United States Patent [19]
`Middleton
`
`3,914,265
`[111
`[45] Oct. 21, 1975
`
`[54] DIALKYLAMINOSULFUR TRIFLUORIDES
`AS FLUORINATING AGENTS
`[75] Inventor: William Joseph Middleton, Chadds
`Ford, Pa.
`[73] Assigneez E_ L Du Pom de Nemours &
`Company, Wilmington, Del.
`
`[56]
`
`3,705,897
`
`References Cited
`UNITED STATES PATENTS
`12/1972 Murphy ......................... .. 260/243 c
`
`Primary Examiner-Nicholas S. Rizzo
`Attorney, Agent, or Firm—Anth0ny P. Mentis
`
`[21] Appl. N0.: 314,022
`
`[52] US Cl ______ " 260/397_3_ 260,482 C; 26O/469; I
`260/465.6; 260/544 B; 260/562 B;
`260/609 R; 260/644; 260/601 H; 260/633;
`260/653; 260/73 L; 260/9l.3 R; 260/212;
`260/239.1
`[51], Int. Cl.2 ...................................... .. C07D 501/20
`[58] Field of Search ........ .. 260/243 C, 465.6, 397.3,
`260/469, 633, 609 R, 653, 562 B, 601 H, 482
`C, 644, 544 B
`
`die
`as
`such
`tri?uorides
`Dialkylaminosulfur
`thylaminosulfur tri?uoride are useful in replacing hy
`droxyl group and carbonyl oxygen with ?uorine in var
`""15 “gamc ~°°mP°"“dS‘
`
`4 Claims, No Drawings
`
`Micro Labs Exhibit 1025
`
`

`

`1
`DIALKYLAMINOSULFUR. TRIFLUORIDES AS
`FLUORINATING AGENTS
`
`l0
`
`BACKGROUND OF THE INVENTION
`1. Field of the Invention
`This invention relates to a new process for preparing
`organic ?uorine-containing compounds. More particu- ,
`larly, it relates to a process for replacing a hydroxyl
`group in organic compounds with a fluorine atom and
`/or the oxygen atom of organic carbonyl compounds
`with two ?uorine atoms by reaction of the hydroxyl or
`carbonyl compound with a dialkylaminosulfur tri?uo
`ride.
`2. Description of Prior Art
`Several materials have been used in the past as ?uori
`nating agents. The use of sulfur tetrafluoride is dis- .
`closed in U.S. Pat. No. 2,859,245 and US. Pat. No.
`2,983,626. W. C. Smith, Angew. Chem. 74, 742 (1962)
`presents a review of its use. W. A. Sheppard, J.A.C.S.
`82, 4751 (1960); 84, 3059 (1962) describes the use of
`phenylsulfur trifluoride. “Fluoroamine reagent”,
`(CI-I3)2-NCF2CFI-ICl, has also been used. All of these
`reagents are not completely satisfactory for one reason
`' or another.
`The dialkylaminosulfur tri?uorides have been previ
`ously reported in the literature but no mention has
`been made of their use as fluorinating agents. The fol
`lowing are mentioned:
`1. G. C. Demitras, R. A. Kent and A. C. MacDiarmid,
`Chem. Incl. (London), 1964, 1712; and G. C. Demitras
`and A. G. MacDiarmid, Inorg. Chem., 6, 1903 (1967).
`These papers describe the preparation of (CH3)ZNSF3
`by the reaction. of SF, with (CH3),NSi(Cl-l3)3. The "F
`35
`nmr spectrum was described.
`2. S. P. Von Halasz and O. Glemser, Chem. Ber., 103,
`594, (1970), show the preparation of (‘CZHQZNSFa by
`reaction of (C2l-l5)2NSi(CI-I3)3 with SF.,. This com
`pound reacts with (Cl-I3),,Si-N=C=N-Si(CH3)_-, to give
`NCN=SFN(C2H5)2. No other chemistry is reported.
`3. S. P. Von I-Ialasz and O. Glemser, Chem. Ber., 104,
`1247 (1971), describe the preparation of RSI} (R =
`MezN, EtzN and piperidino) by the reaction of R
`Si(CH3)3 with SP4. No ?uorination reactions are dis
`
`3,914,265
`2
`hydes, ketones, and carboxylic acids containing up to
`40 carbon atoms and which may be monofunctional or
`polyfunctional. Organic polymeric compositions that
`contain hydroxyl or carbonyl groups, such as cellulose
`and vinyl alcohol homopolymers and copolymers, can
`also be fluorinated with dialkylaminosulfur trifluoride.
`The hydroxyl compounds that can be used in this
`process include monofunctional and polyfunctional ali
`phatic primary, secondary, and tertiary alcohols and
`aromatic, heterocyclic, and aliphatic carboxylic acids,
`all of .which may contain other substituents.
`The carbonyl compounds that can be used in this
`process include aliphatic, heterocyclic, and aromatic
`ketones, aldehydes, and carboxylic acids which may
`also contain other substituents.
`Included also are compounds that contain both hy
`droxyl and carbonyl functions in the same molecule. In
`addition to compounds speci?cally illustrated below by
`example or structural formula, the following com
`pounds can be used in the process of this invention.
`Examples of alcohols that may be used are methanol,
`ethanol, cyclopentanol, phenylethyl alcohol, isopropa
`nol, tert-butanol, stearyl alcohol, polyvinyl alcohol,
`I glycerin and cholesterol.
`25
`Examples of aldehydes that may be used are formal
`dehyde, acetaldehyde, propionaldehyde, phenylacet
`aldehyde, phthaladehyde, piperonal, dodecyl aldehyde,
`n-butyraldehyde, isobutyraldehyde, glyoxal, anthralde
`hyde, anisaldehyde, acrolein, cinnamaldehyde and cro
`tonaldehyde.
