(12) Patent Application Publication (10) Pub. No.: US 2004/0245505 A1 Yoneda Et Al

US 2004O2455.05A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0245505 A1 Yoneda et al. (43) Pub. Date: Dec. 9, 2004

(54) PROCESS FOR THE PRODUCTION OF international application No. PCT/JP01/05017, filed FLUORINATED ORGANIC COMPOUNDS on Jun. 13, 2001. AND FLUORINATINGAGENTS (30) Foreign Application Priority Data (75) Inventors: Norihiko Yoneda, Sapporo-shi (JP); Tsuyoshi Fukuhara, Sapporo-shi (JP); Jun. 13, 2000 (JP)...... 2000-177453 Kazuhiro Shimokawa, Osaka (JP); Jul. 13, 2000 (JP). 2000-212447 Kenji Adachi, Tsukuba-shi (JP); Sep. 18, 2000 (JP)...... 2OOO-281515 Satoshi Oishi, Tsukuba-shi (JP) Nov. 6, 2000 (JP)...... 2OOO-337929 Correspondence Address: Publication Classification ARMSTRONG, KRATZ, QUINTOS, HANSON & BROOKS, LLP (51) Int. Cl." ...... C07C 19/08 1725 KSTREET, NW SUTE 1000 (52) U.S. Cl...... 252/372; 570/161 WASHINGTON, DC 20006 (US) (73) Assignee: Daikin Industries, Ltd., Osaka-shi (JP) (57) ABSTRACT (21) Appl. No.: 10/885,042 A process for the production of a fluorinated organic com pound, characterized by fluorinating an organic compound (22) Filed: Jul. 7, 2004 having a hydrogen atoms using IFs, and a novel fluorination Related U.S. Application Data process for fluorinating an organic compound having a hydrogen atoms by using a fluorinating agent containing IFs (62) Division of application No. 10/296,942, filed on Dec. and at least one member Selected from the group consisting 10, 2002, now Pat. No. 6,784,327, filed as 371 of of acids, bases, Salts and additives. US 2004/0245505 A1 Dec. 9, 2004

PROCESS FOR THE PRODUCTION OF fluorinating organic compounds that have hydroxyl groups, FLUORINATED ORGANIC COMPOUNDS AND carbonyl groups, etc., was hitherto not known. FLUORINATINGAGENTS DISCLOSURE OF THE INVENTION TECHNICAL FIELD 0005 The inventors of the present invention conducted 0001. The present invention relates to a process for extensive research on the above problems. Consequently, fluorinating an organic compound having a hydrogen atom they found that various kinds of organic compounds having or hydrogen atoms using IFs. hydrogen atoms could be fluorinated by using IFs. 0006 Specifically, the present invention relates to the BACKGROUND ART following Items 1 to 12. 0002 The following are known as fluorinating agents for 0007) Item 1. A method for producing a fluorinated fluorinating organic compounds: HF, KF, IF, IFs, tetrabuty organic compound by fluorinating an organic com lammonium fluoride, tris(dimethylamino)Sulfur(trim pound having hydrogen atoms in the presence of IFs. ethylsilyl)difluoride (TASF), SF, diethylaminosulfurtrif luoride (DAST), fluorine gas, XeF, CF, F, CHCOOF, 0008. Item 2. The method for producing a fluorinated CIOF, N-fluoropyridinium triflate, 1-chloromethyl-4- organic compound according to Item 1, wherein the fluoro-1, 4-diazoniabicyclo[2.2.2]octane bis(tetrafluorobo organic compound having hydrogen atoms is fluori rate), 1-hydroxy-4-fluoro-1, 4-diazoniabicyclo2.2.2]octane nated in the presence of IFs and HF. bis(tetrafluoroborate), N-fluorobenzenesulfonimide, etc. 0009. Item 3 The production method according to Item (Sheppard, W. A.; Sharts, C. M. Organic Fluorine Chemistry, 1, wherein the organic compound having hydrogen 1969, W. A. Benjamin...: Chambers, R. D.; Fluorine in atoms is reacted in the presence of IF, HF, and an Organic Chemistry, 1973, Wiley-Interscience.: Hudlicky, M. organic base and/or a room temperature molten Salt. Chemistry of Organic Fluorine Compounds, 1976, Ellis Horwood.: Hudlicky; M. and Pavlath, A. E., Chemistry of 0010 Item 4. The production method according to Organic Fluorine Compounds II, 1995, ACS Monograph Item 1, wherein the organic compound having hydro 187.: N. Ishikawa and Y. Kobayashi, Fluorinated com gen atoms is reacted in the presence of IFs and a room pounds-Chemistry and their application, 1979, Kodansha temperature molten Salt. Ltd.: Outline of chemistry/New fluorine chemistry, 1980, 0011. Item 5. The production method according to Japan Scientific Societys Press: N. Ishikawa, T. Kitazume, Item 1, wherein the fluorination reaction does not and A. Takaoka, Journal of the Society of Synthetic Organic comprise substitution of bromine or iodine with fluo Chemistry, 1979, 37, 606. T. Umemoto, Journal of the rine, nor an addition reaction of iodine fluoride (IF) to Society of Synthetic Organic Chemistry, 1992, 50, 338: S. a double bond or triple bond. D. Taylor, C. C. Kotoris, and G. Hum; Tetrahedron, 1999, 0012 Item 6. The production method according to 55, 12431: Japanese Unexamined Patent Publication No. Item 5, wherein the fluorination reaction is conducted 1997-227531, etc.) in the presence of IFs and at least one member Selected 0003) Among those fluorinating agents, HF, KF, IF, tet from the group consisting of acids, Salts, and additives. rabutylammonium fluoride, and sulfoniumsilicate (TASF) have low reactivity, and therefore have limited uses. SF is 0013 Item 7. The production method according to a toxic gas having a boiling point at -40.4 C., which is Item 5, wherein the fluorination reaction is conducted difficult to handle. Fluorine gas is so active that it is difficult in the presence of IFs and at least one member Selected to control its reaction. Furthermore, it is reported that from the group consisting of bases, Salts, and additives. CFOF., CHCOOF, and CIOF are explosive gases and 0014) Item 8. A fluorinating agent for use in fluorinat should be handled with caution. Diethylaminosulfurtrifluo ing an organic compound having hydrogen atoms, ride (DAST), XeF, N-fluoropyridinium triflate, 1-chlorom which comprises IF, HF, and an organic base and/or a ethyl-4-fluoro-1,4-diazoniabicyclo2.2.2]octane bis(tet room temperature molten Salt. rafluoroborate), 1-hydroxy-4-fluoro-1,4-diazoniabicyclo 2.2.2]octane bis(tetrafluoroborate), 0015) Item 9. A fluorinating agent for use in fluorinat N-fluorobenzeneSulfonimide, etc., are easy to handle and ing an organic compound having hydrogen atoms, enable Selective fluorination; however, they are expensive which comprises IFs and a room temperature molten reagents and this causes a problem in using them for Salt. industrial purposes. 0016. Item 10. A fluorinating agent for use in fluori 0004 IFs is an industrially usable fluorinating agent that nating an organic compound having hydrogen atoms, is a nonexplosive and easy-to-handle liquid having a boiling which comprises IFs and at least one member Selected point at 100.5 C. and a melting point at 9.4° C. Fluorination from the group consisting of acids, Salts, and additives. using IF is employed only in a process of adding IF to 0017) Item 11. A fluorinating agent for use in fluori perfluoroolefin and Substituting iodine of the perfluoroio nating an organic compound having hydrogen atoms, doolefin with fluorine (M. Sakai, Organic Fluorine Chem which comprises IFs and at least one member Selected istry 1, 1970, pp348-351, GIHODO SHUPPAN Co., Ltd.: A. from the group consisting of bases, Salts, and additives. A. Banks, H. J. Haszeldine, and V. Kerrigan, J. Chem. Soc., 1948, 2188. R. D. Chambers, W. K. R. Musgrave, and J. 0018) Item 12. A fluorinating agent for use in fluori Savory, J. Chem. Soc., 1961, 3779.). However, since it is nating an organic compound having hydrogen atoms, difficult to control its high oxidizing property, using IFs for which comprises IF, HF, and triethylamine. US 2004/0245505 A1 Dec. 9, 2004

