JPH03261742A - Production of aromatic-containing cyclic ketone and intermediate thereof - Google Patents

Abstract

PURPOSE:To practically produce the subject compound in high yield by subjecting a stable alkylthiomethyl arylsulfone derivative having a slight malodor and a halogen compound to condensation reaction in a basic condition and hydrolyzing through a new intermediate. CONSTITUTION:A stable alkylthiomethyl arylsulfone derivative expressed by formula I [A is expressed by formula II (R<1> is H, alkyl, alkoxy or halogen); R is alkyl] having a slight malodor is subjected to condensation reaction with a dihalogen compound expressed by formula III (Ar is bi-substituted aromatic group; G is methylene or -CH2OCH2CH2CH2-; X is Cl, Br or I) in a basic condition and hydrolyzed through a new halogen compound expressed by formula IV and a new intermediate composed of a symmetrical sulfonated compound expressed by formula V to afford the aimed aromaticcontaining cyclic ketone expressed by formula VI. Resultant compound is useful as various cyclophane, functional materials or phase-transfer catalyst, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing aromatic cyclic ketones and intermediates thereof. More specifically, the present invention represents the general formula (it [wherein G and Ar have the same meanings as above and represent a silyl group, alkylthio or Fi/% rogen atom]; R represents a lower alkyl group. Representation: X represents a chlorine atom, a bromine atom or an iodine atom. ] and a symmetrical sulfone compound represented by the general formula (5) (wherein, 0% A r XA k and R have the same meanings as above).

Aromatic cyclic ketones can be used as they are or further reacted to give various cyclophanes. These are usefully used as functional materials or phase transfer catalysts.

[Prior Art] Problems to be Solved by the Invention Conventionally, ketones have been prepared using an alkylthioarylsulfone derivative represented by the general formula (1) (wherein A& and R have the same meanings as above). The method of the present inventors was known for producing the same (% KOKAI Publication No. 59-164765 and JP-A No. 60-156654).
No known example of a method for producing an alkyl ketone that includes an aromatic group on the ring. However, there were no known macrocyclic ketone moths that could be called cyclophanes.

Conventionally, a method for producing cyclo-7an having an aromatic chichito group) and a carbonyl group on the ring using innitrile as the source of the carbonyl group has been mentioned (T, I~αUet al,, Te
trahedxor Lett,, vol. 23, 5335
(1982)). However, innitrile (1) easily decomposes in dilute acid water and (2) gradually polymerizes at room temperature, resulting in lack of stability and strong odor, making acid production difficult.

[Means for Solving the Problem] The present inventors have prepared an alkylthiomethyl ester sulfone derivative represented by the general formula (1) (wherein A and R have the same meanings as above). He continues to carry out a wide range of synthetic research using synthetic methods (e.g., Journal of the Society of Organic Synthetic Chemistry, 42I#, p. 1152 (1984);
216860 Publication 1 &) 0 In particular, R is a methyl group, A is p
-) A compound with a +ful group is commercially available under the trade name "Daily MT Sulfone" and is easily available. The present invention was discovered through this series of research.

That is, the present inventors obtained an alkylthiomethylarylsulfone derivative represented by the above general formula (1) and the general formula (2) [wherein, Ar represents a disubstituted aromatic group; G represents a methylene group or -CH, Represents OCH, CH, CH, - group: X
represents a chlorine atom, an odor lA atom, or a Fi iodine atom] by condensing the compound with a dino-rogen compound represented by the following formula under basic conditions and then hydrolyzing it to form the above-mentioned - Mongan 14)
and/or - Through a new compound represented by Monna (5), - Monna (5) [wherein Ar and G have the same meanings as above, and n/Ii1 to
Indicates the number of crabs of 4. To obtain the fang aromatic cyclic ketone represented by ``! I succeeded for the first time in 77 years. This method has almost no odor and is highly stable compared to the method using isonitrile. Stable in acid water and dilute alkaline water).

The 7-aryl group of the alkylthiomethylaryl sulfone derivative represented by the above-mentioned - Monna (1) (corresponds to A in the formula)
Specific examples include phenyl t, p-tolyl group, m
-chlorophenyl group, p-methoxyphenyl group, etc.

2 of the dihalogen compound represented by the above-mentioned hole (2)
Specific examples of substituted aromatic tear groups (Ar in the formula) include 6-,
m-, i or p-phenylene group; 1.3-1, 4-1f
, 5-1,6- or 1,8-7-teleene group: or 1.3-11.4-15.10-anthracenylene group.

The condensation reaction between the alkylthiomethylaryl sulfone derivative represented by the above-mentioned -Moneya (1) and the dihalogen compound represented by the above-mentioned -Monoya (2) requires the presence of a base. Examples include relatively strong bases such as alkali metal hydrides such as sodium hydride and potassium hydride, alkyl lithiums such as n-butyllithium, alkali metal amides such as lithium diisopropylamide, and alkali metal hydroxides such as sodium hydroxide. is preferred.