`.
`Examples of ketones that may be used are acetone,
`cyclohexane, 2~butanone, di-n-hexyl ketone, phorone,
`pinacolone, and acetonaphthone.
`.
`Examples of carboxylic acids that may be used are
`acetic, succinic, maleic, methacrylic, propionic,
`acrylic, stearic, glutaric, phenylacetic, and naphthoic
`acid.
`Although esters, amides and phenols are operable in
`this reaction, they do not work as well as alcohols, alde
`hydes, ketones and acids.
`Generalized equations for the process of this inven
`tion are given below, with Q, X and Y representing the
`radicals of any nature whatsoever attached to the car
`bon containing the oxygen function to be replaced.
`
`closed.
`
`-
`
`'
`
`45
`
`DESCRIPTION OF THE INVENTION
`It has now been found that a compound of the
`
`Formula
`
`’
`
`’
`
`wherein each of R and R‘, alike or different, is a pri
`maryalkyl group of up to 4 carbon atoms, or when
`taken together are —(Cl-I2 ).,-< or -(CH2)5-- will react
`with an organic compound containing hydroxyl and/or
`carbonyl groups to replace such groups with fluorine.
`The reaction can be carried out under mild conditions
`that are often not suitable with known ?uorinating
`agents. For example, the reaction can be run in glass
`equipment at atmospheric pressure and without the use
`of an acid catalyst as may be required with SP4.
`In general, organic compounds that contain hydroxyl
`and carbonyl functions will react with dialkylaminosul
`fur tri?uorides to give organic ?uorine compounds.
`These compounds include monomeric alcohols, alde
`
`55
`
`60
`
`65
`
`with ‘a dialkylaminosulfur tri?uoride is conducted
`under substantially anhydrous conditions. The reaction
`vessel can be made of metal, glass, plastic or ceramic
`
`Micro Labs Exhibit 1025-2
`
`

`

`3.914.295
`3.
`4.
`and can be closed or open to ‘the ‘atmosphere if provi-
`,
`tion of diethyzlaminogand.dirnethylaminosulfur trifluo
`sions to vexclude moisture arejita‘lkenl.v ‘
`ride. The preparation of these, as well, as of piperi‘din'o
`The reaction is conductedfby' charging- Ith'eL-dialk-T I’
`' sulfur tri?uoride, has‘ also been reported by Halarz et
`ylaminosulfurtri?uoride into the: reaction ‘vessel
`a1. Chem. Ber. 1971, 104.
`v
`_
`_
`and then adding the hydroxyl orfca'rbonyl compound.
`Typical preparative procedures are illustrated‘ in Ex
`Alternatively the hydroxyl‘ or carbonyl compound ‘can
`amples A and B.
`I
`becharged ?rst, or the hydroxyl orvcarbonyl compound
`and the dialkylaminosulfur tri?uoride can be. charged
`simultaneously. Solvent is not necessary for the reac
`tion, but the use of a solvent is usually advantageous to
`moderate the reaction. Either'or both of the reactants
`may be dissolved in an inert solvent before ‘mixing or
`the reactants may be charged into an inert solventconl
`tained in the reaction vessel.
`'
`_
`_
`Solvents suitable for the reaction include hydrolca'r-l
`bons such as benzene, xylene, pentane, hexane, decalin
`and isooctane; halocarbons such asmethyléhe' chlo
`ride,‘ ethylene chloride, chloroform, carbon tetrachlo
`ride, chlorobenzene, trichlorofluoromethane; lethers
`such as' diethyl ether, dioxane, tetrahydrofuran, ethyl?
`ene glycol dimethyl ether,,an_d di'ethylenenglyclolidi
`methyl ether; nitriles such as acetonitrileland bénzoni
`trile; nitro compounds such as nitro'm'ethane and nitro-nv
`benzene; or any solvent inert to‘ both of the reactants‘.
`The reaction is conducted at temperatures from
`—100° to +100°. The preferred range for replacing hy
`droxyl‘groups is from —80° to +35°, and the preferred‘
`range for carbonyl compounds is from —20° to -l~80°.
`The time of reaction is generally dependent on the tem
`perature and reactivity of the organic'oxy or 0x0 group.
`Times of an hour or less to a week can be‘us'ed.
`Pressure is not critical.’ Ambient and/or autogenous
`pressures are the most convenient and therefore pre
`
`‘
`
`'
`
`‘
`
`EXAMPLE A _‘
`
`’ Diethylaminosulfur Tri?uoride
`
`_
`
`. :Asolution of 9,6 g (0.66 mole) ofi‘diéthylaminotrime:
`thylsilane in 100 m1,trichloro?'uoromethane;was added
`dnopwiseto a solution of 40 ml (measured at —78°, 0.72
`mole) of sulfur tetrafluoride in 200 ml of trichloro?u-v
`oromethane at —65° to —60°. The reaction mixture was
`warmed to'roomitemperature and then distilled to give
`88.86 g (84%_yield)_ of diethylaminosulfur trifluoride as
`a‘ pale yellow-fliquid, 15p 216147‘? (10 mm)..;
`'
`
`20
`
`'
`
`A
`
`'
`
`'
`
`ExAMEL'E-B ‘
`
`l "
`
`25
`
`39
`
`1. __ " Dimethtylaminos‘ul'fuii,Tri?uoride
`'
`A solution of, 400g
`mole) of dimethylamino- '
`trimethylsilane in 50 ml CCI3F was added dropwise ,to
`a solution of 20ml (measured at —78°, 0.36 mole) of
`sulfurtetra?uoride in "1O0'1nlCCl3F at ~65‘? tor-80°.‘
`The reaction mixture wasdistilled'togive 37 g ofl‘dimi'el
`thylaminosulfur tri?uoride as a pale yellow liquid,
`49°—49.5~° (33 mm); 1H nmr (CCl3F) 8 3.07 pprn (s).
