Method for manufacturing iodine-containing tertiary alcohol esters

Abstract

A method for manufacturing an iodine-containing tertiary alcohol ester includes the following steps: a nucleophilic step, in which an iodine-containing compound represented by the following formula (1) is reacted with a nucleophilic reagent; and an acylation step, in which an acylation agent is added to the reaction solution obtained from the aforementioned nucleophilic step to obtain an iodine-containing tertiary alcohol ester, wherein the aforementioned nucleophilic step and the aforementioned acylation step are performed continuously after the aforementioned nucleophilic step without a separation step.

Description

Technical Field

[0001] This invention relates to a novel method for manufacturing iodine-containing tertiary alcohol esters. Background Technology

[0002] In recent years, advancements in photolithography technology have led to rapid miniaturization of semiconductors (patterns) and pixels in the manufacturing of semiconductor components and liquid crystal display components. A common method for pixel miniaturization is to shorten the wavelength of the exposure light source. Specifically, while ultraviolet light, represented by gamma rays and i-rays, was previously used, far-ultraviolet exposure, such as KrF excimer lasers (248nm) and ArF excimer lasers (193nm), has become central to mass production, further promoting the adoption of extreme ultraviolet (EUV) lithography (13.5nm). Additionally, electron beams (EB) are also used to form fine patterns.

[0003] To date, common anti-corrosion materials are polymeric anti-corrosion materials capable of forming amorphous films. Examples include polymethyl methacrylate, polyhydroxystyrene with acid-dissociable groups, or alkyl polymethyl methacrylate (see, for example, Non-Patent Literature 1).

[0004] In addition, in recent years, there has been development of iodine-containing polymers that are useful for photolithography (see, for example, Patent Document 1).

[0005] Existing technical documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2018-172640

[0008] Non-patent literature

[0009] Non-Patent Document 1: Nobuji Okazaki, 8 others, "40 Years of Photolithography," S&T Publishing, December 9, 2016 Summary of the Invention

[0010] The problem the invention aims to solve

[0011] As described in Patent Document 1, the demand for iodine-containing polymers as corrosion-resistant materials has increased in recent years. Iodine-containing polymers can be synthesized using iodine-containing tertiary alcohol esters, etc. Generally, ester compounds are synthesized by acting an acylating agent on the corresponding alcohol. However, in tertiary alcohol esters, due to the large volume of the corresponding tertiary alcohol, it is sometimes difficult to obtain the ester compound from the alcohol compound using the above methods. Furthermore, in the above methods, it is necessary to separately synthesize / purify the tertiary alcohol, which has disadvantages such as complicated operation and extended manufacturing time.

[0012] In order to solve the above-mentioned problems, the object of the present invention is to provide a method for manufacturing iodine-containing tertiary alcohol esters that can synthesize iodine-containing tertiary alcohol esters with high purity and high efficiency.

[0013] Solution for solving the problem

[0014] In order to solve the above-mentioned problems, the inventors conducted in-depth research and found that by reacting an iodine-containing compound with a specific structure in a specific process, the above-mentioned problems can be solved, and thus the present invention was completed.

[0015] That is, the present invention is as follows.

[0016] <1>

[0017] A method for manufacturing an iodine-containing tertiary alcohol ester, comprising the following steps:

[0018] The nucleophilic step involves reacting an iodine-containing compound, as shown in formula (1), with a nucleophilic reagent; and,

[0019] The acylation step involves adding an acylation agent to the reaction solution obtained from the aforementioned nucleophilic step to yield an iodine-containing tertiary alcohol ester.

[0020] The aforementioned nucleophilic process and the aforementioned acylation process are performed continuously without a separation process after the aforementioned nucleophilic process.

[0021]

[0022] (In the formula,

[0023] A represents an aromatic ring with 6 to 12 carbon atoms.

[0024] -R 1 For -OR 2 (R) 2 - (representing alkyl or aryl), -X (X represents F, Cl, Br, or I), -O-CO-R 4 (R) 4 R represents alkyl, aryl, or of formula (1). 1 The part other than -CO-, -NR 5 R 6 (R) 5 R 6 Each can independently represent a hydrogen atom, alkoxy group, alkyl group, or aryl group. R 5 R 6 Optional bonding to form a ring structure, ), or -OH,

[0025] I represents an iodine atom.

[0026] Y is a monovalent substituent with 0 to 30 carbon atoms.

[0027] n is an integer from 1 to 2.

[0028] m is an integer greater than or equal to 1.

[0029] k is an integer greater than or equal to 0 or 1.

[0030] The total number of n, m, and k does not exceed the number of groups capable of bonding with the aforementioned aromatic ring.

[0031] <2>

[0032] According to the foregoing <1> The method for producing the iodine-containing tertiary alcohol esters, wherein the aforementioned nucleophilic step and the aforementioned acylation step are performed in the same reaction vessel.

[0033] <3>

[0034] According to the foregoing <1> or <2> The method for manufacturing the iodine-containing tertiary alcohol ester is carried out under light-shielding conditions.

[0035] <4>

[0036] According to the foregoing <1> ~ <3> The method for producing an iodine-containing tertiary alcohol ester according to any one of the above methods, wherein the aforementioned nucleophile is a nucleophile other than an organolithium reagent.

[0037] <5>

[0038] According to the foregoing <1> ~ <4> The method for producing an iodine-containing tertiary alcohol ester according to any one of the above-mentioned acylation steps, wherein a nucleophilic catalyst is used in the aforementioned acylation step.

[0039] <6>

[0040] According to the foregoing <1> ~ <5> The method for manufacturing the iodine-containing tertiary alcohol ester described in any one of the following steps includes adding silica gel and removing impurities.

[0041] <7>

[0042] According to the foregoing <1> ~ <6> The method for producing an iodine-containing tertiary ol ester according to any one of the above methods, wherein the compound obtained by reacting the aforementioned iodine-containing compound with the aforementioned nucleophilic reagent in the aforementioned nucleophilic step comprises an iodine-containing tertiary ol salt.

[0043] The effects of the invention

[0044] According to the present invention, a method for manufacturing iodine-containing tertiary alcohol esters capable of synthesizing iodine-containing tertiary alcohol esters with high purity and high efficiency can be provided. Detailed Implementation

[0045] Hereinafter, embodiments of the present invention will be described (hereinafter sometimes referred to as "this embodiment"). It should be noted that this embodiment is an example for illustrating the present invention, and the present invention is not limited to this embodiment.

[0046] In this specification, when using "~" to represent a numerical range as "X~Y", X and Y are included as its endpoints.

[0047] Methods for manufacturing iodine-containing tertiary alcohol esters

[0048] The method for manufacturing an iodine-containing tertiary alcohol ester according to this embodiment (hereinafter, sometimes simply referred to as "the manufacturing method of this embodiment") includes the following steps: a nucleophilic step, in which an iodine-containing compound (hereinafter, sometimes referred to as "raw material iodine compound") represented by formula (1) described later is reacted with a nucleophilic reagent; and an acylation step, in which an acylation agent is added to the reaction solution obtained from the aforementioned nucleophilic step to obtain an iodine-containing tertiary alcohol ester, and the aforementioned nucleophilic step and the aforementioned acylation step are performed continuously after the aforementioned nucleophilic step without a separation step.

[0049] As a compound obtained by reacting the aforementioned iodine-containing compound with the aforementioned nucleophilic reagent in the above-mentioned nucleophilic process, examples include iodine-containing tertiary alkoxides (hereinafter sometimes referred to as "tertiary alkoxides").

[0050]

[0051] (In the formula,

[0052] A represents an aromatic ring with 6 to 12 carbon atoms.

[0053] -R 1 For -OR 2 (R) 2 - (representing alkyl or aryl), -X (X represents F, Cl, Br, or I), -O-CO-R 4 (R) 4 R represents alkyl, aryl, or of formula (1). 1 The part other than -CO-, -NR 5 R 6 (R) 5 R 6 Each can independently represent a hydrogen atom, alkoxy group, alkyl group, or aryl group. R 5 R 6 Optional bonding to form a ring structure, ), or -OH,

[0054] I represents an iodine atom.

[0055] Y is a monovalent substituent with 0 to 30 carbon atoms.

[0056] n is an integer from 1 to 2.

[0057] m is an integer greater than or equal to 1.

[0058] k is an integer greater than or equal to 0 or 1.

