CN1153772C - Dioxaspirocyclic compound with unsaturated side chain and its preparing process - Google Patents

Abstract

The present invention relates to a dioxaspirocyclic compound with an unsaturated side chain and a synthesizing method for the compound. The compound is a spiro enol ether compound, and is synthesized through a four-step reaction of esterification, addition, reduction and cyclization by using the right formula disclosed in the specification as raw materials. The method successfully uses Lewis acid as a catalyst to specifically synthesize a furan diol compound, avoids using an anhydrous and oxygen-free condition of a lithium reagent, and has the advantage of mild, simple and specific reaction conditions. The method can be applied to the industrialized production.

Description

Dioxo spiro cyclic cpds and synthetic method thereof with unsaturated terminal chain

The present invention relates to Garland chrysanthemum extract compounds and synthetic method thereof, promptly have the dioxo spiro cyclic cpds of unsaturated terminal chain and take the Lewis acid as the synthetic Garland chrysanthemum extract compounds of catalyzer specificity-the have method of the oxa-spiro compound of unsaturated terminal chain.

Add up according to pertinent data, be used for the investment of chemistry of pesticide aspect every year above 4,000,000,000 dollars in the world wide, and expense wherein over half is used for sterilant, but the annual due to illness insect pest and running off in vain of farm crop that still has about 15%, the influence that causes thus is especially serious in developing country.And the growth of world population and grain contradiction in short supply will be more and more outstanding, how to prevent disease and pest, the output that increases farm crop is the technical problem of being badly in need of solution at present, and this only relies on scientific and technological advances, certainly be not only the progress of agricultural science and technology, also have the scientific-technical progress in fields such as chemistry.The protection of current farm crop mainly depends on the application of phosphoramidite chemical sterilant, although the unusual practicability and effectiveness of these compounds, but the shortcoming of its existence is apparent equally; At first because these compounds seldom have selectivity when desinsection, usually when killing off the insect pests, the natural enemy of these insects also is unable to escape misfortune, and insect is after developing immunity to drugs, the dosage that then needs to strengthen sterilant just can reach the harmful purpose of going out, and so the consequence of vicious cycle is the destruction of ecotope.Secondly synthetic pesticide generally is difficult to decompose, and also is difficult to by the crop absorption metabolism, and residual agricultural chemicals is trapped on the agricultural-food for a long time, and human body, livestock, environment have been caused very big harm.In order to address these problems, according to colourful disease and pest hedge-antifeedant for insect that each kind of plant of occurring in nature is showed to us, we study.

Crowndaisy chrysanthemum has another name called crowndaisy chrysanthemum, is composite family Chrysanthemum plant, is the common vegetables of spring and autumn in the south of the lower reaches of the Yangtze River, avoids insect infestations because of crowndaisy chrysanthemum has unique perfume.Z.H.Wu, J.Wang, J.C.Li, Y.Z.Chen, A.J.Yu, Z.R.Feng, J.Shen, Y.L.Wu, P.F.Guo, Y.L.Wang, Natural ProductR﹠amp; D discloses analysis crowndaisy chrysanthemum derived essential oil and isolated a kind of compound-crowndaisy chrysanthemum element: 1-Z and 1-E with obvious antifeedant activity, i.e. the spiro ketal enol ether compound that has a long-chain conjugation alkynes side chain of a structure uniqueness.Can be merely from crowndaisy chrysanthemum to isolate the plain activeconstituents of crowndaisy chrysanthemum be to be difficult to meet the demands, moreover in sepn process, its active ingredient mutability, we attempt by synthetic similar compound, further improve its activity, therefore Wu Yulin etc. provides Crowndaisy chrysantheins compound in ZL93112444.1 " Crowndaisy chrysantheins compound ", has following chemical formula A or B:

A furans formula crowndaisy chrysantheins like thing B volution formula crowndaisy chrysantheins like thing

The synthetic method system of this Garland chrysanthemum extract compounds adopts furfural cheap and easy to get to make raw material, press Org.Sny.Coll.III, method in 425 prepares furfuracrylic acid, again with Raney nickel reduce the furans propionic acid, get the furans propyl alcohol through lithium aluminium hydride reduction, continue and the butyllithium effect gets 5-position lithium compound, in same reaction flask, obtain again with the unsaturated aldehyde reaction.

Wu Yulin etc. provide another kind of new Garland chrysanthemum extract compounds again in ZL97106696.5 " a kind of garland chrysanthemum chlorins compound, preparation method and its usage ", promptly have the dioxo spiro cyclic cpds of unsaturated terminal chain:

And provide several synthetic methods that prepare this compounds:

(1), furans propyl alcohol or butanols and butyllithium and unsaturated aldehyde or reactive ketone get the furans diol compound,

(2), furans propyl alcohol or butanols with ethanoyl protect acetylate, obtain the furans acetylate of 2-formaldehyde again through the Vilsmier-Hack reaction, after the reaction of alkynyl negative ion, deacetylation gets the furans diol compound again

(3), with the diol compound of above-mentioned (1), (2) in solvent and room temperature to reflux temperature with protonic acid, silica gel, ion exchange resin or Louis acid catalysis dehydration cyclization takes place,

(4), with (3) product logical hydrogen under the Pd-C catalyst.

