JPS62228032A - Production of 1-substituted-2-chloro-3,3,3-trifluoropropene - Google Patents

Abstract

PURPOSE:To obtain the titled substance by reacting methyl 3-(1-acetoxy-2,2- dichloro-3,3,3-trifluoropropyl)-2,2-dimethylcyclopropanecarboxylate, etc., with zinc powder in an aprotic polar solvent. CONSTITUTION:An alcohol derivative shown by formula I is reacted with zinc powder in an aprotic polar solvent (e.g., DMF or THF) at 30-80 deg.C to give a compound shown by formula II (R' is alkyl, aryl, alkenyl or H; Y is acyl, sulfonyl or alkyl; R=R' when R' is not group shown by formula III and R and Y are bonded to form group shown by formula IV when R' is group shown by formula III). The zinc power is activated with a mineral acid such as hydrochloric acid, sulfuric acid, etc., or a transition metallic compound such as CuCl, AgOAc, NiCl2(PPh3)2, etc., and the amount of the zinc powder used is preferably 1-2 equivalents. The efficiency can be improved by carrying out the reaction under ultrasonic irradiation.

Description

Detailed Description of the Invention [Industrial Field of Application] The present invention relates to a 1-it substituted compound represented by the general formula % (wherein R' is an alkyl group, an aryl group, an alkenyl group, or a hydrogen atom). -Chloro-3,33-) IJ Fluoroprodin production method.

According to the method of the present invention, 42-dimethyl-3-(2-chloro-3,3,3
-IJ fluoro-1-fluoro-cyclopropanecarbonyl) its esters and 2-chloro-1,Ll
-trifluoro-5-methyl-24-hexadiene, etc. (
JP-A-53-95945.54-112820.54-
130537.55-59141.55-89248.
55-111488) can be manufactured.

[Conventional technology]

Generally, the reductive L2-dissociation reaction represented by the following formula is known.

(However, X is CI, Br or Engineering, 2 is C[, J3
r, F, ■, or 0R (R-acyl group, sulfonyl group, or alkyl group), and RR is a hydrogen atom, an alkyl group, or an aryl group. ) As a solvent for the cono reaction, polar solvents such as carboxylic Hs, 7 alcohols, ethers, and amides are widely used, and among them, carboxylic acids such as acetic acid and propionic acid,
Alcohols such as methanol and ethanol are the most frequently used (Maruzen, New Experimental Chemistry Course, Vol. 14, p. 157)
-178).

On the other hand, there is no example of applying the above method to the reduction of the following formula.

OY Su(II) m (In the formula, R' is an alkyl group, aryl group, alkenyl group, or hydrogen atom, and Y is an acyl group, sulfonyl group, or alkyl group. The process of the reduction reaction itself is difficult due to the special environment in which the group is a chlorine atom, which is the least susceptible to reduction among halogen atoms, and the CF+3 group, which often exhibits unusual electronic behavior, is placed adjacent to it. In addition, even if reduction occurs, there are two different leaving groups (OY and Fta) on adjacent carbons, so the selectivity of the two-stage product shown below will be a problem. Become.

CD.

In addition, when Zn reduction was applied to this substrate, no reduction occurred at all with protic polar solvents such as carboxylic acids and alcohols, which were conventionally considered to be the most effective (see Comparative Example below). .

On the other hand, in the past, 2-dimethyl-3-(2-chloroO-3,
As a method for synthesizing 3,3-)lifluoro-1-pro(nyl)cyclopropanecarboxylic acid ester, (113,3
-dimethyl-4oethyl K], 1,1-trichlorotrifluoroethane, followed by cyclization and dehydrohalogenation (JP-A-53-95945.54
-112820゜55-89248), (1111,1
, 1-trifluoro-2-chloro-5-methyl-44-
hexadiene or 1.1.1. -) Refluoro-2
Synthesis method from 2-dichloro-5-methyl-4-hexene and diazoacetic acid ester (JP-A-53-95945.
54-112820, J, Mo1. Cat, 11.
119 (1981)), (till 2-chloro-2
-(2,2-dichloro-3,3-trifluoropropyl) - A method using ring reduction reaction of -3,3-dimethylcyclobutanone (JP-A-56-92830), (IVI
a6-Simethyl-4-(Ll-dihalotrifluoroethyl)-3-oxabicyclo(3,1,0)hexan-2-one Reduction method with zinc in total acetic acid (US Pat.
,,4,235,780) are known. However, both methods require a large number of steps, and in particular, the synthesis of raw materials is complicated in the method (Ill).Also, in the method (1v), it cannot be applied when both of the two halogen atoms are chlorine atoms; 6-dimethyl-4-(ll-dichlorotrifluoroethyl)-3-oxabicycloC3,i
, O) Hexan-2-one (see reference side below) cannot be used, so it has drawbacks such as being difficult to implement industrially.

[Problem that the invention seeks to solve]

The present inventors have repeatedly studied methods for industrially producing the compound represented by the above general formula [I] by overcoming the drawbacks of the conventional methods, and have found that the compound represented by the above general formula [11] Upon reduction of lead-stretching compounds, the general formula [
We have discovered a method for selectively and efficiently producing only the compound represented by 1), and have completed the present invention.

[li! Means for Solving All Problems] The present invention is characterized in that the alcohol derivative represented by the general formula [■] is reacted with curved lead powder in an aprotic solvent. This is a method for producing a compound represented by