`‘IISPECVIFICY EMBODIMENTS OF THE INVENTION .
`111' the illustrative-examples below, all parts are ‘by
`weight unless‘ otherwise stated. '
`
`ferred.
`
`'
`
`'
`
`‘
`
`The mole ratio of‘reactants' is normally chosen for
`maximum yield, 'with one ' equivalent ‘of 'dialk
`ylaminosulfur tri?uoride needed for each equivalentijof
`hydroxyl or carbonyl present. When more than one‘hy
`droxyl or carbonyl group is present in the’cornpound to
`be ?uorinated, the more reactive groups can be'se1ec
`tively reacted by adding the dialkylaminosulfur trifl'uo
`ride to an ‘excess of the po'lyfunctional compound, pref‘
`erably in a solvent to 'insure good mixing.
`' "
`'
`l
`The fluorinated products can be separated from‘ the
`reaction‘ mixture and then puri?ed by any of several
`standard methods, including distillation, chromatogra
`phy, solvent extraction, and recrystallization.
`The ?uorine-containing compounds obtained by this
`process are gasses, liquids, or solids that have many
`uses. They can be used as gaseous or liquid carriers in
`aerosol sprays. They can be used as solvents and thin
`ners in lacquers and paints. They are useful as liquid
`media for the preparation of dispersions’of carbon
`black and graphite and some are useful as insecticides.‘
`They can be used as heat transfer ?uids and refriger
`ants. Most importantly, they can serve as intermediates
`in the preparation of other ?uorine-containing com
`pounds which are otherwise difficult to obtain, includ
`ing pharmaceuticals, herbicides, insecticidesfand other
`pesticides. The polymeric ?uorine-containing products
`prepared by this process are useful for construction of
`water and oil resistant objects, such as films and in pre- _
`paring water and oil resistant coatings.
`lngeneral, the dialkylaminosulfur;tri?uorides,can_be
`-
`65.
`(24,142).
`prepared by the reaction of a,dialkylaminotrimethylsh_ v "
`lane with sulfur tetra'?uoride ata low temperature in an,
`inert solvent. Examples A and B illustrate the prepara-wl
`
`35
`
`45
`
`.
`
`|
`
`EXAMPLE 1
`1 —Fluorooctahe
`A solution of 13.0 g (0.1 riiole) of l-octanol in 25 ml
`of methylene chloride was added draopw‘ise to a solution
`of 16.1 g (0.1 mole) of diethylaminosulfur trifluoride
`in 60 ml methylene chloride cooled to —7_0° to —65".
`The reaction mixture was then warmed to 25° and ‘50
`ml of: water was added.~ The§.lower-_;orga'n'ic layer was ‘
`separated, dried (-MgSO4.)" and then distilled to give '
`
`_ Anal. calcd for "c.,n;,r. c, 7267,11," 121.97; P, 14.37.
`Found: c, 72.76; H, 13.09; F, 14.44.
`
`55
`
`60
`
`EXAMPLE 2
`Ethyl 2-Fluoropr'opionate
`A solution of 1.18 g (0.01 mole) of ethyl lactate in
`2 ml of methylene chloride'=\wa‘s'- slowly‘ injected into-a.
`solution of 1.25 ml (0.01 rfio1“e)_of diethylaminosulfur'
`trifluoride in 51111 of methyle'yr'ie‘chlori'de cooled ‘to’
`—7 8°. The reactionmixture'was then‘ warmed to room?
`temperature‘and mixed ‘with: cold w'atei“. The lower
`layer was separated, washed with‘water, dried (Mgsoo;
`and ‘distilled to give 0.93 _g _(78.’% yield) of ethyl 2
`?uoropropionateas 'a colorless liquid: bp 50°—5'1° (50
`mm); “Fnmr (CC13F) s+1s4l6 ppm (d, q, IF, J = 49,
`
`Anal. Calcd‘for 051150,‘; c, 50.00; 11, 7.57; F, 15.83.
`' Found: c, 50.11;‘11, 7.77; F, 16.01.
`
`I
`
`'
`
`Micro Labs Exhibit 1025-3
`
`

`

`3 ,914.,265
`
`6
`
`5
`EXAMPLE 3
`2-Fluoro-2-methylbutane
`A solution of 11.3 g (0.128 mole) of tert-pentanol in
`25 ml of diethyleneglycol dimethyl ether was added
`dropwise to a solution of 16.1 g (0.1 mole) of die
`thylaminosulfur tri?uoride in 100 ml of diethylene
`glycol dimethyl ether cooled to —70°. The most volatile
`portion of the reaction mixture was distilled out at re
`duced pressure (1 mm) into a receiver cooled with
`solid carbon dioxide. The condensate was redistilled to
`give 7.9 g (88%) of 2-?uoro-2-methylbutane (tert
`pentyl ?uoride): bp 45°—46°; l9F nmr (CCl3F) 8 --1 39.2
`ppm (m)-
`’
`Anal. Calcd for C5H11F: C, 66.62; H, 12.30; F, 21.08.
`Found: C, 66.81; H, 12.47; F, 21.72.
`
`5 .
`
`EXAMPLE 7
`2-Fluoro-2—methyl-3~butyne
`A solution of 1.68 g (0.02 mole) of 2-methyl-_3_
`butyn-Z-ol in 2 ml of diethyleneglycol dimethyl ether
`was added slowly (5 min.) to a stirred solution of 2.5
`ml (0.02 mole) of diethylaminosulfur tri?uoride in" 10
`ml of diethyleneglycol dimethyl ether cooled to —78°.
