CN108383827A - A kind of preparation method of -4 ketone acetal compound of benzo 1,3- bioxin - Google Patents
A kind of preparation method of -4 ketone acetal compound of benzo 1,3- bioxin Download PDFInfo
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- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
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Abstract
The invention discloses a kind of preparation methods of 1,3 bioxin of benzo, 4 ketone acetal compound, including：With the salicylic acid after substitution on salicylic acid or phenyl ring, with 3 alkynyl, 2 butanone after substitution as reaction substrate, using secondary-amine compound as catalyst, in solvent environment, via the cascade reaction approach of the double Michael additions of catalysis, one kettle way obtains 1,3 bioxin of benzo, the 4 ketone acetal compound of racemization.The method substrate spectrum of the present invention is wide, and easy to operate and mild condition, product is easily isolated, and reaction is relatively rapid, in high yield, is not necessarily to metal catalytic, so as to avoid the metal residual in product, the advantages that process green is friendly.The reaction simultaneously, without particular/special requirement, is that can be obtained with buy cheap or facile syntheesis to used substrate and catalyst, so as to make the compound library of the molecule greatly be widened, realizes the efficient green synthesis of target compound.
Description
Technical field
The invention belongs to organic synthesis fields, specifically, it is related to a kind of benzo 1, -4 ketone acetal chemical combination of 3- bioxin
The preparation method of object.
Background technology
Benzo 1,3- bioxin skeletons are the important components of a few class pharmacological activity molecules, and compound is corresponded in AntiHIV1 RT activity with it
Activity in virus, and the inhibiting effect of up to tens of kinds kinases is concerned, while being also important natural of several classes
Product mother nucleus structure ((a), US Pat., US2003013660 (A1), 2003；(b) WO 2006/010642A1,2007；
(c)H.Lin,T.Annamalai,P.Bansod,Y.-C. Tse-Dinh and D.Sun,MedChemComm,2013,4,
1613–1618；(d)US pat., US2009/215728A1,2009；(e)US pat.,US6569897B1,2003；(f)
G.Xu,A. Kannan,T.L.Hartman,et al.Bioorg.Med.Chem.,2002,10(8): 2807-2816.).Cause
This, the method for synthesizing such molecule increasingly becomes one of the research direction that organic synthesis field is concerned.
The reaction for building such skeleton is generally salicylic acid and acetone and is obtained under strong acidic condition such as trifluoroacetic acid catalysis
Corresponding product, or by thionyl chloride (SOCl under 4-dimethylaminopyridine (DMAP) catalysis2) reacted with acetone again with bigcatkin willow
Acid combine finally needed product ((a) A.Hadfield, H.Schweitzer, M.P.Trova and K.Green,
Synth.Commun.,1994,24,1025–1028.；(b)T. Yoshino,I.Sato and M.Hirama,Org.Lett.,
2012,14,4290-4292.), such reaction needs to introduce strong acid to equipment and environment there are complicated for operation in reaction
It is unfavorable to protect, and also influences the further expansion of substrate.In addition to this, salicylic acid can also be catalyzed with dichloromethane in potassium phosphate
Under the conditions of obtain similar skeleton (F.Lin, Q.Song, Y.Gao and X.Cui, RSC Adv., 2014,4,19856.), but
It is that the mechanism of the reaction requires there must be the participation of dichloro- alkane, and is the corresponding carbon structure of in-situ preparation, substrate can only be
Salicylic acid end is done limited group and is expanded, and available substrate is relatively further narrow.
In addition, some other methods also has in the synthetic method for being introduced in this skeleton.The uses such as E.Puniani take
The phenyl salicylate in generation and end group aldehyde reaction, can also obtain such skeleton.But the reaction is to salicylic substitution site and base
There is strict demand in group etc., and is necessary for phenyl salicylate, and another substrate needed for the approach is necessary for end group aldehyde, obtains
Ethylidene ether structure carbon be only tertiary carbon structure, this undoubtedly limits the applicability of this method.
P.Perlmutter and E.Puniani,Tetrahedron Lett.,1996,37,3755–3756.
M.Gandelman etc. uses 1,3-, bis- iodo- 5-5,5- Dimethyl Hydan (DIH) to make adjacent methoxy under illumination condition
Voluntarily cyclization in-situ preparation obtains corresponding phenylpropyl alcohol 1 to yl benzoic acid, 3- bioxin -4- ketone rings, but the reaction be iodine actually from
The by-product photocatalytically swapped by the carboxyl of base and benzoic acid, yield only only have 21%.
K.Kulbitski,G.Nisnevich and M.Gandelman,Adv.Synth.Catal.,2011, 353,
1438–1442.
Such ring closure reaction of metal catalytic also has been reported that.L.Wei etc. uses copper acetate, 8-hydroxyquinoline as ligand,
The product of Gandelman etc. can be also obtained using o-iodobenzoic acid and dichloromethane cyclization, which requires to make using DMF molten
Agent, while potassium hydroxide is added, and 110 DEG C are warming up to, condition is harsh.In addition to this, S.Porcel groups are urged using silver acetate
Change, under the conditions of high temperature (120 DEG C), makes adjacent allyloxy benzoic acid itself cyclization, the reaction condition is harsh, and yield is very
It is low.Similarly, N.Sakai groups use adjacent propynyloxy yl benzoic acid as substrate, in double (bis- Ya Benzyl benzylacetones) palladium [Pd
(dba)2] with obtain this class formation under Phosphine ligands t-BuXPhos collective effects, but the reaction requires high temperature (110 DEG C), needs
More expensive palladium catalyst is used, and yield is equally relatively low.