[0059] The total number of n, m, and k does not exceed the number of groups capable of bonding with the aforementioned aromatic ring.

[0060] Typically, a method for synthesizing iodine-containing tertiary alcohol esters can be described as follows: reacting an iodine-containing compound with a nucleophilic reagent (nucleophilic step), and then reacting an acylinter with the resulting compound (acylinting step), thereby synthesizing the desired iodine-containing tertiary alcohol ester.

[0061] However, in cases where a large amount of impurities are generated during the nucleophilic process, it is desirable to remove these impurities by quenching the active substance generated in the nucleophilic reaction to obtain an iodine-containing tertiary alcohol, followed by separation / purification, in order to improve the yield. However, if the separated iodine-containing tertiary alcohol is used, esterification of this alcohol can sometimes be difficult in the acylation process. The reason for this is uncertain, but one possible explanation is that the iodine-containing tertiary alcohol has a large molecular structure, thus hindering its reaction with acylating agents such as acid anhydrides due to steric hindrance.

[0062] In contrast, the manufacturing method of this embodiment generates the corresponding tertiary alkoxide by acting a nucleophile on the iodine-containing compound shown in formula (1), and by reacting the alkoxide directly with an acylating agent without quenching and separating it, an iodine-containing tertiary alkoxide can be obtained.

[0063] In this embodiment, the manufacturing method uses an iodine-containing compound of formula (1) with a site showing -(C=O)-R (R being an atom other than carbon) as a raw material, thus generating fewer impurities compared to using iodine-containing ketone compounds or the like as raw materials. Therefore, it is unnecessary to quench the active body (tertiary alkoxide) generated by the nucleophilic reaction and separate it as an iodine-containing tertiary alcohol after the nucleophilic step. Furthermore, since the manufacturing method of this embodiment continuously performs the nucleophilic and acylation steps without a separation step after the nucleophilic step, it is possible to synthesize an iodine-containing tertiary alcohol ester from the iodine-containing compound of formula (1) without using an iodine-containing tertiary alcohol.

[0064] Therefore, according to the manufacturing method of this embodiment, iodine-containing tertiary alcohol esters can be obtained easily, with high purity and high efficiency.

[0065] The manufacturing method of this embodiment will be described in detail below.

[0066] <Nucleoside Infection Process>

[0067] The nucleophilic step in this embodiment is a step of reacting the iodine-containing compound (the raw iodine compound) shown in formula (1) with a nucleophilic reagent. If the raw iodine compound is reacted with the nucleophilic reagent, an iodine-containing tertiary alkoxide (tertiary alkoxide) can be obtained as the active body.

[0068] (The iodine-containing compound shown in formula (1))

[0069] The iodine-containing compound (raw iodine compound) used in the nucleophilic process is the compound shown in formula (1). As mentioned above, the raw iodine compound is a compound having a site shown as -(C=O)-R (R being an atom other than carbon).

[0070]

[0071] In equation (1),

[0072] A represents an aromatic ring with 6 to 12 carbon atoms.

[0073] -R 1 For -OR 2 (R) 2 - (representing alkyl or aryl), -X (X represents F, Cl, Br, or I), -O-CO-R 4 (R) 4 R represents alkyl, aryl, or of formula (1). 1 The part other than -CO-, -NR 5 R 6 (R) 5 R 6 Each can independently represent a hydrogen atom, alkoxy group, alkyl group, or aryl group. R 5 R 6 Optional bonding to form a ring structure, ), or -OH,

[0074] I represents an iodine atom.

[0075] Y is a monovalent substituent with 0 to 30 carbon atoms.

[0076] n is an integer from 1 to 2.

[0077] m is an integer greater than or equal to 1.

[0078] k is an integer greater than or equal to 0 or 1.

[0079] The total number of n, m, and k does not exceed the number of groups that can bond with the aforementioned aromatic ring.

[0080] Additionally, when k and n are both 2 or higher, each R 1 Y and Y can be the same or different.

[0081] In formula (1), A represents an aromatic ring with 6 to 12 carbon atoms. Examples of this aromatic group include benzene, naphthalene, and biphenol, with benzene rings and naphthalene rings being preferred, and benzene rings being even more preferred.

[0082] In equation (1), R 1 Indicates -OR 2 (R) 2 - (representing alkyl or aryl), -X (X represents F, Cl, Br, or I), -O-CO-R4 (R) 4 R represents alkyl, aryl, or of formula (1). 1 (part other than -CO-), -NR 5 R 6 (R) 5 R 6 Each can independently represent a hydrogen atom, alkoxy group, alkyl group, or aryl group. R 5 R 6 (Optional bonding to form a ring structure), or -OH.

[0083] In equation (1), n ​​represents an integer from 1 to 2. Considering reactivity and other factors, 1 is preferred.

[0084] -OR 2 Together with the -(C=O)- site in formula (1), they form an ester group.

[0085] R 2 Indicates alkyl or aryl.

[0086] As R 2 The alkyl and aryl groups shown are not particularly limited and can include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, eicosyl, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloeicosyl, adamantyl, vinyl, propenyl, butenyl, phenyl, naphthyl, anthracene, phenanthrene, tetraphenyl, benzo[a]phenanthrene, pyrene, benzo[a]pyrene, azulene, fluorene, etc. They may contain ether bonds, ketone bonds, and ester bonds.

[0087] The groups in the examples above include isomers. For example, propyl includes n-propyl and isopropyl, and butyl includes n-butyl, sec-butyl, isobutyl, and tert-butyl.

[0088] As mentioned above, R 2 The alkyl group shown is preferably an alkyl group with 1 to 30 carbon atoms, more preferably an alkyl group with 1 to 7 carbon atoms, and particularly preferably an alkyl group with 1 to 4 carbon atoms.

[0089] In addition, as mentioned above, R 2 The aryl group shown is preferably an aryl group with 6 to 20 carbon atoms, more preferably an aryl group with 6 to 16 carbon atoms, and particularly preferably an aryl group with 6 to 12 carbon atoms.

[0090] As mentioned above, R 2 The alkyl or aryl groups shown are preferably methyl, ethyl, propyl, butyl, or benzyl, more preferably methyl, ethyl, propyl, or butyl, and particularly preferably methyl or ethyl. It should be noted that when n is 2 or more, each R... 2 They can be the same or different.

[0091] -X together with the -(C=O)- site in formula (1) constitutes an acyl halide group. X represents F, Cl, Br or I, preferably Cl, F or Br, further preferably Cl or F, and particularly preferably Cl. It should be noted that when n is 2 or more, each X can be the same or different.

[0092] -O-CO-R 4 Together with the -(C=O)- site in equation (1), it forms an anhydride group. R 4 R represents alkyl, aryl, or of formula (1). 1 The part other than -CO-.

[0093] As R 4 Examples of alkyl and aryl groups shown can be cited for the above R 2 Examples of alkyl and aryl groups are shown.

[0094] As mentioned above, R 4 The alkyl group shown is preferably an alkyl group with 1 to 30 carbon atoms, more preferably an alkyl group with 1 to 7 carbon atoms, and particularly preferably an alkyl group with 1 to 4 carbon atoms.

[0095] In addition, as mentioned above, R 4 The aryl group shown is preferably an aryl group with 6 to 20 carbon atoms, more preferably an aryl group with 6 to 16 carbon atoms, and particularly preferably an aryl group with 6 to 12 carbon atoms.

[0096] As mentioned above, R 4 The alkyl or aryl groups shown are preferably methyl, ethyl, propyl, butyl, or phenyl, more preferably methyl, ethyl, or propyl, and particularly preferably methyl or ethyl. It should be noted that when n is 2 or more, each R... 4 They can be the same or different.

[0097] R 4 R represents expression (1) 1 In the case of parts other than -CO-, the raw material iodine compound has a dimer structure as shown in the following formula (1-1).

[0098]

[0099] In equation (1-1), A and R 1 I, Y, m, and k are the same as in equation (1). o independently represents 0 or 1. It should be noted that the total number of o, m, and k does not exceed the number of groups capable of bonding with the aforementioned aromatic ring. Furthermore, when o and k are both 1 or more, each R... 1 Y and Y can be the same or different.

[0100] -NR 5R 6 Together with the -(C=O)- site in formula (1), they form an amide group.

