Entitled: alpha, storage method of α- difluoro acetaldehyde alkyl hemiacetal
Technical field
[0001]
　The present invention, alpha, a method for the storage of α- difluoro acetaldehyde alkyl hemiacetal.
Background technique
[0002]
　Α is expressed by the formula [1], alpha-difluoro acetaldehyde are compounds useful as intermediates for the material or medicines, agricultural chemicals advanced materials field.
[Formula 1]

　difluoromethyl (-CHF 2 ) is one fluorine atom two and a hydrogen atom with a high electronegativity, are attached to the same carbon atom. This unique structure is water-repellent, transparency synthesized various materials therewith, is believed to closely related to characteristics such as low dielectric property, specific bioactivity, mimic effects. Thus, alpha, alpha-material is that used difluoro acetaldehyde as building blocks, in the field of advanced materials field and pharmaceutical and agrochemical intermediates, have been the subject of active research and development.
[0003]
　Such alpha, method for producing α- difluoro acetaldehydes, the presence of a catalyst, to esters having a difluoromethyl group, a reduction reaction using a hydride reducing agent such as lithium aluminum hydride is known (Non Patent Document 1). Further, the applicant, alpha, alpha-difluoro acetic acid esters to the presence of a ruthenium catalyst, hydrogen (H 2 discloses a method by reduction reaction with) (Patent Document 1).
[0004]
　On the other hand, substances that aldehydes are unstable, gradually is known to polymerize with other aldehydes molecules (Non-patent Document 2). For aldehyde that is an object of the invention, which are directly connected difluoromethyl group is a strong electron withdrawing group, self-polymers, Mizuwatai, hemiacetal body, acetalized, and that these structural features compound combined like, also be obtained as a plurality of stable equivalents, disclosed in Patent Document 1.
[0005]
　Thus, aldehydes difluoromethyl group are directly connected tended easily converted into a plurality of compounds. Therefore, the applicant, alpha, alpha-difluoro acetaldehyde, in the presence of an alcohol represented by the general formula [2], represented by the general formula [3] alpha, form alpha-difluoro acetaldehyde alkyl hemiacetal to place, by adjusting the amount of alcohol coexisting, the hemiacetal is easily stably present in the system (improvement of storage stability), together with a compound other than the hemiacetal (dimer) also found specific phenomenon hardly generated as much, have reported that effect in Patent Document 2.
[Formula 2]

wherein, R 1 represents an alkyl group or a substituted alkyl group. ]
[Formula 3]

[wherein, R 1 is the general formula [2] R in 1 same as. ]
CITATION
Patent Document
[0006]
Patent Document 1: WO 2014/115801 Patent
Patent Document 2: International Publication No. WO 2016/017318
Non-Patent Document
[0007]
Non-Patent Document 1: The Journal of Organic Chemistry, 1997, 62 (25), 8826-8834.
Non-Patent Document 2: Synthetic Organic Chemistry, Volume 19, No. 3 (1961), 254 - 260
Summary of the Invention
Problems that the Invention is to Solve
[0008]
　alpha, alpha-difluoro acetaldehyde, self polymer, Mizuwatai, hemiacetal and the like, as obtained it stable equivalents, since it is already well-known fact in the patent literature mentioned above, those skilled in the art referring to these patent documents, alpha, alpha-presence of difluoro acetaldehyde and alcohol, represented by the general formula [3] alpha, it is easy to form the alpha-difluoro acetaldehyde alkyl hemiacetal.
[0009]
　Further, in the method described in Patent Document 2, alpha, alpha-term storage as difluoro acetaldehyde hemiacetals becomes possible and it can be said that this compound phenomenon peculiar to the general formula [4] alpha, alpha-difluoro acetaldehyde dimers can be suppressed the generation of (hereinafter, simply herein may be referred to as "dimer").
[Formula 4]