The alcohol derivative represented by the general formula [■], which is a raw material of the present invention, can be produced in high yield from industrially easily available aldehydes (see the reference side below). These alcohol derivatives include 3-(1-acetoxy-
Methyl 2,2-dichloro-3,3,3-trifluoropropyl)-22-dimethylcyclozolononocarboxylate, 3-(1-acetoxy-2,2-dichloro-3,,1
%3-4lifluoropropyl)-2,2-dimethylcyclopronoξenecarboxylic acid ethyl ester, 3-(1-acetoxy-22-9chloro-a3.3-1-IJfluoropropyl)-42-dimethylcyclopropancar Pontic acid (3
-phenyl-2-methylphenyl)methyl, 3-(1-
(3-phenoxyphenyl)methyl acetoxy-Z2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethylcyclopropanecarboxylate, 3-(1-acetoxy-22-dichloro-3,3,3) -Trifluoropropyl)-22-dimethylcyclopropanecarboxylic acid cyan(3-phenoxyphenyl)methyl, 3-(1-
Acetoxy-2,2-cyclolo&3.3- ) +
) fluoropropyl)-22-dimethylcyclopropanecarbonyl(fluorophenyl)methyl, 3-(
1-benzoyloxy-22-dichloro-3,λ3-trifluoropropyl)-22-dimethylcyclobronomethylphonm(3-phenyl-2-me-f-)lephenyl)methyl, 3-(1-benzoyloxy) -2,2=dichloro-3,3,3-trifluoropropyl)-2,2
-Cyano(3-phenoxyphenyl)methyl dimethylcyclopropanecarphonate, 3-(1-methanesulfonyloxy-2,2-')chloro-3,3°3-trifluoropropyl)-22-dimethylcyclopropanecarphonate (3-phenyl-2-methylphenyl)methyl ponate, 3-
[1-(p-)luenesulfonyloxy)-12-dichloro-3,3,3-trifluoropropyl'>2.2-
Dimethylcyclopropanecarboxylic acid (3-phenyl-2
-)f-ruphenyl)methyl, 3-(]-]methoxy22-dichloro3.33-trifluoropropyl)-
(3-phenyl-2-methylphenyl)methyl 22-dimethylcyclopropanecarboxylate, 3-7 setoxy 2
2-dichloro-11,1-)refluorr+-5-methyl-4-hexe;/, 3-methanesulfonyloxy-2,
2-dicil] rJ-1, l, l) refluoro-
5-methyl-4-hexene, 6,6-cymethyl-4-(
Ll-dichlorotrifluoroethyl)-3-oxahycyclo[3,1,0)hexan-2-one, 1-phenyl acetate-42-dichloro-λ leak3-) IJ fluoroprozal, 1-phenyl methanesulfonate -2,2-dichloro-&3,3-trifluoropropyl, vinegar 9l-(
4-chlorophenyl)-22-cyclo33.3-
) IJ fluoropropyl, 1-C3,4-dichlorophenyl acetate)-22-cyclo3.3.3-toIJ
Fluoropropyl and the like can be used.

The amount of 11 sebium used is 0.5 equivalent to a large excess, preferably 1 to 2 equivalents.

You can use commercially available ready lead powder directly, but
Preferably coCIA with a mineral acid such as hydrochloric acid or sulfuric acid,
-tuI, Cu'-tlz, CuJJr2, (/1
, (acac)2 (copper(11) acetylacetonate)
, kgoAc , N i CQ 2, Nic flood 2 (P
Ph3) 2, N1CQ2 (CH3C1su2, revised (PPh
3) 4, PdCf12, Pd(OAC)2, PdC12
Those activated with transition metal compounds such as (Pph3)2 and Pd(99h3)4 can be used. Efficiency can be improved by performing the reaction under ultrasonic irradiation.

Examples of non-10-ton solvents include amides such as dimethylformamide and hexamethylphosphoric triamide, ureas such as N,N-dimethylpropylene urea, tetrahydrofuran,
Ether thread solvents such as dioxane and diethyl ether, tertiary amines such as pyridine and triethylamine, etc. can be used.

The reaction proceeds at a temperature of 0°C to 150°C, but a temperature of 30°C to 80°C is preferred for efficient performance.

Hereinafter, the present invention will be explained in more detail with reference to Reference Examples, Examples, and Comparative Examples.

Reference Example 1 DMF of 22-dimethyl-3-formylcyclopropanecarbontfW ethyl 174yy (1,02mmoQ)
96"g of bent lead powder (1,47mm) per 1 solution
．． 1.1°-trichlorotrifluoroethane (1,35
Add 6 m1 (3,00 mm of water) and incubate for 2 hours at 0℃ for 5
The mixture was stirred at 0°C for 10 hours. 2 ml of saturated ammonium chloride aqueous solution was added, and the mixture was extracted with diethyl ether (2 mg x 3).

The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure using FJ to obtain a crude product. 2,2-Dimethyl-3-(1-hydroxy-2
, 2-dichloro-3,3,3-trifluoropropyl)
Ethyl cyclopropanecarboxylate (2 stereoisomers (5
4:46) Mixture) 188■ was isolated. Yield: 58 cm.

"H-NMR (CD(43): (relative to main stereoisomer) δ1.22 (s, 3H), 1.25 (
θ, 3H), 1.29 (t13H), 1.69 (cl,
II (), 1.94 (del,, IH).

2.63 (broad, IH), 3.82 (b
road, IH).

4.10-4.20 (m, 2H) (for the minor stereoisomer) δ 1.26 (t, 3)J).

1.30 (s, 3H), 1.33 (s, 3H), ],,
70 (d.

IH), 1.82 (δ4.IH), 2.43 (broa
d, IH).

3.82 (broad d, IH), 4.10
-4.20 (m.

2H) 1914'-NMR (CDCfi, -CF'Cl13)
: (relative to the main isomer) δ-74,3(θ).

(subl I) δ-74,7(s) IR(ne
at):3465,1710,1260.1200cr
tt”Mass (m/z (%)): 277 (
M”-0tO,I 1 ), 197(13), 142
(11), 141 (100), 125 (16), 113
(59), 98(20), 97(18).

95 (30), 69 (18), 67 (22), 59 (2
9), 55(41), 53(10), 43(30).

41 (39), 39 (17), 29 (1), 27 (18
) Elemental analysis value: Calculated value for C□□H□5Cυ2'303: C, 4089; H, 4,68% Actual value: C
,41,02; H,4,67% Reference Example 2 3-(]-]hydroxy-22-
dichloro33.3-trifluoropropyl)-22-
Dimethylcyclopropanecarpone [(3-phenyl-2
-methylphenyl)methyl 113186%. A portion was subjected to thin layer chromatography (silica gel, dichloromethane) and two stereoisomers (A: colorless oil, RfO
, 45 (cn2cQ2).

B: Colorless crystal, RfO, 33 (Cn2cf12))
k separated.

Physical properties of stereoisomer A “H-NMR (CLlCJ 3): δ1.26 (θ,
6H), 1.76 (d.

