JPS60255740A - 1-ethyl-3-halogeno-tricyclo(2.2.1.02,6)heptane and its preparation - Google Patents

Abstract

NEW MATERIAL:1-Ethyl-3-halogeno-tricyclo[2.2.1.0<2>,<6>]heptane of formula I (X is Cl or Br; wavy line shows that the substitution configuration is exo or endo). EXAMPLE:1-Ethyl-3-bromo-tricyclo[2.2.1.0<2>,<6>]heptane. USE:Useful as a carbon nucleus or modification group of pharmaceuticals, agricultural chemicals, perfumes, etc. PREPARATION:The compound of formula I can be prepared by reacting ethylidenebicycloheptene of formula II with the hydrohalogenic acid of formula HX in a solvent or in the absence of solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel halogenated hydrocarbon, more specifically, a compound of the following formula (D (in the formula, or CI straddle 13r, and the wavy line ~~ indicates that the substitution position is exo or endo). 1-ethyl-3-halogeno-tricyclo(
2,2,1,0'') Hezotan and its manufacturing method.

Conventionally, ethylidene picyclohedetene (hereinafter r[
(abbreviated as cBHJ) undergoes various addition reactions in the presence of strong acids, such as carmenic acid [Japanese Patent Publication No. 49-30
No. 105, No. Org.

Kbim,, 13.2085 (1977)), alcohol (U.S. Pat. No. 4,308,159), or isocyanic acid (Japanese Patent Publication No. 11,222/1989), a structure is formed according to the following reaction formula. 281 compounds with different
It is known that a mixture of 1) and (■) is produced.

(II) (1) (IV) (In the formula, Nu- represents a nuclear group, and the meaning of the wavy line M is the same as above) In this actual situation, the present inventors have realized II! We investigated the addition reaction of hydrogen halide to 8H, and either reacted gaseous hydrogen halide or obtained a mixture of a compound with structure (IV) and a previously unknown isomer. No particular improvement in selectivity was observed. However,
IIBHK hydrogen halide*t-reacted,
Surprisingly, only the new compound of formula (1) very selectively
Moreover, they found that it can be obtained in high yield, and completed the present invention.

That is, the present invention deals with 1-ethyl-3-
The present invention provides halogeno-tricyclo(2,2°1.0!.6)hebutane and a method for producing the same.

The compound (1) of the present invention is produced by reacting with a halogenated hydrochloric acid represented by the following formula (wherein X is the same as above) in a l1iBH1 solvent or without a solvent.

To carry out the present invention, [CBH and hydrochloric acid or hydrogen bromide]
! Just stir and mix. The HOJ concentration of hydrochloric acid is 5-36
%, and the HBr concentration of the bromide water Xw1 is preferably 5 to 47%.

The amount of hydrogen halide should be at least equivalent to 1nB11, but from the viewpoint of economy and post-processing, the amount should be between equivalent and 10%.
The reaction temperature is preferably 0°C to 100°C, preferably 10°C to 50°C. The reaction may be carried out without a solvent, or it is preferable to use a solvent in view of ease of layer separation after the reaction is completed. Examples of the solvent include lamps such as #iD-hexane, ether, benzene, toluene, chloroform, and the like. The amount of solvent Fi is not particularly limited, or in consideration of ease of isolation, it is preferably from the same volume to 2 times the volume of 18H JIi. It is established by the following fact that the structure shown by
), it is divided into two beaks (CG) where X=Br
:ac ratio, 34/66, X=C1:G (3 ratio, 23/7
7).

According to the results of gas mass analysis of the reaction products, these two beaks correspond to the compositional formula H1, Since they are very similar, it is expected that they correspond to two types of isomers. Therefore, a single compound was obtained by reacting the reaction product with lithium and t-sitanol and decomposing it to a hydrocarbon. Furthermore, its IIC-NMR spectrum matched the l''c-NMR spectrum of the compound represented by the following formula (to) described in the literature [Zb, Org, Kbi!o,, 13.208
5 (1977)]. Therefore, it is concluded that the reaction product has a structure represented by the linear formula (υ) and is a mixture of two compounds (Ekyne and Endo isomers) in which the steric configuration of the halogen atom is different.