[0101] R 5 R 6 Each can independently represent a hydrogen atom, alkoxy group, alkyl group, or aryl group. As R 5 R 6 Examples of alkyl and aryl groups shown can be cited for the above R 2 Examples of alkyl and aryl groups are shown. Additionally, as R... 5 R 6 The alkoxy groups shown can be categorized as groups with oxygen atoms bonded to these alkyl or aryl groups.

[0102] As mentioned above, R 5 R 6 The alkyl group shown is preferably an alkyl group having 1 to 30 carbon atoms, more preferably an alkyl group having 1 to 7 carbon atoms, and particularly preferably an alkyl group having 1 to 4 carbon atoms. Furthermore, as the aforementioned R... 5 R 6 The aryl group shown is preferably an aryl group with 6 to 20 carbon atoms, more preferably an aryl group with 6 to 16 carbon atoms, and particularly preferably an aryl group with 6 to 12 carbon atoms. As described above, R... 5 R 6 The alkoxy group shown is preferably an alkoxy group with 1 to 30 carbon atoms, more preferably an alkoxy group with 1 to 7 carbon atoms, and particularly preferably an alkoxy group with 1 to 4 carbon atoms.

[0103] From a reactive point of view, the above R 5 R 6 Preferably, at least one is an alkyl group, more preferably an alkyl group having 1 to 30 carbon atoms, and even more preferably an alkyl group having 1 to 7 carbon atoms.

[0104] Additionally, R 5 R 6 Ring structures can be formed by arbitrary bonding. Besides carbon atoms, such ring structures can also contain oxygen, sulfur, nitrogen, and other atoms. -NR 5 R 6 In, as R 5 R 6 The ring structures formed by bonding can be exemplified by morpholine, pyrrole, benzotriazole, etc.

[0105]

[0106] As mentioned above, R 5 R 6 The combination of R is preferred. 5 : Methyl, ethyl, propyl, butyl, benzyl, R 6The combination of methoxy, ethoxy, propoxy, and butoxy groups is further optimized for R. 5 : Methyl, ethyl, benzyl, R 6 Methoxy, ethoxy, propoxy, with R being particularly preferred. 5 : Methyl, ethyl, R 6 : Methoxy, ethoxy

[0107] It should be noted that when n is 2 or more, each R 5 R 6 They can be the same or different.

[0108] -OH and the -(C=O)- site in formula (1) together form an acid group (-COOH).

[0109] As described above, in the manufacturing method of this embodiment, in formula (1) "-(C=O)-R 1 The group indicated corresponds to any one of ester, acyl halide, acid anhydride, amide, or carboxylic acid groups, wherein "-(C=O)-R" represents any one of these groups. 1 The groups indicated by "" are preferably ester groups or acyl halide groups, with ester groups being particularly preferred.

[0110] In formula (1), "I" represents an iodine atom, and m represents an integer greater than or equal to 1. Considering the sensitization effect, m is preferably 1 to 5, further preferably 1 to 4, and especially preferably 1 to 3.

[0111] In formula (1), "Y" represents a monovalent substituent with 0 to 30 carbon atoms. Examples of such substituents include alkyl groups with 1 to 30 carbon atoms, alkoxy groups with 1 to 30 carbon atoms, alkoxyalkyl groups or hydroxyalkyl groups with 2 to 30 carbon atoms, aldehyde groups, halogen atoms other than iodine, formyl groups, nitro groups, amino groups, mercapto groups, or hydroxyl groups. Among these groups, those capable of having substituents may further have substituents.

[0112] As a monovalent substituent with 0 to 30 carbon atoms represented by Y, from the viewpoint of polarity regulation and sensitization effect, halogen atoms other than hydroxyl, alkoxy, alkyl, alkenyl, alkynyl, acyl, and iodine are preferred, and halogen atoms other than hydroxyl, alkoxy, alkyl, alkenyl, and iodine are even more preferred, and halogen atoms other than hydroxyl, alkoxy, alkyl, and iodine are particularly preferred. Examples of Y other than alkoxy groups of hydroxyl, methoxy, and ethoxy groups include -OMOM (methoxymethoxy), -OEM (ethoxymethoxy), -OTHP (tetrahydro-2H-pyran-2-yloxy), and -OEE (1-ethoxyethoxy). In addition, in formula (1), k represents an integer of 0 or more, and from the viewpoint of reactivity, 0 to 2 is preferred.

[0113] Hereinafter, specific examples of iodine-containing compounds represented by formula (1) are shown. However, the iodine-containing compounds represented by formula (1) are not limited to the specific examples described below. In the following chemical formulas, “Me” represents methyl, “Et” represents ethyl, “Pr” represents propyl, “Bu” represents butyl, “Ac” represents acetyl, “THP” represents tetrahydropyranyl, “EE” represents ethoxyethyl, and “EM” represents ethoxymethyl. In addition, the description of “NMeOMe” etc. refers to an amide group with -Me (methyl) and -OMe (methoxy) respectively bonded to N (nitrogen atom).

[0114]

[0115]

[0116]

[0117]

[0118]

[0119] The iodine-containing compound represented by formula (1) in this embodiment can be synthesized by known methods. Although not particularly limited, the iodine-containing compound represented by formula (1) can be manufactured by appropriately selecting methods such as: introducing halogens from an amino group by a Sandmeier reaction or the like; reacting iodine chloride in an organic solvent (e.g., Japanese Patent Application Publication No. 2012-180326, Japanese Patent Application Publication No. 2000-256231, Japanese Patent Application Publication No. 2010-159233, J. Chem. Soc. 636, 1943); or adding iodine dropwise to an alkaline aqueous solution of phenol in the presence of β-cyclodextrin under alkaline conditions (Japanese Patent Application Publication No. 63-101342, Japanese Patent Application Publication No. 2003-64012).

[0120] (nucleophilic reagent)

[0121] In the nucleophilic step, the iodine compound shown in formula (1) is reacted with a nucleophile. For typical iodine-containing compounds, a metal halide exchange reaction usually occurs with the nucleophile, leading to matrix decomposition. In particular, when an organolithium reagent is used as the nucleophile, the metal halide exchange reaction proceeds readily. Therefore, it is preferable to use a nucleophile other than an organolithium reagent, and even more preferable not to use an organolithium reagent.

[0122] There are no particular limitations on the nucleophile reagent other than organolithium reagents, but organomagnesium reagents and organocerium reagents are preferred, with organomagnesium reagents being particularly preferred. For example, Grignard reagents containing magnesium are preferred. Examples of Grignard reagents include methyl magnesium bromide and ethyl magnesium bromide.

[0123] In the nucleophilic process, the nucleophile is preferably used in an amount of 2 equivalents or more relative to the raw material iodine compound in this embodiment. In order to efficiently consume the raw material iodine compound, it is more preferably used in an amount of 2.5 equivalents or more, and particularly preferably used in an amount of 2.5 to 6 equivalents.

[0124] (Conditions for the nucleolysis process, etc.)

[0125] In the nucleophilic process, in order to improve reactivity, the reaction temperature of the raw material iodine compound and the nucleophile is preferably room temperature to 110°C, more preferably 30°C or higher and 110°C or lower, and particularly preferably 30°C or higher and 66°C or lower.

[0126] In the nucleophilic process, the reaction time is not particularly limited, and the preferred range varies depending on the choice of raw materials and the desired yield. From the perspective of suppressing impurities, a reaction time of 0.1 to 48 hours is preferred, more preferably 0.1 to 24 hours, and particularly preferably 0.1 to 12 hours.

[0127] In the nucleophilic process, in addition to the raw material iodine compound and nucleophilic reagent, solvents, esters, acyl halides, acid anhydrides, amides, and other known additives used in the nucleophilic reactions of acids can be used as needed. For example, cerium chloride can be cited as a known additive.

[0128] The solvent is not particularly limited; any solvent capable of being used for the nucleophilic reaction of the iodine compound can be used. For example, a variety of reaction solvents can be used, including polar aprotic solvents, protic polar solvents, and nonpolar aprotic solvents. A single protic polar solvent or a single polar aprotic solvent can also be used. Furthermore, mixtures of polar aprotic solvents, mixtures of protic polar solvents, mixtures of polar aprotic solvents and protic polar solvents, and mixtures of aprotic or protic solvents and nonpolar solvents can be used, with polar aprotic solvents or mixtures thereof being preferred. The reaction solvent is effective but not essential.