[wherein, R 1 is R in the general formula [2] 1 same as. ]
[0010]
　Thus, although the method disclosed in Patent Document 2 is a useful method in the preservation of the hemiacetal, the method that some limitations (within the system to storage conditions is neutral, the content of water it is 1000ppm or less, the total number of moles of alcohol in the system is, alpha, alpha-difluoro acetaldehyde 1.15 times the total number of moles, at most 4.00 times) has, for a long period of time carrying out the storage, was not necessarily a simple method.
[0011]
　Further, as described in the, alpha, alpha-difluoro acetaldehyde, although improved storage stability by forming a hemiacetal, decomposition proceeds during the storage, difluoro acetic acid will by-produced as a degradation product it was (Comparative example to be described later). Once the difluoroacetate thus generated, this compound itself is a strong acid, since it affects the material of the reaction vessel by this amount is increased, alpha, not suitable for long-term storage of α- difluoro acetaldehyde Met.
[0012]
　Therefore, difluoro acetaldehyde hemiacetal, conditions degrade during storage does not proceed, that is, the findings for improving the storage stability has been desired.
Means for Solving the Problems
[0013]
　In view of such problems, the present inventors have conducted extensive studies. As a result, the general formula [3] with α represented, alpha-difluoro acetaldehyde alkyl hemiacetal, an inert gas atmosphere, upon storage in a gas-liquid state and a vapor phase and a liquid phase in a closed container, the gas the oxygen concentration of the phase section 5000ppm or less, and, by the light shielding conditions, obtained a finding that the formation of difluoro acetic acid does not itself decomposed can be suppressed, thereby completing the present invention.
[0014]
　That is, the present invention provides the following [Invention 1] - provides the inventions described in [Invention 6].
[0015]
　[Invention 1]
　general formula [3] with α represented, the α- difluoro acetaldehyde alkyl hemiacetal, oxygen (O 2 ) or an atmosphere of an inert gas, the gas having a gas phase and the liquid phase in the sealed container a method of storing a liquid state, oxygen (O in the vapor phase in the container 2 ) concentration is adjusted to be 5000ppm or less, then, alpha, alpha-difluoro acetaldehyde alkyl hemiacetal, under dark conditions, the vessel in comprising the step of storing, method.
[0016]
　[Invention 2]
　The storage is carried out in a temperature range of -50 ~ 80 ° C., the method according to the invention 1.
[0017]
　[Invention 3]
　comprising the following steps, alpha, storage method α- difluoro acetaldehyde alkyl hemiacetal.
　[First Step]
　alpha represented by the general formula [3], and supplies the α- difluoro acetaldehyde alkyl hemiacetal to the container, within the container, the alpha, a liquid phase consisting of α- difluoro acetaldehyde alkyl hemiacetal , forming a gas-liquid state with a vapor phase portion.
　[Second Step]
　After the first step, the oxygen (O into the container 2 a) or inert gas filled, step of adjusting so that the oxygen concentration in the gas phase in the vessel becomes 5000ppm or less.
　[Third Step]
　After the second step, and sealing the container, alpha, the α- difluoro acetaldehyde alkyl hemiacetal, under dark conditions, the step of storing in a container.
[0018]
　[Invention 4]
　In the third step, the storage performed at a temperature range of -50 ~ 80 ° C., the method according to the second aspect.
[0019]
　[Invention 5]
　represented by the general formula [5] alpha, alpha-difluoro acetic acid esters and the alcohol represented by the general formula [2] and a solvent in the presence of a base and a ruthenium catalyst, hydrogen (H 2 ) by reaction with the general formula [3] with α represented, to produce α- difluoro acetaldehyde alkyl hemiacetal, then use the hemiacetal as a starting material, the method according to any one of inventions 1 to 4 .
[Chemical Formula 5]