This reaction is carried out in a solvent, and when the base is an alkali metal hydride, alkyllithium or alkali metal amide, an aprotic solvent inert to the base such as tetrahydrofuran or toluene is preferably used. I can give it to you. In particular, dimethylformamide
The combination of IJium (hydrogenation) is suitable in terms of economy, smoothness of reaction, and yield. When the base is an alkali hydroxide, it can be prepared in an aprotic solvent such as tetrahydrofuran or toluene in the presence of a phase transfer catalyst such as a tetraalkylammonium salt, or in a two-phase system using a water-aprotic solvent combination. It is a good idea to implement it.

Dihalogen compound represented by general formula (2) and general formula (1)
The amount of the alkylthiomethylarylsulfone derivative represented by ) may be equimolar, or either may be used in excess.

The reaction proceeds smoothly at -60°C to 100°C. Under the above conditions, the condensation reaction of the present invention proceeds in high yield.

The intermediate obtained by the condensation reaction is a halogen compound represented by the formula (4) (where XXG, Ar, R, and M have the same meanings as above) and the general formula (5) ( It is a symmetrical sulfone compound represented by the formula (in which GXAr, R& and human have the same meanings as above).

The halogen compound represented by the general formula t41 is
) When the amount of the alkylthiomethylarylsulfone derivative used is as low as CL5 to 1.2 equivalent weight relative to the dihalogen compound represented by the general formula (2), a large amount is produced, and the amount of the alkylthiomethylarylsulfone derivative represented by The symmetrical sulfone compound* produced when the amount of the alkylthiomethylaryl sulfone derivative represented by the general formula (1) used is as large as 1.8 to 2.5 equivalents relative to the dihalogen compound represented by the general formula (2). Easy to generate.

Also, Monana (halogen compound represented by 47, general 5c [
Since the compound represented by 5) is an intermediate, the amount of the compound produced increases as the reaction temperature becomes milder.

After separating this compound vJd rate, it may be used for the next bipolar #-forming bath medium decomposition, but it may also be used for the crude reaction product H and the first stage of the process.

That is, the halogen compound represented by the above-mentioned pattern (4) is cyclized by further heating. Also, the above-
The symmetrical sulfone compound represented by the symbol (5) is cyclized by an additional reaction with the dihalogen 1ζ represented by the symbol (3) above in the presence of a base. The base used and the reaction conditions may be the same as described above, but higher temperatures are required.

The cyclized product is then subjected to hydrolysis, but since the cyclized product is unstable, the cyclized product is usually subjected to the hydrolysis without being purified.

Hydrolysis conditions include a method of heating under acidic conditions such as methanol-chloroform in the presence of sulfuric acid (refer to the present inventors, t# Publication No. 164765/1983); (li) in the presence of water; A method using ultraviolet photolysis (refer to the present inventors' patent publication No. 156654/1983), (-)
A method of heating in the presence or absence of sodium hydrogen carbonate under basic conditions such as water-ethylene glycol or under neutral conditions (see the present inventors' patent publication No. 156621/1983), etc. . These methods each have 1i
It is selected by taking into consideration the instability or stability of a single substituent group against acids, light, bases, heat, etc.

Each condition will be explained in more detail.

(1) # Conditions (2) To obtain the aromatic cyclic ketone of the general formula t31, K is an organic solvent, such as lower alcohols such as methanol or ethanol, or an ether additive such as diethyl ether or 1,2-dimethoxyethane. It is preferable to carry out the reaction in the presence of an acid. As an acid, hydrochloric acid, i! Examples include organic acids such as trifluoro-Itli& and p-toluenesulfonic acid, such as nitric acid and perchloric acid. The amount of acid used (t#iFgr per mole) may be sufficient, but the reaction is accelerated by using a large amount. The reaction proceeds from room temperature to 150°C, but the reaction rate and I!
! From the viewpoint of ease of temperature control, it is preferable to use fIm's R-temperature from room temperature.

(Photolysis: Photolysis is usually carried out by irradiating ultraviolet light in a solvent. The ultraviolet light may be any ultraviolet light that can be absorbed by the A80 group of the alkylthiomethylarylsulfone derivative represented by the general formula (1). Generally from 300nm
UV rays having a wavelength in the range of 200nrn are preferable, and ultraviolet rays having a wavelength of #i290nm to 220nm are more preferable.

However, with short wavelength ultraviolet rays, many side reactions occur due to photoexcitation of parts other than the intended ones, and the desired general formula (3
) leads to a decrease in the yield of aromatic lacrimal cyclic ketone.

In addition, the absorption efficiency is poor for ultraviolet rays of soon nm or more, making it impractical.