IH), 1.97 (dd, IH), 2.19 (8,3H
).

2.59 (d, tH), 3.81 (a-a, IB),
5.18 (a, zH), 7. +55-750(,5H
)191! '-NIt4R(CDC43-Cse'C:f
i, ): δ-74,6(S)11-? (neat)
:3460(broacl), 1728.1711°12F+7.1220,1200,1180.1113
゜873, 760.702 cm"-' +Aass(m/z(%))=476(M+2.tr
ace), 474 (M”, trace), 182 (
16), 181 (100).

180(91), 179(10), 166(38).

For original yarn and part: C23H23Cu2iL'303 *-t 'rh +M: C, 58, 12;
H, 4, 88% actual value: C, 57, 99; H, 5,
Physical property value of 04th stereoisomer B mp: 155-156°C 't-+-NMR (CD(43): δ131(θ, 3
B), 1.32(θ.

3H), 1.79(d, 1)]), 1.93(ad, I
H).

2.19 (s, 3H), 2.35 (d, IH),
3.82 (t.

IH), 5.20 (s, 2H), 7.2-7
．． 4 (m, August) 19F”-JMR (CDC43-
CFCυ3): δ-74,3(s) t((KJ3r)
:3425.1711.1260.1227°1200
, 1184.706 cm ”MassCm/z (%)
):277(trace), 19B<14)i18
2 (15), 181 (100), 180 (90).

179(17), 167(10), 166(40).

165(63), 152(10), 151(10).

57 (22), 56 (11), 43 (17), 41 (2
]), 28 (20), 18 (18) elemental analysis value” C2
Calculated value for 3H23”'2'303: e, 58.
12; H, 4,88φ median value: C, 58,40;
H,4,96CH Reference Example 3 Ph 3-(]-]Hydroxy-Z2- in the same manner as Reference Example 1
dichloro33.3-)lifluoropropyl)-22-
3-phenogysiphenylmethyl dimethylcyclopropanecarboxylate was obtained in a yield of 74 cm.

Two stereoisomers were isolated by partial thin layer chromatography (silica gel, dichloromethane).

Physical property value H-NMR (CDCl2) of stereoisomer (RfQ.70 (CH2CQ2)): δ1.21. (s, 3H
), 1.24 (S.

3H), +73 (a, xH), t, q4 (da, IH
).

2.44 (d, IH), 3.79 (dd, IH), 5.
07(s.

2T'f), 6.8-7.4 (m, 8H)1
9iI'-fllMR(eLl(4-(;i!□Cρ3
): δ-75, 0(s) Engineering R (neat): 3480,
17], 3,1588,1490°1255,1180
．． 870 cm-1Mass [m/Z (%)']: 47
8 (M +2.3), 476 (M, 4) 200 (5),
184 (16), 183 (100), 77 (6), 1
8 (6) Elemental analysis value: C2□H21CQ, divided value for 2i1″304: C, 55, 36; f-L, 4.43% Actual value: C, 55, 39; ) (, 453 Thi stereoisomer (RfO, 55 (Cf(2C(!2)') physical property value 1)
1-NMR (CDCl2): δ1.28 (s, :
(tl), 132 (s.

31(), 1.74(d, 1B), 1.81(dd, I
H).

2.35 (d, I H) * 3.78 (dd,
IB), 5.06 (s.

2H), 6.8-7.4 (m, 8B) 19F-INMR (C1) (43-CLi'C!13)
: δ-74, 6(S) Engineering R (neat): 3470.
1728.17] 3.1587°1491, 1254.
1200.870.692 cm-'Mass [m/z
(%)]: 478 (M +2.1.6), 476 (M
.

2.2), 184 (16), 183 (100), 89 (
6).

77(9), 55(10), 51(6), 41(6) Elemental analysis value: Calculated value for C2□H2□ci2ir3o4: C, 55, 36; ) [, 4, 43% Actual value: C
, 55, 43;
mol) to pyridine 1rrt1. Acetic anhydride 1+xe was added, and the mixture was stirred at room temperature for 5 hours. After concentration under reduced pressure, distillation by column chromatography (silica gel, dichloromethane-hexane approximately 1:1) yields 22-dimethyl-3-(1-acetoxy-22-dichloro-33,
3-) IJ fluoropropyl) ethyl cyclopropanecarboxylate (mixture of two stereoisomers (55:45))
322■ was obtained. Yield 93%.

'H-NMR (CDCl3) = (relative to the main isomer) δ
1.24 (s, 3H), 1.26 (t, 3H), 1
．． 32 (s, 3H).

1.59 (d, IH), 2.06 (da, I
H), 2.13 (s.

3H), 4.09-4.22 (m, 2H),
5.35 (d, IH) (relative to cutting tool outer body) δ
1.17 (Sun, 3H), 1.26 (θ, 3H), 1.
26(t,3)1), 1.77(d,,1)j).

201[d,])l), 215(El,:u)l)
, 4.09-4.22 (to, 218), 5.
28(d, IH) 19se-f'JMR(CI)Cf
, -C1i'CQ3): (for the main foreign body) a
-755<8) (relative to the outer body of the cutting tool) δ-74,6 (s) King R (naa
t): 1769, 1732, 1374, 1262°12
50.1208,1188,1030 cm-'Ma
ssl: m/z (%)'):331((M+2)-
C1l, tra, cs).

329 ke (M-CQ, 2.7), 197(11), 14
1 (37), 113 (18), 43 (If) O), 29
(26).

28 (23), l8 (15) Elemental analysis value: C□3H17CI12”i for 304
t4M' value: C, 42,76; H, /1.6
9% actual value: C, 42,75; l-1,4,59
% Reference Example 5 Similar to Reference Example 4, 3-(1-acetoxy-22-
dipoo-:133-t+)fluoropropyl)-2,
(3-phenyl-2-methylphenyl)methyl 2-dimethylcyclopropanecarboxylate was obtained in a yield of 98%.

Rf:046 (CH2Cf12-hexane 1:1)'
H-INMR (CDC, C3): δ1.27 (s, 3H
)t 1.33(”.

3H), 1.70 (d, IH), 2.09 (s, 3H)
.