[wherein, R 2 represents an alkyl group or a substituted alkyl group. ]
[0020]
　[Invention 6]
　the general formula [3] with α represented, R in the α- difluoro acetaldehyde alkyl hemiacetal 1 is a methyl group or an ethyl group, The method according to any one of Inventions 1 to 5.
[0021]
　According to the present invention, alpha, alpha-a decomposition product of difluoro acetaldehyde alkyl hemiacetal, an effect that generation of difluoro acetic acid can be suppressed.
DESCRIPTION OF THE INVENTION
[0022]
　The present invention will be described in detail. The scope of the invention should not be restricted to these descriptions, even with the addition to the following examples, can be suitably changed and then practiced within a range not departing from the spirit of the present invention. Note that all of the publications cited herein, for example, prior art documents, and publications, patent publications and other patent documents, are incorporated herein by reference.
[0023]
　Α represented by the general formula [3] is an object of the present invention, R in the α- difluoro acetaldehyde hemiacetal 1 represents an alkyl group or a substituted alkyl group. In addition, R in the dimer represented by the general formula [4] 1 for also, R in the hemiacetal 1 is synonymous with.
[0024]
　( "Alkyl group" referred to herein, indicates that the "unsubstituted alkyl") alkyl group is a linear or branched alkyl group having 1 to 10 carbon atoms, 3 to 10 carbon atoms It shows a cyclic alkyl group. For example, a methyl group, an ethyl group, n- propyl group, i- propyl, n- butyl group, i- butyl, s- butyl, t- butyl group, n- pentyl group, n- octyl group, n- decyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group. Substituted alkyl groups, on any of the carbon atoms of the alkyl group, any number and any combination, have a substituent. Substituents according a halogen atom, a lower alkoxy group, lower haloalkoxy group, cyano group or lower alkoxycarbonyl group. Specifically, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, fluoromethoxy group, chloromethoxy group, bromomethoxy group, a methoxycarbonyl group, an ethoxycarbonyl group and a propoxycarbonyl group. In this specification, the term "lower", having 1 to 6 carbon atoms, means a straight-chain or branched chain or cyclic (in the case of 3 or more carbon atoms).
[0025]
　Alpha formula [3], alpha-Of-difluoro acetaldehyde alkyl hemiacetal, R 1 that is a methyl group or an ethyl group, i.e., alpha, alpha-difluoromethyl acetaldehyde methyl hemiacetal or alpha, alpha-difluoro-acetaldehyde ethyl hemiacetal are preferably used from ease of availability.
[0026]
　Subjected to storage, alpha represented by the general formula [3], as a manufacturing method of α- difluoro acetaldehyde alkyl hemiacetal, for example, represented by as described in Patent Document 1, the general formula [5] alpha, alpha-difluoro acetic acid esters and the alcohol represented by the general formula [2] and a solvent in the presence of a base and a ruthenium catalyst can be prepared by reacting with hydrogen.
[0027]
　Further, hydride reduction, etc. difluoro acetic ester disclosed in Non-Patent Document 1, can be prepared by known methods, methods described in Patent Document 1, particularly advantageous in the production of the hemiacetal in large scale is there. Since it is important in the practice of the present invention, it will be described below this manufacturing method.
[0028]
　Α represented by the general formula [5], R in the α- difluoro acetates 2 represents an alkyl group or a substituted alkyl group, each definition, R in the general formula [3] or the general formula [4] 1 as synonymous.
[0029]
　Ruthenium catalysts which can be used in this reaction is not particularly limited, for example, it is preferable to use a ruthenium catalyst represented by the following general formula [6] or formula [7].
[Formula 6]

[wherein, each R is independently a hydrogen atom, an alkyl group, a substituted alkyl group, an aromatic ring group or substituted aromatic ring group, Ar each independently represent an aromatic ring group or substituted aromatic ring group, X each independently formal charge of -1 or 0 ligand (the total formal charge of the three X is -2) represents, n represents represents an integer of 1 or 2 independently. ]
[Chemical Formula 7]

wherein, Ph represents a phenyl group. ]
[0030]
　Alkyl group as defined ruthenium catalyst represented by the general formula [6], R in the general formula [3] or the general formula [4] 1 is synonymous with. Aromatic ring group of the ruthenium catalyst is an aromatic heterocyclic group containing an aromatic hydrocarbon group or a nitrogen atom, a hetero atom such as an oxygen atom or a sulfur atom. Having 6 to 18 carbon atoms Specific examples of the aromatic hydrocarbon group, a phenyl group, a naphthyl group and an anthryl group, also aromatic heterocyclic group a pyrrolyl group (a nitrogen protecting body Specific examples of heteroatom-containing including), pyridyl group, furyl group, including also a thienyl group, indolyl group (the nitrogen-protected form), quinolyl group, a benzofuryl group and benzothienyl group.
[0031]
　Ruthenium catalyst represented by the general formula [6], the "substituent" in the substituted alkyl group and substituted aromatic ring group, an alkyl group or an aromatic ring group of the, on any of the carbon atoms, any number and in any combination, refers to those present. Substituents according a halogen atom, a lower alkyl group, lower haloalkyl group, a lower alkoxy group, lower haloalkoxy group, cyano group, lower alkoxycarbonyl group, aromatic ring group, a carboxyl group, protected carboxyl group, an amino group, an amino protection of groups is a protecting member such as a hydroxyl group, and a hydroxyl group. Specifically, fluorine, chlorine, bromine, methyl group, ethyl group, propyl group, fluoromethyl group, chloromethyl group, bromomethyl group, a methoxy group, an ethoxy group, a propoxy group, fluoromethoxy group, chloromethoxy group, bromomethoxy containing group, a methoxycarbonyl group, an ethoxycarbonyl group, polypropoxylated isobornyl group, a phenyl group, a naphthyl group, an anthryl group, (including nitrogen-protected form) a pyrrolyl group, a pyridyl group, a furyl group, a thienyl group, also an indolyl group (the nitrogen-protected form ), quinolyl group, a benzofuryl group, etc. benzothienyl group.
[0032]
　Further, the substituted alkyl group of ruthenium catalyst represented by the general formula [6], any carbon atoms in the alkyl group of the - carbon single bond, in any number and any combination, carbon - carbon double bond or carbon - it is also possible to replace the carbon triple bond (of course, an alkyl group substituted with these unsaturated bonds may also have a similar said substituent). Depending on the kind of substituents in some cases a substituent is itself involved in side reactions, but can be minimized by adopting suitable reaction conditions. Further, "according substituent" of the the "aromatic ring group" of a halogen atom, a lower alkyl group, lower haloalkyl group, a lower alkoxy group, lower haloalkoxy group, cyano group, lower alkoxycarbonyl group, a carboxyl group, protection of carboxyl group, amino group, protected amino group, protected, etc. hydroxyl groups and hydroxyl groups can also be substituted. Furthermore, a pyrrolyl group, an indolyl group, a carboxyl group, an amino-protecting group and hydroxyl group, Protective Groups in Organic Synthesis, Third Edition, 1999, John Wiley & Sons, a protecting group as described in Inc. or the like.
[0033]
　Of the ruthenium catalyst represented by the general formula [6], a ruthenium catalyst represented by the following formula {(trade name "Ru-MACHO", manufactured by Takasago International Corporation) is commercially available as} has high activity, particularly preferred.
[Formula 8]