To obtain these ultraviolet rays, a mercury lamp (low pressure, medium pressure, high pressure) or a xenon lamp can be used, and a Pycoll filter may be used to block ultraviolet rays with wavelengths as short as 220 am. When carrying out this reaction, there is a tendency for the yield to increase when water is present. If necessary, the reaction may be carried out in the presence of a base.The addition of this base does not cause the reaction system to become acidic, but the addition of the base does not cause the 2f-type aromatic group, substituent Ar or G to be exposed to acidic conditions. Even when the compound has an unstable moiety, the aromatic cyclic kettle represented by the general formula (3) can be obtained in good yield. Furthermore, these bases can capture the sulfinic acid (A80.H) produced by the reaction in the form of its salt, making it easier to isolate the aromatic cyclic ketone represented by the general formula (3) produced. It becomes extremely easy.

As the solvent, commonly used organic solvents may be used, but in the case where water and a base are present together, polypropylene solvents such as methanol, ethanol, acetonitrile, dioxa 7, etc. are preferably used. The reaction temperature is determined from the point of view of easy control.
The reflux temperature of the solvent may be 1 degree from 20° C., and it is usually carried out under water cooling.

(1) Basic or neutral conditions: Heating and decomposition are usually performed under water-methanol, water-dioxane,
A polar solvent such as water-ethylene glycol is used, and if necessary, a base such as sodium hydroxide, potassium hydroxide, sodium hydrogencarbonate, phosphoric acid-sodium hydrogencarbonate, etc. is allowed to coexist. Heating is carried out in an oven at a temperature of 50° C. to the reflux temperature of the reaction solution, and is completed in 1 hour to 10 days. Usually, the higher the temperature and the higher the base concentration, the more accelerated the reaction will be.

[Effects of the Invention] According to the method of the present invention, aromatic cyclic ketones, which have conventionally been synthesized using isonitrile compounds that are unstable and have a strong odor, and the above-mentioned - Monka (3), which could not be synthesized in the past, can be synthesized. The aromatic cyclic ketone represented above is stable and has little odor.
The compound represented by pattern (1) can be practically produced in high yield by a method using a nerthiomethane sulfone derivative.

In addition, the aromatic cyclic ketone represented by the above-mentioned formula (5) thus obtained is reacted with tl or further to give various cyclo7anes. These are usefully used as functional materials or phase transfer catalysts.

[Example 7] The present invention will be explained in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto.

Hereinafter, Tol represents a p-)lyl group, and Me represents a methyl group.

Example t α, α′-dibromo p-xylene tasy (melon 95r
tmol) and sulfoy 110f (I A9mm
ol) in 60d of toluene, trioctylmethylammonium chloride (TOMAC) 11 GI
After adding IIi (cL275 Blood Test 1), 50 d of aqueous sodium hydroxide solution was added dropwise.

After stirring at 60°C for 4 hours, the reaction solution was poured into water and extracted three times with chloroform. All organic counterfeits were washed with water. After drying with magnesium sulfate, reduce pressure #Jl
A yellow oil 4.1682 was obtained. Silica gel column chromatography (chloroform)
p-bis[2-methylf-(p-)lylsulfonyl]ethelcobenzene (2) 1812 was obtained as colorless lE&. Yield 86%. 1) was further purified by recrystallization from chloroform-hexene to give a sample for analysis. 1:1tI of two diastereomers (dt and meso) from HNMR (270MHz)
It became clear that it was a s compound.

Colorless crystal, mp 157-1681::(Rio C1
Form-hexane) HNMR (270MHz, COCl, )a:
7.87 (4H, d, J=a2Hz), 7.5
8 (4H, d, J=a6Hz), Z12 (4H,
s), 5a 2 (2H, dd, J= 115. L6
klz), 557 (2H/2. d d, J
= 142. 13Hz), 556 (2H/2.dd
, J=14.2, 13Hz), 2.61 (2H/2.
dd, J=1 a, 5. 1 t2Hz),
260 (2H/2.dd, J=14.5.
I L2klz), 2-47 (6H, s), zl 13 (6H/2.S), 2-110 (6H/2.S), IR (KBr) 2940.1590, 1290, 1140, 1085,
Calculated as 810°645 country-1 Cas 鴇@0484 i[C:5&40. ) I: 5,65 actual measurement [C: 5a
45. H: 5.69 Example 2 α, α'-buomo m-xin t84f (&97mm
o 1) and sulfone 1005r (IK9mmol)
was dissolved in toluene Sow/, trioctylmethylammonium chloride 110M9 ((1275mmo+)
After that, 30ml of 45% aqueous sodium hydroxide solution was added dropwise. After stirring at 60°C for 3 hours, the reaction solution was poured into water and extracted with chloroform. Waterfowl were further extracted three times with chloroform. All organic layers were combined and washed with water. After drying with magnesium sulfate, concentrate under reduced pressure to obtain a yellow oil! L9139 was obtained. m-Bix[2
-)t-tylthio-2-(ρ-tolylsulfonyl)ethyl]benzene (512,681F) was obtained as colorless crystals.