2.13 (aa, IH a) t 2.22 (s, 3
H), 5.25 (s.

2H), 5.40 (d, IH), 7.2-7.5 (pro 8
B) 19F-RMH (CDCQ3-CFCρ3): δ-
75,5(s)IR(neat):1754,1749
,1,730,1256°1228.1204,118
8,1160,1028°758,702 cm-”MassCm/Z(%)):518(M+2.tr
ace), 516 (M, trace), 182 (15
), 181(100).

180 (86), 166 (28), 165 (30), 4
Three-component analysis value: Calculated value for C25H25Cu2F304 2 C, 58,04; H, 4, 87% Missing value: C, 58, 31; H, 4, 91% Reference Example 6 Same as Reference Example 4 3-phenoxyphenylmethyl 3-(1-acetoxy-δ2-dichloro-3a3-to!Jfluoropropyl)-22-dimethylcyclopropanecarboxylate was obtained in a yield of 98%.

1H-RMH (CDCl2): From the spectrum of a mixture of two stereoisomers (with respect to the main isomer) δ], 22 (s, 3H)
, 1.31 (August, March), 1.66 (d, 1.H),
2.07 (s, 3H).

2.08 (da, IH), 5.11 (8, 2
H), 5.35 (d, IH), 6.90-7.15 (
m, 5H), 7.25-7.40 (m, 4H) (relative to the cutting tool outer body) δ1.16 (s, :3H)
t 1.24 (s , 3H) e 1.84 (d , I
H)-2,03 (clcl, IB) 213 (Japanese,
3H), 5.09 (d, IH), 5.12 (d.

1) (), 5.28 (d, IH), 6.90-7.15
(m, 5H) 7.25-7.40 (m, 4H) 19F'-NMR (CDCρ3-CFC!13): (relative to main isomer) δ-76,0 (8) (cutting tool outer body ) δ-75,2(s)IR(nea
t): 1767.1732, 1588, 1492°14
46.1374, 1255, 1205, 1168°H)
28.692 cm-1 Mass [m/z (%)]: 521 (M +3.1)
, 520(M"+2.3), 51JM +1.],)
, 51) 1 (M , 4) 184 (16), 183 (10
0), 43(55) Reference Example 7 Z2-dimethyl-3-(1-hydroxy-2,2-dichloro-33,3-) IJ fluorozlovir) cyclopropane carbon 79 (2-meth-3-phenyl 406 mW (0,855 mmo[) of lean methanesulfonyl in 2 ml of diethyl ether solution.
079rne (1,0mmo[+,), triethylamine 0.143ml (1,0mmon) k /J11
．． f - Stirred at room temperature for 1 hour. After adding 5 ml of hexane to remove the inorganic salts, the mixture was concentrated under reduced pressure. Thin layer chromatography (silica gel.

Dichloromethane-hexane 1:I) and remove! By preparing colorless oily 42-dimethyl-3-(I-mesyloxy-22-dichloro-3,3,3-)lifluoropropyl)cyclopropanecarboxylic powder (2-#fsil--
458 mg of phenylphenyl)methyl was obtained. Yield 97
%.

1M-4VMR (CDCβ3): δ1.26.1.31.1. for a mixture of two stereoisomers. :H, 1, 38
(s, combined terror H), 1.9-2.3 (2H),
2.18.2.20 (s.

3H in total), 3. (, 13, 3, 1, 3 (5, 3H in total).

4.88 = 4.99 (d, 1H)p 5.19
(s, 2H), 7.1-7.5 (m, 8H) 19F'-IIMR (C:1) C43-(J'Cf13
) : δ-73,7,-74,8(S) IR(neat) : ] 72! J, I 360.
] 252. I 230-1160 (broad)
, 928,808,761°704cm' Mass (m/z (%)): 554 (M +2
．． trace), 552 (M, trace), 1
82(17), 181(100).

180 (45), 179 (11), 166 (32).

Elemental analysis value "C24H25CQ2" Total τ') value for 305S 2G, 52.09: It, 4.55 coefficient Actual measured value: C, 52,02; ) i, 4.68% Example 8 2. 2-dimethyl-3-(1-hydroxy-42-dichloro-31h 3-toIJfluoropropyl)cyclopronoguncarpone rM(2-methyl-3-phenylphenyl)methyl 390 d(9(0,821mmoQ,
) in 2rnl of diethyl ether solution with 0% benzoyl chloride.
, 114 tnl (0.98 mmoQ) triethylamine 0137 was added and stirred at room temperature for 12 hours. Further, 0.23 rnl of benzoyl chloride, 0.28 ml of )') ethylamine were added, and the mixture was stirred overnight at room temperature.

Hexane 5ffl/! After removing all the inorganic salts, it was concentrated under reduced pressure.

Purification by thin layer chromatography (silica gel, dichloromethane-hexane 1:1) yielded 3 as a colorless oil.
175 m7f of (2-methyl-3-phenylphenyl)methyl 2-dimethyl-3-(1-benzoyloxy-42-dichloro-3.3-fluoropropyl)cyclopropanecarboxylate was obtained. Yield 37%.

1M-NMR(CI)Cfi, ): δ1.32(s,
3H), 1.40 (s.

3H), 1.81 (d, 1B), 2.21 (
dd, 1l-1), 5.07(s, 2H),
5.58 (d, IH), 7.0-7.6 (m,
IIH).

7.9-8.1 (2H) 19F'-fNMR (UDCfi3-CF'Cf13)
:δ-755 (Sun, 3F) IR (neat): 1732
, 1450, 10fi8, 1028, 889°836.
830,799,762,706 cm 'MaSs
mlz (%)]: 580 (M +2.trace),
578 (M, trace), 182 (16), 181 (
100).

180(94), 179(10), 166(35).

165 (36), 105 (35), 77 (10) Genro analysis value: Calculated value for C3oH2□CQ2F304: C
,62,19; f(,4,70chi Actual value: C,6
226; H, 478% Reference Example 9! 1ri lead powder 1.509 (24,0 mmol), cuprous chloride 99'/ng (1,0 mmofi) eDMF'
After suspending in 20 mg and stirring for 5 minutes in a chamber of 1.
, 1,1-trichlorotrifluoroethane 4.75 m
e (40,0 mmol)' and then cool it in a room with occasional ice cooling. I! The mixture was stirred for 20 minutes.