wherein, Ph represents a phenyl group. ]
　When reacting with hydrogen, it is necessary to carried out in the presence of a base, the three X ligand of the ruthenium catalyst, at least one BH 4 when taking the reaction in the absence of a base It can also be carried out.
[0034]
　Meanwhile, the ruthenium catalyst represented by the general formula [7], it is also possible to prepare in a known manner, which is commercially available under the trade name of "Ru-SNS" (manufactured by Sigma-Aldrich Japan LLC) it is convenient to use.
[0035]
　Furthermore, in addition to the ruthenium catalyst mentioned above, for example, Angew. Chem. Int. Ed . 2013, 52, 2538-2542, Organometallics 2012, 31, 5239-5242, Angew. Chem. Int. Ed. 2012, 51, 2772 -2775 and Angew. Chem. Int. Ed. 2006, 45, include a ruthenium catalyst according to 1113-1115 and the like. Its typical show (ruthenium homogeneous catalyst) in FIG. 1 (abbreviations / Et; ethyl, t-Bu; tert-butyl group, Ph; phenyl, i-Pr; isopropyl), naturally but it is not limited thereto. Even these ruthenium catalysts can be used under the same reaction conditions.
[Formula 9]

[0036]
　The amount of the ruthenium catalyst, alpha, alpha-difluoro acetic acid esters may be used 0.000001 mol or more with respect to 1 mol, preferably from 0.00001 to 0.005 mol, from 0.00002 to 0.002 mol particularly preferred.
[0037]
　Base is an alkali metal hydrogen carbonates, alkali metal carbonates, alkali metal hydroxides, tetraalkylammonium hydroxide, alkali metal alkoxides, organic bases, alkali metal bis (trialkylsilyl) amides, and alkali metal is a borohydride or the like. Specifically, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium and potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, tetramethylammonium hydroxide, tetraethylammonium hydroxide, water oxidation tetra n- propyl ammonium, tetra-n- butylammonium hydroxide, lithium methoxide, sodium methoxide, potassium methoxide, lithium ethoxide, sodium ethoxide, potassium ethoxide, lithium isopropoxide, sodium isopropoxide, potassium isopropoxide, lithium tert- butoxide, sodium tert- butoxide, potassium tert- butoxide, triethylamine, diisopropylethylamine, 4-dimethylaminopyridine pin Jin, 1,8-diazabicyclo [5.4.0] undec-7-ene, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, lithium borohydride, sodium borohydride and potassium borohydride and the like. Among these alkali metal alkoxides (carbon number of alkoxide 1-6) are preferred, lithium methoxide, sodium methoxide and potassium methoxide particularly preferred.
[0038]
　Incidentally, as the synthesis examples described below, sodium methoxide is available as a normal methanol solution. Therefore, in the reaction system, so that the methanol remains. That is, methanol, at least a portion would serve as the alcohol represented by the general formula [2].
[0039]
　Of the alcohols represented by the general formula [2], R 1 is α represented by general formula [3] described above, R of α- difluoro acetaldehyde hemiacetal 1 is synonymous with.
[0040]
　Specific compounds of the alcohols methanol, ethanol, n- propanol, isopropanol, butanol, tert- butanol, although benzyl alcohol and the like, among these, methanol, ethanol, n- propanol, isopropanol are preferable, among them, methanol and ethanol, readily available anhydrous reagents in large scale, moreover alpha, alpha-difluoro acetaldehyde alkyl hemiacetal stability improving effect for greater especially preferred.
[0041]
　Amount of use of the case of using a base, the starting materials alpha, alpha-difluoro acetic acid esters 1 mole may be used more than 0.001 mol with respect to, preferably 0.005 to 5 moles, 0.01 to 3 moles It is particularly preferred.
[0042]
　The amount of hydrogen gas, alpha, alpha-difluoro acetic acid esters may be used more than 1 mol per 1 mol, preferably large excess, a large excess particularly preferred under pressure (hydrogen pressure will be described later).
[0043]
　Hydrogen pressure is not particularly limited, usually, 10 ~ 0.01 MPa (absolute pressure reference. Hereinafter, in this specification the same), and preferably from 6 ~ 0.1 MPa, and more preferably 5 ~ 0.3 MPa.
[0044]
　The amount of the reaction solvent, the raw alpha, alpha-difluoro acetic acid esters 1 mole may be used 0.03 L (liter) or more with respect to, preferably 0.05 ~ 10L, particularly preferably 0.07 ~ 7L .
[0045]
　The reaction time may be performed within 72 hours, because it varies from a source substrate and the reaction conditions, gas chromatography, liquid chromatography to follow the progress of the reaction by an analytical means nuclear magnetic resonance, etc., decrease in the raw material substrate the point at which no longer observed almost the end point should be set. Thus α represented by the general formula [3] can be produced is α- difluoro acetaldehyde alkyl hemiacetal, can be used as a starting material in the preservation method of the present invention.