Yield 72%. Analytical samples were obtained by recrystallization from dichloromethane-hexane. 'HNMR (500MH
2 types of diastereo from z)? -(dt and meso
) was found to be a 1:1 mixture of

Colorless crystals, mp 157-160°C (dichloromethane-hexane) lHNMR (500MHz, CDCL, )δ near,
88 (4H/2.d, J=&25Hz), 7, 87 (
4H/2. d, J=lL25Hz), 139
(4H/2.d, J=a55Hz), 7:
58 (4H/2.d, J=a55Hz)
, 7.22 (IH, t, J=74Hz), 7.08
(2H/2.dd, J==z4.L2Hz), 7, 0
7 (2H/ 2. dd, J==7.4. 2
．． 2Hz), 7.00 (IH/2.diffuse
d t ), 19 B (IH/2.diffus
ed t), 583 (2H/2.dd, J=j
t8, 2.7Hz), A82 (2H/2.dd,
J= 1t8. L7Hz), 55B (2H, di
ffused dd), 161 (2H/2.dd
, J==1ta, 110Hz), 2.58 (2H/
2. dd, J=1 t8,1 (LOHz), 147
(6H,s), Z 10 (6H/2.s), 2.09 (6H/2.s) IR (KBr) 1590 1440 129G, 1145.
1080°805 cwL-' C□H1°0. Calculated as S4 @ C: 5a40. H: 545 Actual value C: 51144. H: a67 implementation fM5α,α'-dibromozyme p-t') ether 874
N! (146 mmol) and sulfone 1t162F (5
-58 mmol)) in 20 ml of x:y, and while stirring at room temperature, trioctylmethylammonium chloride bQxxy (Q15 mmol) and 408
1 t of hydric acid, sodium aqueous solution? l[10d was added. 70
After stirring at °C for 14 hours, the reaction solution was poured into 30°C of water and extracted four times with chloroform. All organic layers were combined and washed with water. After drying with magnesium sulfate, it was concentrated under reduced pressure to obtain yellow oil 1232f. Separate and purify using silica gel column chromatography (chloroform),
p,p'-bis[2-methylthio-2-(p-)9lsulfonyl)ethyl]biphenyl ether (4) L557
F was obtained as a colorless oil. Revenue: $88%.

Colorless oil "HNMR (270MHz, COCl, )δ: Z
88 (4H, d, J=a2Hz), 7.38
(4H, d, J=a5Hz), 7, 13 (4H,
d, J=&5Hz), 491(4H,d, J=&
5Hz), 582 (2H, dd, J=1t5,10H
z), A37 (2H, dd, J: 14° 5.AOHz)
, 2.60 (2H, dd, J=14.5, 115Hz)
, 2.48 (6H, S), 114 (6H, 5) NIL (Liquid Jl) 2925° 145 1595° 1085° 1500, 1302° 7sec-” 1240° Executed fallen hair a: n=2; b: n= 4 Sodium hydride (60% content, oil diffusion) 1058
7 (257 mmol) of DMFjlllli solution 10-1
, p-bis[2-methylthio-2-(p-tolylsulfonyl)ethyl]benzene (21267η(cts.

@l) and α, α′-dibromo p-xylene 1301
9 ((149 mmo 1 ) f) DMF solution 10a
ff was added dropwise at room temperature over 5 hours. After stirring at room temperature for 19 hours, 2 d of a saturated ammonium chloride aqueous solution was added to stop the reaction. The reaction solution was poured into water and extracted five times with diethyl ether. All the organic layers were combined and washed twice with saturated brine. After drying with magnesium sulfate, it was concentrated under reduced pressure to obtain 203η of brown oil. Dissolve this in chloroform 151II, methanol 10@j and concentrated sulfur #! 1- was added, and the mixture was heated under reflux for 3 hours. The reaction solution was poured into water and extracted five times with chloroform. All organic layers were combined and washed with water. After drying with magnesium sulfate,
Concentration under reduced pressure gave 193η of a brown oil.

A warm compound 64WI9 containing a cyclic ketone body was obtained as a yellow oil by thin layer silica gel chromatography (chloroform:ethyl acetate=20:1). This product was separated and purified by recycle preparative HPLC (column, JAIGEL-1H; developing solvent, chloroform), [33coparacyclophane-2.11-di3/(≦)13”P
% yield tt6% and [54” paracyclophane-2,11
, 20,29-tetraone (仝)'''P % Yield: 56% was obtained in the form of colorless crystals.