[0129] As preferred solvents, from the viewpoint of continuously using them in the acylation reaction, THF (tetrahydrofuran), cyclopentylmethyl ether, 2-methyltetrahydrofuran, diethyl ether, and toluene are preferred, with THF being even more preferred. The amount of solvent used in the nucleophilization step is not particularly limited, but from the perspective of reactivity and solubility, for example, relative to 100 parts by mass of iodine raw material, it can be preferably set to 280-4200 parts by mass, even more preferably 280-1700 parts by mass, and particularly preferably 320-1700 parts by mass.

[0130] One-pot process

[0131] The manufacturing method of this embodiment does not proceed through a separation step after the nucleophilic step, but instead performs the aforementioned nucleophilic step and the aforementioned acylation step consecutively. Here, "separation step" refers to the step of separating the compound generated in the nucleophilic step after the nucleophilic step and before the acylation step. Here, the iodine-containing tertiary alkoxide (tertiary alkoxide) shown in the following formula (2) can be cited as an example of the compound generated in the nucleophilic step. The following tertiary alkoxide is an active form corresponding to the raw material iodine compound.

[0132]

[0133] (In equation (2), A, I, Y, n, m, and k are the same as in equation (1). Rx and Ry each independently represent monovalent substituents derived from the nucleophile. It should be noted that the total number of n, m, and k does not exceed the number of groups that can bond with the aromatic ring shown in A. In addition, when n and k are 2 or more, each of Y, Rx, and Ry can be the same or different.)

[0134] In equation (2), Rx and Ry each independently represent a monovalent substituent derived from a nucleophile. Examples of monovalent substituents include methyl, ethyl, propyl, and butyl. Specific examples of Rx and Ry include methyl, ethyl, propyl, and butyl.

[0135] Furthermore, in the manufacturing method of this embodiment, the nucleophilic step and the acylation step can be carried out continuously using the same reaction vessel, or different reaction vessels can be used for the nucleophilic step and the acylation step. However, from the viewpoint of efficiency, it is preferable to carry out the nucleophilic step and the acylation step in the same reaction vessel.

[0136] <Acylation Process>

[0137] The acylation step in this embodiment is a step in which an acylation agent is added to the reaction solution obtained from the nucleophilic step to obtain an iodine-containing tertiary alcohol ester as the target.

[0138] In the manufacturing method of this embodiment, instead of quenching the active body (tertiary alkoxide) obtained in the nucleophilic step and separating it as an iodine-containing tertiary alcohol and using the alcohol in the acylation step, the tertiary alkoxide can be reacted directly with the acylating agent without converting it into a tertiary alcohol. Therefore, iodine-containing tertiary alcohol esters can be obtained with high purity and high efficiency.

[0139] As examples of iodine-containing tertiary alcohol esters, the following formula (3) can be used as examples.

[0140]

[0141] (In equation (3), A, I, Y, n, m, k, Rx, and Ry are the same as in equation (2). It should be noted that the total number of n, m, and k does not exceed the number of groups that can bond with the aromatic ring shown in A. In addition, when n and k are 2 or more, each of Y, Rx, and Ry can be the same or different.)

[0142] As an acylating agent, there is no particular limitation on the compound used in the acylation reaction of tertiary alkoxides. From the viewpoint of reactivity, acid anhydrides and acyl halides are preferred, and acid anhydrides are more preferred. Examples of acid anhydrides include methacrylic anhydride, acrylic anhydride, and acetic anhydride. From the perspective of the intended use of the product, methacrylic anhydride and acrylic anhydride are preferred. Similarly, examples of acyl halides include methacryloyl chloride, acryloyl chloride, and acetyl chloride. From the perspective of the intended use of the product, methacryloyl chloride and acryloyl chloride are preferred.

[0143] In the acylation process, from the viewpoint of reactivity, the acylation agent is preferably used in an amount of 2 equivalents or more relative to the raw material iodine compound in this embodiment. In order to efficiently consume the tertiary alkoxide, it is more preferably used in an amount of 2.5 equivalents or more, and particularly preferably used in an amount of 2.5 to 7.0 equivalents.

[0144] (nucleophilic catalyst)

[0145] In the manufacturing method of this embodiment, a nucleophilic catalyst is preferably used to improve the reactivity of the acylating agent. As a nucleophilic catalyst, there is no particular limitation as long as it is capable of being used for the acylation reaction of tertiary alkoxides. For example, from the perspective of acylating agent activation, 4-dimethylaminopyridine (DMAP), 4-pyrrolidinylpyridine (PPY), 9-azajulolidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) are preferred, with 4-dimethylaminopyridine (DMAP) being even more preferred.

[0146] In the acylation process, from the viewpoint of efficiently carrying out the reaction, the nucleophilic catalyst is preferably used in an amount of 0.01 to 1.0 equivalent relative to the iodine feedstock. In order to efficiently consume the tertiary alkoxide, it is more preferable to use an amount of 0.01 to 0.5 equivalent or more, and particularly preferably 0.01 to 0.1 equivalent.

[0147] (Conditions for the acylation process, etc.)

[0148] In acylation, in order to improve reactivity, the reaction temperature when adding the acylating agent to the reaction solution obtained in the nucleophilic step is preferably -20~50°C, more preferably -10~40°C, and particularly preferably 0~30°C.

[0149] In acylation, the reaction time is not particularly limited, and the preferred range varies depending on the selection of the acylating agent, the nucleophilic catalyst, and the desired yield. As for the reaction time, considering the efficient consumption of the tertiary alkoxide, 0.1 to 48 hours is preferred, 0.1 to 24 hours is more preferred, and 0.1 to 12 hours is particularly preferred.

[0150] In the acylation process, in addition to acylation agents and nucleophilic catalysts, solvents and well-known additives used in the acylation reactions of tertiary alkoxides can also be used as needed. Examples of well-known additives include Bi(OTf)3, Sc(OTf)3, and ZnCl2.

[0151] There are no particular limitations on the solvent used; any solvent suitable for the acylation reaction of tertiary alkoxides can be used. From the viewpoint of directly using the solvent used in the nucleophilic step, THF (tetrahydrofuran), cyclopentylmethyl ether, 2-methyltetrahydrofuran, diethyl ether, and toluene are preferred, with THF being even more preferred. The amount of reaction solvent used in the acylation step is not particularly limited; the solvent used in the nucleophilic step can be used directly. For example, the amount of solvent can be appropriately adjusted relative to 100 parts by mass of the iodine starting material or tertiary alkoxide (preferably an iodine compound), preferably 280 to 4200 parts by mass, even more preferably 280 to 1700 parts by mass, and particularly preferably 320 to 1700 parts by mass.

[0152] The iodine-containing tertiary alcohol esters obtained by the reaction can be purified as desired high-purity monomers using known purification methods such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, separation and purification using activated carbon, and combinations thereof. The purification process will be described later.

[0153] (shading conditions)

[0154] Iodine-containing compounds and compounds with polymerizable groups sometimes decompose or polymerize due to light, leading to a decrease in purity. Therefore, in order to improve the purity of iodine-containing tertiary alcohol esters, the manufacturing method of this embodiment is preferably carried out under light-shielding conditions. In other words, the manufacturing method of this embodiment is preferably carried out under light-shielding conditions. Specifically, it is preferred that at least one of the nucleophilic step and the acylation step in this embodiment is carried out under light-shielding conditions, and it is even more preferred that at least both the nucleophilic step and the acylation step are carried out under light-shielding conditions.

[0155] Here, "performed under light-shielding conditions" refers to performing the process under warm yellow light or in an environment where light with wavelengths below 500 nm is attenuated. While not specifically limited, the nucleophilic and acylation processes are preferably performed under light intensity of 10 mW / m² below 500 nm. 2 The following will proceed.

[0156] (Other processes)

[0157] In addition to the nucleophilic and acylation processes, the manufacturing method of this embodiment may also include other processes. Examples of such other processes include purification, adsorption, and polymerization inhibitor addition.

[0158] -Purification Process-

[0159] The purification process applicable to the manufacturing method of this embodiment is not particularly limited, and methods described in International Publication 2015 / 080240, International Publication 2018 / 159707, etc., can be used. Specifically, the purification method includes the following steps: dissolving the aforementioned compound in an organic solvent that is not readily miscible with water to obtain an organic layer; contacting the organic layer with an acidic aqueous solution for extraction treatment, thereby causing the metal components contained in the organic layer (organic phase) containing the aforementioned compound and the organic solvent to migrate to the aqueous phase; and then separating the organic layer from the aqueous phase. The organic solvent that is not readily miscible with water is generally an organic solvent classified as a non-water-soluble solvent. There are no particular limitations on the organic solvent used, but an organic solvent that can be safely used in semiconductor manufacturing processes is preferred. The amount of organic solvent used is typically about 10% by mass relative to the compound used.