The compound (1) of the present invention is a highly reactive halide and is an important intermediate that can be used as a carbon core or a modifying group in, for example, pharmaceuticals, agricultural chemicals, fragrances, etc.

For example, a compound represented by the following formula (X) (wherein R1, R, and , for example, the same or different represent a methyl group or an ethyl group) is known to be important as a fragrance. (Japanese Patent Application Laid-Open No. 59-10536). According to the descriptions in tj4B13s9-tosa6 and JP-A-59-10542, compound (X) is synthesized according to the following reaction formula.

(Vl) (Vil) 1AjH4 -→ (X) (wherein, XI is, for example, a chloro group, R#'i, for example, d-ethyl group, R, and R21d are the same as above), and further compound (vl) The synthesis method for the compound (Vl) is not described in the above-mentioned publication, but according to the method described in the literature, the compound (Vl)
is synthesized according to the following formula (Zb, Or g,
Khim, , 2085 (1977)).

That is, a mixture of (XI) and (X[l) obtained by adding carmenic acid to KBH in the presence of a strong acid is separated by distillation or the like, and after π, compound (■) 1 is hydrolyzed to form alcohol (X
I) and further t-oxidation thereof.

In this way, conventionally, in order to obtain compound (X) 1i-, 7 steps were required from [CBH, and intermediate (XI
) and 011)', which required a complicated operation.

On the other hand, the compound of the present invention (1) tj, Bauvea
Since a compound of the formula (■) is obtained in the uli reaction,
According to the present invention, according to the following formula, compound (■) t-1 can be obtained in two steps from CBH, and therefore compound (X) can be obtained in four steps from E8H. Furthermore, according to the present invention, only compounds having a nortricyclo[12,1゜03.6]heptane skeleton can be selectively synthesized, so the yield can be substantially increased, and there is no need to separate isomers during the process. can be synthesized advantageously.

HX I7DMF (It)-→(D-published (■)-→(■)-1→(X)(
In the formula, X is the same as above. DMFij: Dimethyl formaldehyde) Next, the present invention will be explained with reference to Examples and Reference Examples.

Example 1 1-ethyl-3-bromo-tricyclo[2°2,1,
0"l']Hezotane: To a solution of zsa (120f, 1 mol) in ether (200d), 47% hydrobromic acid (344 t, HBr2 moA/) is added with vigorous stirring at room temperature over 2 hours. 4 more
After stirring for 9 hours, the organic layer was allowed to stand, separated from the aqueous layer, and combined with the aqueous layer extracted three times with ether (100 d). The organic layer was treated with saturated saline (50 tIlt) twice.
Wash twice with saturated sodium bicarbonate solution (50 m/), and then wash with saturated saline solution (
After washing twice with 50 m), dry with sodium sulfate.

Next is the organic layer color ether all rotary eva? rater
and distilled under reduced pressure to obtain the target product 169F (preparation 1B
A yield of 84.0% based on H is obtained.

Boiling point: 88.0-90.0℃/15mmHg Elemental analysis: Analysis value: 0.53.9%, H, 6.7% Calculated value: C, 5
4, (1, H, 6,5% engineering R (liquid film, tym-')
: 3060 (C-E)”H-NMR (ODO7g
Solvent, TMB order I standard, δ) ~ 0.93 ((H,, triple IR), 1.1 ~ 2.3 (complex multiplet), 4.0 (
OH-Br) Go-Mass (relative intensity): For GO analysis, a capillary column (methyl silicon,
50m) By using t-, it is divided into two peaks. Each square/9 turn is very similar, Brom's end.

It is an exo isomer.

Peak 1 (OC ratio, 31) 202 (M++2.2), 200 (M+, 2).

121 (82), 105 (58), 93 (62).

91 (91), 79 (84), 66 (100).

55 (50), 43 (43) Peak 2 (Go ratio, 66%) 202 (M++ 2.1), 200 (M+, 1) 121 (
80), 105(54), 93(62).