`The volatile portion of the reaction mixture was dis
`tilled out of the reaction mixture under reduced pres
`sure (2 mm)land condensed in a cold trap. Redistilla
`tion gave 1.47 g (75%) of 2-?uoro-2-methyl-3—butyne
`as a colorless liquid: bp 43244"; 19F nmr (cc1,F) s
`—129.3 ppm (septet, d, 1F, J = 20, 5 Hz); IH nmr
`(CCI3F) 5 1.57 ppm (d, 6H, J = 19.5 Hz) and 5 2.58
`ppm (d, 1H, J = 5 Hz).
`-
`Anal. Calcd for C5H7F: C, 73.44; H, 7.20; F, 19.36.
`Found: C, 73.68; H, 7.28; F, 19.19.
`
`EXAMPLE 4
`1,1-Di?uoro-3-methylbutane
`A 1.72-g (0.02 mole) sample of isovaleraldehyde was
`slowly injected into a stirred solution of 2.5 ml (0.02
`mole) of diethylaminosulfur tri?uoride in 10 ml of
`CClaF at 25°. The reaction mixture was stirred for 30
`min., and then mixed with 25 ml of water. The lower
`organic layer was separated, washedwith water, dried
`(MgSO4) and distilled to give 1.73 g (80%) of
`1,1-difluoro-3-methylbutane as a colorless liquid: bp
`59°-60°; l9F nmr (CCISF) 6 -115.5 ppm (d, t, 2F, J =
`58, 17 Hz).
`Anal. Calcd for CsHmFz: C, 55.54; H, 9.33; F, 35.14.
`Found: C, 55.77; H, 9.61; F, 35.15.
`
`20
`
`25
`
`30
`
`EXAMPLE 5
`
`EXAMPLE8
`3-Fluoro~2,2,3-trimethylbicyclo[2.2.1lheptane
`A solution of 3.08 g (0.02 mole) of exo~1,7,7
`trimethylbicyclo[2.2.1lheptanol (borneol) in 15 ml of
`CCl3F was slowly added to a solution of 2.5 ml (0.02
`mole) of diethylaminosulfur tri?uoride in 10 ml of
`CCl3F cooled to —78°. The reaction mixture was
`warmed to room temperature and water was added.
`The lower layer, was separated, washed with water, 5%
`aqueous NaHCO’-3 and water again, and then dried
`(MgSO4). Evaporation to dryness gave 2.87 g of a
`white solid composed of 20% camphene and 80% 3
`?uoro-2,2,3-trimethylbicyclo[2.2.1lheptane. Recrys
`tallization from 'pentane removed most of the -cam
`phene to give 1.97 g of the ?uoroheptane as colorless
`crystals: mp 93°—'94°; 19F nmr (CCI3F) 6 —134.4 ppm (q,
`1F, J = 24 Hz); IH nmr (CClaF), absorption due to
`methyl groups at 8 0.93 ppm (s) and 1.24 ppm (d, J =
`24 Hz).
`'
`Anal. Calcd for CIOHUF: C, 76.87; H, 10.87; F,
`40
`12.16. Found: C, 76.99; H, 11.21; F, 11.97.
`The reaction was repeated, using endos1,7,7
`trimethylbicyclo[2.2.l ]heptanol instead of the exo iso
`mer to give 1.72 ‘g of the same fluoroheptane, mp
`93°-94°.
`
`35
`
`2-Fluoro-3-butene and 1-Fluoro-2-butene
`A solution of 1.44 g (0.02 mole) of 3-butene-2-ol in
`2 ml diethyleneglycol dimethyl ether was slowly in
`jected into a stirred solution of 2.5 ml (0.02 mole) of
`diethylaminosulfur tri?uoride in 10 ml of diethylene
`glycol dimethyl ether cooled to —78°. The reaction mix;
`ture was warmed to 0° and the volatile products were
`distilled out into a cold trap at reduced pressure to give
`1.3 ml of colorless liquid. Gas chromatographic analy
`sis showed the product was a mixture containing 78%
`2-t'luoro-3-butene and 22% of the isomeric 1-?uoro-2
`45
`butene. The product was redistilled to give 1.07 g of
`colorless liquid: bp 24°-27°; l9F nmrCCIBF) 8 ~l71.6
`ppm (78%, d, q, d, d, J = 46.7, 24, 13.0, 2.7 Hz) and 6
`—210.0 ppm (22%, t, m, J = 50 Hz).
`Anal. Calcd for C4H1F: C, 64.83; H, 9.53; F, 25.64.
`Found: C, 65.11; H, 9.79; F, 25.37.
`This reaction was repeated, except‘ that 2,2,4
`trimethylpentane was used as solvent instead of .di
`methyl ether of diethyleneglycol to give 1.4 ml of a
`mixture containing 91% 2-fluoro-3-butene and 9% 1
`fluoro-2-butene.
`
`50
`
`EXAMPLE 9
`1—Fluoro-2iisopropyl-5—methylcyclohexane‘
`A solution of 3.12 g (0.02 mole) of (-)-menthol in 10
`ml of CC13F was slowly injected into a solution of 2.5
`ml (0.02 mole) of diethylaminosulfur tri?uoride in 10
`ml of CClgF cooled to —78°. The reaction mixture was
`warmed to room? temperature and mixed with water.
`The organic layerwas separated, washed with 5% NaH
`CO3, dried (MgSO4) and distilled to give 1.58 g (50%)
`of 1-?uoro-2-isopropyl-5—methylcyclohexane as a col
`orless liquid: bp 40° (5 mm); l9F nmr (CClaF) 8 —175.9
`ppm (d, J = 50 Hz to m, 11% width 21 Hz).