3-Methyl-2-butynal 1.819 (21,5 mm
o (k) Dropped at 60℃ for 10 minutes, then added at the same temperature to 4 to 11
The time was agitated. Saturated ammonium chloride water bath solution 50me'
and extracted with diethyl ether 1.0 orug.

The organic layer was dried over anhydrous magnesium sulfate, filtered 7 times, and concentrated under reduced pressure. Purification by column chromatography (silica gel, dichloromethane-hexane 1=2-2:1) yielded 5,5-dichloro-fi+'46 as a colorless oil.
- IJ fluoro-2-)f-2-hexene-/
A total of 300 g of /4-ol was obtained. Yield 60%.

M-NMR(el)Cρ3): δ1°77(d, J=1
．． 411. z 3H).

1.81 ((1, J=1.4Hz, 3H), 2.
08 (broad,.

IH), 4.8(+(d, J'=8.11IZ, I
H), 5.33 (d.

J=8. ]lIz, IH) 19F"-NMR (CD(43-CF"Cρ3): δ-
74,6(s)IR(neat):3420,1258
,1204,1052,872゜724 m ” Mass [mlz (%)] 221 (trace)
, 219 (trace).

85 (100), 55 (10), 41 (29), 39 (
12) Elemental analysis value: Calculated value for C7H9CI12F30: C, 35, 47: H, 3, 83% Actual value:
C, 35,30; H, 3,83% Reference Example 10 δ2-dichloro-1,1,1-)lifluoro-5-methyl-4-hexen-3-ol 116■ (0,489m
0.2 vrJ of acetic anhydride and 0.2 vrJ of pyridine were added to the mixture, and the mixture was stirred at room temperature for 8 hours. After concentration under reduced pressure, purification by thin layer chromatography (silica gel, dichloromethane-hexane 1:1) yielded a colorless oil of 3-acetoxy-δ2-dichloro-Ll, 1-trifluoro-5-
131 inches of methyl-4-hexene were isolated. Yield 96%
.

1u-NMR (CD(43): δ1.83 (s,
6H), 2 old (θ.

3H), 5.28 (d, J = 9.3) 1z, IH), 6
．． 08 (d, J = 9.3) 1z + I H) 19 hi- to MR (CDCρ3): δ-75, 1 (Sun) IR (neat): 1767.1254, 1208,
1190゜1024cm” Mass [mlz (%)] = 280 (M +2.tra
ce), 278 (M, trace), 183 (10
) + 85 (100) + 43 (88), 41 (10),
28(12) Elemental analysis value: C9H1□Cl12F302
Calculated value for: C, 38, 73; ) 1, 3.9
7% actual value: C, 3875; H, 3, 94%22
-dichloro-1,1,1-)lifluoro-5-methyl-
4-hexen-3-ol 950 scraps (4,01 mmo
n) sodium acetate 50Tng, diketene 0.5m
1 k was added, and the mixture was stirred at 80° C. for 4 hours. The entire reaction mixture was directly purified by column chromatography (silica gel, dichloromethane-hexane 1:1) to give 3-acetylacetoxy-2,2-dichloro-1 as a colorless oil.
1,1-trifluoro-5-methyl-4-hexene (containing about 15% enol tautomer) 1.1.39 was obtained. Yield 88%.

'H-N'MfCDCf13): δ1.83 (s
, 6H), 2.26 (s.

3H), 3.46(e, 2B), 5.28(d
,,J=9.611z.

IH), 6.08 (d, J = 9.611z, I
H) For tautomer: δ1.97 (8,3H), 5
．． 03(E+.

] IH), 6.17 (d, , J=9.6Hz
, ] IH, others cannot be identified.

1911゛-edition R (CDC43-CF”Ce3): δ
-75,0(s)IN(neat):3480.175
6.1728.1255゜1210, 11.88.11
49 cm-'Mass (m/z (%)): 285 (
M-CL2), 183(9).

127(5), 86(6), 8J100), 84(5)
.

83(5), 69(6)y 67(7), 58(5),
55(9), 44(12), 43(48), 41
(24) #39 (14), 29 (13), 27 (9) Elemental analysis I M: C, □H13CI12 = 1 for all 303 Calculated value: C, 4] 14; H, 4,08% Actual value: C, 4089; H, 3,96th Reference example 12 3-acetylacetoxy-22-dichloro-1,1,1
-) Refluoro-5-methyl-4-hexene 28
19 (0,399rr+yr+oQ) in 1ml acetonitrile solution of triethylamine 0.060mg (0
,43 mmo, (),1)-Toluenesulfonyl azide 80 μm (0,41 mmop) was added, and J was heated at room temperature for 30 minutes.
I stirred it.

After confirming the disappearance of the raw materials by TLC, the mixture was heated with 1 ml of 1.2 M sodium hydroxide and stirred at room temperature for 1 hour. After extraction with diethyl ether (2 m 7 x 3 times) and dichloromethane (2 m x 1 x), it was dried over anhydrous magnesium sulfate. After the desiccant was filtered off, the residue was concentrated under reduced pressure to obtain a crude product. Thin layer chromatography (silica gel, dichloromethane-hexane 1:1
) to give pale yellow oily 3-diazoacetoxy-42-dichloro-1,1,1-)! 100 ml of J fluoro-5-mef-4-hexene was obtained. Yield 82%
”Hiv MR (CDCN a): δ185 (
s, 6 H) * 477 (s.

IH), 5.30 (d+J=9.6Hz+IH),
6.1.3 (d.