Can be owing to the synthetic of intermediate in this method-furans diol compound must obtain by lithium reagent reaction, cause cost too high and be difficult to suitability for industrialized production like this.In order to reduce cost, avoid using lithium reagent, we by exploring, successfully are that catalyzer specificity ground has synthesized the furans diol compound with the Lewis acid on the basis of this patent.

Purpose of the present invention just provides a kind of oxa-spiro compound with unsaturated terminal chain, and its general molecular formula is:

Wherein: R=C _mH _2m+1, m=1-6, F, Cl, Br, CH ₃COO, CH ₃O, C ₂H ₅O, NO ₂, phenyl, naphthyl; X=C, O; N=1-3.

Another object of the present invention just provide a kind of with the Lewis acid for the synthetic Garland chrysanthemum extract compounds one of catalyzer specificity has the method for the oxa-spiro compound of unsaturated terminal chain, it is achieved by the following scheme, promptly with Be raw material, after acetylize, under Louis acid catalysis, Fu-Ke reaction take place, obtain corresponding 5 furanones, obtain corresponding furans diol compound after the reduction then with corresponding chloride compounds.Again this furans diol compound is promptly obtained having the Garland chrysanthemum extract compounds of the oxa-volution of unsaturated terminal chain behind cyclization.Reaction formula is as follows:

Concrete reactions steps is:

1, esterification: the furans propyl alcohol is dissolved in the non-polar solvent, in this system, adds organic bases, fully stir the back and add acetic anhydride, react completely, get corresponding esterification products until the furans propyl alcohol;

2, substitution reaction: the product of esterification is dissolved in the non-polar solvent, and refluxes after adding corresponding acyl chlorides and Lewis acid,, get corresponding carbonyl product until reacting completely;

3, reduction reaction: the carbonyl product that will go up the step reaction is dissolved in the polar solvent, and behind the reductive agent of adding equivalent, stirring reaction can obtain diol compound;

4, cyclization: diol compound is dissolved in the non-polar solvent, the Lewis acid post-heating that adds equivalent is to 80-100 ℃, react completely, remove Lewis acid after the cooling, can be had the Garland chrysanthemum extract compounds of the oxa-volution of unsaturated terminal chain accordingly.

In the four-step reaction provided by the present invention, esterification and reduction reaction are conventional reaction, and key of the present invention is substitution reaction, cyclization; Substitution reaction is that catalyzer specificity ground has synthesized the furans diol compound with the Lewis acid; And in cyclization, successfully synthesized the Garland chrysanthemum extract compounds of oxa-volution with unsaturated terminal chain by lewis acidic catalysis.

Wherein: non-polar solvent is a methylene dichloride, 1,2-ethylene dichloride, benzene, toluene; Organic bases is triethylamine, pyridine, 4-dimethylaminopyridine DMAP; Lewis acid is ZnCl ₂, CuSO ₄.5H ₂O, AlCl ₃, FeCl ₃Reductive agent is NaBH ₄, KBH ₄Polar solvent is ethanol, methyl alcohol, DMF, acetonitrile, DMSO.

The present invention successfully is that catalyzer specificity ground has synthesized the furans diol compound with the Lewis acid compared with prior art, avoids using the anhydrous and oxygen-free condition of lithium reagent, has reaction conditions gentleness, easy and single-minded advantage, but and suitability for industrialized production.

Following examples help to understand the present invention, but are not limited to content of the present invention:

Embodiment 1

1.26g the furans propyl alcohol is dissolved in the CH of 50ml ₂Cl ₂In, in system, add 2.02gEt ₃N and 100mlDMAP after fully stirring, add 1.02gAc at normal temperatures ₂O, TLC point plate reacts completely until the furans propyl alcohol, and conventional processing gets product 1.58g.

This product is dissolved in 1 of 100ml, in the 2-ethylene dichloride, and the benzoyl chloride of adding 10mmol, fully stir the back and add anhydrous ZnCl ₂, reflux, until reacting completely the saturated NaHCO of reaction solution ₃Obtain corresponding carbonyl compound after the washing drying;

After this carbonyl compound of 10mmol is dissolved in the dehydrated alcohol of 50ml, add the NaBH of equivalent ₄, normal temperature stirred 10 hours down, added 10ml water again, continued to stir 2 hours, obtained diol compound after the conventional processing;

The above-mentioned diol compound of 10mmol is dissolved in the 50ml toluene, adds the CuSO of equivalent ₄.5H ₂O is heated to 85 ℃, and TLC point plate is followed the tracks of, and until reacting completely, cooled and filtered is removed CuSO ₄.5H ₂O, purifying behind the concentrated filtrate promptly gets final product, and yield is 95%.