0019. In the present invention, examples of a organic glycine, alanine, phenylalanine, cysteine, aspartic compound having hydrogenatoms include; compounds hav acid, glutamic acid, threonine, histidine, lysine, ing an OH group, ketones (including diketone, f-ketocar methionine, proline and like 20 kinds of natural boxylic acid, f-ketoester); aldehydes, Schiff base, hydra amino acids, lactic acid, citric acid, malic acid, Zone and like imines, esters, Sulfides, olefins or epoxy, tartaric acid and like hydroxycarboxylic acids. aromatic compounds (phenylhydrazine derivatives, phenol derivatives, 2-naphthol derivatives, aniline derivatives); and 0027 (2) Ketones (including diketone, B-ketocarboxylic thiocarbonyl compounds, etc. acid, f-ketoester), aldehydes, imines, such as Schiff base, hydrazone, etc., and esters 0020. In fluorine substitution in a organic compound having hydrogen atoms, the following atom and groups are 0028. The following reactions are exemplified: substituted with fluorine: hydrogen atom (CH->CF), carbo nyl group (CO->CF), hydrazino group (Ph-NHNH->Ph F; C=N-NH->CF), hydroxyl group (C-OH->C-F), epoxy group (C-O-->C-F), etc. 0021 (1) Compounds Having an OH Group 0022. The following reactions are exemplified:

0023 in the above formulas, R' represents an alkyl group that may have a Substituent, an aralkyl group that may contain a Substituent, an alkenyl group that may contain a Substituent, an acyl group that may contain a Substituent, a cycloalkyl group that may contain a Substituent, a hetero cycloalkyl group that may contain a Substituent, or a mono-, 0029) in the above formulas, X represents O or NR'(R' di- or tri-saccharide that may contain a protecting group. R' represents a hydrogen atom, an alkyl group that may contain represents an alkyl group that may contain a Substituent, an a substituent, an aralkyl group that may contain a substitu aryl group that may contain a Substituent, an aralkyl group ent, an aryl group that may contain a Substituent, an alkenyl that may contain a Substituent, an alkenyl group that may group that may contain a Substituent, a cycloalkyl group that contain a Substituent, an acyl group that may contain a may contain a Substituent, a heterocycloalkyl group that may Substituent, a cycloalkyl group that may contain a Substitu contain a Substituent, a heterocyclic group that may contain ent, a heterocycloalkyl group that may contain a Substituent, a Substituent, an alkoxy group that may contain a Substitu or a mono-, di- or tri-saccharide that may contain a protect ent, an aryloxy group that may contain a Substituent, an ing group. amino group, a monoalkylamino group that may contain a 0024. In the present specification, “may contain a sub Substituent, a dialkylamino group that may contain a Sub Stituent includes both cases where a Substituent is contained Stituent, an acyl group that may contain a Substituent, or an and not contained. For example, an alkyl group that may acylamino group that may contain a Substituent). R, R, contain a Substituent includes alkyl groups and alkyl groups and R may be the same or different and each represents a having a Substituent. hydrogen atom, an alkyl group that may contain a Substitu ent, an aralkyl group that may contain a Substituent, an aryl 0.025 Specific examples of compounds having an OH group that may contain a Substituent, an alkenyl group that group include aplliphatic alcohols, Such as methanol, etha may contain a Substituent, a cycloalkyl group that may nol, n-propanol, isopropanol, n-butanol, isobutanol, tert contain a Substituent, a heterocycloalkyl group that may butanol, pentanol, hexanol, octanol, decanol, palmityl alco contain a Substituent, a heterocyclic group that may contain hol, Stearyl alcohol, oleyl alcohol, etc., alicyclic alcohols, a Substituent, an alkoxy group that may contain a Substitu Such as benzyl alcohol, a mono-, di- or tri-saccharide having ent, an aryloxy group that may contain a Substituent, a at least one non-protected hydroxyl group, cyclohexyl alco monoalkylamino group that may contain a Substituent, a hol, ascorbic acid, etc., Steroid alcohols, Such as cholesterol, dialkylamino group that may contain a Substituent, an acyl cholic acid, cortisone, etc.; and group that may contain a Substituent, or an acylamino group 0026 carboxylic acids, such as acetic acid, trifluo that may contain a substituent. R and R* may bond to each roacetic acid, propionic acid, acrylic acid, meth other and form a ring structure. R represents an alkyl group acrylic acid, crotonic acid, butyric acid, Valeric acid, that may contain a Substituent, an aralkyl group that may isovaleric acid, pivalic acid, lauric acid, myristic contain a Substituent, or an aryl group that may contain a acid, palmitic acid, Stearic acid, oleic acid, linoleic Substituent. acid, linolenic acid, cinnamic acid and like aliphatic mono-carboxylic acids, oxalic acid, Succinic acid, 0030 Examples of substances having a ring structure malonic acid, glutaric acid, adipic acid, maleic acid, include 4-membered rings, 5-membered rings, 6-membered fumaric acid, citric acid and like polycarboxylic rings, and 7-membered rings of aliphatic compounds that acids, benzoic acid, Salicylic acid, (o-, m-, p-)ph may contain a Substitute, etc. thalic acid, nalidixic acid, nicotinic acid and like 0031 Examples of ketones include acetone, methyl ethyl aromatic carboxylic acids, pantothenic acid, biotin ketone, acetylacetone, acetoacetic acid, acetoacetate, cyclo and like Vitamins having carboxylic acid groups, hexanone, acetophenone, benzophenone, propiophenone, US 2004/0245505 A1 Dec. 9, 2004