J=9.6Hz, IH) 19F-IVMR (CDC43-CF(43): δ-
75,0(s)IR(neat):2]20,1710
, 1,376.1210°1188.1163 cm
-' Maser m/Z (%) ): 278 (],
3) t 276 CM” N2 +17), 221
(20), 219 (33), 213 (47) 185 (2
5), 184 (20), 183 (64), 147 (30
), 143 (44), 127 (49), 125 (54)
97 (25), 79 (21), 77 (24), 70 (6
9) 69 (77), 53 (26), 51 (20), 43
(31) 42 (69), 41 (100), 39 (79)
, 29 (23) 28 (89), 27 (30), 18 (5
3) Elemental analysis values: Calculated values for C9H9C flood 2 and '3N202: C, 35,43; H, 2,97;
N, 9.18 cm Actual value: C, 3545; H, 2,8
6; N, 9.21%υ Copper (11) acetylacetoner) 1m7 under nitrogen atmosphere
(7J) Heating 3tttl dioxane solution to reflux, 3-
Diazoacetoxy-λ2-dichloro1.1.1-)
IJ fluoro-5-methyl-4-hexene 381ng
(0,12 mmoff,) dioxane 0.5 me solution 7 ('j 'i: : :3 o min.
．． After refluxing for 5 hours, 5 ml of water was added and extracted with diethyl ether (10 ml x 2).

The entire organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by thin layer chromatography (silica gel, dichloromethane-hexane 1:2) yielded colorless crystals of 4-(1,1-dichlorotrifluoroethyl)-
fi, 6-dimethyl-3-oxabicyclo[3,1,0
) Hexan-2-one 26η was obtained. Yield: 75 cm.

mp: 66-68°C "H-NMR (CL) C13): δ1.25 (s, 6H
), 2.11 (d.

J=5.7FJz, IH), 2.36 (d,
J=5.7Hz, IH).

4.61 (s, IH) 19F-NMR (CD (4-ctt'c43): δ-
75,2(s)IR(KBr):1802,1260,
1,212,1194°1070.1,012,908
cm-”Mass [m/Z (%)): 278 (M++
2.2), 276 (M”.

3), 243 (32), 241 (92), 199 (23
).

197 (64), 161 (34), 141 (4'7),
125 (100) = 97 (86), 8], (63) *
79(35)-69(31), 67(39), 53(
48), 43 (51) 41 (100), 39 (62),
29 (21), 27 (43) Elemental analysis value: C9H9CQ
Calculated value for 2F302: C, 39,02; )1
, 3.27 coefficient actual measurement value: C, 38, 98; H, 32
0% benzaldehyde 2.129 (20, Ommo[
), 1, II-) 452 g of dichlorotrifluoroethane
All of 111 lead powder 1449 (22,1 mmo, U) was added to a DMF' 20 tnl bath solution of (24,1 mmop) and stirred at room temperature for 3 hours and at 50°C for 2 hours. 3 rJrnl of saturated ammonium chloride aqueous solution was added, and the mixture was extracted with diethyl ether (30 m/? x 2 times). After drying over anhydrous magnesium chloride, it was filtered and concentrated under reduced pressure to obtain a crude product. 1-Phenyl-22-dichloro- as a colorless oil was obtained by distillation under reduced pressure.
3,3゜3-trifluoroprono2nol 4.495H
I got r.

Yield 86%.

bp-: 100℃ (bath temperature) / 1 trrm Hg”
H-NMR (CDCl2): δ2.90 (d, ,
J=5)1z, IH).

5.20 (a, J=51'lz, IH), 7.25-7
．． 55(m, 5H)19F'-NMR(CL)C flood-C
FCρ3): δ-74,4(E+)IR(neat):
3460, 1248, 1188, 1,061, 87a7
66.712,700,666.612 Tan-1 Mas
s [m/z (%)): 260 (M +2.tr), 25
8 (M.

tr), 107 (100), 79 (55), 77 (30
).

Elemental analysis value: Calculated value for C9H7C12F30: C
,41,73; H,2,72 Actual measurement value: C,41
, 44; H, 282% Reference Example 16 Phenyl-1-propanol 9 (2,39 mmo
12) 1 pyridine and 1 ml of acetic anhydride! was added and stirred at room temperature for 4 hours. After adding 30 iJ of diethyl ether, it was washed with water (20 m/× twice). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. Thin layer chromatography (silica gel.

By sheathing with dichloromethane-hexane (1:2), a colorless oily 1-acetoxy-22-dichloro-3,
(3-trifluoro-1-phenylpro-ξ689~
I got it. Yield: 96 cm.

"H-NMR (CL) (J3): δ2.15 (s, 3
H), 6.35 (s.

1) (), 7.3-7.6 (m, 5H) 19F'l-
to Ml((CDCIl-CFCdan,): δ-74,7(
s) Engineering R (neat): 1767.1373, 1248
,1,204°1040.1028,938,840,
699 Tan-1Ma88[:m/Z(%)C302(M
+2. trace), 300 (M, trac
e), 149(27), 107(87).

79 (14), 77 (13), 43 (100) Elemental analysis value: Measured value for C1□H9CQ2I1130□:
C, 43,88; H, 3,01% actual value: C, 43
,79; )i, 2.79% Reference Example 11゜1-phenyl-Z2-dichloro-3,3,3-)lifluoro-1-pronognol 258~(1,00 mmoυ
) of ether 10m/solution with triethylamine 0,42
tnl! (3, Ommo[), methanesulfonyl chloride 0, 155 m/ (2,0 mmail)ffi added,
The mixture was stirred at 0° C. for 2 hours and at room temperature for 1 hour. hexane 10
After adding a salt and separating the precipitated inorganic salt 'fcP, the filtrate was concentrated under reduced pressure.

Methanesulfone fig2-dichloro-3,3,3-trifluoro-
1-phenyl-1-propyl 287'In9? Obtained. Yield 85%.

') i-NMR (CDCl2): δ2.65 (s
, 3H), 6.00 (a・IH), 7.2-7.
9(m, 5H) 19F-RkAR(CDCIl3-Ck'CQ3):
δ-75,0(8)IR: 1369,1191,9
62,900,819,740°701 cm-” Ma, ss (m/z (%)): 338 (M +2.
trace), 336(M, 4), 185(5]),
107 (100), 79 (26), 77 (22), 50
13), 15(11) Elemental analysis value 20□. H9Cp2F
Wi calculation 11 for '303S: C, 35, 6
3; H, 2,69% Actual value: C, 35,56;
H, 270% Example I Z Stereoisomerism of 2-dimethyl-3-(1-acetoxy-2,2-dichloro-33,3-trifluoropropyl)cyclopropanecarbon v(2-methyl-3-7enylphenyl)methyl Rf039 (CH2C!12-
Hexane 1:1) 384m9 (0,074mm)
oQ ) in a 3 ml solution of DMF O! If! Add 6 ml of chlorine and stir at 60°C for 2.5 hours.
A silica gel short column was used to collect 116 inorganic materials [7].