IR(film)：3086，3022，2984，2981，1653，1594，1492，1449；

¹HNMR(300MHz，C ₆D ₆)：δ7.88(2H，m)，7.31(2H，m)，7.11(1H，m)，5.96(1H，d＝5.5Hz)，5.72(1H，dd，J＝0.7Hz，5.6Hz)，5.34(1H，s)，4.00(1H，m)，3.67(1H，m)，2.00-1.88(2H，m)，1.62-1.46(2H，m)ppm；

Ms(m/z)：215(M ⁺+1，29)，214(M ⁺，58)，184(25)，172(13)，158(17)，127(21)；

HRMS：C ₁₄H ₁₄O ₂

Calculated value: 214.0994

Measured value: 214.0955

Embodiment 2

Reactions steps is with embodiment 1, and different is reaction conditions and reaction reagent, and wherein non-polar solvent is 1 in the esterification, and 2-ethylene dichloride, organic bases are pyridine; Non-polar solvent is a benzene in the addition reaction, and corresponding acyl chlorides is for being AlCl to chlorobenzene acyl chlorides, Lewis acid ₃Reduction reaction Semi-polarity solvent is that methyl alcohol, reductive agent are KBH ₄Non-polar solvent is a toluene in the cyclization, and Lewis acid is ZnCl ₂, temperature of reaction is 80 ℃, reaction product is

mp：82.5-84℃

IR(KBr)：3080，2993，1645，1578，1451；

¹HNMR(300MHz，CDCl ₃)：δ7.53(2H，m)，7.24(2H，m)，6.33(1H，d，J＝5.5Hz)，6.06(1H，d，J＝5.5Hz)，5.35(1H，s)，4.25(1H，m)，4.02(1H，m)，2.36-2.06(2H，m)ppm；

Ms(m/z)：250(M ⁺+2，35)，249(M ⁺+1，22)，248(M ⁺，100)，220(48)，206(18)，178(12)，129(22)，115(28)；

Ultimate analysis: C ₁₄H ₁₃ClO ₂:

Calculated value: C:67.61 H:5.27 Cl:14.25;

Measured value: C:67.49 H:5.25 Cl:14.31;

Embodiment 3

Reactions steps is with embodiment 1, and different is reaction conditions and reaction reagent, and wherein non-polar solvent is a benzene in the esterification, and organic bases is DMAP; Non-polar solvent is a toluene in the addition reaction, and corresponding acyl chlorides is that naphthoyl chlorine, Lewis acid are FeCl ₃Reduction reaction Semi-polarity solvent is that DMF, reductive agent are KBH ₄Non-polar solvent is a toluene in the cyclization, and Lewis acid is AlCl ₃, temperature of reaction is 95 ℃, reaction product is

mp：135-137℃

IR(KBr)：3087，2975，2964，1633，1458，1432；

¹HNMR(300MHz，C ₆D ₆)：δ8.20-7.23(7H，m)，6.02(1H，d，J＝5.5Hz)，5.50(1H，s)，4.07(1H，m)，3.71(1H，m)，2.04-1.50(4H，m)ppm；

Ms(m/z)：264(M ⁺，100)，236(37.9)，179(25.7)，165(32.2)，139(15.4)；

Ultimate analysis: C ₁₈H ₁₆O ₂:

Calculated value: C:81.80 H:6.10;

Measured value: C:81.49 H:6.18

Embodiment 4

Reactions steps is with embodiment 1, and different is reaction conditions and reaction reagent, and wherein non-polar solvent is a toluene in the esterification, and organic bases is a triethylamine; Non-polar solvent is a benzene in the addition reaction, and corresponding acyl chlorides is that m-nitro acyl chlorides, Lewis acid are AlCl ₃Reduction reaction Semi-polarity solvent is that methyl alcohol, reductive agent are NaBH ₄Non-polar solvent is a toluene in the cyclization, and Lewis acid is CuSO ₄.5H ₂O, temperature of reaction is 90 ℃, reaction product is

mp：160-162℃；

IR(KBr)：3092，2906，1650，1527，1099，938；

¹HNMR(300MHz，C ₆D ₆)：δ8.58(1H，s)，8.06-7.52(3H，m)，6.54(1H，d，J＝5.5Hz)，6.33(1H，d，J＝5.5Hz)，5.64(1H，s)，4.20(1H，m)，3.99(1H，m)，2.36-2.13(4H，m)ppm；

Ms(m/z)：259(M ⁺，100)，243(12)，231(45)，217(5)，187(5)，

171(4)，153(5)，115(32)；

Ultimate analysis: C ₁₄H ₁₃NO ₄:

Calculated value: C:64.86 H:5.05 N:5.40;

Measured value: C:64.75 H:4.96 N:5.23;