4-piperidone, 1-oxo-1,2-dihydronaphthalene, benzylidene heterocyclic group that may contain a Substituent. Alter acetophenone (chalcone), deoxybenzoin, and ketals thereof, nately, R and R may form 4 to 8-membered rings with etc. carbon atoms with or without having a heteroatom in the 0.032 Examples of aldehydes include acetoaldehyde, ring. In the rings, they may be Substituted with a halogen propionaldehyde, buthylaldehyde, isobutylaldehyde, Valer atom, an OXO group, an alkyl group that may contain a aldehyde, isoValeraldehyde, acrylaldehyde, benzaldehyde, Substituent, an aralkyl group that may contain a Substituent, cinnamaldehyde, anisaldehyde, nicotinealdehyde, or acetals an aryl group that may contain a Substituent, an alkenyl group that may contain a Substituent, a cyano group, or an thereof, etc. amino group. R and R represent a hydrogen atom, an 0.033 Examples of imines of Schiff base, hydrazone and alkyl group that may contain a Substituent, an aralkyl group the like include condensates of ketone or aldehyde with an that may contain a Substituent, an aryl group that may appropriate primary amine. contain a Substituent, an alkenyl group that may contain a Substituent, a cycloalkyl group that may contain a Substitu 0034 (3) Sulfides (including dithioacetal and dithioketal) ent, a heterocycloalkyl group that may contain a Substituent, 0035. One or two hydrogen atoms of methylene that is a heterocyclic group that may contain a Substituent, an located adjacent to a Sulfur atom are Substituted with fluo alkoxy group that may contain a Substituent, an aryloxy rine atoms, or a Sulfur atom is Substituted with fluorine: group that may contain a Substituent, a monoalkylamino group that may contain a Substituent, a dialkylamino group CF-S R (a-1) that may contain a Substituent, an acyl group that may contain a Substituent, or an acylamino group that may R-CHRB-S-R-R-CFR-S-Ra (a-2) contain a substituent. Alternately, R and R may form a R-CO-CH-S-R-R-CO-CFH-S R->R-CO-CF-S-R (b-1) 4-membered ring, 5-membered ring, 6-membered ring or R-CO-CHR-S-R->R-CO-CFR 7-membered ring of an aliphatic that may contain a Sub S-R (b-2) stituent, or R, R, and C may form RRC=C(SR)-->RRCH-CF-SR (c) ReR3C(SR3a) (SRa")-ReRCF, (d) R-C(SR) (SR)(SR")->R-CF, (e) R° C(SR) (SR)-S-R-S-(SR")- (SR)--R (f) 0036) in the above formulas, R, R', and R" may be the same or different and each represents an alkyl group that may contain a Substituent, an aralkyl group that may contain 0037) R represents an alkylene group or an arylene a Substituent, an aryl group that may contain a Substituent, group. an alkenyl group that may contain a Substituent, a cycloalkyl group that may contain a Substituent, a heterocycloalkyl 0038 Examples of sulfides include methyl ethylsulfide, group that may contain a Substituent, a heterocyclic group methylbenzyl Sulfide, 2-phenylthioacetate, 2-phenylthioac that may contain a substituent, or R and R" bond to each etophenone, CH-CO-CH-SCH, bis(methylthio)meth other and represent a 4-membered ring, 5-membered ring, ylbenzene, 2-octyl-1,3-dithiane, 2-phenyl-2-trifluorom 6-membered ring, or 7-membered ring of an aliphatic that ethyl-1,3-dithiolane, tris(ethylthio)hexane, may contain a substituent. R and R represent an alkyl 4-tris(methylthio)toluene, etc. group that may contain a Substituent, an aralkyl group that may contain a Substituent, an aryl group that may contain a 0.039 (4) Olefins or Epoxies Substituent, an alkenyl group that may contain a Substituent, 0040. The following fluorine addition reactions are a cycloalkyl group that may contain a Substituent, a hetero exemplified: cycloalkyl group that may contain a Substituent, a hetero cyclic group that may contain a Substituent, an alkoxy group that may contain a Substituent, an aryloxy group that may contain a Substituent, an amino group, a monoalkylamino group that may contain a Substituent, a dialkylamino group O F OH that may contain a Substituent, an acyl group that may contain a Substituent, an acylamino group that may contain a Substituent, a cyano group, an alkylsulfinyl group that may 0041) in the above formula, R', R', R', and Reach contain a Substituent, an aralkylsulfinyl group that may represent a hydrogen atom, an alkyl group that may contain contain a Substituent, an arylsulfinyl group that may contain a Substituent, an aralkyl group that may contain a Substitu a Substituent, a cycloalkylsulfinyl group that may contain a ent, an aryl group that may contain a Substituent, an alkenyl Substituent, a heterocycloalkylsulfinyl group that may con group that may contain a Substituent, a cycloalkyl group that tain a Substituent, a Sulfinyl group bonded by a heterocyclic may contain a Substituent, a heterocycloalkyl group that may group that may contain a Substituent, an alkylsulfonyl group contain a Substituent, or a heterocyclic group that may that may contain a Substituent, an aralkylsulfonyl group that contain a Substituent. may contain a Substituent, an arylsulfonyl group that may contain a Substituent, a cycloalkylsulfonyl group that may 0042 Examples of epoxies include oxirane, 1,2-epoxy contain a Substituent, a heterocycloalkylsulfonyl group that ethylbenzene, 1-chloro-2,3-epoxypropane, C.C.'-epoxy may contain a Substituent, or a Sulfonyl group bonded by a bibenzyl, etc. US 2004/0245505 A1 Dec. 9, 2004

0043 (5) Aromatic Compounds -continued 0044) A fluorine substituent is introduced in an aromatic R5a ring by the following reaction. Fluorination of an aromatic R5 OH IFs ring in a phenol derivative or aniline derivative can be He carried out by fluorinating it using IF or the like, then reducing it by Zinc powder or like reducing agents, to obtain R.Sc the targeted fluorine compound. R5d R5a R5a 0045 (5-1) Phenylhydrazine Derivatives RSb O RSb OH 0046) A phenylhydrazine residue that may contain a Reduction Substituent can be Substituted with a fluorine atom. F RSc F RSc F R5d R5d R5a ree NHNH IF 0050 in the above formulas, R, R, R and Reach represents a hydrogen atom, an alkyl group, an aralkyl R-R s -- group, an aryl group, an alkoxy group, a nitro group, a cyano > R5e group, a halogen atom, an acyl group, an amino group, a monoalkylamino group, a dialkylamino group, an acylamino R5a R5a group, or an alkylthio group. 0051. In a starting material in which all atoms or groups re F re I in the Ortho- and para-positions are Substituted, fluorine R-R d " R-R s atoms are introduced into the ortho- or para-position, form > R5e > R5e ing compounds having a fluorine quinonoid structure (e.g., Example 47). 0052. In the above example, phenol that may contain a Substituent is used as a phenol derivative; however, it is also 0047 in the above formula, R, R,R,R, and R. possible to introduce fluorine atoms into benzene-based each represents a hydrogen atom, an alkyl group, an aralkyl aromatic compounds or condensed polycyclic hydrocarbons group, an aryl group, an alkoxy group, a nitro group, a cyano that may be Substituted and have electron-releasing groups group, a halogen atom, an acyl group, an amino group, a Such as a hydroxyl group, an alkoxy group, etc. monoalkylamino group, a dialkylamino group, an acylamino 0.053 (5-3) 2-naphthol Derivatives group, or an alkylthio group. 0054 Acarbon atom in the 1-position of naphthol can be Subjected to mono- or di-fluorination. 0048 (5-2) Phenol Derivatives 0049. A phenol derivative forms the difluorinated quinonoid structure as shown below by reacting with IFs. Thereafter, by reducing the resultant compound, a phenol derivative having fluorine introduced in the ortho- or para position is produced.