[5s]Pa2cyclophane-2,11-dione (mi) colorless crystal; mp 209-210°C (dichloromethane-hexane) HNMR (270MHz, COCl, ) δ: 48
5 (8H, S), 573 (8H, 5) IR (KBr) 1690.1505, 1425, 1415, 1245° 1230.1080, 565 scratch-1 MA88 (EI) 264 (M”) [34] Paracyclo Fan-2,11,20,29-tetraone (2) Colorless crystals; mp) 285°C (Chloroform) HNMR
(270MHz, COCl, )δ: Melon 91 (14H
,S), 544(16H,5) In(KBr) 1707.1510, 1425.1315, 1110°106031-1 M8 (EI, 70eV) 528(M”) Examples & Sodium hydride (60th content, oil diffusion) 100I
lv (Z5 mmo 1 ) of DMF suspension 1 Ωd,
m-bis[2-methylthio-2-(p-)lylsulfonyl)ethylcobenzene t4233JP (α44ka01)
and α, α′-dibromo m-xylene 116119 (
44 mmol) of DMF solution was added dropwise at room temperature over 55 hours. After stirring at room temperature for 36 hours, 2 d of saturated ammonium chloride aqueous solution was added to stop the reaction.

The reaction solution was poured into water and extracted three times with ethyl acetate. After drying with magnesium sulfate, concentrate under reduced pressure to obtain brown oil 3.
59111i was obtained. Chloroform 5111
Add 5 d of methanol and 5 d of 4N sulfuric acid,
The mixture was heated under reflux for 5 hours. The reaction solution was poured into water and extracted five times with chloroform. All organic layers were combined and washed with water. After drying with magnesium sulfate, it was concentrated under reduced pressure to obtain 284 ml of yellow oil. Highly polar substances were removed by silica gel column chromatography (benzene:ethyl acetate=10:1) to obtain a yellow oil of 236η. This product is recycled and preparatively separated) (PLC (column, JAIGEL)
-IH; developing solvent, chloroform) to separate nI, [
3'] metacyclo7an-2.11-dione 1c) 16
η (yield 16 arcs) was obtained as colorless crystals.

[33 cometacyclor: 177-2.11-dione colorless crystal; mp 198-199°C (chloroform-hexene) HNMR (270MHz, C0CL,) δ near, 5
2 (2H.

7.18 (4H.

! L7B (2H.

554 (8H.

IR(KBr) t, J=&6Hz), dd, J=6,6. 1.6Hz), diff
sed, t), 5) 3025, 2925°808.708-1 M5 (EI, 70 eV 264 (M) 688) 1602°1104° Example & Sodium hydride (60% oil diffusion) 100Mf
(2.5 mmol) of DMF! Add p, p'-bis[2-methylthio-2-(p-)lylsulfonyl)ethyl]biphenyl ether (±) 17 to 10 aJ of efi solution.
DMF solution of rJM9 ((L48mmof) 20
It was added dropwise at room temperature over the entire hour. After stirring at room temperature for 62 hours, saturated ammonium chloride aqueous solution (2 g/) was added,
The reaction was stopped. The reaction solution was poured into water and extracted three times with diethyl ether. All the organic layers were combined and washed twice with saturated brine. It was dried over magnesium sulfate and concentrated under reduced pressure to obtain 371η of a brown oil. Dissolve this in 5 dK of chloroform, add 5 d of methanol and 4N sulfuric acid (15 g/
was added and heated under reflux for 5 hours. The precipitated crystals were washed with chloroform to obtain 5 colorless crystals. This one is 'H
From the retention time of NMR (270 MHz) k and molecular sieve column HPLC, [-3"] (4,4'
) Biphenyl ether cyclophane-2,18-dione (4). Yield: 2.4.

Colorless crystals; mp) 295°C (chloroform) HNMR
(270MHz) J: 480 (8H, d, J=&6Hz), 6
．． 72 (8H, d, J=a6Hz), 567 (
8H, 5) IR (KBr) 2920.1720, 1600, 1495.1238C
IIl-'α,α'-bis(5-iodopropoxy)-
p-*shi L/7 tA97t (2-55mmO1) and M
T −x s, E:y 1379F (&38 mmol
) in DMF50a#, and under water cooling, sodium hydride (60% oil diffusion) 595; IQ (9,8
5 mmol) was added. 40 minutes under water cooling, 80 minutes at room temperature
After stirring for several minutes, water (2d) was added under water cooling to stop the reaction. The reaction solution was poured into water and extracted four times with diethyl ether.

All the organic layers were combined and washed twice with saturated brine. After drying with magnesium sulfate, the mixture was concentrated under reduced pressure to obtain a viscous pre-colored oil with a weight of 2.5879. Silica gel column chromatography (benzene: ethyl acetate: 20:1
) to separate and purify α,α′-bis[4-methylthio-4
-(p-)lylsulfonyl)butoxy'-p-xylene (5) 1,444 f''II: Obtained as a pale yellow oil. Yield 88%.