[0046]
　In this hydrogenation reaction, once, alpha, alpha-difluoro acetaldehyde (Formula equivalent to [1]) is generated, and reacts with alcohol present in the system, a stable alkyl hemiacetal (formula [ 3] α represented, is rapidly converted into α- difluoro acetaldehyde alkyl hemiacetal). Thus, the starting material in this storage method is represented by the general formula [3] alpha, alpha-other-difluoro acetaldehyde alkyl hemiacetal, an alcohol represented by the general formula [2], and the general formula [4] there may contain dimer (examples below), even in such a starting material, storage method of the present invention can be suitably implemented.
[0047]
　Next, a description how to save in the present invention.
[0048]
　The present invention has the general formula [3] with α represented, the α- difluoro acetaldehyde alkyl hemiacetal, oxygen (O 2 ) or an atmosphere of an inert gas, the gas having a gas phase and the liquid phase in the sealed container a method of storing a liquid state, oxygen concentration in the gas phase in the vessel is adjusted to be 5000ppm or less, then, alpha, the α- difluoro acetaldehyde alkyl hemiacetal, under dark conditions, be stored in a container , it is characterized in.
[0049]
　Further, even when saving by the following steps, for inclusion in embodiments of the present invention, for these steps, it will be described below in order.
　[First Step]
　alpha represented by the general formula [3], the α- difluoro acetaldehyde alkyl hemiacetal, then fed to the kettle, within the container, the alpha, liquid phase consisting of α- difluoro acetaldehyde alkyl hemiacetal and a step of forming a gas-liquid state with a vapor phase portion.
　[Second Step]
　After the first step, and sealing the container, followed oxygen (O within the container and 2 ) or filled with an inert gas, oxygen concentration in the gas phase portion within said vessel is 5000ppm or less step of adjusting to.
　[Third Step]
After the second step, and sealing the container, alpha, the α- difluoro acetaldehyde alkyl hemiacetal, under dark conditions, the step of storing in a container.
[0050]
　[1st to 3rd steps]
　alpha represented by the general formula [3], when supplying the α- difluoro acetaldehyde alkyl hemiacetal in a container, the container used is a closed can keep gas-liquid state in the container a container, as long as the material that does not transmit oxygen under dark conditions (including glass lining) glass vessel, stainless steel or the like, both can be suitably used. For example, fixed storage container at a storage tank, and a container such as a drum for use in transportation.
[0051]
　In the present invention, firstly, alpha, and supplies the α- difluoro acetaldehyde alkyl hemiacetal into the container.
　When supplying the hemiacetal to the container, alpha, alpha-difluoro acetaldehyde alkyl hemiacetal, 20% or more and less than 99% of the volume of the container, preferably filled less than 95% to 50%. Filling amount is dependent on the size of the vessel used, so that in this range, may be performed while adjusting, but the hemiacetal of interest in the present invention is less than 20% by volume of the container and thus the amount to be saved is small. This is the actual the hemiacetal produced, means that the number of working steps to be saved increases, not be economical. On the other hand, if the volume of the container becomes 99% or more, the volume change in the hemiacetal is caused by variations in temperature of the external (out of the container), it may cause leakage of container breakage or internal liquid. In a closed container, when keeping the oxygen concentration ranges disclosed in the present invention, not only gas phase only, the liquid phase portion (alpha, alpha-difluoro acetaldehyde alkyl hemiacetal) it is necessary to consider also the dissolved oxygen concentration (container oxygen concentration range of the inner varies with time, because it may affect the preserving effect of the present invention).
[0052]
　After feeding the hemiacetal to the vessel, nitrogen, filled with an inert gas such as argon, is not particularly limited method of filling inert gas into the container. For example,
　as described in the Examples below, the container alpha, alpha-after supplying difluoro acetaldehyde alkyl hemiacetal into the container, the liquid phase portion of the vessel inert gas (liquid phase section, alpha, alpha - after bubbling are) included difluoro acetaldehyde alkyl hemiacetal, sealing the vessel, or,