R5a RSb OH IFs He

R5d R.Sc R5a R5a RSb O Rib OH Reduction F R5d F R5d F R.Sc R.Sc US 2004/0245505 A1 Dec. 9, 2004

0059. Using aniline that may contain a substituent or -continued naphthylamine that may contain a Substituent as an aniline R5a F R5g derivative also allows introducing a fluorine atom in an RSb O aromatic ring. 0060 (6) Thiocarbonyl Compounds (including thioke tone, thioester, thiocarbonic ester, thioamide, dithiocarboxy late, and dithiocarbamate) 0061 The following reactions are exemplified:

R° C(=S)-SR->R CF-SR->R-CF, (b) 0055) in the above formulas, R,R,R,R,R,R, 0062) in the above formulas, RandR may be the same and R may be the same or different and each represents a or different and each represents a hydrogen atom, an alkyl hydrogen atom, an alkyl group, an aralkyl group, an aryl group that may contain a Substituent, an aralkyl group that group, an alkoxy group, a nitro group, a cyano group, a may contain a Substituent, an aryl group that may contain a halogen atom, an acyl group, an amino group, a monoalky Substituent, an alkenyl group that may contain a Substituent, lamino group, a dialkylamino group, an acylamino group, or a cycloalkyl group that may contain a Substituent, a hetero an alkylthio group. cycloalkyl group that may contain a Substituent, a hetero 0056 (5-4) Aniline Derivatives cyclic group that may contain a Substituent, an alkoxy group that may contain a Substituent, an aryloxy group that may 0057 Similar to a phenol derivative, an aniline derivative contain a Substituent, a monoalkylamino group that may forms the difluorinated quinonoid structure as shown below contain a Substituent, a dialkylamino group that may contain by reacting with IFs. Then, by reducing the resultant com a Substituent, an acyl group that may contain a Substituent, pound, an aniline derivative having fluorine introduced in or an acylamino group that may contain a Substituent. Rand the ortho- or para-position is produced. R* may bond to each other and form a ring structure. R' represents an alkyl group that may contain a Substituent, an aralkyl group that may contain a Substituent, an aryl group R5a that may contain a Substituent, an alkenyl group that may RSb NH contain a substituent, a cycloalkyl group that may contain a 2 IFs Substituent, a heterocycloalkyl group that may contain a --- Substituent, or a heterocyclic group that may contain a R5d Substituent. 0063 Examples of thiocarbonyl compounds include R.Sc O-methyl cyclohexanecarbothioate, O-propyl 1-piperidin R5a R5a ecarbothioate, methyl dithiobenzoate, thiobenzophenone, Rib NH RSb NH2 O-phenyl thiobenzoate, N,N-dimethylphenylthioamide, ethyl 3-quinolinedithiocarboxylate, trifluoromethane car Reduction bothioylnaphthalene, N-methyl-N-phenyl trifluo F R5d F R5d romethanethioamide, N-benzyl-N-phenylheptafluoropro F panethioamide, R.Sc R.Sc R5a S R5 NH2 IFs Ph O Her O, t X-s, R.Sc O R5d O O S etc. R5a R5a X=s. O Rib NH RS NH2 O Reduction He C C F R.Sc R.Sc F F R5d R5d 0064. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, Sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, 0.058 in the above formulas, R, R, R and Reach tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octa represents a hydrogen atom, an alkyl group, an aralkyl decyl and like C-C alkyl groups having Straight chains or group, an aryl group, an alkoxy group, a nitro group, a cyano branched chains, preferably methyl, ethyl, n-propyl, isopro group, a halogen atom, an acyl group, an amino group, a pyl, n-butyl, isobutyl, Sec-butyl, tert-butyl, pentyl, hexyl and monoalkylamino group, a dialkylamino group, an acylamino like C-C alkyl groups having Straight chains or branched group, or an alkylthio group. chains. US 2004/0245505 A1 Dec. 9, 2004

0065 Examples of alkoxy groups include methoxy, and a Sulfonyl group having a heterocyclic group bonded ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, Sec thereto are as described above. butoxy, tert-butoxy, pentyloxy, hexyloxy and like C-C, 0081. The number of Substituents in an alkyl group alkoxy groups having Straight chains or branched chains. having Substituents, an alkoxy group having Substituents, or 0.066 Examples of alkenyl groups include a vinyl group, an alkenyl group having Substituents is generally 1 to 5, and an allyl group, a 3-butenyl group and like C-C alkenyl preferably 1 to 3. Examples of Substituents include halogen, groups, etc. C-C alkoxy, C-C alkylthio, cyano, nitro, an amino group, a hydroxyl group and the like. Examples of an alkyl group 0067 Examples of halogens include a fluorine atom, a having halogens include an alkyl group in which one or chlorine atom, a bromine atom, an iodine atom, etc. more hydrogen atoms are Substituted with fluorine. 0068 Examples of aryl groups include a phenyl group, a 0082 The number of substituents in an aralkyl group naphthyl group, etc. having Substituents, an aryl group having Substituents, an 0069. Examples of aryloxy groups include a phenoxy aryloxy group having Substituents, a cycloalkyl group hav group, a naphthyloxy group, etc. ing Substituents, a heterocycloalkyl group having Substitu ents, a heterocyclic group having Substituents, a monoalky 0070) Examples of aralkyl groups include 2-phenylethyl, lamino group having Substituents, a dialkylamino group benzyl, 1-phenylethy, 3-phenylpropyl, 4-phenylbutyl and having Substituents, an acylamino group having Substitu like C7-Co aralkyl groups, etc. ents, an alkylsulfinyl group having Substituents, an aralkyl 0071 Examples of cycloalkyl groups include cyclopro Sulfinyl group having Substituents, an arylsulfinyl group pyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, having Substituents, a cycloalkylsulfinyl group having Sub cyclooctyl and like C-C cycloalkyl groups, etc. Preferable Stituents, a heterocycloalkylsulfinyl group having Substitu are C-C-7 cycloalkyl groups. ents, a Sulfinyl group to which a heterocyclic group having Substituents is bonded, an alkylsulfonyl group having Sub 0.072 Examples of heterocycloalkyl groups include Sub Stituents, an aralkylsulfonyl group having Substituents, an stances in which one or more carbon atoms forming the arylsulfonyl group having Substituents, a cycloalkylsulfonyl above described ring structure of cycloalkyl groups are group having Substituents, a heterocycloalkylsulfonyl group Substituted with atoms of nitrogen, oxygen, Sulfur, etc. having Substituents, or a Sulfonyl group to which a hetero 0.073 Examples of monoalkylamino groups include cyclic group having Substituents is bonded is generally 1 to amino groups mono-Substituted with the above-described 5, preferably 1 to 3. Examples of substituents include C-C, C-C alkyl groups. alkyl groups, a halogen atom, C-C alkoxy groups, C-C, alkylthio groups, cyano, nitro, an amino group, a hydroxyl 0.074 Examples of dialkylamino groups include dimethy lamino, diethylamino, di-n-propylamino, diisopropylamino, group and the like. dibutylamino, dipentylamino, dihexylamino and like amino 0083. The number of Substituents in a 4- to 7-membered groups di-Substituted with the above-described C-C alkyl ring of aliphatics having Substituents is generally 1 to 5, and groupS. preferably 1 to 3. Examples of Substituents include C-C, alkyl groups, a halogen atom, C-C alkoxy groups, C-C, 0075 Examples of acylamino groups include formy alkylthio groups, cyano, nitro, an amino group, a hydroxyl lamino, benzoylamino, acetylamino, propionylamino, n-bu tyrylamino and like C-C acylamino groups. group, carboxy ester and the like. In addition, 0.076 Examples of alkylthio groups include -S-(C-C, alkyl groups), etc. (C-C alkyl groups are the same as described above.) 0.077 Examples of heterocyclic groups include piperidyl, -)-()- furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrrolyl, pyr rolidinyl, triazolyl, benzothiazolyl, benzoimidazolyl, Oxa diazolyl, thiadiazolyl, indolyl, pyrazolyl, pyridazinyl, cin 0084) is also included in 4- to 7-membered ring of nolinyl, quinolinyl, isoquinolinyl, quinoxalinyl, pyradinyl, aliphatics having Substituents. pyridyl, benzofuryl, benzothienyl, tetrazolyl, etc. 0085 Examples of acyl groups having substituents include a chloroacetyl group, a bromoacetyl group, a dichlo 0078 Examples of acyl groups include formyl, acetyl, roacetyl group, a trifluoroacetyl group and like Substituted propionyl, n-butyryl, isobutyryl, Valeryl, isoValeryl, pivaloyl acetyl groups, a methoxyacetyl group, an ethoxyacetyl and like C-acyl groups having Straight chains or branched group and like acetyl groups Substituted with alkoxy groups, chains, benzoyl and a Substituted acyl group. a methylthioacetyl group and like acetyl groups Substituted 0079 Specific examples of an alkyl group, an aralkyl with alkylthio groups, a phenoxyacetyl group, a phenylth group, an aryl group, a cycloalkyl group, a heterocycloalkyl ioacetyl group, a 2-chlorobenzoyl group, a 3-chlorobenzoyl group, and a heterocyclic group in an alkylsulfinyl group, an group, a 4-chlorobenzoyl group, a 4-methylbenzoyl group, a aralkylsulfinyl group, an arylsulfinyl group, a cycloalkyl 4-t-butylbenzoyl group, a 4-methoxybenzoyl group, a 4-cy Sulfinyl group, a heterocycloalkylsulfinyl group, and a Sulfi anobenzoyl group, a 4-nitrobenzoyl group and like Substi nyl group having a heterocyclic group bonded thereto are as tuted benzoyl groups, etc. described above. 0086 AS for the production method and fluorinating 0080 Specific examples of an alkyl group, an aralkyl agents of the present invention, it is preferable to use, in group, an aryl group, a cycloalkyl group, a heterocycloalkyl addition to IFs, 1 to 4 members and preferably 1 to 3 group, and a heterocyclic group in an alkylsulfonyl group, members Selected from the group consisting of acids, bases, an aralkylsulfonyl group, an arylsulfonyl group, a salts and additives. More preferably, 1 to 3 members except cycloalkylsulfonyl group, a heterocycloalkylsulfonyl group, for the combination of an acid, a basic and a Salt are used. US 2004/0245505 A1 Dec. 9, 2004