[0160] Specific examples of the organic solvents used include those described in International Publication No. 2015 / 080240. Among these, toluene, 2-heptanone, cyclohexanone, cyclopentanone, methyl isobutyl ketone, propylene glycol monomethyl ether acetate (PGMEA), ethyl acetate, etc., are preferred, with toluene, cyclohexanone, and propylene glycol monomethyl ether acetate being particularly preferred.

[0161] As the aforementioned acidic aqueous solution, it can be appropriately selected from aqueous solutions formed by dissolving commonly known organic and inorganic compounds in water. For example, substances described in International Publication 2015 / 080240 can be cited. These acidic aqueous solutions can be used individually or in combination of two or more. Examples of acidic aqueous solutions include aqueous solutions of inorganic acids and aqueous solutions of organic acids. Examples of inorganic acid aqueous solutions include aqueous solutions containing one or more of the following: hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acid aqueous solutions include aqueous solutions containing one or more of the following: acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, methanesulfonic acid, phenolsulfonic acid, p-toluenesulfonic acid, and trifluoroacetic acid. The pH range of the acidic aqueous solution is approximately 0 to 5, more preferably approximately 0 to 3.

[0162] -Adsorption Process-

[0163] Typically, some polymers of compounds with polymerizable groups are produced as impurities, sometimes reducing purity. Therefore, the manufacturing method of this embodiment may include a step (adsorption step) in which an adsorbent is added and dispersed after the reaction to remove impurities from the reaction solution obtained after the nucleophilic and acylation steps.

[0164] The adsorbent is not particularly limited, and examples include silica gel, modified silica gel, activated carbon, activated alumina, zeolite, hydrotalcite, Florisil, activated clay, diatomaceous earth, synthetic adsorbents, and ion exchange resins. Examples of modified silica gel include sulfuric acid-supported silica gel. From the viewpoint of effectively adsorbing polar groups contained in high molecular weight impurities, silica gel, zeolite, activated alumina, ion exchange resins, and modified silica gel are preferred; silica gel, modified silica gel, and ion exchange resins are more preferred; and silica gel is even more preferred. In other words, the manufacturing method of this embodiment may include the steps of adding silica gel to the reaction solution and removing impurities.

[0165] Examples of methods for using an adsorbent include: adding the adsorbent to a reaction solution obtained after nucleophilic and acylation processes, stirring, and then filtering to remove the adsorbent; passing the reaction solution obtained after nucleophilic and acylation processes through a container, column, filter, or similar material filled with the adsorbent; etc. From a manufacturing point of view, the method of adding the adsorbent to the reaction solution and stirring is preferred.

[0166] The amount of adsorbent can be appropriately set according to the adsorbent used, the iodine-containing tertiary alcohol ester, the solvent, the temperature, the desired yield, etc., and is not particularly limited. From the viewpoint of high purity, the amount of adsorbent used is preferably 0.01 to 100 parts by mass relative to 1 part by mass of the iodine-containing tertiary alcohol ester of the target compound, more preferably 0.1 to 50 parts by mass, and even more preferably 0.3 to 20 parts by mass.

[0167] In the adsorption process, the temperature is not particularly limited, but the preferred range varies depending on the adsorbent, the concentration of the target iodine-containing tertiary alcohol ester, the content of high molecular weight impurities, etc. From the viewpoint of adsorption performance, it is preferably -80°C or higher and 80°C or lower, more preferably -50°C or higher and 60°C or lower, even more preferably -30°C or higher and 50°C or lower, and particularly preferably -20°C or higher and 30°C or lower. When silica gel is used as the adsorbent, the temperature range is preferably -80°C or higher and 80°C or lower.

[0168] -Polymerization inhibitor-

[0169] The manufacturing method of this embodiment preferably involves adding a polymerization inhibitor during the acylation, purification, or adsorption process.

[0170] As polymerization inhibitors, commercially available products can be used. Examples include: 2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxo radical, N-nitrosophenylhydroxyamine ammonium salt, N-nitrosophenylhydroxyamine aluminum salt, N-nitroso-N-(1-naphthyl)hydroxyamine ammonium salt, N-nitrosodiphenylamine, N-nitroso-N-methylaniline, nitrosonaphthol, p-nitrosophenol, N,N'-dimethyl-p-nitrosoaniline and other nitroso compounds, phenothiazine, methylene blue, 2-mercaptobenzimidazole and other sulfur-containing compounds, N,N'-diphenyl-p-phenylenediamine, N... Amines such as -phenyl-N'-isopropyl-p-phenylenediamine, 4-hydroxydiphenylamine, and aminophenol; quinones such as hydroxyquinoline, hydroquinone, methylhydroquinone, p-benzoquinone, and hydroquinone monomethyl ether; phenols such as p-methoxyphenol (also known as p-hydroxyanisole), 2,4-dimethyl-6-tert-butylphenol, catechol, 3-sec-butylcatechol, and 2,2-methylenebis-(6-tert-butyl-4-methylphenol); imides such as N-hydroxyphthalimide; oximes such as cyclohexane oxime and p-quinone dioxime; and dialkyl thiodipropionate, etc. The amount of polymerization inhibitor added is, for example, 0.001 to 10 parts by weight, preferably 0.01 to 1 part by weight, relative to 100 parts by weight of the iodine-containing tert-ol ester.

[0171] [Composition for membrane formation]

[0172] The iodine-containing tertiary alcohol esters obtained by the manufacturing method of this embodiment can be used for various applications, such as for film-forming compositions. For example, the film-forming composition can be a photolithography film-forming composition suitable for semiconductor photolithography film formation. Additionally, the film-forming composition can be a photoresist film-forming composition suitable for photoresist film formation (i.e., a "photoresist composition"). Furthermore, the aforementioned film-forming compositions can be used for upper layer film formation (i.e., "upper layer film-forming composition"), intermediate layer formation (i.e., "intermediate layer film-forming composition"), lower layer film formation (i.e., "lower layer film-forming composition"), etc. For the purpose of improving the patterning performance of the photolithography process in the photoresist layer, they can primarily or secondarily perform functions such as anti-reflection, prevention of secondary electron diffusion, and other optical or electromagnetic radiation functions, as well as improving pattern quality resulting from pattern collapse, defects, and pattern shape maintenance caused by chemical and physical effects. According to the composition of this embodiment, a film with high sensitivity can be formed, and a good photoresist pattern shape can also be imparted.

[0173] The film-forming composition containing iodine-containing tertiary alcohol esters obtained by the manufacturing method of this embodiment can also be used as an optical component forming composition using photolithography. Besides being used in thin film or sheet form, optical components are also useful as plastic lenses (prism lenses, biconvex lenses, microlenses, Fresnel lenses, viewing angle control lenses, contrast-enhancing lenses, etc.), retardation films, electromagnetic wave shielding films, prisms, optical fibers, solder resists for flexible printed wiring, anti-plating layers, interlayer insulating films for multilayer printed circuit boards, photosensitive waveguides, liquid crystal displays, organic electroluminescent (EL) displays, photoelectric semiconductor (LED) elements, solid-state imaging elements, organic thin-film solar cells, pigment-sensitized solar cells, and organic thin-film transistors (TFTs). The aforementioned composition is particularly suitable as a component for solid-state imaging elements requiring high refractive index, namely, embedded films and planarization films on photodiodes, planarization films before and after color filters, microlenses, and planarization and conformal films on microlenses.

[0174] Example

[0175] The present invention will be further described in detail below with reference to examples and comparative examples, but the present invention is not limited to these examples in any way.

[0176] [Determination Method]

[0177] [LC (Liquid Chromatography) Determination Conditions]

[0178] The LC values ​​in each embodiment were determined as follows.

[0179] Device name: Manufactured by Shimadzu Corporation (Nexera-i LC-2020C 3D)

[0180] Column: Waters XBridge BEH C18 (2.5μm 3.0×75mm)

[0181] Detector: PDA; Flow rate: 0.7 mL / min; Column oven temperature: 40 °C; Autosampler temperature: 15 °C; Injection volume: 1.0 μL (2 mg / mL THF solution).