`Anal. Calcd for CwHwF: F, 12.01. Found: F, 12.12.
`
`55
`
`EXAMPLE 6
`
`l-Fluoro-2-butene and 2-Fluoro-3-butene
`
`' The procedure described for Example 5 was re
`peated, except that 2-butene-l-ol was used in place of
`3-butene-2-ol. When diethyleneglycol dimethyl ether
`was used as solvent, 1.37 ml of a product containing
`72% 2-?uoro-3-butene and 28% 1-?uoro-2-butene was
`obtained. When 2,2,4-trimethylpentane was used as
`solvent, 1.5 ml ofa product containing 64% 2-?uoro-3
`butene and 36% 1~fluoro~2~butene was obtained.
`
`65
`
`EXAMPLE 10
`F luorocyclooctane
`A solution of 2.56 g (0.02 mole) of cyclooctanol in
`2 ml CClgF was slowly added to a stirred solution of 2.5
`ml (0.02 mole) of diethylaminosulfur tri?uoride in 10
`ml of CCISF at —78°. The reaction mixture was warmed
`to room temperature and water was added. The lower
`
`Micro Labs Exhibit 1025-4
`
`

`

`7"
`layer was separated, washed with water, 5% NaHCO3,
`water again, and then dried (MgSO4). The solvent was
`removed by evaporation at reduced pressure to give 2.5
`g of colorless liquid. Analysis by gas chromatography
`and nuclear magnetic resonance indicated-that the‘
`product ‘consisted of 70% fluo'rocycl’ooctane and 30%
`cyclooctene.
`'
`19F nmr (CCl3F) 8 “160.5 ppm (d, p, 1F, J .=‘ 46,
`
`3,914,265"
`
`8.
`Anal. Calcd for (381-18172: C, 67.70; H, 5.67; F, 26.73.
`Found: C, 67.72; H, 5.73; F, 26.83.
`
`EXAMPLE 15
`
`' 3,3,7,7-‘Tetra?uoro-l,5-dimethylbicyclo[3.3.0]octane
`and
`3,3_-Di?uoro-l,5-dimethylbicyclo[3.3.0]octan
`
`7-one ‘
`
`'
`
`'
`
`A " solution of 8.3 g (0.05 mole) of 1,5
`dimethylbicyclo[3.3.0]octane-3,7-dione and 17.7 g
`(0.1 1 inch) of diethylaminosulfur tri?uoride in 50 ml
`of benzene" was heated at re?ux for 24 hr and then
`cooled and poured into 100 ml of water. The organic
`layer was separated, dried (MgSO4), and the benzene
`was distilled off. The residue was sublimed at 150° (1
`mm) to give 6.3 g of a 80:20 mixture of 3,3,7,7
`tetra?uoro-l,5-dimethylbicyclo[3.3.0]octane and 3,3
`di?uoro-l,5-dimethylbicyclo[3.3.0]octan-7-one.
`The mixture was separated by liquid chromatography
`on an A1203 column using pentane and ether. The tetra
`?uoride (3.7 g) was obtained as white, waxy crystals
`with a camphor-like odor: ‘mp 106°—109°; l9F nmr
`(CCl3F) 8' —86.2 ppm (JHF = 14 Hz) and —86.6 ppm
`
`(JHp-_=
`
`v
`
`’
`
`Anal. Calcd for C1o1-I“F4':C, 57.14; H, 6.71; F, 36.15.
`Found: c,'57.12; H, 6.82; F, 36.14.
`The difluoride (0.8 g) was obtained as light yellow
`crystals: _mp 145°—l50°; l9F nmr (CCl3F) 8 —80.9 and
`—81.0 ppm (JFH ='14 Hz); ir (KBr) 5.72 p. (C=0).
`Anal. Calcd for C1oH14F2O: C, ‘63.81; H, 7.50; F,
`20.19. Found: C, 63.07; H, 7.31; F, 20.87.
`
`' EXAMPLE 16
`
`v
`
`I Benzal Fluoride
`
`Hz).
`
`'
`
`I
`
`“ ,
`
`‘
`
`V
`
`IH nmr_i(_ffor ?uorocyclooctane) (CCl3F) 6 4.55 ppm‘
`(d, 1H, 461-12) and& 1.2 to 2.4 (m, 141-1).
`
`10
`
`EXA'MPLE l1_ ‘
`,
`Benzyl Fluoride
`A solution of 2.16 g (0.02 mole) of benzyl alcohol in
`5 ml CCl3F was slowly injected into a solution of 2.5 ml -
`(0.02 mole) of diethylaminosulfur tri?uoride in 10 ml
`of CCl3F cooled to —78°. The reaction mixture was'
`warmed to room temperature and then slowly mixed
`with water. The lower layer was separated, washed with
`water, dried (MgSO4) and then distilled to give 1.65 g
`(75%) of benzyl ?uoride, bp 139°; 19F nmr (CCIQF) 8
`—207.5 ppm (r, J = 49 Hz).
`‘
`f
`.
`
`15
`
`20
`
`EXAMPLE l2‘
`
`Benzyl Fluoride ‘
`
`25
`
`A solution of 0.90 ml (0.01 mole) of dime
`thylaminosulfur tri?uoride in 5 ml methylene chloride
`was cooled to —78°, and a solution 0171.08 g ‘(0.01
`30
`mole) of benzyl alcohol in 2 ml methylene chloride was
`slowly injected. The reaction mixture was warmed‘ to
`room temperature and mixed with water. The lower
`layer was separated, dried (MgSO4) and analyzedtby
`gas chromatography. and 19F nmr. The analyses showed
`that benzyl fluoride was formed in near-quantitative
`
`yield.