91 (84), 79 (80), 66 (100).

55(52), 43(38) 11c-N MR (cDcls filtration medium, TMS internal standard, δC.

Multiplicity): The isomer corresponding to aC peak 2.

11.8(q), 17.7(1,2L6(t).

24.0(d), 28.7(s), 32.0(t).

34.7(t), 39.5(d), 57.6(d) Example 2 1-Ethy#-3-chloro-tricyclo(2,2,1,0''+@)hezokun: 1cBH( 12of, 1 mol) of ether (200-
) Add 36% hydrochloric acid (2039, HCl2 mol) to the solution while stirring vigorously, making sure that the reaction temperature does not rise significantly (
(20-30℃) Add over 1 hour while cooling with water. After stirring for an additional 12 hours, the organic layer was separated from the aqueous layer by standing and combined with the aqueous layer extracted three times with ether (150-). Next, the organic layer' was washed and dried in the same manner as in Example 1, and the desired product 141 was removed by vacuum distillation.
f (yield 90.1- based on ICBH charged) is obtained.

Boiling point: s 9.0-90.5℃/26mmHg Elemental analysis: Analysis value: 0.6L8%, H, 8.6% Calculated value: c, 69.0%, H, 8.4% film,
clR-”): 3070 (SiO-H)lH-NMR
(CD0h bath medium, TMS internal standard, δ)0.9 ((H
8, triplet), l, 2-2.1 (complex multiplet #).

3.9 (OH-Br) Go-Mas Day (Relative Intensity) In the -7'j GO analysis using a capillary column (methyl silicon r som;, a mixture of compounds of 21! Since they are very similar, it is clear that they are endo and exo isomers of chlor.

Peak l (Go ratio, 23%): 158 (M”+2.5), 156 (M+, 16) #12
0 (37), 105 (61), 93 (34).

91(87), 79(67), 77(31).

66 (100), 65 (31) Peak 2 (Go ratio, 77%): 158 (M++2.5), 156 (M'', 16).

120 (38), 105 (59), 93 (34).

91 (95), 79 (62), 77 (36).

66(100), 65(32) t3c-N MR (cpcz, @ medium, TM8 internal standard, δC1 multiplicity) Isomer corresponding to GC peak 2.

11.8(q), 17.3(a), 22.8(t).

23.7(d), 28.4(s), 31.2(t).

34.7(t), 39.4(d), 65.3(d) Reference Example 1 1-ethyl-3-bromo-tricyclo[
2,2,1,glJ heptane (10,0 fs 49.8
mmol)”ibit@rt-butanol (11,
Li pieces (L46 f, 0.498 gram equivalent) were added to a THF (20 m) solution of L46 f, 148 mmol) at room temperature and stirred well. After stirring for 8 hours, the temperature is increased until the THF refluxes, and the mixture is stirred at this temperature for 30 minutes, followed by ice cooling. Next, under ice-cooling, methanol (10d) was carefully added dropwise to react with excess L1. After confirming that gold i@Li has disappeared, extracted water (ioolRt) is further added dropwise, and then the product is extracted from the aqueous layer with D-hexane (10011it). The extracted organic layer was washed with saturated saline, dried over magnesium sulfate, and distilled under normal pressure.
Ethyltricyclo(2,2,.

1.QL・] Hezota y3.49F (Sales $57.411)
is obtained.

If you perform O-NMR analysis on this product, you will find that the standard ethyltricyclo[2,2,1,0''I4)buty [zb
, Org, Kbim, , 15 (2), 32
(1979)), and the structure was confirmed.

1" O-N MR (CDCl, 1.7M8 internal standard, δC1 multiplicity): 12.4 (ct), 16.1 (d), 23.1 (t).