Embodiment 5

Reactions steps is with embodiment 1, and different is reaction conditions and reaction reagent, and wherein non-polar solvent is a toluene in the esterification, and organic bases is a triethylamine; Non-polar solvent is a benzene in the addition reaction, and corresponding acyl chlorides is 3,4, and 5-trimethoxy benzoyl chloride, Lewis acid are CuSO ₄.5H ₂O; Reduction reaction Semi-polarity solvent is that acetonitrile, reductive agent are NaBH ₄Non-polar solvent is a toluene in the cyclization, and Lewis acid is AlCl ₃, temperature of reaction is 100 ℃, reaction product is

mp：73-74℃；

IR(KBr)：3080，2895，2837，1654，1606，1583，1463，1364cm ^-1；

¹HNMR(300MHz，C ₆D ₆)：δ7.20(1H，s)，7.14(1H，s)，6.04(1H，d，J＝5.5Hz)，5.75(1H，d，J＝5.5Hz)，5.31(1H，s)，4.02(1H，m)，3.94(3H，m)，3.71(1H，m)，3.58(6H，s)，1.95-1.51(4H，m)ppm；

Ms(m/z)：304(M ⁺，100)，276(20.3)，261(40.6)，259(10.4)，220(10.2)；

Ultimate analysis: C ₁₇H ₂₀O ₅:

Calculated value: C:67.09 H:6.62;

Measured value: C:66.84 H:6.89;

Embodiment 6

Reactions steps is with embodiment 1, and different is reaction conditions and reaction reagent, and wherein non-polar solvent is a methylene dichloride in the esterification, and organic bases is a pyridine; Non-polar solvent is a methylene dichloride in the addition reaction, and corresponding acyl chlorides is for being 2nCl to ethoxycarbonyl benzoyl chloride, Lewis acid ₂Reduction reaction Semi-polarity solvent is that DMSO, reductive agent are NaBH ₄Non-polar solvent is a toluene in the cyclization, and Lewis acid is CuSO ₄.5H ₂O, temperature of reaction is 96 ℃, reaction product is

mp：93-95℃

IR(KBr)：3043，2905，1705，1650，1255，1062，748，639cm ^-1；

¹HNMR(300MHz，C ₆D ₆)：δ8.36(2H，d，J＝8.49Hz)，7.90(2H，d，J＝8.67Hz)，6.01(1H，d，J＝5.2Hz)，5.83(1H，d，J＝5.2Hz)，5.34(1H，s)，4.05(1H，m)，3.75(1H，m)，3.63(1H，s)，2.03-1.53(4H，m)ppm；

Ms(m/z)：273(28.1)，272(100)，244(42.3)，241(19.0)，242(17.2)，199(18.1)，129(18.0)，115(23.6)；

HRMS：C ₁₆H ₁₆O ₄：

Calculated value: 272.4033;

Measured value: 272.3445;

Embodiment 7

Reactions steps is with embodiment 1, and different is reaction conditions and reaction reagent, and wherein non-polar solvent is a toluene in the esterification, and organic bases is DMAP; Non-polar solvent is a toluene in the addition reaction, and corresponding acyl chlorides is that O-methoxy benzoyl chloride, Lewis acid are AlCl ₃Reduction reaction Semi-polarity solvent is that ethanol, reductive agent are NaBH ₄Non-polar solvent is a toluene in the cyclization, and Lewis acid is CuSO ₄.5H ₂O, temperature of reaction is 90 ℃, reaction product is

mp：57-59℃

IR(KBr)：3080，2897，2840，1650，1583，1512，1463，1364cm ^-1；

¹HNMR(300MHz，C ₆D ₆)：δ8.70(1H，m)，7.09(2H，m)，6.63(1H，m)，6.29(1H，s)，6.04(1H，d，J＝5.5Hz)，5.68(1H，d，J＝5.43Hz)，4.01(1H，m)，3.67(1H，m)，3.36(3H，s)，1.99-1.28(4H，m)ppm；

Ms(m/z)：244(100)，245(22.7)，216(16.11)，159(10.4)，131(10.8)，115(7.9)，108(10.9)，97(9.2)；

HRMS：C ₁₅H ₁₆O ₃：

Calculated value: 244.1100;

Measured value: 244.1098;

Ultimate analysis: C ₁₅H ₁₆O ₃:

Calculated value: C:73.75 H:6.60;

Measured value: C:73.70 H:6.82;

Embodiment 8

Reactions steps and reaction conditions are with embodiment 2, and different is reaction reagent, and wherein corresponding acyl chlorides is for being 80 ℃ to fluorobenzene acyl chlorides, temperature of reaction, and reaction product is

Molecular formula: C ₁₄H ₁₃FO ₂

F.W.：232.09；

¹⁹FNMR(90MHz，C ₆D ₆)δ：34.0ppm；

¹HNMR(300MHz，C ₆D ₆)δ：7.66(m，1H)，6.96(m，1H)，5.94(d，J＝5.5Hz，1H)，5.72(d，J＝5.5Hz，1H)，5.21(s，1H)，3.98(m，1H)，3.66(m，1H)，1.95~1.48(m，4H)ppm；

MS(m/z，abundance)：232(M ⁺，100)，204(31.4)，201(17.8)，190(19.4)，176(8.9)，162(11.3)，148(11.6)，133(15.3)；

IRv _max(cm ^-1)：2988，1657，1506，1221，1084，938，849，755，543；

HRMS C ₁₄H ₁₃FO ₂：

Calculated value: 232.0900,

Measured value: 232.0928.