[0182] The determination was performed within the range of eluent (%) from ultrapure water:MeCN:1% phosphoric acid aqueous solution (0:98:2) to (93:5:2).

[0183] [GPC Measurement Conditions]

[0184] Device name: Manufactured by Shimadzu Corporation (Nexera-i LC-2020C 3D)

[0185] Column: ACQUITY APC XT45 (molecular weight cutoff 200-5000)

[0186] Detector: PDA; Flow rate: 0.3 mL / min; Column temperature: 30℃; Autosampler temperature: 15℃; Standard curve: None; Injection volume: 1.0 μL (2 mg / mL THF solution).

[0187] Eluent: THF for LC

[0188] [Structure of the compound]

[0189] The structure of the compound was determined using a Bruker Avance 500 III spectrometer under the following conditions. 1 It was confirmed by H-NMR determination.

[0190] Frequency: 500MHz

[0191] Solvent: CDCl3 or d6-DMSO

[0192] Internal Standard: TMS

[0193] Measurement temperature: 23℃

[0194] In addition, regarding 13 C-NMR measurements were performed using the same apparatus under the following conditions.

[0195] Frequency: 125MHz

[0196] Solvent: CDCl3 or d6-DMSO

[0197] Internal standard: using solvent

[0198] [Example 1]

[0199]

[0200] (Pronucleation process)

[0201] Under light-shielded conditions (an environment with reduced light wavelengths below 500 nm under a yellow lamp (Panasonic, trade name: fluorescent lamp with anti-scattering film for semiconductor factories <pure yellow> (FLR40SYFMP); hereinafter the same), a 200 mL three-necked flask was prepared, and 38 mL of dehydrated THF and 5.0 g (19.1 mmol) of methyl 4-iodobenzoate (raw iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.) were added. The flask was cooled to an internal temperature below 10 °C under a flow of N2 and stirred for 30 minutes. Then, 57 mL (57 mmol, 1.0 M THF solution) of methyl magnesium bromide (nucleophile: Grignard reagent) was added to the 200 mL three-necked flask over 5 minutes. The internal temperature was then restored to 25 °C over 15 minutes, and then increased to 50 °C over 20 minutes, with stirring continuing for 40 minutes.

[0202] (Acylation process)

[0203] Next (without separating the compound generated in the nucleophilic process), after cooling to an internal temperature below 10°C, 10.3 g (66.8 mmol) of methacrylic anhydride (acylizing agent) was added dropwise over 5 minutes. Then, 0.23 g (1.91 mmol) of DMAP (nucleophilic catalyst) was added in one go, and the temperature was restored to an internal temperature of 25°C over 20 minutes, followed by stirring for 3 hours.

[0204] After cooling to an internal temperature below 10°C, 15 g of saturated ammonium chloride aqueous solution was added dropwise over 5 minutes. Next, 45 g of ion-exchanged water was added dropwise over 10 minutes, followed by the addition of 300 g of toluene. After stirring for 15 minutes and allowing to stand, the aqueous layer was removed. Another 60 g of ion-exchanged water was added, stirred for 15 minutes, allowed to stand, and the aqueous layer was removed. This process was repeated twice. The recovered organic layer was concentrated by vacuum distillation while a small amount of air was blown in, until the solvent components disappeared, yielding a crude product. The crude product was purified by silica gel column chromatography to obtain the iodine-containing tertiary alcohol ester (1) (4.7 g, 14.2 mmol) as the target.

[0205] 1 mg of p-hydroxyanisole was added as a polymerization inhibitor to the obtained iodine-containing tertiary alcohol ester.

[0206] The results of the analysis showed that the crude product had an LC purity of 87% and a GPC purity of 88% at 220 nm, while the iodine-containing tertiary alcohol ester obtained after column purification had an LC purity of 99% and a GPC purity of 99% at 220 nm.

[0207] The obtained compound was subjected to NMR analysis under the aforementioned conditions, and the following peaks were observed, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1) described above. δ (ppm) (d-DMSO): 7.68 (2H, Ph), 7.16 (2H, Ph), 6.03 (1H, =CH2), 5.66 (1H, =CH2), 1.85 (3H, -CH3), 1.71 (6H, -CH3)

[0208] [Example 2]

[0209]

[0210] (Pronucleation process)

[0211] Under light-shielded conditions, prepare a 200 mL three-necked flask and add 38 mL of dehydrated THF and 5.1 g (19.1 mmol) of 4-iodobenzoyl chloride (raw material: iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.). Stir for 30 minutes under N2 flow while maintaining an internal temperature below 10 °C. Then, add 57 mL (57 mmol, 1.0 M THF solution) of methyl magnesium bromide (nucleophile: Grignard reagent) to the 200 mL three-necked flask over 5 minutes. Continue stirring for 40 minutes under ice-shielded conditions to maintain an internal temperature below 10 °C.

[0212] (Acylation process)

[0213] Next (without separating the compound generated in the nucleophilic step), 10.3 g (66.8 mmol) of methacrylic anhydride (acylizer) was added dropwise over 5 minutes. Then, 0.23 g (1.91 mmol) of DMAP (nucleophilic catalyst) was added in one go, and the mixture was allowed to recover to an internal temperature of 25°C over 20 minutes, followed by stirring for 3 hours. After cooling to an internal temperature below 10°C, 15 g of saturated ammonium chloride aqueous solution was added dropwise over 5 minutes. Next, 45 g of deionized water was added dropwise over 10 minutes, followed by the addition of 300 g of toluene. After stirring for 15 minutes and allowing to stand, the aqueous layer was removed. Another 60 g of deionized water was added, and the mixture was stirred for 15 minutes, allowed to stand, and the aqueous layer was removed. This process was repeated twice. The recovered organic layer was concentrated by vacuum distillation while a small amount of air was blown in, until the solvent components disappeared, yielding a crude product. The crude product was purified by column chromatography using silica gel to obtain an iodine-containing tertiary alcohol ester (4.5 g, 13.6 mmol) as the target compound.

[0214] 1 mg of p-hydroxyanisole was added as a polymerization inhibitor to the obtained iodine-containing tertiary alcohol ester.

[0215] The results of the analysis showed that the crude product had an LC purity of 85% and a GPC purity of 86% at 220 nm, while the iodine-containing tertiary alcohol ester obtained after column purification had an LC purity of 97% and a GPC purity of 98% at 220 nm.

[0216] The obtained compound was subjected to NMR analysis under the aforementioned determination conditions, and the same peaks as in Example 1 were found, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1).

[0217] [Example 3]

[0218] In Example 1, no light-shielding conditions were established (operated under normal fluorescent light), and the same procedure as in Example 1 was followed to obtain an iodine-containing tertiary alcohol ester. The tertiary alcohol ester (4.4 g, 13.3 mmol) was purified by column chromatography using silica gel.

[0219] The results of the analysis showed that the crude product had an LC purity of 80% and a GPC purity of 83% at 220 nm, while the iodine-containing tertiary alcohol ester obtained after column purification had an LC purity of 96% and a GPC purity of 97% at 220 nm.

[0220] The obtained compound was subjected to NMR analysis under the aforementioned determination conditions, and the same peaks as in Example 1 were found, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1).

[0221] [Example 4]

[0222]

[0223] (Pronucleation process)

[0224] Under light-shielded conditions, prepare a 100 mL three-necked flask, add 10 mL of dehydrated THF and 0.5 g (1.91 mmol) of methyl 4-iodobenzoate (raw material: iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.), and stir for 15 minutes under a nitrogen stream while cooling to an internal temperature below -70°C. Then, add 3.0 mL (4.2 mmol, 1.4 M cyclopentyl methyl ether solution) of lithium methyl ether (nucleophile: organolithium reagent) to the 100 mL three-necked flask over 5 minutes, and stir for 15 minutes.

[0225] (Acylation process)

[0226] Next (without separating the compounds generated in the nucleophilic step), 1.03 g (6.68 mmol) of methacrylic anhydride (acylizing agent) was added dropwise over 1 minute. Then, 0.023 g (0.19 mmol) of DMAP (nucleophilic catalyst) was added in one go, and the mixture was allowed to recover to an internal temperature of 25°C over 10 minutes, followed by stirring for 3 hours. After cooling to an internal temperature below 10°C, 5 g of saturated ammonium chloride aqueous solution was added dropwise over 1 minute. Next, 15 g of ion-exchanged water was added dropwise over 2 minutes, followed by the addition of 100 g of toluene. After stirring for 15 minutes and allowing to stand, the aqueous layer was removed. Another 30 g of ion-exchanged water was added, and the mixture was stirred for 15 minutes, allowed to stand, and the aqueous layer was removed. This process was repeated twice. The recovered organic layer was concentrated by vacuum distillation while a small amount of air was blown in, until the solvent components disappeared, yielding the crude product. The crude product was purified by silica gel column chromatography to obtain the iodine-containing tertiary ester of the target compound (0.013 g, 0.0394 mmol, yield 2%).