After washing the silica gel with ether, the organic layers were combined and concentrated under reduced pressure. Thin layer chromatography (silica gel.

42-dimethyl-3-(2-chloro-3,
3,3-toIJfluoro(1-i)cyclopropaneservonic acid (2-methyl-3-phenylphenyl)
29.8717 methyl was obtained. Yield 95%, )I-NM
Hey R! 5(Zl:(E+-89: 11).

'HN MR(CDCu 3) ” ((Zl/ (E
l mixture) for one fZ body: δ1.23 (S
, 3H), 1.35 (θ.

3H), 1.82 (d, IH), 2.22 (s, 3H
), 2.42 (dd, IH), 5.20Le, 2H),
6.10 (dp, IH) 7.15-7.5 (m, 8H) For +a body: δ1.23 (θ, 3H), 1.29
(8.

3) 1), 5.85 (d, IH) Other signals are (Zl
Indistinguishable from the body.

19I! '-NMR (CDCl2-C'=”C13)
: (Z) body, δ-687(s, 3F): (g) body,
δ-62,5 (s, 3F) IR (neat): 1,73
2,1284,1228,1167°1144.111
6,765,707 crn 'Stereoisomer (Rf O,46(CH2
A reduced product was similarly obtained from Cρ2-hexane 1:])).

(Z) : (E) = 93 : 7 (H-tVM
R quantification).

Example 2 2.2-dimethyl-3-(1-benzoyloxy-22
-dichloro-3,3,3-trifluoropropyl)cyclopropanecarboxylic acid (2-methyl-3-7-trifluoropropyl) /l
/ 7 x = methyl 561119 (0,09
7 mmofl) D M F' 0.1. Add 8"? (0.12 mmo, Oi) of zinc powder to ml solution, 60℃
The mixture was stirred for 6 hours. Hereinafter, in the same manner as in Example 1, 22-
Dimethy/+,--3-(2-chloro-a3.3-trifluoro-1-bro-vinyl)cyclopropanecarboxylic acid (2-y'fk-3-phenylphenyl)methyl 40
I got ~. Yield 98 cm (Z): (E) = 86:
14゜Example 3 2.2-dimethyl-3-(1-mesyloxy-42-dichloro-33,3-1!7fluorozlopyl)cyclopropanecarboxylic acid (2-methyl-3-phenylphenyl)methyl 170■(0 , 307 mmo, 9) DM
F O, 211n of zinc powder in 5ml solution? (0.32m
+nofl) and stirred at 50°C for 1 hour. Thereafter, in the same manner as in Example 1, 123■ of (2-methyl-3-phenylphenyl)methyl 22-dimethyl-3-(2-chloro-1'a3-trifluoro-1-propenyl)cyclopropanecarboxylate was obtained. Ta. Yield: 95.

(Z): 1)=88: 12. , Example 4 3-phenoxyphenylmethyl 22-dimethyl-3-(1-acetoxy-42-dichloro-3,33-trifluoropropyl)cyclopropanecarboxylate 260 m!
D M F 1 yrtl of /(0,501 mmoQ)
34 'n' of bent lead powder in solution! (0,52/mmoQ)
k was added, and the mixture was stirred at 60°C for 6 hours. Thereafter, in the same manner as in Example 1, Z2-dimethyl-3-(2-chloro-3,3,
3-phenoxyphenylmethyl 3-trifluoro-]-furotakunyl)cyclopropanecarboxylate 157 was obtained. Yield 74%.

"l(-NMR(CDCl2): δ1.21(s, 3H), 1.30(
s.

3H), 1.76 (d, IFI), 2.37 (d(1,
1)T).

5.06 (s, 2H), 6.08 (d,
IH), 6.8-7.4 (m, 8H): δ1.22 (s, 3H), 1.70 (for (E) body
d.

IH), 5.82 (a, IH) 19F-NMR (CDCf!3-CF'C crime,): (
δ-69,2(θ) for the Z) body; δ-62,9 for the (E) body (S) Engineering R(neat): 1732.
158g, 1492,1283゜1256.1221,
1167.1140,1113゜693ctn-'' Example 5 Z2-dimethyl-3-(1-acetoxy-22-dichloro-33,3-1lifluoropropyl)cyclopropanecarboxylic acid (3-phenoxyphenyl)methyl 49 scraps T Hl!' of (0,094 mmol) 0.2 m
91 ngk of curved lead powder was added to the l solution, and the mixture was stirred at 50°C for 23 hours. The reaction solution was directly purified by thin layer chromatography (silica gel, dichloromethane-hexane 1:2) to obtain 22-dimethyl-3-(2-chloro-33,3-)lifluoro-]-furonyl as a colorless oil. ) Cyclopropanecarbonyl(3-phenoxyphenyl)methyl 3
I got 5m9f. Yield: 88. (Z): (E)=77
: 23゜Example 6 Ethyl 2.2-dimethyl-3-(1-acetoxy-2,2-cyclo3.3.3-trifluoropropyl)cyclopropanecarboxylate] 831n? (0,500
mmoG in DMF' 0.5 ml solution! Add Iu lead powder 35719 (0.54 mmol) and heat at 50°C.
The mixture was stirred for 4 hours. 1 ml of saturated ammonium chloride aqueous solution
'ff: Added and extracted with diethyl ether (1 m/X 5 times). After drying with anhydrous magnesium sulfate, filtration,
It was concentrated under reduced pressure. Thin layer chromatography (silica gel,
Purification with dichloromethane-hexane (1:3) yielded 22-dimethyl-3-(2-rioo-δ3) as a colorless oil.
, 3-trifluoro-]-flobenyl)cyclopropanecarboxylate, 116 μl of ethyl cyclopropanecarboxylate were obtained. Yield 86%.

(Z): (Ifl) = 6: ].

"H-NMR (CDCl2): (Z): (E)
= 6: 1 mixture has δ1.24 (day, 3H), 1.28 (t, 3H), 1.
．． 33(s, 3H).