0.087 Specific examples of acids include Sulfuric acid, 0097 Sodium, ppotassium, lithium and like alkali nitric acid, phosphoric acid, polyphosphoric acid, hydrogen metals, fluoride, fluoric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, hypochlorous acid, chlorous acid, chloric 0098 magnesium oxide, calcium oxide and like acid, perchloric acid, perbromic acid, periodic acid and like alkaline earth metal oxides, hydrogen halides, or hydrohalic acid, hypohalous acid, 0099 ammonia, ammonium hydroxide, tetramethy halous acid, halogen acid, and perhalogen acid; lammonium hydroxide, tetraethylammonium 0088 fluorosulfonic acid, chlorosulfonic acid, hydroxide, tetrabuthylammonium hydroxide, octyl methaneSulfonic acid, ethaneSulfonic acid, trifluo triethylammonium hydroxide, benzyltrimethylam romethaneSulfonic acid, difluoromethaneSulfonic monium hydroxide and like ammonium hydroxide acid, trichloromethaneSulfonic acid, perfluorobu salts, or AMBERLITE(R) resin and like polymer taneSulfonic acid, perfluorooctaneSulfonic acid, ben carrying ammonium hydroxide Salts, etc.; ZeneSulfonic acid, toluenesulfonic acid, nitrobenze neSulfonic acid and like Sulfonic acids, or 0100 aliphatic amine (primary amine, secondary polystyreneSulfonic acid, fluorinated Sulfonic acid amine, tertiary amine), alicyclic amine (Secondary resin (Nafion-H) and like polymer carrying Sulfonic amine, tertiary amine), aromatic amine (primary acids, amine, Secondary amine, tertiary amine), heterocy 0089 formic acid, acetic acid, propionic acid, chlo clic amine and like organic bases, and mixtures roacetic acid, bromoacetic acid, dichloroacetic acid, thereof. trichloroacetic acid, trifluoroacetic acid, glycolic 0101 Specific examples of aliphatic primary amines acid, lactic acid, benzoic acid, oxalic acid, Succinic include methylamine, ethylamine, propylamine, butylamine, acid and like mono- or poly-carboxylic acids, pentylamine, hexylamine, cyclohexylamine, ethylenedi 0090 SO, BF, BC1, B(OCH), AlCl, AlBr, amine, etc. Specific examples of aliphatic Secondary amines SbF, SbCl, SbF5, PF, PFs, ASF, ASC1, ASFs, include dimethylamine, diethylamine, dipropylamine, dibu TiCl, NbF5, TaF5 and like Lewis acids or their ether tylamine, dipentylamine, dihexylamine, dicyclohexylamine, complexes, etc. Specific examples of aliphatic tertiary amines include 0091) HBF, HPF, HASF, HSbF, HSbO1 and like trimethylamine, triethylamine, diisopropylethylamine, N.N., acids formed between Lewis acids and hydrogen N',N'-tetramethylethylenediamine, etc. halides, or their ether complexes, 0092 or mixtures of two or more members 0102 Specific examples of alicyclic secondary amines described above. The acids used here may be Sup include piperidine, piperazine, pyrrolidine, morpholine, etc. ported by Several kinds of carriers. Examples of Specific examples of alicyclic tertiary amines include N-me carriers include SiO, methylated SiO2, Al2O, thylpiperazine, N-methylpyrrolidine, 5-diazabicyclo4. 3. Al-O-WB, MoC), ThC), ZrO, TiO, Cr-O, Ononane-5-ene, 1,4-diazabicyclo2. 2. 20ctane, etc. SiO-Al-O, SiO TiO, SiO-ZrO, TiO 0.103 Specific examples of aromatic amines include ZrO, Al-O-BO, SiO-WO, SiO-NHF, aniline, methylaniline, dimethylaniline, N,N-dimethyla HSOCl-Al-O, HF-NH-Y, HF-Al-O, NHF-SiO-Al-O, AIF. Al-O, Ru-F- niline, haloaniline, nitroaniline, etc. Al-O, F-Al-O, KF-Al-O, AIPO, AIF, baux 0104 Specific examples of heterocyclic amines include ite, kaolin, activated carbon, graphite, Pt-graphite, pyridine, pyrimidine, piperazine, quinoline, imidazole, etc., ion-exchange resin, metal Sulfate, chloride, Al and and further include polyaryl amine, polyvinylpyridine and like metals, Al-Mg, Ni-Mo and like alloys, poly like polymer carrying amine compounds, etc., and mixtures Styrene and like polymers, etc. thereof. 0093. The amount of the above-described acids used in the present invention can be Selected from a catalytic 0105 The amount of the above-described bases used in amount to an excessive amount. The preferable amount is the present invention can be Selected from a catalytic 0.01 to 100 moles, and more preferably 0.1 to 20 moles per amount to an excessive amount. The preferable amount of mole of the organic compound containing a hydrogen atom the bases used is 0.01 to 20 moles, and more preferably 0.1 to be fluorinated. It is also possible to use the above to 10 moles per mole of the organic compound containing a described acids as a reaction Solvent. In this case, the amount hydrogen atom to be fluorinated. of Solvent used can be Selected from little to excessive. 0106. In the present invention, when an acid as a reaction 0094. The bases or organic bases used in the present Solvent, and a metal, metal hydroxide, metal hydride, metal invention include the ones generally used, Such as Sodium alkoxide, metal oxide, or organic base as a base are used, a hydroxide, potassium hydroxide, lithium hydroxide, metal Salt of an acid or a Salt of an organic base is naturally rubidium hydroxide, cesium hydroxide, magnesium hydrox produced from a reaction between the acid and base. ide, calcium hydroxide, barium hydroxide and like hydrox 0107 The salts used in the present invention are com ides of alkali metals or alkaline earth metals, pounds generated by a reaction between an acid and a base, 0095 Sodium methoxide, sodium ethoxide, sodium and mainly include the compounds obtained by the reaction butoxide, potassium methoxide, potassium ethoxide, between the above-mentioned acids and bases. potassium butoxide, lithium methoxide, lithium 0.108 For example, metal salts or ammonium salts of ethoxide and like alkali metal alkoxides; Sulfuric acids or Sulfonic acids, Such as Sodium Sulfate, 0096 sodium hydride, potassium hydride, lithium Sodium hydrogensulfate, potassium Sulfate, potassium hydride, calcium hydride and like hydrides of alkali hydrogenSulfate, lithium Sulfate, cesium Sulfate, calcium metals or alkaline earth metals, Sulfate, magnesium Sulfate, ammonium Sulfate, triethylam US 2004/0245505 A1 Dec. 9, 2004 monium Sulfate, pyridinium Sulfate, trimethylpyridinium 0116 Sodium nitrate, potassium nitrate, ammonium Sulfate, polyarylammonium Sulfate, polyvinylpyridinium nitrate, pyridinium nitrate and like metal Salts or Sulfate, Sodium methaneSulfonate, ammonium methane amine Salts of nitric acid; Sulfonate, tetramethylammonium methaneSulfonate, potas sium ethaneSulfonate, lithium butaneSulfonate, Sodium ben 0117 NaBF, KBF, LiBF, NaSbF, NaAsF, ZeneSulfonate, Sodium toluenesulfonate, Sodium NaPF, NHBF, NHSbF, NH, PF and like metal trifluoromethaneSulfonate, Sodium polystyreneSulfonate, Salts or amine Salts formed between Lewis acids and etc., hydrogen halide, 0109 sodium formate, ammonium formate, sodium 0118 tetramethylphosphonium fluoride, tetrameth acetate, potassium acetate, lithium acetate, magne ylphosphonium acetate, tetraphenylphosphonium Sium acetate, calcium acetate, ammonium acetate, fluoride and like phosphonium Salts; methylammonium acetate, diethylammonium 0119) (CH), NF, 1-ethyl-3-methylimidazolium acetate, triethylammonium acetate, tetraethylammo fluoride, (CH3)-N-(HF), (CHS)NF-(HF), nium acetate, pyridinium acetate, Sodium propi (n-CH)-N-(HF), (n-CHo). NF-(HF), onate, potassium propionate, Sodium butyrate, pol BF.EtO-(HF), when (n=1 to 20), and like room yarylammonium butyrate, polyvinylpyridinium temperature molten Salts having fluoride anions or acetate, Sodium isobutyrate, Sodium Valerianate, HF: Sodium nonanoate, Sodium chloroacetate, Sodium bromoacetate, Sodium trichloroacetate, Sodium trif 0120 and mixtures thereof. luoroacetate, Sodium glycolate, Sodium lactate, 0121 Examples of the additives used in the present Sodium benzoate, Sodium oxalate, Sodium Succinate, invention include halogen, interhalogen compounds, poly Sodium polyacrylate and like metal Salts or ammo halides and the like. Specific examples of halogens include nium Salts of carboxylic acids, iodine, bromine, chlorine, etc. Among those, iodine and 0110 Li Br, LiI, NaBr, NaI, KBr, KI, RbBr, Rb1, bromine are preferable, and iodine is more preferable. CsBr, CsI, BeBr, Bel, MgBr, Mg, CaBr, Cal, Specific examples of the interhalogen compounds include SrBra, Sr., BaBr, Bala, ZnBr, Zn, CuBr, CuI2, one, two or more members of CIF, BrF, IC1, IBr, IC1, IC1, CuBr, CuI, AgBr, AgI, AuBr, AuI, NiBr, NiI, but are not limited to them. PdBr, PdL, PtBr, Pt, CoBr, CoI, FeBr, FeBr, 0.122 Specific examples of the polyhalides include one, FeI, FeI, MnBr, MnI, CrBr, Cr, PbBr, Pb, two or more members of LiCl, NaCl. I, KCl I, CsCl I, SnBr, SnI, SnBri, SnI and like metal salts; RbCl. I, Me NCII, Et NCII, PrNCII, BuNCII, 0111 NHBr, NH, I, MeNHBr, MeNHI, MeNBr, PhNMeCl I, PhCHNMeCl I, MeSCII, CIIP, KCIL, MeNI, Et NBr, Et