[0227] 1 mg of p-hydroxyanisole was added as a polymerization inhibitor to the obtained iodine-containing tertiary alcohol ester.

[0228] The obtained compound had an LC purity of 95% at 220 nm and a GPC purity of 96%.

[0229] The obtained compound was subjected to NMR analysis under the aforementioned determination conditions, and the same peaks as in Example 1 were found, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1).

[0230] [Example 5]

[0231]

[0232] (Pronucleation process)

[0233] Under light-shielded conditions, prepare a 200 mL three-necked flask and add 38 mL of dehydrated THF and 5.0 g (19.1 mmol) of methyl 4-iodobenzoate (raw material: iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.). Under N2 flow, stir for 30 minutes while maintaining an internal temperature below 10 °C. Then, add 57 mL (57 mmol, 1.0 M THF solution) of methyl magnesium bromide (nucleophile: Grignard reagent) to the 200 mL three-necked flask over 5 minutes. After restoring the internal temperature to 25 °C over 15 minutes, bring the internal temperature to 50 °C over 20 minutes and continue stirring for 40 minutes.

[0234] (Acylation process)

[0235] Next (without separating the compound generated in the nucleophilic step), after cooling to an internal temperature below 10°C, 110.3 g (66.8 mmol) of methacrylic anhydride (acylizing agent) was added dropwise over 5 minutes. Then, the internal temperature was restored to 25°C over 20 minutes, and stirring continued for 3 hours. After cooling to an internal temperature below 10°C, 15 g of saturated ammonium chloride aqueous solution was added dropwise over 5 minutes. Next, 45 g of ion-exchanged water was added dropwise over 10 minutes, followed by the addition of 300 g of toluene. After stirring for 15 minutes and allowing to stand, the aqueous layer was removed. Another 60 g of ion-exchanged water was added, stirred for 15 minutes, allowed to stand, and the aqueous layer was removed; this process was repeated twice. The recovered organic layer was concentrated by vacuum distillation while a small amount of air was purged, until the solvent components disappeared, thus obtaining the crude product.

[0236] The analysis of the crude product showed that the LC purity at 220 nm was 62%, with 25% unreacted tertiary alcohol remaining.

[0237] The obtained compound was subjected to NMR analysis under the aforementioned determination conditions, and the same peaks as in Example 1 were found, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1).

[0238] [Example 6]

[0239]

[0240] (Pronucleation process)

[0241] Under light-shielded conditions, prepare a 200 mL three-necked flask and add 38 mL of dehydrated THF and 5.0 g (19.1 mmol) of methyl 4-iodobenzoate (raw material: iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.). Under N2 flow, stir for 30 minutes while maintaining an internal temperature below 10 °C. Then, add 57 mL (57 mmol, 1.0 M THF solution) of methyl magnesium bromide (nucleophile: Grignard reagent) to the 200 mL three-necked flask over 5 minutes. After restoring the internal temperature to 25 °C over 15 minutes, bring the internal temperature to 50 °C over 20 minutes and continue stirring for 40 minutes.

[0242] (Acylation process)

[0243] Next (without separating the compounds generated in the nucleophilic process), after cooling to an internal temperature below 10°C, 10.3 g (66.8 mmol) of methacrylic anhydride (acylizing agent) was added dropwise over 5 minutes. Then, 0.23 g (1.91 mmol) of DMAP (nucleophilic catalyst) was added in one go, and the mixture was allowed to recover to an internal temperature of 25°C over 20 minutes, followed by stirring for 3 hours. After cooling to an internal temperature below 10°C, 15 g of saturated ammonium chloride aqueous solution was added dropwise over 5 minutes. Next, 45 g of ion-exchanged water was added dropwise over 10 minutes, followed by the addition of 300 g of toluene. After stirring for 15 minutes and allowing to stand, the aqueous layer was removed. Another 60 g of ion-exchanged water was added, stirred for 15 minutes, allowed to stand, and the aqueous layer was removed. This process was repeated twice. The recovered organic layer was concentrated by vacuum distillation while a small amount of air was blown in, until the solvent components disappeared. Then, 5.0 g of silica gel was dispersed at 25 °C and filtered to obtain the iodine-containing tertiary alcohol ester (4.9 g, 14.8 mmol) as the target analyte. The LC purity of the obtained tertiary alcohol ester at 220 nm was 90%, and the GPC purity was 91%.

[0244] The obtained compound was subjected to NMR analysis under the aforementioned determination conditions, and the same peaks as in Example 1 were found, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1).

[0245] [Example 7]

[0246] In the experiment described in Example 6, without dispersion treatment using silica gel, the LC purity at 220 nm was 87% and the GPC purity was 88% without column purification.

[0247] The obtained compound was subjected to NMR analysis under the aforementioned determination conditions, and the same peaks as in Example 1 were found, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (1).

[0248] [Comparative Example 1]

[0249] (Synthesis of tertiary alcohols and methacrylation)

[0250]

[0251] (Pronucleation process)

[0252] Under light-shielded conditions, a 100 mL three-necked flask was prepared, and 25 mL of dehydrated THF and 1.23 g (5.0 mmol) of 4-iodoacetophenone were added. The flask was stirred for 30 minutes under N2 flow while maintaining an internal temperature below 10 °C. 6.0 mL (6.0 mmol, 1.0 M THF solution) of methyl magnesium bromide (nucleophile: Grignard reagent) was added over 5 minutes to the 100 mL three-necked flask, followed by stirring for 1 hour. Then, 10 g of saturated ammonium chloride aqueous solution was added dropwise over 5 minutes, followed by 50 g of ethyl acetate. After stirring for 15 minutes and allowing to stand, the aqueous layer was collected. 50 g of saturated brine was added, stirred for 15 minutes, allowed to stand, and the aqueous layer was collected. The recovered organic layer was concentrated by vacuum distillation until the solvent components disappeared, and then purified by silica gel column chromatography to separate the tertiary alcohol (0.82 g, 3.1 mmol) as the target analyte.

[0253] (Acylation process)

[0254] Under light-shielded conditions, a 100 mL three-necked flask was prepared, and 13 mL of dehydrated THF and 1.0 g (3.8 mmol) of the tertiary alcohol obtained by the above method were added. The mixture was stirred for 30 minutes under N2 flow while cooling to an internal temperature below 10 °C. Then, 0.74 g (5.7 mmol) of N,N-diisopropylethylamine (DIPEA) was added to the 100 mL three-necked flask in a single addition, followed by 0.05 g (0.41 mmol) of DMAP (nucleophilic catalyst). Next, 0.48 g (4.6 mmol) of methacryloyl chloride (acylizing agent) was added dropwise. The mixture was allowed to recover to an internal temperature of 25 °C over 10 minutes, and then stirred for at least 3 hours. The reaction was monitored by TLC, but the reaction did not proceed to completion, and the target compound could not be obtained.

[0255] [Example 8]

[0256] (Synthesis using ethyl ester raw materials)

[0257] Synthesis of 2-(4-iodophenyl)propane-2-yl methacrylate

[0258]

[0259] (Pronucleation process)

[0260] Under light-shielded conditions, prepare a 500 mL three-necked flask, add 36 mL of dehydrated THF and 10.0 g (36.2 mmol) of ethyl 4-iodobenzoate (raw material: iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.), and stir for 30 minutes under N2 flow while maintaining an internal temperature below 10 °C. Then, add 91 mL (91 mmol, 1.0 M THF solution) of methyl magnesium bromide (nucleophile: Grignard reagent) to the 500 mL three-necked flask over 40 minutes. Afterward, restore the internal temperature to 25 °C over 15 minutes, then maintain the internal temperature at 50 °C over 20 minutes, and continue stirring for 120 minutes.