　alpha, after supplying α- difluoro acetaldehyde alkyl hemiacetal into the container, sealing the container, alpha, after α- difluoro acetaldehyde alkyl hemiacetal was vacuum operation so as not to be discharged out of the vessel, blowing an inert gas into the liquid phase in the vessel, or bubbling an inert gas into the liquid phase portion, exemplified etc It is.
　In either case, as well as reducing the dissolved oxygen concentration in the liquid phase portion, at the same time the gas phase of the vessel will be gradually replaced with the inert gas.
[0053]
　Incidentally, to increase the removal efficiency of dissolved oxygen, it is preferable to use a stirring operation, or degassing operations the liquid phase portion to those methods. Depending on the size of the storage of the hemiacetal, it is possible to reduce efficiently the oxygen concentration by combining these methods appropriately.
[0054]
　The type of inert gas used nitrogen, the gas which does not adversely influence the reaction such as argon.
[0055]
　Next, in the present invention, the oxygen concentration in the gas phase portion, 5000 ppm or less, preferably 1000ppm or less, particularly preferably to adjust the oxygen in the container so that the 300ppm or less.
　It is not limited to the specific method for preparation method of the oxygen concentration. For example,
　(1) is adjusted so that the oxygen concentration range of the by introducing an inert gas into the vessel, or,
　blowing and (2) oxygen, nitrogen, a mixed gas of an inert gas such as argon, lowering the oxygen concentration in the container to the appropriate range or,
　(3) alpha, alpha-difluoro acetaldehyde alkyl hemiacetal sealed vessel containing, under vacuum in the container, method and the like.
　In the case of blowing the oxygen, nitrogen, a mixed gas of an inert gas such as argon, each ratio in the mixed gas of oxygen and inert gas is not particularly limited.
[0056]
　By adopting these conditions, alpha, alpha-polymerization of difluoro acetaldehyde alkyl hemiacetal, although the reaction such as oxidation can be sufficiently prevented, among these, the adjustment method of (1) or (2) the oxygen concentration in the gas phase, for easily adjusted to 5000ppm or less is preferably used.
[0057]
　Incidentally, the range of the oxygen concentration in the gas phase, for example, it is also possible to adjust to less than 10 ppm (less than 0 ppm ~ 3 ppm), since a sufficient preservative effect can be obtained in the range of oxygen concentration mentioned above in the present invention, for example, it is not necessary to lower the oxygen concentration to the limit of the numerical around 0 ppm. In order to reduce the oxygen concentration to the limit of the number, in the present invention alpha, after filling the α- difluoro acetaldehyde alkyl hemiacetal in a container, sealed, it is necessary to perform to severe vacuum conditions. However, alpha, alpha-difluoro acetaldehyde alkyl hemiacetal itself, since sometimes would be discharged to the outside of the container, that the oxygen concentration ranges disclosed in Examples below, the load in terms of equipment surfaces and workmanship not applied, it can be said that the preferred embodiment.
[0058]
　Temperature subjected to preservation is not particularly limited, it is usually possible, is stored in a temperature range of -50 ~ + 80 ℃. Among them, for example, it is preferably stored at -40 ~ + 70 ° C., about room temperature (10 ~ 30 ℃) is particularly preferred.
Example
[0059]
　Hereinafter, a detailed explanation of the present invention through examples, the present invention is not limited to these examples. Here, the determination of product (composition ratio and yield), and the reaction mixture was calculated based on the "mole%" of compositions obtained by measuring the nuclear magnetic resonance spectrometer (NMR). In addition, "n.d." in the table indicates that it is undetected.
[0060]
　[Synthesis Example] alpha, alpha-difluoro-acetaldehyde ethyl hemiacetal (abbreviation: DFAL-EtOH) Synthesis of
　alpha stainless steel pressure reaction vessel, alpha-difluoro-ethyl acetate 109 g (0.88 mol), represented by the following formula ruthenium catalyst 0.107 g (0.18 mmol), (0.22 mol as sodium methoxide) of a 28% sodium methoxide methanol solution 42 g, methanol 290mL was added, the reaction vessel was replaced five times with hydrogen gas, hydrogen pressure It was set to 1.0 MPa, and was stirred for 8 hours at 15 ° C..
[Chemical Formula 10]