`
`'
`
`'
`
`I
`
`'
`
`A 25-ml (0.2 mole) sample of diethylaminosulfur tri
`?uoride was added dropwise over a period of 30 min.
`. to a stirred solution of 21.2 g (0.2 mole) of benzalde
`hyde in 75 ml of methylene chloride at 25°. The reac
`tion mixture was cooled to keep the temperature below
`35°. Stirring was continued for 2 hr, and then 100 ml
`of water was added. The lower layer was separated,
`washed with 5% NaHCOa solution and then water, and
`dried (KZCOQ). Distillation gave 19.2 g (75%) ofbenzal
`?uoride; bp 57° (35 mm); "P nmr (CCl3F) 8 —110.9
`ppm (d, J = 57.5 Hz).
`
`40
`
`EXAMPLE 13
`4,4-Di?uorohexane
`A solution of 16.1 g (0.1 mole) diethylaminosulfur"
`tri?uoride in 10 ml CClaF was added dropwise to a so
`lution of 11.4 g (0.1 mole) of 4-heptanone in 52 ml
`CCI3F. Water, 5 11.1, was added as a catalyst, and the re
`action mixture was stirred at room-temperature for'l
`week. Distillation gave 9.2 g (68%) of 4,4
`di?uorohexane, bp 90°—110°, contaminated with a
`small amount of an immiscible liquid. The distillate was
`washed with water, dried (MgSO4) and redistilled to
`50
`give 7.1 g of pure product: bp 110°—11l°; no” 1.3644;
`19F nmr (CCI3F) —98.6 ppm (p, 2F, J = 15 Hz)/1H nmr
`(CClsF) 60.95 ppm (m, 6H), 1.55 ppm (m,v8l-1).
`Anal. Calcd for C1HHF2': C, 61.74; H, 10.36; F,
`27.90. Found: C, 62.13; H, 10.16; F, 28.07.
`
`45
`
`EXAMPLE 17
`Benzoyl Fluoride
`Diethylaminosulfur tri?uoride, 2.5 ml (0.02 mole)
`was slowly added to a stirred solution of 2.44 ‘g (0.02
`mole) of benzoic acid in 20 ml methylene chloride
`cooled to 0°. Powdered sodium ?uoride, 1 g, was added
`to remove ‘the HF, and the reaction mixture was fil
`tered. The ?ltrate wasdistilled to give 1.98 g (80%) of
`benzoyl ?uoride as a colorless liquid, bp 50° (10 mm)
`(identified by its infrared spectrum).
`
`EXAMPLE l8
`Benzotrifluoride
`Diethylaminosulfur tri?uoride, 8.05 g (0.05 mole)
`was added dropwise to'a solution of 2.44 g (0.02 mole)
`of benzoic acid in 20 ml of diethyleneglycol dimethyl
`ether cooled to 0°. Sodium ?uoride (1 g)v was then
`added to‘remove the HF, and the reaction mixture was
`~ warmed to 80° for 20 hr. The most volatile products
`were distilled fromythe reaction mixture and then redis
`
`65
`
`, EXAMPLE 14
`1,1-Di?uoroethylbenzene
`A solution of 2.5 ml (0.02 mole) of diethylaminosul
`fur tri?uoride and 2.4 g (0.02 mole) of acetophenone
`in 12 ml of ethyleneglycol dimethyl ether was heated to
`re?ux for 20 hrs. and then cooled and mixed with wa
`ter. The reaction mixture was extracted with CCl3F,
`and the extract was dried (MgSO4) and distilled to give
`0.8 g of recovered acetophenone, bp 108°—l12° (40
`mm), and 1.2 g (66% yield, 42% conversion) of
`1,1-di?uoroethylbenzene: bp 64°-65° (40 mm); 19F
`nmr (CCl3F) 8 —87.7 ppm (q, J = 18 Hz).
`
`Micro Labs Exhibit 1025-5
`
`

`

`37,914,265‘
`
`10
`cm“; “F nnir (CHCl;,) 8 116.43 (d (JHF = 57 Hz),
`-—CH_E_, (one of A'+Aa isomers)) and and 115.82 (d
`(JHF = 57 Hz), —CH_E_2 (other isomer)); ‘H .nmr
`(CDCl_-,) 8 3.5 (2, m, C2-C_l-_l2 (Aa-isome?), 3.74 (2, s,
`thienyl -—'C?z), 4.94 (l, d (J = 6 Hz), Cr?), 5.91 (1,
`dd (J = 6 Hz, .1‘ =10 Hz), Cr?), 6.72 (1, t (JHF = 57
`
`tilled to give 1.46 g (50%) of benzotrifluoride; .bp
`102°-.-l03°; l9F nmr (CClgF).
`.
`
`EXAMPLE 19
`Preparation of Benzhydryl 3-Fluoromethyl-7-(2
`thienylacetamido)-3-cephem-4-carboxylate~l-oxide
`
`5
`
`,
`
`CH2C12
`
`.
`
`o-
`lg
`
`@0320}:
`
`.
`
`g /
`
`o
`
`1
`
`cner
`_co2cn
`
`To a solution of 0.483 g (3.0 mmoles) of die
`thylaminosulfur tri?uoride in 10 mlof CH2Cl2 at —78°
`under N2 was added a solution of 1.61 g (3.0 mmoles)
`of
`benzhydryl
`3-hydroxymethyl-7-(2
`thienylacetamido)-3-cephem-4-carboxylate-l-oxide in
`50 ml of CHZCIZ and the mixture was stirred at —-78° for
`0.5 hr, then poured» into 100 ml of water. The CHzClz
`layer was dried (MgSO4) and evaporated in vacuo. The
`residue was chromatographed on silica gel with 9:1
`CHzcz-acetone to yield 0.095 g of benzhydryl 3
`fluoromethyl-7-(2-thienylacetamido)~3—cephem-4-car
`boxylate-l-oxide in fractions 12-15, rf== 0.60 on tlc
`with 9:1 CH2Cl2-acet0ne; mp 205.5°—207.5° d; ir
`(CHCl3) 3450 (amide N-H), 1805 (B-lactam C=O),
`1725 (ester C=O), 1680 (amide C=O), 1495 (“amide
`11” band), and 700 (aromatic) cm“.