NI, BuNBr, BuNI, PhMeNBr, Me NCII, 2,2'-bipyridinium u-chlorodichlorodiodate, PhMeNI, PhCHNMeI, pyridinium bromide, pyri 2,2'-biquinolinium ti-chlorodichlorodiiodate, KCII, dinium iodide, chloropyridinium iodide, methylpy Me NCII, Me NCII, Et NCls, PhASC1, KCIF, ridinium iodide, cyanopyridinium iodide, bipyri Me NCIF CsClF, CsClFI, KBrCII, NH. BrCII, dinium iodide, quinolium iodide, isoquinolium MeNBrCII, MeNBrC1, BuNBrC1, MeNBrC1L, iodide, N-methylpyridinium bromide, N-methylpy CsBrFI, NaBrF., KBrF, CsBrF, MeNBrF, CsBrF, ridinium iodide, N-methylguinolium iodide and like MeNBrF, Et NBrC1, CsBr, Me NBr, EtBr, BuNBr, pyridinium Salts or ammonium Salts; PhCHNMeBr, pyridinium tribromide, Br,P, CsBri, MeNBri, Me NBr, MeNBr, KBrC1, Me NBr Cl, 0112 MePBr, MePI, Et PI, PriPI, BuPBr, BuPI, BuNBrC1, KBr-I, MeNBr I, BuNBr I, 2,2'-bipyri PhPBr, PhPI and like phosphonium salts; dinium u-bromodibromodiiodate, NaF.I, KFI, CSFI, CsFI, CSFI, KI, CSI, Me, NI, EtNI, PrNI, BuNI, 0113 sodium fluoride, potassium fluoride, cesium pyridinium triiodide, MeNIs, EtNIz, MeNIo, MePBr, fluoride, ammonium fluoride, tetraethylammonium MePI, Me, PIBr, Me PIC1, Et PI, BuPI, Ph.PI, fluoride, tetrabutylammonium fluoride, polyarylam PhPBr, Ph PIBr, but are not limited to them. monium fluoride, Sodium chloride, ammonium chlo ride, Sodium hypochlorous acid, Sodium chlorite, 0123. In the production method of the present invention, Sodium chlorate, Sodium perchlorate, Sodium perbro IFs can be used in the amount of 0.2 to 20 moles, preferably mate, Sodium periodate and like metal Salts or amine 0.3 to 5 moles, and more preferably 0.4 to 2 moles per mole Salts of hydrogen halides, hypohalous acids, halous of organic compound having a hydrogen atom and additives acids, halogen acids, or perhalogen acids; can be used in an amount from 0.1 to 10 times (molar ratio) based on the organic compound to react at -70° C. to 200 0114 Sodium carbonate, potassium carbonate, C., and preferably -20° C. to 100° C. lithium carbonate, Sodium hydrogencarbonate, potassium hydrogencarbonate, lithium hydrogencar 0.124. Use of a reaction solvent is not necessary, but bonate, calcium carbonate, magnesium carbonate preferably it is used. Specific examples of the reaction and like carbonates, Solvents include pentane, hexane, heptane, cyclohexane, petroleum ether and like aliphatic Solvents, dichlo 0115 Sodium phosphate, potassium phosphate, romethane, dichloroethane, chloroform, fluorotrichlo Sodium hydrogenphosphate, Sodium dihydrogen romethane, 1,1,2-trichlorotrifluoroethane, 2-chloro-1,2-di phosphate, ammonium phosphate, pyridinium phos bromo-1,1,2-trifluoroethane, 1,2- phate and like metal Salts or amine Salts of phospho dibromohexafluoropropane, 1,2-dibromotetrafluoroethane, ric acid; 1,1-difluorotetrachloroethane, 1,2-difluorotetrachloroet US 2004/0245505 A1 Dec. 9, 2004 hane, heptafluoro-2,3,3-trichlorobutane, 1,1,1,3-tetrachlo analysis after the completion of reaction were conducted in rotetrafluoropropane, 1,1,1-trichloropentafluoropropane, the same manner as that of Method A. 1,1,1-trichlorotrifluoroethane, polychlorotrifluoroethylene and like aliphatic halide Solvents, methyl formate, ethyl 0133) Method B formate, methyl acetate, ethyl acetate, propyl acetate, methyl 0134) An IF/EtN-3HF (1:1 molar ratio) solution (1.2 propionate, Y-butyrolactone, propylene carbonate and like mmol) and a reaction solvent (2 ml) were held in a PFA ester Solvents, acetonitrile, propionitrile and like nitrile vessel (15 ml). While stirring at room temperature, a Sub Solvents, benzene, chlorobenzene, toluene, dichlorobenzene, strate (1.0 mmol) dissolved in a reaction solvent (2 ml) was fluorobenzene, nitrobenzene and like aromatic Solvents, added hereinto, and allowed to react at a predetermined diethylether, dipropylether, tetrahydrofuran and like ether temperature for a predetermined period of time. solvents, N,N-dimethyl formamide(DMF), dimethylsulfox 0135 Method C ide (DMSO), water, nitromethane, N,N-diethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, 1,3-dim 0.136 An IF/EtN-3HF (1:1 molar ratio) solution (1.2 ethyl-2-imidazolidinone (DMI), tetramethylurea, 1,3-dim mmol) and a reaction solvent (2 ml) were held in a PFA ethylpropyleneurea, hexamethylphosphoramide (HMPA), vessel (15 ml). While stirring at -78 C., a substrate (1.0 mmol) dissolved in a reaction Solvent (2 ml) was added, and etc. They are used singularly or as a mixture of two or more then allowed to react at room temperature for a predeter members. mined period of time. 0125 The order of adding organic compounds and IFs, acids, bases, Salts, or additives can be arbitrary So far as long 0137 Method D time intervals do not exist between them. 0138 An IF/EtN-3HF (1:1 molar ratio) solution (1.2 mmol) and a solvent (20 ml) were held in a PFA vessel (100 0.126 AS for postprocessing after the reaction, it is pos ml). While stirring at room temperature, a substrate (1.0 Sible to add various kinds of organic or inorganic reducing mmol) dissolved in a reaction solvent (20 ml) was added agents to reduce the excessively oxidized organic com hereinto using a dropping apparatus in one hour and Stirred pounds, or to reduce IF or the oxidative compounds derived for one hour. from IFs that remain in an excessive amount. 0139 Method D' 0127 Specific examples of Such reducing agents include Zinc powder, tin, tin chloride, iron, aluminium, Sodium 0140. After the completion of the reaction of Method D, thiosulphate, butyltinhydride, Sodium borohydride, lithium 3N of HCl aqueous solution (20 ml) was added to an organic aluminium hydride, etc.; however, as long as they are layer washed with water, and Stirred using an excessive reductive compounds, the reducing agents are not limited to amount of Zn powder (room temperature, one hour). After filtering Solid Substances, isolation and purification was the above examples. performed. BEST MODE FOR CARRYING OUT THE 0.141. In the Method column on Tables 1 to 6, the asterisk INVENTION (*) indicates that, instead of the IFs/EtN-3HF (1:1 molar 0128. The present invention will be explained in more ratio) solution, an IF (1.2 mmol)/CHCl (0.46 g) solution detail referring to the Examples and Comparative Examples was used. given below. However, the Scope of the present invention is 0142. In the tables, “*2 indicates that, instead of the not limited to these examples. IFs/EtN-3HF (1:1 molar ratio) solution, an IFs/Et NF (1:1 molar ratio) solution was used, and “*3” indicates that EXAMPLE instead of the IFs/Et-N-3HF (1:1 molar ratio) solution, an IF/EtN-5HF (1:1 molar ratio) solution was used. 0129. Organic compounds having hydrogen atoms, which serve as starting materials, are fluorinated using IF 0143 Method E under the conditions listed in Tables 1 to 6 shown below. The 0144 IF (1.2 mmol) and a solvent (4 ml) were held in a results are shown in Tables 1 to 6. PFA vessel (20 ml). While stirring at room temperature, EtN (1.2 mmol) was added droppwise. Five minutes later, 0130. The reaction conditions of reaction Methods A, B, a Substrate (1.0 mmol) was added and stirred at room C, D, D', E, F, G, H, I, and J are described below. temperature for three hours. After adding 2-fluoronitroben 0131 Method A Zene (1.0 mmol) to the reaction Solution as an internal Standard, a portion of the reaction Solution was taken out and 0132) An IF/EtN-3HF (1:1 molar ratio) solution (1.2 diluted by acetonitrile-d3, and the yield of the fluorinated mmol) and a reaction solvent (4 ml) were held in a PFA vessel (15 ml). While stirring at room temperature, a Sub substance was obtained by 'F-NMR. Strate (1.0 mmol) was added hereinto, and allowed to react 0145 Method F at a predetermined temperature for a predetermined period of time. After the completion of the reaction, the reaction 0146 IF/EtN-3HF (1.2 mmol) and a solvent (10 ml) mixture Solution was neutralized by a Sodium bicarbonate were held in a PFA vessel (100 ml) and heated to 40° C. aqueous Solution, and reduced by a 10%. Sodium thiosul Then, 10 ml of a solvent solution of a substrate (1.0 mmol) phate aqueous Solution. The resultant product was extracted was added thereinto and stirred at 40 C. for 30 minutes. by ether, and isolated and purified using column chroma After cooling, fluorobenzene (1.0 mmol) was added to the tography. The resultant product was analyzed based on reaction Solution as an internal Standard, a portion of the NMR, IR, and MS, and the reaction yield was obtained as reaction Solution was taken out and diluted by acetonitrile the isolation yield of the resultant product against the d3, and the yield of the fluorinated substance was obtained substrate. In Methods B to E and H to J, postprocessing and by 'F-NMR. US 2004/0245505 A1 Dec. 9, 2004