24.4(s), 31.8(11), 34.2(t).

aS, 4(t) Reference Example 2 1-Ethyltricyclo[2,2,1,0"°"] to butane-3-cartoxyaldehyde Synthesized according to Example 1, 1-ethyl to -3-promote Rishif o (2,2-1
-0”']heptane (20,1?, 100 mmol),
Dry dimethylformamide (7,31f, 100 mmol) and lithium sand (5,10f, 17.3 eq.) in a completely dry Tay (40 m) plus an ultrasonic cleaner (200 m,
45KHz) t- to react. At the beginning of the reaction, heat is generated violently, so cool with ice and be careful not to let the reaction temperature exceed 40°C.

The reaction time is about 15 minutes.

Next, 5% salt M was added dropwise to the reaction solution under water cooling to decompose unreacted lithium, then ether (300 m) was added to separate the layers, and the ether layer was diluted with saturated brine (50 m) three times. Wash. The ether layer dried with sulfur 1j[-rgnesicum was concentrated in a vacuum evaporator and further distilled under reduced pressure to yield 1-ethyltricyclo[2.2.1.gL"]butane-3-cartoxyaldehyde 6541 ( Yield: 43.
6%) t-obtain.

Boiling point: 58.0-60.0°C/lmmHg Elemental analysis: Analysis value: 0.80.0%, H, 9.5% Calculated value: 0,
80.0%, H, 9,1 Engineering R (f [membrane + 611-'): 3o60 (Si c
-n), 1720 (νc=o)”H-NMR (cvcl
z solvent, TMB internal standard, δ) 0.93 (OHs,
3 weight), 1.2-1.7 (complex multiplex III),
2.3(-an-cHo), 9.7(-+:ap
) Go-Mass (relative intensity) For aC analysis, a capillary column (methyl silico y,
50111), it is divided into two peaks,
Since the (l-turns) of each mass are very similar, it can be seen that there are endo and exo isomers of the homil.

Peak 1 (ac ratio, 58ch): 150 (M, 5), 121 (100), 103 (27
).

93 (26), 91 (42), 79 (49), 77 (2
6).

55 (36), 43 (24), 41 (30) peak 2 (
Go ratio, 42%): 150 (M, 4), 121 (100), 103 (25
).

93(31), 91(3g), 79(49), 77(2
6).

55 (36), 43 (24), 41 (29) Reference example 3 1! ! 8H (10 (1,0,833 mol) K hydrogen chloride gas is blown in under water cooling. Due to heat generation, the reaction temperature rises and 1
The temperature will be 5℃. Adjust the gas blowing speed to maintain this temperature. When the entire reaction was followed by Go analysis, the BH peak completely disappeared in about 3 hours, indicating that the reaction was completed.

When this reaction solution is distilled under reduced pressure, hydrogen chloride is added to ICBH and the t compound has a boiling point of 79.5-86.0℃715mm
122.7f (yield 94.1%) was obtained in the Hg range.

This compound was converted into Polyyeater FF (101)
Go analysis using a column revealed that it was divided into four peaks and consisted of a mixture of four isomers.

Peak 1 (Gc ratio): 6011 Peak 2 (1): 20 Peak 3 (1): 15 Peak 4 (1): 5% C-NMR (ODOJ8 solvent, TM8 internal standard, δC
2 multiplicity): In the 0-NMR analysis, no peak corresponding to compound (D was detected. In addition, the compounds corresponding to peak 1 and peak 2, which are the main products, have the following formulas 0GV) and (0GV) and ( ff).

(Xll/) (XV) Peak 1: 14.1(Q), 34.6(t), 36.0(
t), 36.8(d).

42.8(t), 546(a), 61.2(d), 11
6.7 ((1).

141.2(s) Peak 2: 10.0((1), 36.0(t), 42.5(t
), 44.0(t).

49.0(d), 54.6(d), 81.2(s)
, 133.3(a).

xa9.2(a) that's all

Claims (1)

[Claims] 1. 1-ethyl-3-halogeno-tricyclo [
2,2,1,oz,g) Hegetan. 2. Reacting ethylidene bicyclohegetene represented by the general formula ([0) with a hydrohalic acid represented by the following formula (wherein, X represents C! or ij Br) in a solvent or without a solvent. The following formula (
1) l-ethyl-3-halogeno-tricyclo(2,2,1,0".6 ]
Manufacturing method of hezotan.