1.77 (d, IH), 2.40 (ddct, 1B),
4.10-4.22 (m, 2H), 6.15 (dq,
lH), (E) body δ1.21 (s, 3
H), 1.27 (t, 3H).

1.28 (s, 3H), 1.69 (a, IH), 2.3
8-2.44 (m, 2H), 4.10-4.22 (m,
2H).

The total absorption of 5.89 (d, IH) can be achieved.

19f8”-N!v!R (CD0 crime, -CF(43):
δ-68,9(s, 3F) for <z>body;
(E) δ~625(d,]Ir) Engineering R (neat): 1731, 1286, 1229, 1
176゜1]42cfn-'' Example 7 3-acetogycyZ2-dichloro-1,1,1-trifluoro-5-methyl-4-hexene 142■(0,50
9mmoQ) DMF O, 5rue solution with 36In' of zinc powder! (0,57mmoff) Copper chloride (I1
17 ngk was added and stirred at 50°C for 6 hours. water 2rttl
, After adding several drops of concentrated hydrochloric acid, pentane (3 m/X 4 times)
The extract was dried over anhydrous magnesium sulfate.

After removing the desiccant, the filtrate was carefully concentrated under reduced pressure at 0°C to obtain 77 cm of 2-chloro-1,1,1-toIJfluoro-5-methyl-2,4-hexadiene as a colorless oil. . Yield: 82 cm. (E): (Z)-85: 1 s
(H-NMR quantification) “H-NMR (C1)Cf3):
(E) δ1.87(8゜3I(), ], 9
6(8,3H)t 6.13 (c3., J-11
, 1Hz.

IH), 7. Old (d, , T-11, HIz, IH
) : For (Z) body, δ6.83(d, J-11
, 111z, IH) Example 8, i-('L1-dichlorotrifluoroefl)-6,
6-dimethyl-3-oxabicyclo(3,1,0)hexane-2-off 237nW (0,083mmojJ
) in a DMFlytl solution of zinc powder 6TRg (0,09
mmoQ)i was added, and the mixture was stirred at 60°C for 15 hours. water 1
After making the mixture acidic by adding 0.5 ytl of concentrated hydrochloric acid, the mixture was extracted with diethyl ether (3 times x 4 times). After drying over anhydrous magnesium sulfate, filtration and concentration under reduced pressure yield colorless crystals of dis-
16.9 µ of 42-dimethyl-3-(2-chloro-3,3,3-4-refluoro-1-pro-nyl)cyclopropanecarboxylic acid was obtained. Yield: 84. (Z): (E)
=g3:7 (H-NMR quantification).

mp: 103 105°C (sublimation)'H-NMR
(CI)C43): δ1.33(
s.

6H)-1,96(eL, J=8Hz, IHL
2.22 (da, J-8,911z-IH)+
6.83 ((1, J-982, IH); (BE)
To the body δ6.52 (d,, T-911z, IH)
19r-NMJCDC, -CFCQ3): (Z) form, δ-68,8(8): (E) form, δ-62,
0(8)IR(KBr):1708,1437,129
3,1272°1238.1194,1146,112
8 cttt-'Example 8 Il Acetic acid 1-phenyl-2.2-one chloro-3,3,3-trifluoropropyl # 150mg<0.500mmof
l) D M F Q, 5 me bath solution zinc powder 40
(0.61 mmop) was added and stirred at 50°C for 2 hours. After adding all of 0.5 ml of water and diethyl needles, GLC analysis (internal standard nidodecane) was performed. 1-phenyl-2-chloro Yield of -3,3,3-1-refluoro-1-proR 88%.

H-NMR (CDCf13): δ7.2-7.5 (
m, 4H), 7.5-7.8 (m, 2H).

"F'-NMR (CDC flood, -CDCf13): (
Z)-isomer, δ-69,3(d, J-0,8
Hz); for the (E)-isomer, δ-62,1(
8) IR(neat):1307,12]6,1176.1
140,962°692cm' Mas day [m/z (%) C208 (M +2.34)
, 207CM"+1.10), 206(M, 10
0), 171(39).

15] (59), 102 (16), 75 (11), 5]
(15), 50(10) Elemental analysis value: Calculated value for C7H6Cf1ll'3: C, 52, 32; H, 2, 93 coefficient actual value: C,
52,05; H, 2,89% Example 9 22-dichloro-LLI-trifluoro-3-mesyloxy-3-phenylpropane 193
Add 41 ml of zinc powder to the DMF 0.8 ml solution of (1,).
〃l(0.63mmoll) f added, 3.5 at 60℃
Stir for hours.

1-phenyl-2-chloro-43 in the same manner as in Example 8
The yield of a-trifluoro-1-prohane was determined. Yield 65%.

Comparative Example 1 3-(1-acetoxy-2,2-dichloro-3,313
-) IJ fluoropropyl)-2,2-dimethylcyclopropanecarboxylic acid ethyl ester, 7071+1i1(0,
Add 1 part of zinc powder to 20.2 ml of vinegar solution of 19 mmo (1).
47'V (0.21 mmoU)k was added, and the mixture was stirred at -○@C for 9 hours. TLC analysis showed that no reaction had occurred.

Comparative Example λ3 When the compound of the following formula was completely reacted under the same conditions as in Comparative Example 1, no reduction was observed.

(Comparative example 2) (Comparative example 3)

Claims (1)

[Scope of Claims] 1-, represented by the general formula R'CH=C(Cl)CF_3, is obtained by reacting an alcohol derivative represented by the general formula RCH(OY)CCl_2CF_3 with zinc dust in an aprotic polar solvent. Method for producing substituted 2-chloro-3,3,3-trifluoropropene (wherein R' is an alkyl group,
It is an aryl group, an alkenyl group or a hydrogen atom, and Y is an acyl group, a sulfonyl group or an alkyl group. In addition, in the case of ▲There are mathematical formulas, chemical formulas, tables, etc.▼, R=R', and in the case of ▲There are mathematical formulas, chemical formulas, tables, etc.▼, R is integrated with Y, and ▲There are mathematical formulas, chemical formulas, tables, etc. Forms a group represented by ▼. ).