Embodiment 9

Reactions steps and reaction conditions are with embodiment 3, and different is reaction reagent, and wherein corresponding acyl chlorides is that m-nitro acyl chlorides, temperature of reaction are 88-90 ℃, and reaction product is

Molecular formula: C ₁₄H ₁₃NO ₄

F.W.：259.26；

m.p.：70-72℃；

¹HNMR(300MHz，C ₆D ₆)δ：8.58(s，1H)，8.06~7.52(m，3H)，6.54(d，J＝5.5Hz，1H)，6.33(d，J＝5.5Hz，1H)，5.64(s，1H)，4.20(m，1H)，3.99(m，1H)，2.36~2.13(m，4H)ppm；

MS(m/z，abundance)：259(M ⁺，100.00)，242(92.7)，231(38.1)，217(47.3)，89(29.4)，63(31.7)，55(27.0)；

IRv _max(cm ^-1)：3092，2980，1650，1527，1367，1099，938；

Ultimate analysis C ₁₄H ₁₃NO ₄:

Calculated value: C, 64.86; H, 5.05; N, 5.40;

Measured value: C, 64.75; H, 4.96; N, 5.23.

Embodiment 10

Reactions steps and reaction conditions are with embodiment 2, and different is reaction reagent, wherein corresponding acyl chlorides be between methylbenzene acyl chlorides, temperature of reaction be 94-96 ℃, reaction product is

Molecular formula: C ₁₅H ₁₆O ₂

F.W.：228.30：

¹HNMR(300MHz，C ₆D ₆)δ：7.87(d，J＝7.7Hz，1H)，7.46(s，1H)，7.30(td，J ₁＝2.4Hz，J ₂＝7.6Hz，1H)，6.95(d，J＝7.4Hz，1H)，5.98(dd，J ₁＝2.6Hz，J ₂＝5.6Hz，1H)，5.89(dd，J ₁＝2.1Hz，J ₂＝5.4Hz，1H)，5.37(s，1H)，4.02(m，1H)，3.66(m，1H)，2.13(s，3H)，1.99~1.49(m，4H)ppm；

MS(m/z，abundance)：228(M ⁺，100.00)，229(25.95)，200(24.49)，129(16.78)，197(12.02)，198(11.18)，115(9.05)，185(7.48)；

IRv _max(cm ^-1)：2978，1647，1355，1182，1130，1094，951，823，698；

HRMS?C ₁₃H ₁₆O ₂：

Calculated value: 228.3034;

Measured value: 228.3054.

Embodiment 11

Reactions steps and reaction conditions are with embodiment 4, and different is reaction reagent, and wherein corresponding acyl chlorides is that meta-methoxy benzoyl chloride, temperature of reaction are 98-100 ℃, and reaction product is

Molecular formula: C ₁₅H ₁₆O ₃

F.W.：244.30；

m.p.：57-59℃；

¹HNMR(300MHz，CDCl ₃)δ：7.60(s，1H)，7.43(d，J＝7.8Hz，1H)，7.19(m，1H)，6.85(m，1H)，5.94(d，J＝5.7Hz，1H)，5.50(d，J＝5.3Hz，1H)，5.31(s，1H)，3.97(m，1H)，3.64(m，1H)，3.44(s，3H)，1.98-1.45(m，4H)ppm；

MS(m/z，abundance)：244(M ⁺，100.0)，216(23.8)，131(25.5)，115(23.6)，108(31.8)，97(23.5)，91(23.0)，77(22.5)；

IRv _max(cm ^-1)：2995，2558，1654，1573，1479，1293，1158，1050，944，884，692；

Ultimate analysis C ₁₅H ₁₆O ₃:

Calculated value: C, 73.75; H, 6.60;

Measured value: C, 73.51; H, 6.65.

Embodiment 12

Reactions steps and reaction conditions are with embodiment 5, and different is reaction reagent, wherein corresponding acyl chlorides be between bromobenzene acyl chlorides, temperature of reaction be 82 ℃, reaction product is

Molecular formula: C ₁₄H ₁₃O ₂Br;

F.W.：293.15；

m.p.：41-43℃；

¹HNMR(300MHz，C ₆D ₆)δ：8.06(t，J＝1.7Hz，1H)，7.55(d，J＝7.8Hz，1H)，7.14(m，1H)，6.86(t，J＝7.8Hz，1H)，5.82(d，J＝5.6Hz，1H)，5.66(d，J＝5.5Hz，1H)，5.05(s，1H)，3.92(m，1H)，3.59(m，1H)，1.90-1.43(m，4H)ppm；

MS(m/z，abundance)：294(M ⁺+1，93.39)，293(M ⁺，52.31)，292(100.0)，264(40.12)，115(65.3)，89(41.3)，41(29.9)；

IRv _max(cm ^-1)：2984，2893，1653，1590，1361，1178，1090，945，817，687；

Ultimate analysis C ₁₄H ₁₃O ₂Br:

Calculated value: C, 57.36; H, 4.47;

Measured value: C, 57.05; H, 4.72.