`Anal. Calcd for CZ1H23N2O5SZF: C, 60.22; H, 4.28; N,
`5.20; F, 3.54. Found: C, 59.40; H, 4.29; N, 5.20; F,
`3.60.
`
`EXAMPLE 20
`Preparation of Benzhydryl 3-Di?uoromethyl-7-(2
`thienylacetamido)-3~cephem-4-carboxylate
`
`25
`
`30
`
`35
`
`40
`
`Hz), —C?Fz), and 7.3 (13, m, aryl + thiophene —H);
`uv max (C2H5OH) 265 nm (7400).
`
`
`
`Anal. Calcd for C21H22N204S2F2: C, N, 5.18. Found: C, 59.82; H, 3.94; N, 5.01.
`
`H,
`
`EXAMPLE 21
`1,4-Diisopropyl-2-benzoyl Fluoride
`To 4.12 g (0.02 mole) 1,4-diisopropyl-2-benzoic acid
`in 25 ml cold benzene was added dropwise through a
`syringe 2.5 ml (0.02 mole) diethylaminosulfur tri?uo
`ride. The exothermic reaction was controlled by an ice
`bath. The solution was poured into water and extracted
`with benzene. The benzene was evaporated off yielding
`3.94 g (96% yield) of the acid ?uoride.
`Anal: ir consistent with an authentic sample.
`
`EXAMPLE 22
`1 ,Z-Di?uoroethane
`A solution of 620 mg (0.01 mole) of ethylene glycol
`in 2 ml of diethyleneglycol dimethyl ether was slowly
`added to a stirred solution of 2.5 ml (0.02 mole) of die
`thylaminosulfur tri?uoride in 10 ml of diethyleneglycol
`
`Uc?Jli-j 111 ""L 2‘ 3' Um?” '
`
`Y
`
`(c
`
`)N--SF ‘
`
`in
`
`/
`
`OH
`
`I
`
`.
`
`.
`
`I
`
`'
`
`2
`cm?
`
`002011
`
`002
`CH
`
`A solution of 0.518 g of benzhydryl 3-formyl-7-(2
`thienylacetamido)-3-cephem-4-carboxylate and 1.0 ml
`of diethylaminosulfur tri?uoride in 25 ml CH,C12 was
`stirred at 27° for 2.0 hr and then poured into 25 ml of
`water. The CH2Cl2 phase was dried (MgSO4) and
`stripped in vacuo. The residue was chromatographed
`on silica with CHCls to yield 0.264 g (49%) of a 1:1
`mixture of A'"':A2 benzhydryl 3-difluoromethyl-7-(2
`thienylacetamido)-cephem-4-carboxylates; ir (CHCl3)
`3450 (amide N-H), 1820 (B-lactam C=O), 1750 (ester
`C=O), 1695 (amide C=0), and 1510 (“amide I1” band)
`
`60
`
`65
`
`dimethyl ether cooled to —78". The reaction mixture
`was warmed to room temperature and the most volatile
`components were distilled out under reduced pressure
`into a cold trap. Redistillation gave 0.35 ml of 1,2
`difluoroethane as a colorless liquid; bp 25°-27°; u‘F
`nmr (CCl3F) 8 —225.9 ppm (m).
`EXAMPLE 23
`l-Chloro-2-?uoroethane
`A solution of 1.61 g (‘0.02 mole) of ethylene chloro~
`hydrin in 2 m1 diethyleneglycol dimethyl ether was
`
`Micro Labs Exhibit 1025-6
`
`

`

`1
`
`:
`.
`
`3,914,265;
`11,
`l2
`Diethylaminosulfur trifluoride, 2.5 ml (0.02 mole),
`slowly added to a solution _of.2'.5 ml (0.02 mole) die
`thylaminosulfur tri?uoride in 10ml of diethyleneglycol 3
`‘ was slowly injected into a ‘stirred solution of 211 g_ of
`polyvinylbutyral (containing 21 weight % of polymer- ‘
`dimethyl ether cooled, to —-7_8‘.’, The rea'ction‘mixture 1
`ized polyvinylalcohol in random distribution) in 100 mlv
`was warmed to room‘ temperature, and the most volatile .
`portionwasdistilledoutunder reduced pressure into a, 5 -
`ofethyleneglycol dimethyl ether cooled to 0°. The re- -
`cold trap. Redistillation gave 1.1-1 g:(69%v) of 1,-chloro_-.
`' action-mixture was slowly warmed to room tempera-1
`2-?uoroethane as a colorless liquid, bp 50°—53°; l9F
`ture, and the solution was evaporated to dryness under
`nmr (CCl3F) 8 —219.8 ppm (t, t,'1F, J = 48, 25 Hz).
`reduced pressure, first at room temperature and then
`at 605’. There was'obtained 2.1 g of rubbery ?lm which
`EXAMPLE :24
`10 had improved oil and water repellent properties over
`the untreated polyvinylbutyral."
`‘
`'
`'
`" M811" Foundi F, 2.34%
`>
`.v
`EXAMPLE 26
`
`l-(Di?u0r0methy1)n'aphthalene
`_
`.