Pale yellow oil "HNMR (500MHz, COCl, ) δ: 7
．． 81 (4H, d, J=a3Hz), 7.54 (4
H, d, J = aOH2), 7.27 (4H, S), 4.46 (4H, S), 175 (2H, dd, J = 1 t5, 16Hz), 14
8 (4H, t, J=405Hz), 2.45 (6H
,l), L54~227 (2H,m), zly(6H,l, L98~t?0 (2H,m), 180~171 (2H,m'), t65~1.57 (2H,m) IR (liquid 1li) 1600.1280, 1140, 1080.820 tan-
1 Example a Sodium hydride (oil diffusion containing 60 tons) 2364 (
592mmo I) (D DMF @turbidity 5oar
, α, α′-bis[4-methylthio-4-(p-tolylsulfonyl)butoxy>-p-xylene (5) 820
q (t26 mmol) and α,α'-bis(5-iodopropoxy)-p-xylene 615j9 (129 mmol)
101 ml of DMF solution of 1) was added dropwise at room temperature over 5 hours, and after further stirring at room temperature for 255 hours, water (3d) was added under water cooling to stop the reaction. Pour the reaction solution into water,
Extracted four times with diethyl ether. All the organic layers were combined and washed twice with saturated brine. After drying with magnesium sulfate, it was concentrated under reduced pressure to obtain a red-yellow oil 829iy. 15 d of methanol, 7 d of chloroform and 15 ml of concentrated sulfuric acid were added, and the mixture was heated under reflux at 75° C. for 3 hours. The reaction solution was poured into water and extracted four times with chloroform. All the organic layers were combined, washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 665η of pale yellow oil. Separation was performed by silica gel column chromatography (chloroform and ethyl acetate) to obtain 287q of yellow oil. This product eventually crystallized and was purified by recrystallization with cyclohexane-chloroform.
27-thitraoxer [111 coparacyclophane-6
,25--)on(ri 2 j 9 qwo was obtained. Yield 3
5%.

Colorless crystals; mp92-0 to 915°C (cyclohexane C!roform) 1HNMR (270MHz, COCl,) δ 2g
(81 (, S), hair 45 (8H, s), 547 (8H, t, J = 59H1), 2.53 (8H, t, J = 7.5Hz), t8
6 (8H, t t, J=7.3.59Hz)IR
(KBr) 1700.1415,1340,1120,1100°850-1 M5 (EI, 70eV) 497 (M+1) Example 9 a-bromo-σ'-[1-methylthio-1-(p-tolylsulfonyl) Synthesis of α, α′-dibromo p-xylene 565 mg (2,
14 mmal) and -sulfo7 (1) 458 mg
(2.05 mmol) was dissolved in DMF15tn/-
Sodium hydride (contains 60%) while stirring at 20°C.

94 mg (245 mmol) of oil diffusion) was added.

After stirring for i at −20 °C for 5 h and at room temperature for 2.5 h,
The reaction was stopped by adding 2 ml of a saturated ammonium chloride aqueous solution. Pour the reaction solution into 50 mA of water.

Extracted four times with ethyl acetate. All the organic layers were combined, washed twice with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 942 zg of yellow oil. Silica gel column chromatography (hexane: ethyl acetate =
4:1) to separate and purify σ-bromo a'-[1-
420 mg of methylthio-1-(p-)9lsulfonyl)methyl]p-xylene (6) was obtained as colorless crystals.

Yield: 52.

Colorless crystals (hexane-dichloromethane) mp 121
．． 0-12 5℃ 'HNMR (270MHz, CDCIg) δ: 7.8
7 (2H, d, J=a2Hz >7.59 (2H
,d, J=&2Hz )Z 32 (2H,d, J
=a2Hz)Z 14 (2H, d, J=a2H1
) 4.47 (2H, ll) 584 (jH, dd, J=115.5oHz) 5s
9 (*H9dd, J=14s, 50Hz)z63 (t
H, dd, J=145.115H1) zas<sH,
s) 2.13 (3H, g) IR (KBr) 1590, 1295. tt48. 1085. s17
,658°575cm-' C17Hte Os Ss Br Calculated value: c;
5i13. H; a, s.

Actual value: C; 51.21, H: 4.76 Example 10 [3n] Synthesis of paracyclophane (2) 1:B=
2 b:n=4 c:11=3 Sodium hydride (60% content, oil diffusion) 116m
g (2.90 mmol) in DMF suspension 10 h
a-bromo-al-[1-methylthio-1-(p-)
IJ lunulfonyl) methyl] p-xylene y (6) 3
88 mg ((L97 mmol) of DMF solution 10
nj was added dropwise over 3 hours at room temperature. After stirring at room temperature for 22 hours, 2 ml of a saturated ammonium chloride aqueous solution was added to stop the reaction. The reaction solution was poured into 30 ml of water, and extracted three times with ethyl acetate. Combine all organic layers and wash twice with saturated saline.

After drying with magnesium sulfate, it was concentrated under reduced pressure to obtain 217 mg of brown oil. Add this to chloroform f 5m
Dissolve in 1 rJml of methanol and 1 m of concentrated sulfur
1 was added thereto, and the mixture was heated under reflux for 5 hours.