Embodiment 13

Reactions steps and reaction conditions are with embodiment 6, and different is reaction reagent, and wherein corresponding acyl chlorides is that m-trifluoromethyl benzoyl chloride, temperature of reaction are 86-90 ℃, and reaction product is

Molecular formula: C ₁₅H ₁₃F ₃O ₂

F.W.：282.27；

¹⁹FNMR(90MHz，C ₆D ₆)δ：-15.3ppm；

¹HNMR(300MHz，C ₆D ₆)δ：8.15(s，1H)，7.68(d，J＝7.9Hz，1H)，7.22~

6.99(m，2H)，5.85(d，J＝5.6Hz，1H)，5.68(d，J＝5.3Hz，1H)，5.08(s，1H)，3.93(m，1H)，3.58(m，1H)，1.94~1.42(m，4H)ppm；

MS(m/z，abundance)：282(M ⁺，100.00)，173(67.35)，145(43.82)，54(42.62)，254(42.44)，42(38.80)，95(30.45)；

IRv _max(cm ^-1)：2983，1734，1449，1332，1129，1077；

HRMS.C ₁₄H ₁₃F ₃O ₂：

Calculated value: 282.2743;

Measured value: 282.2739.

Embodiment 14

Reactions steps and reaction conditions are with embodiment 7, and different is reaction reagent, and wherein corresponding acyl chlorides is 3, and 5-difluoro benzoyl chloride, temperature of reaction are 92-95 ℃, and reaction product is

Molecular formula: C ₁₄H ₁₂O ₂F ₂

F.W.：250.24；

¹⁹FNMR(90MHz，C ₆D ₆)δ：32.0ppm；

¹HNMR(300MHz，C ₆D ₆)δ：7.30(m，2H)，6.44(m，1H)，5.75(d，J＝5.3Hz，1H)，5.66(d，J＝5.5Hz，1H)，4.96(s，1H)，3.83(m，1H)，3.52(m，1H)，1.79～1.36(m，4H)ppm；

MS(m/z，abundance)：250(M ⁺，100.00)，151(42.74)，152(36.33)，222(30.49)，219(16.73)，125(15.76)，220(15.31)；

IRv _max(cm ^-1)：2980，1661，1462，997，950，786；

HRMS.C ₁₄H ₁₂F ₂O ₂：

Calculated value: 250.2460;

Measured value: 250.2438.

Embodiment 15

Reactions steps and reaction conditions are with embodiment 1, and different is reaction reagent, and wherein corresponding acyl chlorides is that anthracene acyl chlorides, temperature of reaction are 90 ℃, and reaction product is

Molecular formula: C ₂₂H ₁₈O ₂

F.W.：314.38；

m.p.：125-128℃；

¹HNMR(300MHz，C ₆D ₆)δ：8.38(d，J＝8.8Hz，2H)，8.13(s，1H)，7.81(d，J＝8.4Hz，2H)，7.33(m，4H)，6.19(d，J＝5.6Hz，1H)，6.02(s，1H)，5.79(d，J＝5.4Hz，1H)，3.61(m，1H)，3.49(m，1H)，1.74~1.18(m，4H)ppm；

MS(m/z，abundance)：314(M ⁺，100.00)，231(69.14)，215(56.06)，43(42.52)，202(40.23)，57(34.08)，229(32.26)；

IRv _max(cm ^-1)：3042，2888，1652，1438，1364，1177，1104，1011，948，733；

Ultimate analysis C ₂₂H ₁₈O ₂:

Calculated value: C, 84.05; H, 5.77;

Measured value: C, 83.72; H, 5.71.

Embodiment 16

Reactions steps and reaction conditions are with embodiment 5, and different is reaction reagent, and wherein corresponding acyl chlorides is

Temperature of reaction is 95 ℃, and reaction product is

Molecular formula: C ₂₃H ₂₁O ₄SN;

F.W.：407.50；

m.p.：151-152℃；

¹HNMR(300MHz，C ₆D ₆)δ：8.56(s，1H)，8.29(d，J＝8.2Hz，1H)，7.70(d，J＝8.2Hz，2H)，7.43(d，J＝7.7Hz，1H)，7.20(m，1H)，7.07(m，1H)，6.39(d，J＝8.2Hz，2H)，5.95(d，J＝5.6Hz，1H)，5.71(d，J＝5.6Hz，1H)，5.44(s，1H)，4.04(m，1H)，3.66(m，1H)，2.05(m，1H)，1.89(m，1H)，1.56(m，5H)

ppm；

MS(m/z，abundance)：407(M ⁺，97.02)，252(100.00)，408(33.58)，91(31.26)，224(24.91)，253(23.99)，222(20.70)；

IRv _max(cm ^{- 1})：2888，1655，1595，1448，1369，1174，1094，975，811，749，670，580；

Ultimate analysis C ₂₃H ₂₁O ₄SN:

Calculated value: C, 67.79; H, 5.20; N, 3.44;

Measured value: C, 67.98; H, 5.13; N, 3.32.