[0261] (Acylation process)

[0262] Next (without separating the compounds generated in the nucleophilic process), the mixture was chilled to an internal temperature below 10°C, and 0.44 g (3.6 mmol) of DMAP (nucleophilic catalyst) was added in a single addition, followed by dropwise addition of 16.2 g (105 mmol) of methacrylic anhydride (acylizing agent) over 5 minutes. Then, the mixture was allowed to recover to an internal temperature of 25°C over 20 minutes, and stirring was continued for 1 hour.

[0263] After cooling to an internal temperature below 10°C, 91g of a 20% ammonium chloride aqueous solution was added dropwise over 20 minutes, stirred overnight, and allowed to stand. The aqueous layer was then removed. 52g of toluene and 40g of a 5% sodium bicarbonate aqueous solution were added, stirred for 15 minutes, allowed to stand, and the aqueous layer was removed. This process was repeated three times. Next, 40g of deionized water was added, stirred for 15 minutes, allowed to stand, and the aqueous layer was removed. This process was repeated three times. The recovered organic layer was concentrated by vacuum distillation while a small amount of air was blown in until the solvent components disappeared, yielding a crude product. The crude product was purified by silica gel column chromatography to obtain the iodine-containing tertiary alcohol ester (10.2g, 30.8mmol) as the target.

[0264] 1 mg of p-hydroxyanisole was added as a polymerization inhibitor to the obtained iodine-containing tertiary alcohol ester.

[0265] (Analysis Results)

[0266] The results of the analysis showed that the crude product had a purity of 90% at 220 nm by LC and 92% by GPC. The iodine-containing tertiary alcohol ester obtained after column purification had a purity of 99% at 220 nm by LC and 99% by GPC.

[0267] The obtained compound was subjected to NMR analysis under the aforementioned conditions, and the following peaks were observed, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (2-(4-iodophenyl)propane-2-yl methacrylate). δ (ppm) (d-DMSO): 7.68 (2H, Ph), 7.16 (2H, Ph), 6.03 (1H, =CH2), 5.66 (1H, =CH2), 1.85 (3H, -CH3), 1.71 (6H, -CH3)

[0268] [Example 9]

[0269] Synthesis of 2-(3-iodophenyl)propane-2-yl methacrylate

[0270]

[0271] In the synthesis of 2-(4-iodophenyl)propane-2-yl methacrylate described in Example 8, 9.5 g (36.2 mmol) of methyl 3-iodobenzoate (raw material iodine compound; purchased from Sigma-Aldrich) was used instead of ethyl 4-iodobenzoate, and 2-(3-iodophenyl)propane-2-yl methacrylate was obtained in the same manner.

[0272] (Analysis Results)

[0273] The results of the analysis showed that the crude product had an LC purity of 88% at 220 nm and a GPC purity of 90%, while the iodine-containing tertiary alcohol ester obtained after column purification had an LC purity of 99% at 220 nm and a GPC purity of 99%.

[0274] The obtained compound was subjected to NMR analysis under the aforementioned conditions, and the following peaks were observed, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (2-(3-iodophenyl)propane-2-yl methacrylate). δ (ppm) (d-DMSO): 7.69 (1H, Ph), 7.62 (1H, Ph), 7.32 (1H, Ph), 7.12 (1H, Ph), 6.04 (1H, =CH2), 5.67 (1H, =CH2), 1.83 (3H, -CH3), 1.69 (6H, -CH3)

[0275] [Example 10]

[0276] Synthesis of 2-(2-iodophenyl)propane-2-yl methacrylate

[0277]

[0278] In the synthesis of 2-(4-iodophenyl)propane-2-yl methacrylate described in Example 8, 9.5 g (36.2 mmol) of methyl 2-iodobenzoate (raw material iodine compound; purchased from Sigma-Aldrich) was used instead of ethyl 4-iodobenzoate, and 2-(2-iodophenyl)propane-2-yl methacrylate was obtained in the same manner.

[0279] (Analysis Results)

[0280] The results of the analysis showed that the crude product had an LC purity of 91% and a GPC purity of 92% at 220 nm, while the iodine-containing tertiary alcohol ester obtained after column purification had an LC purity of 99% and a GPC purity of 99% at 220 nm.

[0281] The obtained compound was subjected to NMR analysis under the aforementioned conditions, and the following peaks were observed, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (2-(2-iodophenyl)propane-2-yl methacrylate). δ (ppm) (d-DMSO): 7.94 (1H, Ph), 7.62 (1H, Ph), 7.32 (1H, Ph), 6.93 (1H, Ph), 6.05 (1H, =CH2), 5.68 (1H, =CH2), 1.81 (3H, -CH3), 1.73 (6H, -CH3)

[0282] [Example 11]

[0283] Synthesis of 2-(3-iodo-4-methoxyphenyl)propane-2-yl methacrylate

[0284]

[0285] In the synthesis of 2-(4-iodophenyl)propane-2-yl methacrylate described in Example 8, 10.6 g (36.2 mmol) of methyl 3-iodo-4-methoxybenzoate (raw material iodine compound; purchased from Tokyo Chemical Industry Co., Ltd.) was used instead of ethyl 4-iodobenzoate, and 2-(3-iodo-4-methoxyphenyl)propane-2-yl methacrylate was obtained in the same manner.

[0286] (Analysis Results)

[0287] The results of the analysis showed that the crude product had an LC purity of 89% at 220 nm and a GPC purity of 90%, while the iodine-containing tertiary alcohol ester obtained after column purification had an LC purity of 99% at 220 nm and a GPC purity of 99%.

[0288] The obtained compound was subjected to NMR analysis under the aforementioned conditions, and the following peaks were observed, confirming the chemical structure of the iodine-containing tertiary alcohol ester compound (2-(3-iodo-4-methoxyphenyl)propane-2-yl methacrylate). δ (ppm) (d-DMSO): 7.79 (1H, Ph), 7.38 (1H, Ph), 6.80 (1H, Ph), 6.02 (1H, =CH2), 5.66 (1H, =CH2), 3.88 (3H, O-CH3), 1.80 (3H, -CH3), 1.69 (6H, -CH3)

[0289] The entire disclosure of Japanese Patent Application No. 2024-030044, which is filed on February 29, 2024, is incorporated herein by reference.

[0290] In addition, all documents, patent applications and technical standards described in this specification are incorporated herein by reference to the same extent as those specifically and separately described herein.

Claims

1. A method for manufacturing an iodine-containing tertiary alcohol ester, comprising the following steps: The nucleophilic step involves reacting an iodine-containing compound, as shown in formula (1), with a nucleophilic reagent; and, The acylation step involves adding an acylation agent to the reaction solution obtained from the nucleophilic step to yield an iodine-containing tertiary alcohol ester. The nucleophilization and acylation processes are performed consecutively after the nucleophilization process without a separation process. In equation (1), A represents an aromatic ring with 6 to 12 carbon atoms. -R 1 For -OR 2 -X, -O-CO-R 4 -NR 5 R 6 or -OH, where, R 2 Indicates alkyl or aryl, X represents F, Cl, Br or I, R 4 R represents alkyl, aryl, or of formula (1). 1 The part other than -CO-, R 5 R 6 Each independently represents a hydrogen atom, alkoxy group, alkyl group, or aryl group, R 5 R 6 Ring structures are formed by optional bonding. I represents an iodine atom. Y is a monovalent substituent with 0 to 30 carbon atoms. n is an integer from 1 to 2. m is an integer greater than or equal to 1. k is an integer greater than or equal to 0 or 1. The total number of n, m, and k does not exceed the number of groups that can bond with the aromatic ring.

2. The method for manufacturing iodine-containing tertiary alcohol esters according to claim 1, wherein, The nucleophilic process and the acylation process are carried out in the same reaction vessel.

3. The method for manufacturing the iodine-containing tertiary alcohol ester according to claim 1, wherein it is carried out under light-shielding conditions.

4. The method for manufacturing iodine-containing tertiary alcohol esters according to claim 1, wherein, The nucleophile is a nucleophile other than an organolithium reagent.

5. The method for manufacturing iodine-containing tertiary alcohol esters according to claim 1, wherein, A nucleophilic catalyst is used in the acylation process.

6. The method for manufacturing iodine-containing tertiary alcohol esters according to claim 1, comprising the steps of adding silica gel and removing impurities.

7. The method for producing iodine-containing tertiary alcohol esters according to claim 1, wherein, The compound obtained by reacting the iodine-containing compound with the nucleophilic reagent in the nucleophilic process comprises an iodine-containing tertiary alkoxide.

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