The reaction solution was poured into 40ml of water and extracted five times with chloroform. After washing all the organic layers together with 200 ml of water and drying with magnesium sulfate.

It was concentrated under reduced pressure to obtain 150 mg of brown oil. By thin layer silica gel chromatography (chloroform), 611B g of a mixture containing a cyclic ketone body was obtained as a yellow oil. This material is recycled for preparative HPLC (column, J
AIGEL-1H; developing solvent, chloroform) to separate and purify [3”]]valacyclophane-2.11
-dione 5k) t tmg (yield a3%) and [3'
]] Paracyclophane - 2.1t, 2o trione (c)
20 mg (yield 1 to 6%) ★ and [5']]valacyclophane-211.20.29-tetraoy(b)11
mg (yield aol) were obtained as colorless crystals.

[53] Paracyclophane-2,11,20-)ion colorless crystals (chloroform) mp 214-216°C (dce-)” HNMR (2
7ΩMH2,eDcI3) δ[76(12H,s) 565(12H,1) IR(KBr) 1708.1700,1508,1410,1255°104B,810,555,535cm-'M8(EI
, 70ev) m/z 397 (MH", 71), 596 (M"
, 37).

368 (10), 340 (7), 312 (8), 221
(4), 2091), 20B(6), 207(8).

195 (8), 193 (10), 131 (34)
.

118(5), 105(15), 104(100).

1oS (1S), 78 (1o), 77 (6), 57 (5
).

15(5) Example 11 Synthesis of a-bromo-ff'-[1-methylthio-1-(p-tolylsulfonyl)methyl]m-xylene α al-dibromo-p-xylene 400 g (1!h1
mmol) and x lehyhy(1) 127 g (I
1 mmol) in DMF 40 m/[, -20'
Sodium hydride (containing 60%) while stirring at C.

7k6mg (17.9mmol) of oil diffusion) was added.

After stirring at -20°C for 4 hours and at -15°C for 1 hour, water
ml was added to stop the reaction. The reaction solution was poured into 50ml of water and extracted three times with diethyl ether. All organic layers were combined, washed twice with saturated saline, and dried over magnesium sulfate.

It was concentrated under reduced pressure to obtain 7,049 g of a yellow oil. The σ-promo σ′-[1
-methylthio-1-(p-)lylsulfonyl)methyl]
2-180 g of m-xylene (7) was obtained as colorless crystals. Yield: 36.

'HNMR (270MHz, "CDCIs) δ:
7.8 J3 (2H, d, J=&2Hz)7.
59 (2H, d, J = a2H1) 129-Zll
(4H, m) 446 (2H, II) A85 (IH, dd, J = 12.0.KOHz)
560 (IH, dd, J=14.o, 1oHz)2
．． 62 (IH, dd, J=140.12.0Hz
)248(3H,g) zls<sH,ts) IR(KBr) 2925.1590,1295,1138,1083°735.695.665,588,510cm-"Execution N12 [sn] Metacyclophane combination ff ( 2)\80!To/B==2 Sodium hydride (contains 60%, oil diffused) 80mg
(2,00 mmol) suspended in DMF! 10m1! to, σ
-bromoa'-[1-methylthio-1-(p-)IJ
DM of m-xylene(wa) 7 a O6rng (102 mmo 1 )
The mixture was added dropwise to 10 ml of F solution over 3 hours at room temperature. After stirring at room temperature for 18 hours, 2 ml of water was added to stop the reaction.The reaction solution was mixed with 5 ml of water.
Pour 0 ml of the mixture and extract with ethyl acetate three times. All the organic layers were combined, washed twice with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 385 Bg of brown oil.

This product was dissolved in 6 ml of chloroform, 6 ml of methanol and #16 sulfuric acid were added, and the mixture was heated under reflux for 5 hours. The reaction solution was poured into 30 mg of water and diluted with chloroform for 3 hours.
Extracted twice. All the organic layers were combined, washed with 150 ml of water, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 254 mg of brown oil. By silica gel column chromatography (chloroform), 92 mg of a mixture containing a cyclic ketone body was obtained as a yellow oil.

This material is recycled for preparative HPLC (column).