Embodiment 17

Reactions steps and reaction conditions are with embodiment 1, and different is reaction reagent, and wherein corresponding acyl chlorides is

Temperature of reaction is 98 ℃, and reaction product is

Molecular formula: C ₁₅H ₁₄O ₅:

F.W.：274.28；

m.p.：140-143℃；

¹HNMR(300MHz，C ₆D ₆)δ：7.76(d，J＝1.5Hz，1H)，7.19(d，J＝1.5Hz，1H)，6.74(m，1H)，5.89(d，J＝5.7Hz，1H)，5.5(d，J＝5.9Hz，1H)，5.31(m，2H)，5.25(s，1H)，4.17(m，1H)，3.61(d，J＝5.2Hz，1H)，3.38～3.16(m，4H)

ppm；

MS(m/z，abundance)：274(M ⁺，100.0)，275(27.5)，229(5.7)，217(5.9)，216(8.4)，139(7.6)，103(4.3)，102(4.8)；

IRv _max(cm ^-1)：2974，2097，1650，1482，1257，1037，942，907，829，

528；

Ultimate analysis C ₁₅H ₁₄O ₅:

Calculated value: C, 65.69; H, 5.14;

Measured value: C, 65.55; H, 5.06.

Embodiment 18

Molecular formula: C ₁₄H ₁₃NO ₅

F.W.：275；

m.p.：92-93℃；

¹HNMR(300MHz，C ₆D ₆)δ：8.59(t，J＝1.9Hz，1H)，7.83(m，1H)，7.70(m，1H)，6.81(m，1H)，5.80(d，J＝5.7Hz，1H)，5.54(d，J＝6.1Hz，1H)，5.01(s，1H)，4.22(m，1H)，3.54(d，J＝11.8Hz，1H)，3.31(m，4H)ppm；

MS(m/z，abundance)：275(M ⁺，100)，276(41.5)，217(24.6)，171(12.7)，139(24.4)，115(59.7)，89(14.9)，73(24.3)；

IRv _max(cm ^-1)：3096，2973，1655，1525，1348，1240，911，808，832，736，676，578；

Ultimate analysis C ₁₄H ₁₃NO ₅:

Calculated value: C, 61.09; H, 4.73; N, 5.09;

Measured value: C, 61.08; H, 4.74; N, 5.07.

Embodiment 19

Reactions steps and reaction conditions are with embodiment 1, and different is reaction reagent, and wherein reactant is a furans butyl ether alcohol, and corresponding acyl chlorides is for being 80 ℃ to chlorobenzene acyl chlorides, temperature of reaction, and reaction product is

Molecular formula: C ₁₄H ₁₃ClO ₃

F.W.：264.70；

m.p.：118-120℃；

¹HNMR(300MHz，C ₆D ₆)δ：7.62(dd，J ₁＝2.0Hz，J ₂＝9.2Hz，2H)，7.19(dd，J ₁＝2.0Hz，J ₂＝9.2Hz，2H)，5.83(d，J＝5.7Hz，1H)，5.51(d，J＝5.7Hz，1H)，5.14(s，1H)，4.16(td，J ₁＝3.4Hz，J ₂＝11.1Hz，1H)，3.58(d，J＝11.8Hz，1H)，3.34-3.17(m，4H)ppm；

MS(m/z，abundance)：264(M ⁺，100.00)，266(34.96)，207(28.25)，206(75.89)，205(31.04)，139(49.34)，115(77.74)，89(38.99)；

IRv _max(cm ^-1)：2980，2876，1643，1358，1207，909，854，567；

Ultimate analysis C ₁₄H ₁₃ClO ₃:

Calculated value: C, 63.52; H, 4.95;

Measured value: C, 63.51; H, 4.86.

Embodiment 20

Reactions steps and reaction conditions are with embodiment 22, and different is reaction reagent, wherein corresponding acyl chlorides be between methylbenzene acyl chlorides, temperature of reaction be 85 ℃, reaction product is

Molecular formula: C ₁₅H ₁₆O ₃

F.W.：248.81；

¹HNMR(300MHz，C ₆D ₆)δ：7.93(d，J＝7.9Hz，1H)，7.61(s，1H)，7.25(t，J＝7.6Hz，1H)，6.92(d，J＝7.1Hz，1H)，5.93(d，J＝5.8Hz，1H)，5.54(d，J＝5.2Hz，1H)，5.36(s，1H)，4.24(m，1H)，3.65(d，J＝11.8Hz，1H)，3.31(m，4H)，2.21(s，3H)ppm；

MS(m/z，abundance)：244(M ⁺，100)，243(37.7)，186(57.6)，158(37.3)，139(39.2)，129(41.7)，115(48.6)，43(37.4)；

IRv _max(cm ^-1)：2971，2855，1652，1602，1353，1207，1092，910，827，696，579；

Ultimate analysis C ₁₅H ₁₆O ₃0.25H ₂O:

Calculated value: C, 72.41; H, 6.68;

Measured value: C, 72.57; H, 6.91.

