenosulfonic acid, naphthalenesulphonic acids, 2-xylenesulfonic acids, methanesulfonic acid, sulfuric acid. and camphor sulfonic acids.

4. A process according to claim 1, characterized in that a catalytic amount of the protic acid is used.

5. A process according to claim 1, characterized in that the dialkoxy metal used is di (C2-C3 alkoxy) methane.

6. A process according to claim 1, characterized in that the reaction temperature is about 40-150 ° C and at a pressure of about 1 atmosphere.

7. A process according to claim 1, characterized in that the solvent is an inert non-halogenated solvent.

8. A process for preparing a compound of Formula I which is racemic or enantomerically enriched at its chiral center * where: R1 is F, Cl, or fluoroalkoxy of 1 to 3 carbon atoms, and R2 is an alkyl of 1 to 3 carbon atoms, characterized in that they comprise: (a) ) reacting a compound of Formula III, which is racemic or enantomerically enriched in *, co "the compound of Formula IV in the presence of a protic acid catalyst in an inert solvent H2N-NHC02CH2CH2 (C6H5) IV pana form a comp to s of F rmul a I I and (b) reacting the compound of Formula II cor. a di (C 1 -C 3 alkoxy) methane in the presence of the same protic acid catalyst and inert solvent as used in step (a) under conditions that allow rapid removal of the alcohol as a by-product by distillation.

9. A process according to claim 1, characterized in that it "further comprises the preparation of an ar.ropodicide insecticide of Formula VII by (a) hydrogenating the compound of Formula I to form a compound of Formula V V (b) reacting the compound of Fó-lamu V with the compound of Formula VI SAW to form a compound of Formula VII having substantially the same absolute configuration as the compound of Formula I