JAIGEL-1H (developing solvent, chloroform) yield: 15 Example 5.10 Cycloto-5-dioxer 7. a-o-benzenolidecanone base sodium hydride (ha eumetal-containing oil diffusion) 103m
g (2,57 mmol) of σ, σ'-bis(3-iodopropoxy) into 1 ml of DMI i'll suspension.
-〇-xylene 196 mg ((L41 mmol),
Sulfone fl) 96mg (C10-4mmol
) was added dropwise at room temperature over 3 hours. After stirring at room temperature for 14 hours, 2 ml of saturated ammonium chloride aqueous solution was added to stop the reaction. Pour the reaction solution into 20ml of water.
A! ' and extracted three times with 20 ml of 5-dimethyl ether (1 x 3). All the organic layers were combined, washed twice with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 144 mg of brown oil. 5 m of this stuff in chloroform
Dissolve 1TIC, 5mg in methanol and 4N-sulfur Ml [
15 ml was added thereto, and the mixture was heated under reflux for 2 hours. Add the reaction solution to 2 parts water.
The mixture was poured into a volume of 0 ml and extracted three times with chloroform. All the organic layers were combined, washed with 50 mg of water, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 128 mg of brown oil. Thin layer silica gel chromatography (ethyl benzene diacetate = 10 = 1) gave a mixture 64y (g) containing a cyclic ketone body as a yellow oil. ) and purified by 5°10
-dioxa-7,8-e = penzosic a trideca-7-
16 mg of en-1-one (also) was obtained as a colorless oil. Yield 16mm colorless oil” HNMR (270MHz, CDC15) J: 129 (
4H08) 448 (4H, a) &52 (4H, t, J=56Hz) 2.54-2.50 (4H@m) t96-t87 (4H, m) IR (KBr) 2920.2850.1704.1090 .742cm
-”Example 14 Synthesis of 5.11-dioxa-7,9-m-benzenocyclotetradodecanone Sodium hydride (60% content, oil diffusion) 1036
1 g (2-57 mmol) of DMFll! Turbid liquid 10I
to nl, σ, a'-bis(5-iodopropoxy)-m
-xylene t96 mg (a41 mmol) and sulfo y
(1) DMF solution of semg (cL41 mmol) 10
ml was added dropwise over 3 hours at room temperature. After stirring at room temperature for 17 hours, 2 ml of saturated ammonium chloride aqueous solution was added to stop the reaction. The reaction solution was poured into 20 ml of water and extracted 5 times with diethyl ether. All organic layers were combined, washed twice with saturated saline, and dried over magnesium sulfate.

Concentration under reduced pressure gave 259 B g of brown oil. This was dissolved in 5 ml of chloroform, 5 ml of methanol and 5 mj of 4N sulfuric acid were added, and the mixture was heated under reflux for 3 hours.
Pour the reaction solution into 20m7 of water.

Extracted with chloroform three times. All the organic layers were combined, washed with 0 ml of water, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 185 mg of brown oil. Thin layer silica gel chromatography (benzene: ethyl acetate =
10:1).

A mixture c1 (Isvng) containing a cyclic ketone body was obtained as a yellow oil. Recycle this material by preparative HPLC (
Column, JAIGEL-1H: developing solvent.

3.11-dioxabicyclo[1t,s,1]butadeca-(17),
50 mg of 1s, 15-trien-7-one (f) was obtained as colorless crystals. Yield 5Ω colorless crystals (chloroform-hexane) pH NMR (270MHz, CDCIg) δ: 7.4
5 (tH, diffused t)7.20 (
IH, dfffuged t ) 7.112 (2H,
dfffuged dd) 4.56 (4H, 8) 127 (4H, t, J=S6Hz)zvO(4H1
t, J=sbHz) IJ7 (4H, quint, J=S6H1) IR (KB
r) 286G, 1705, 1440, 1412, 1117゜1070.1032,775-zH''

Claims (1)

[Claims] (1) General formula (1) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) [In the formula, A is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^
1 represents a hydrogen atom, a lower alkyl group, an alkoxy group, or a halogen atom; R represents a lower alkyl group. ] and the general formula (2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) [In the formula, Ar represents a disubstituted aromatic group; G represents a methylene group or -CH_2OCH_2CH_2CH_2- group, and X represents a chlorine atom, bromine atom or iodine atom] is condensed under basic conditions, and then hydrolyzed.
General formula (3) ▲There are numerical formulas, chemical formulas, tables, etc.▼ (3) [In the formula, Ar and G have the same meanings as above, and n represents an integer from 1 to 4. ] A method for producing an aromatic cyclic ketone represented by: (2) General formula (4), which is an intermediate for the above manufacturing method ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) [In the formula, A is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R ^
2 represents a hydrogen atom, a lower alkyl group, an alkoxy group or a halogen atom); B represents a lower alkyl group; Ar represents a disubstituted aromatic group; G is a methylene group or -CH_2OCH_2CH_2C
represents a H_2- group; X represents a chlorine atom, a bromine atom or an iodine atom; ] A halogen compound represented by. (5) General formula (5), which is an intermediate for the above manufacturing method ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (5) [In the formula, A is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^
1 represents a hydrogen atom, a lower alkyl group, an alkoxy group or a halogen atom); R represents a lower alkyl group; A
r represents a di-substituted aromatic group; G is a methylene group or -CH_2OCH_2CH_2C
Represents H_2CH_2- group. ] A symmetrical sulfone compound represented by.