Embodiment 21

Reactions steps and reaction conditions are with embodiment 22, and different is reaction reagent, and wherein corresponding acyl chlorides is that benzoyl chloride, temperature of reaction are 95 ℃, and reaction product is

Molecular formula: C ₁₄H ₁₄O ₃

F.W.：230.26；

m.p.：75-76℃；

¹HNMR(300MHz，C ₆D ₆)δ：7.92(d，J＝7.3Hz，2H)，7.27(t，J＝7.7Hz，2H)，7.07(m，1H)，5.89(d，J＝5.6Hz，1H)，5.52(d，J＝6.0Hz，1H)，5.32(s，1H)，4.22(td，J＝3.7Hz，J ₂＝10.7Hz，1H)，3.63(d，J＝11.7Hz，1H)，3.33-3.18(m，4H)ppm；

MS(m/z，abundance)：230(M ⁺，100.00)，231(26.14)，172(21.71)，144(11.29)，139(12.42)，117(9.99)，116(11.12)，115(17.08)；

IRv _max(cm ^-1)：2980，1647，1491，1360，1242，1092，906，786，696；

Ultimate analysis C ₁₄H ₁₄O ₃:

Calculated value: C, 73.26; H, 6.13;

Measured value: C, 73.03; H, 6.09.

Claims (6)

1, a kind of dioxo spiro cyclic cpds with unsaturated terminal chain is characterized in that its general molecular formula is:

Wherein: R=C _mH _2m+1, m=1-6, F, Cl, Br, CH ₃COO, CH ₃O, C ₂H ₅O, NO ₂, X=O, n=1; Perhaps R=methylene-dioxy X=O, n=1; Perhaps

X=C, n=0.

2, a kind of synthetic method with dioxo spiro cyclic cpds of unsaturated terminal chain, it is characterized in that with furans alcohol be raw material, obtain having the Garland chrysanthemum extract compounds of the oxa-volution of unsaturated terminal chain through esterification, replacement, reduction, cyclisation four-step reaction, its reaction formula is as follows:

Wherein: R=C _mH _2m+1, m=1-6, F, Cl, Br, CH ₃COO, CH ₃O, C ₂H ₅O, NO ₂, X=O; N=1; Perhaps R=methylene-dioxy

X=O, n=1; Perhaps

X=C, n=0.

3, synthetic method as claimed in claim 2 with dioxo spiro cyclic cpds of unsaturated terminal chain, it is characterized in that in the esterification furans alcohol being dissolved in the non-polar solvent, in this system, add organic bases, fully stir the back and add acetic anhydride, react completely, get corresponding esterification products until furans alcohol, wherein non-polar solvent is a methylene dichloride, 1, the 2-ethylene dichloride, benzene, toluene; Organic bases is triethylamine, pyridine, 4-dimethylaminopyridine.

4, synthetic method as claimed in claim 2 with dioxo spiro cyclic cpds of unsaturated terminal chain, it is characterized in that in the substitution reaction product of esterification is dissolved in the non-polar solvent, and reflux after adding corresponding acyl chlorides and Lewis acid, until reacting completely, get corresponding carbonyl product; Wherein non-polar solvent is a methylene dichloride, 1,2-ethylene dichloride, benzene, toluene; Lewis acid is ZnCl ₂, CuSO ₄.5H ₂O, AlCl ₃, FeCl ₃

5, synthetic method as claimed in claim 2 with dioxo spiro cyclic cpds of unsaturated terminal chain, it is characterized in that in the reduction reaction carbonyl product of substitution reaction is dissolved in the polar solvent, after adding the reductive agent of equivalent, stirring reaction can obtain diol compound; Wherein polar solvent is ethanol, methyl alcohol, DMF, acetonitrile, DMSO; Reductive agent is NaBH ₄, KBH ₄

6, synthetic method as claimed in claim 2 with dioxo spiro cyclic cpds of unsaturated terminal chain, it is characterized in that in the cyclization diol compound of reduction reaction is dissolved in the non-polar solvent, the Lewis acid post-heating that adds equivalent can be had the Garland chrysanthemum extract compounds of the oxa-volution of unsaturated terminal chain accordingly to 80-100 ℃; Wherein non-polar solvent is a methylene dichloride, 1,2-ethylene dichloride, benzene, toluene; Lewis acid is ZnCl ₂, CuSO ₄.5H ₂O, AlCl ₃, FeCl ₃