0147 Method G confirmed that the targeted compounds were obtained by 0148 IF/EtN-3HF (1.5 mmol), iodine (3.0 mmol), and comparing the Spectrum data obtained in the Examples of a solvent (30 ml) were held in a PFA vessel (100 ml). Under the present invention with the known spectrum data. an ice-cold atmosphere, a Substrate (1.0 mmol) dissolved in 10 ml of Solvent was added thereinto and stirred under the ice-cold atmosphere for 30 minutes and at room temperature 1N1-1N1-1N1-1 for 30 minutes. After cooling, fluorobenzene (1.0 mmol) was N added to the reaction Solution as an internal Standard, and then a portion of the reaction Solution was taken out and diluted by acetonitrile-d3, and the yield of the fluorinated 0167 Tetradecanoyl fluoride: substance was obtained by 'F-NMR. 0168 H-NMR (CDC1) & 0.88 (3H, t, J=6.7 Hz), 1.25 0149 Method H 1.32 (20H, m), 1.64-1.71 (2H, m), 2.50 (2H, t, J=7.3 Hz); 0169 'F-NMR (CDC1) & 44.8 (s); 0150. An IF/EtN-3HF (1:1 molar ratio) solution (1.2 mmol) and reaction solvent (8 ml) were held in a PFA vessel 0170 IR (neat, cm) 2925, 2854, 1845, 1467, 1081. (15 ml). While stirring at room temperature, a substrate (1.0 mmol) was added thereinto and allowed to react at a predetermined temperature for a predetermined period of time. 0151 Method I 0152) An IF/EtN-3HF (1:1 molar ratio) solution (1.2 mmol) and a reaction solvent (4 ml) were held in a PFA vessel (15 ml). While stirring at room temperature, a Sub strate (1.0 mmol) dissolved in a reaction solvent (4 ml) was added thereinto and allowed to react at a predetermined temperature for a predetermined period of time. 0171 4-Fluoro-2,6-dimethyl-phenylamine: 0172 'H-NMR (CDC1) & 2.16 (6H, s), 3.42 (2H, bs), 0153 Method J 6.67 (2H, d, J=9.2 Hz); 0154) An IF/EtN-3HF (1:1 molar ratio) solution (5.0 mmoles) and a reaction solvent (4 ml) were held in a PFA 0173 'F-NMR(CDC1) 8-128.3 (1F, t, J=9.2). vessel (15 ml). While stirring at room temperature, a Sub strate (1.0 mmol) was added thereinto and allowed to react OH at a predetermined temperature for a predetermined period of time. O155 The 'F-NMR signals (F, 8 ppm) of IF/3HF and IF/EtN/3HF are shown below. 0156 (1) IF/3HF O157 IF (1F, 55 ppm), (4F, 6.4 ppm), HF(3F, -194 ppm) 0.174 2,6-Di-tert-butyl-4-fluoro-phenol: 0158 (2) IF/EtN/3HF 0175 H-NMR (CDC1) 8: 1.42 (18H, s); 4.94(1H, s); 0159 Measuring temperature: 25° C. 6.87 (2H, d, J=10.2 Hz); 0160 One wide single peak was observed at the 8 value 0176) 'F-NMR(CDC1) 8: -124.7 (1F, t, J=102); of -53 ppm. 0177) IR (neat, cm); 3642; 2961: 1599; 1428; 1236; 0.161 Measuring temperature: -40 C. 1149; 964; 867; 776; 0162 Two wide single peaks were observed at the 8 0178 MS m/z: 224 (M); 209 (M*-Me); 57; values of 7.5 ppm and -160 ppm. (Integration ratio: approxi 0179 HRMS Calc. for CHOF: m/z 224.1576. Found: mately 1:1) m/Z 224.1571. 0163 Measuring temperature: -60 C. 0164. Three wide single peaks were observed at the 8 values of 3 ppm, -154 ppm, and -162 ppm. (Integration ratio: approximately 2:1:1) 0165 From comparison of the 'F-NMR signals of IF/ 3HF and IFs/EtN/3HF, the compounds generated from IF/EtN/3HF have complexes formed therein. 0166 Spectrum data of the compounds obtained by the present invention are shown below. Regarding the com pounds for which spectrum data is not shown, it was