　After the reaction was completed 19 than F-NMR analysis, alpha, converting 65% of the α- ethyl difluoroacetate, selectivity of DFAL-EtOH was 91%. 19 F-NMR internal standard alpha, alpha, and quantified by α- trifluorotoluene.
　Was added acetic acid 13.2 g (0.22 mol) to the reaction-terminated liquid, the pH became 8, it is determined that became substantially neutral, was discontinued added. This liquid was directly distilled (bottom temperature ~ 66 ° C., vacuum degree ~ 2.1 kPa) by subjecting to obtain a methanol solution containing DFAL-EtOH. The solution precision distillation (35 theoretical plates, distillation temperature 92 ° C., vacuum degree ~ 35 kPa) to separate most of the methanol by. Ethanol 96g in the still (bottom) of (2.08 mol) was added distilled to continue to give 45.9g of DFAL-EtOH as a fraction.
　The fraction, ethanol, DFAL-EtOH, found that contains "dimer" from ethyl hemiacetal represented by the following formula, each of purity (mole%) ethanol 8.6 wt%, DFAL -EtOH is 83.6wt%, "dimer" was 7.1wt%. The yield considering the purity was 41%.
Formula 11]

　with a fraction obtained in this Synthesis Example was carried out following Examples and Comparative Examples.
[0061]
　[Example 1-2, Comparative Example 1-2]
　glass container having an internal volume of 100 ml, alpha, alpha-difluoro-acetaldehyde ethyl hemiacetal (83.6wt%), and ethanol (8.6 wt%), the following formula the mixture 50g of dimer (7.1wt%) represented in filling, after filling with nitrogen, to mixture was subjected to bubbling operation with nitrogen gas.
[Formula 12]

　by bubbling operation, respectively the oxygen concentration in the container, about 16000 ppm (Example 1), upon reaching approximately 7000ppm (Example 2), a mixed gas of oxygen and nitrogen, the oxygen concentration in the container is filled in the container so that the values shown in Table 1 below and then sealed from light.
　Next, install the sealed container in a thermostatic chamber and left for 24 hours at constant temperature of 70 ° C.. After 24 hours, the container was taken out from the constant temperature bath, the content liquid to confirm the presence or absence of degradation product as measured by nuclear magnetic resonance analyzer (NMR). The results are shown in Table 1.
[0062]
[Table 1]

　From Table 1, in Examples 1-2, can not difluoro acetic acid confirmed to be a practical problem, alpha, alpha-difluoro-acetaldehyde ethyl hemiacetal it can be seen that no degradation. In contrast, in Comparative Example 1-2, formation of difluoro acetic acid was confirmed a decomposition product.
[0063]
　[Example 3, Comparative Example 3-5]
　to the contents quartz cell container of the product 10 ml, alpha, alpha-difluoro-acetaldehyde ethyl hemiacetal (83.6wt%), and ethanol (8.6 wt%), table by the following formula It is the filling the mixture 5.0g of dimeric (7.1wt%), after filling in a nitrogen atmosphere, to a mixed solution was subjected to bubbling operation with nitrogen gas.
[Formula 13]

　by bubbling operation, where the oxygen concentration in the container becomes 6000 ppm, oxygen and mixture of nitrogen, after the oxygen concentration in the container was filled to a value shown in Table 2 below, the sealing did.
　Thereafter, the vessel was placed 7 hours to different environments irradiation conditions at 25 ° C., to confirm the formation of the degradation product. The results are shown in Table 2.
[0064]
[Table 2]