`Diethylaminosulfur trifluoride, 25 ml (ca.-O.2'mole_). '
`was added dropwise to a stirred solution of 31.24 g
`(0.20 mole) of l-naphthaldehyde in 100 ml methylene .15
`chloride at 25°. The reaction mixture was stirred for 18
`hr, and then mixed w.ithf100 "m‘l'of ice-water. The lower
`organic layer was'separated, washed with 5% NaHCOs
`solution and then water, and dried (MgSO4). Distilla
`tion gave 16.4 g (72% yield, 46% conversion) of l
`(di?uoromethyl)naphthalene, bp _78°—79° (0.4 mm)
`and'1l.2 'g"(3’6%) of recovered. naphthaldehyde. fQF'
`hmr (CCL3F) 5-1111 ppm (11,1 ? 56 Hz‘). ‘H‘nmr
`(CCléF) 8 8.3 to,_'7._l ppm (in, 7'aromatic'1-l) and 86.98
`
`I
`_' Fluol'inationv of Cellulose
`A throughly ‘dried ‘Soxhlet‘thimble, 33 mm in diame
`ter and 94 mm long ‘(3.90 g‘), made of highly puri?ed
`cellulose, was suspended in a solution of 2.5 ml die
`thylaminosulfur trifluoride in 250 m] methylene chlo
`ride at 25°‘for 24 hr. The thimble was removed, washed
`with methylene chloride, and dried in vacuum. The"
`treated thimble’was water-repellent, as shown by the
`fact that it held liquid water for at least 5 hr before any
`seepage occurred. An untreated thimble allowed water
`to vpass through rapidly. Analysis indicated that the
`treated thimble contained 0.69%?uorine.
`‘Equations for additional reactions that can be ae
`t 30 complished by using this process'are illustrated below.
`
`ppm(t,J=56Hz).v '
`
`'
`
`“
`
`Anal. Calcd for CHI-181:2: c, 74.15; H, 4.53; F, 21.32.
`Found: c, 74.22; H, 4.16; 1?, ‘21.18.
`
`25
`
`I
`'_
`"EXAMPILlII‘ZS v‘
`"
`' ‘l
`L
`Y
`Fluorination of»Polyvinylbutyral/Polyvinyl ‘Alcohol-V ,
`
`0H
`
`'
`
`I \ '/o -
`
`.,
`
`
`
`cuv _ ‘ , <]3H(CHn)¢
`
`'
`
`‘
`
`Hydroxyl ‘for
`Carbonyl Cpd. _.
`
`-
`
`o
`
`CH(CH3)2
`
`Dial kylaminosulfur
`Tri?uoride
`
`Product
`
`' HOCHgCHgO-CHgCHgCN.
`
`l
`
`N-—-SF;|
`
`.FCHzCH-2OCH¢CH,CN
`
`l
`
`(CH;|)¢NCO—CH¢CH2OH ’
`
`C’"
`
`>N-SF;
`
`CH3 .
`
`'
`
`||
`
`'
`
`(CHnhNCOcHiCHzF
`
`BrCHzCH2OH
`
`(nv—C4H9l¢'NSF3
`
`BrCH¢CHgF
`
`uocmcu
`
`CHQOCHJIOH
`
`Obi-SP3
`
`FCHgCH
`
`1 equivalent ‘Q
`
`(CgH5)gNSF3
`
`1 equivalent
`
`CHabCHgCF
`
`‘
`
`ll
`
`CHGOCH,COH_
`
`I
`
`.
`
`(CH3)2NSF3
`
`CHQOCH’CFQ
`
`-
`
`"
`
`'
`
`"
`
`‘
`
`'
`
`2 equivalents
`
`-
`
`.
`
`.
`
`'
`
`I
`
`_ @—@—ICH,COCH,CH,OH (cu-toms};
`
`@-@—CH=COCH=CHt
`
`~lT—COCH2OH
`
`ct-la
`
`(CHzOzNSF; I
`
`' " "
`
`N—-COCH,F
`
`cHa
`
`Micro Labs Exhibit 1025-7
`
`

`

`14
`
`—-CH:
`
`13
`
`3,914,265
`
`-Continued
`
`Dialkylaminosulfur
`Tri?uoride
`
`Product
`
`(C:Hs):NSF:\
`2 equivalents
`
`(CH3):NSF3
`l equivalent
`
`(CH3):NSF3
`
`2 equivalents
`
`(CH3):NSF;|
`2 equivalents
`
`(CH3)=NSF;
`
`(Cd-191N551
`
`(CHa):NSFa
`
`0
`
`H CH;
`
`O
`
`F(CH¢)|F
`
`F(CH;)4OH
`
`FCH,CCH,F
`
`(FCH=CH;),S
`
`FCH,CH,NO,
`
`F
`
`F
`
`Hydroxyl or
`Carbonyl Cpd.
`
`H0(CH,).0H
`
`HO(CH,)4OH
`
`HOCH-ECHgOH
`
`'
`
`(HOCH,CH,),S
`
`HOCHgCl'hNO,
`
`HO
`
`HO
`
`I claim:
`l. A process for producing a fluorinated compound
`comprising contacting a compound of the formula
`
`taken together are -(CH,)4— or —(CH2),-—; with a
`monomeric alcohol under substantially anhydrous con
`ditions at a temperature range of -—l00° to +l00°C.
`2. The process of claim 1 carried out at --80° to
`
`-3s."c.
`_
`3. The process of claim 1 wherein the said reactant
`is a polyhydric alcohol.
`4. The process of claim 1 wherein the said reactant
`is a monohydric alcohol.
`Ill
`ll‘
`
`*
`
`Ik
`
`*
`
`40
`
`wherein each of R and R‘, alike or different, is a pri
`mary alkyl group of up to