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0343. In Tables 1 to 6 shown above, “Tol” represents a 1-7. (Canceled). tolyl group (CH-CH ), “Ph” represents a phenyl 8. A fluorinating agent for use in fluorinating an organic group, "Et represents an ethyl group, "Me' represents a compound having hydrogen atoms, which comprises IFs, methyl group, "Bu' represents a butyl group, "Ac' repre HF, and an organic base and/or a room temperature molten Salt. Sents an acetyl group, and "iPr' represents an isopropyl 9. A fluorinating agent for use in fluorinating an organic grOup. compound having hydrogen atoms, which comprises IFs and 0344 As described above, according to the present a room temperature molten Salt. 10. A fluorinating agent for use in fluorinating an organic invention, it is possible to fluorinate various kinds of organic compound having hydrogen atoms, which comprises IFs and compounds having hydrogen atoms and to obtain corre at least one member Selected from the group consisting of sponding fluorine compounds. acids, Salts, and additives. 11. A fluorinating agent for use in fluorinating an organic INDUSTRIAL APPLICABILITY compound having hydrogen-atoms, which comprises IFs and at least one member Selected from the group consisting 0345 According to the present invention, using IF, of bases, Salts, and additives. which is an industrially available, nonexplosive, and easy to 12. A fluorinating agent for use in fluorinating an organic handle liquid having a boiling point at 100.5 C. and a compound having hydrogen atoms, which comprises IFs, melting point at 9.4° C., it is possible to fluorinate various HF, and triethylamine. kinds of organic compounds having hydrogen atoms and to obtain corresponding fluorine compounds. k k k k k