　From Table 2, in Example 3, can not difluoro acetic acid confirmed to be a practical problem, alpha, alpha-difluoro acetaldehyde alkyl hemiacetal it can be seen that no degradation. In contrast, in Comparative Example 3-5, formation of difluoro acetic acid was confirmed a decomposition product.
[0065]
　[Example 4-5, Comparative Examples 6-10]
　having an internal volume of 100ml transparent, shading in each of the glass container, alpha, of α- difluoro acetaldehyde ethyl hemiacetal (83.6wt%), ethanol (8.6 wt %) and after dimer represented by the following formula a mixture 50g of (7.1Wt%) was filled under nitrogen and bubbling nitrogen gas.
[Chemical Formula 14]

　by bubbling, after the oxygen concentration in the container was filled to a value shown in Table 3 below, sealed (but not sealed containers for Comparative Example 10 was an open system). Then, under sunlight vessel at 25 ° C., placed for 30 days, confirmed the formation of degradation products. The results are shown in Table 3 below.
[0066]
[Table 3]

　From Table 3, in Example 4-5, not difluoro acetic acid which is a practical problem observed, alpha, alpha-difluoro acetaldehyde hemiacetal it can be seen that no degradation. In contrast, in Comparative Examples 6-10, the generation of difluoro acetic acid was observed a degradation product.
[0067]
　From the above results, the present invention is, by storing at a specific oxygen concentration and the light-shielding conditions, for a long period, without generation difluoroacetate, it can be said that effective preservation methods.
Industrial Applicability
[0068]
　METHOD alpha, of α- difluoro acetaldehyde alkyl hemiacetal storage of the present invention, storage of pharmaceutical and agrochemical intermediates, storage, is to be expected as a distribution method.
The scope of the claims
[Claim 1]
Α represented by the general formula [3], the α- difluoro acetaldehyde alkyl hemiacetal, oxygen (O 2 storage) or an atmosphere of an inert gas, in a gas-liquid state and a vapor phase and a liquid phase in the sealed container a method of oxygen (O in the vapor phase in the container 2 is) concentration adjusted to 5000ppm or less, then, alpha, the α- difluoro acetaldehyde alkyl hemiacetal, stores shading conditions, in a vessel comprising the step, way.
Formula 15]

wherein, R 1 represents an alkyl group or a substituted alkyl group. ]
[Claim 2]
The storage is carried out in a temperature range of -50 ~ 80 ° C., The method of claim 1.
[Claim 3]
Comprising the following steps, alpha, storage method α- difluoro acetaldehyde alkyl hemiacetal.
　[First Step]
　alpha represented by the general formula [3], and supplies the α- difluoro acetaldehyde alkyl hemiacetal to the container, within the container, the alpha, a liquid phase consisting of α- difluoro acetaldehyde alkyl hemiacetal , forming a gas-liquid state with a vapor phase portion.
[Formula 16]

wherein, R 1 represents an alkyl group or a substituted alkyl group. ]
　[Second Step]
　After the first step, the oxygen (O into the container 2 a) or inert gas filled, step of adjusting so that the oxygen concentration in the gas phase in the vessel becomes 5000ppm or less.
　[Third Step]
　After the second step, and sealing the container, alpha, the α- difluoro acetaldehyde alkyl hemiacetal, under dark conditions, the step of storing in a container.
[Claim 4]
Wherein in the third step, the stored at a temperature range of -50 ~ 80 ° C., The method of claim 2.
[Claim 5]
Α represented by the general formula [5], alpha-difluoro acetic acid esters of the general formula and the alcohol represented a solvent [2], the presence of a base and a ruthenium catalyst, hydrogen (H 2 is reacted with) Accordingly, the general formula [3] alpha, to produce α- difluoro acetaldehyde alkyl hemiacetal, then use the hemiacetal as a starting material, the method according to any one of claims 1 to 4.
[Formula 17]

wherein, R 2 represents an alkyl group or a substituted alkyl group. ]
[Formula 18]

wherein, R 1 represents an alkyl group or a substituted alkyl group. ]
[Claim 6]
Α represented by the general formula [3], alpha-R in difluoro acetaldehyde alkyl hemiacetal 1 is a methyl group or an ethyl group, The method according to any one of claims 1 to 5.