((a)Y.Liu,M.Huang and L.Wei,New J.Chem.,2017,41,4776–4778.
(b)Y.Ogiwara,K.Sato and N.Sakai,Org.Lett.,2017,19,5296-5299.
(c)U.A.Carrillo-Arcos,J.Rojas-Ocampo and S.Porcel,Dalton Trans.,
2016,45,479–483.)
In conclusion benzo 1 is synthesized at present, and in the method for 3- bioxin -4- ketone compounds skeletons, common method
Such as trifluoroacetic acid/acetone, light reaction and metal catalytic cyclization synthesis strategy, due to the limitation (strong acid/strong of reaction condition
Alkali/metal catalytic/high temperature/anhydrous and oxygen-free condition etc.), there are many defects.
Invention content
It is an object of the invention to overcome the deficiencies of the prior art and provide a kind of high income, by-product is few, can realize temperature
Complete the preparation method of -4 ketone acetal compound synthesis of benzo 1,3- bioxin in next step with condition.
To achieve the goals above, the present invention adopts the following technical scheme that：
A kind of benzo 1, the preparation method of -4 ketone acetal compound of 3- bioxin, after replacing on salicylic acid or phenyl ring
Salicylic acid, with the 3- alkynyl -2- butanone after substitution as reaction substrate, using secondary-amine compound as catalyst, molten
In agent environment, via the cascade reaction approach of the double Michael additions of catalysis, one kettle way obtains the benzo 1 of racemization, 3- bioxin-
4 ketone acetal compounds, are shown below：
In above-mentioned benzo 1, -4 ketone acetal compound preparation method of 3- bioxin, the benzo 1,3- bioxin -4
The molecular formula of ketone acetal compound is：
Wherein：
Substituent R1For one or more substituted group of hydrogen on aromatic rings Ar, the group be selected from fluorine, chlorine, bromine,
Iodine, trifluoromethyl (- CF3), naphthenic base that alkyl that carbon atom number is 1-10, carbon atom number are 1-10, carbon atom number 1-10
Alkoxy, carboxyl, ester group-COOR, amide groups-CONH2Or-CONHR or-CONRR ', hydroxyl, nitro, carbon atom number 6-
20 aryl, and the above-mentioned group with one or more secondary substituent groups；The secondary substituent group is selected from carbon atom number
For the aryl of 6-20, carbon atom number be 1-10 alkyl, carbon atom number be 1-10 alkoxy, trifluoromethyl, nitro, hydroxyl
And halogen group；R and R ' be selected from carbon atom number be 6-20 aryl, carbon atom number be 1-10 alkyl；
Substituent R2The alkyl for being 1-10 for carbon atom number, carbon atom number be 6-20 aryl and one of them or
The above-mentioned group that multiple hydrogen are replaced by secondary substituent group；It is described secondary substituent group be selected from carbon atom number be 6-20 aryl, carbon
Alkoxy that alkyl that atomicity is 1-10, carbon atom number are 1-10, trifluoromethyl, nitro, amino, carbon atom number 1-10
Substituted amido, hydroxyl and halogen group；
Substituent R3For hydrogen, carbon atom number is the alkyl of 1-10, and carbon atom number is the alkoxy of 1-10, and carbon atom number is
The aryl of 6-20, carbon atom number be 6-20 aryloxy group and one or more hydrogen replaced by secondary substituent group it is upper
State group；The secondary substituent group is arbitrarily to be derived from the alkyl, carbon that aryl, carbon atom number that carbon atom number is 1-20 are 1-10
Substituted amido, hydroxyl and the halogen that alkoxy that atomicity is 1-10, trifluoromethyl, nitro, amino, carbon atom number are 1-10
Plain group.
In above-mentioned benzo 1, the preparation method of -4 ketone acetal compound of 3- bioxin, the salicylic acid and 3- alkynes
The molar ratio of base -2- butanone is 1:1, the dosage of secondary amine class catalyst is the 1~20% of the amount of salicylic substance.
In above-mentioned benzo 1, the preparation method of -4 ketone acetal compound of 3- bioxin, the secondary amine class catalyst
For nafoxidine, indoline, tetrahydroquinoline, 1,2- dihydroquinoline, morpholine, piperidines, piperazine, pyrazoles and pyrazolidine, oxazoles
The above-mentioned secondary amine that alkane or one or more hydrogen are substituted with a substituent；The substituent group includes hydroxyl, carboxyl, ester group-COOR,
Amide groups-CONH2Or the alkyl that-CONHR or-CONRR ', carbon atom number are 1-10, carbon atom number are the alkoxy of 1-10, carbon
Atomicity is the aryl of 6-20, and carbon atom number is that the aryloxy group of 6-20 and one or more hydrogen are replaced by secondary substituent group
Above-mentioned group；It is described secondary substituent group be the aryl of carbon atom number 6-20, the aryloxy group that carbon atom number is 6-20, carbon atom
Number is the alkyl and halogen group, carboxyl, hydroxyl, amino, trifluoromethyl, trimethyl silicon substrate, triethyl group silicon substrate, three fourths of 1-10
Base silicon substrate, trimethylsiloxy group, triethyl group siloxy, tributyl siloxy or azido；The R and R ' that this place is mentioned are choosing
From carbon atom number be 6-20 aryl, carbon atom number be 1-10 alkyl；
In above-mentioned benzo 1, the preparation method of -4 ketone acetal compound of 3- bioxin, the secondary amine class catalyst
Further include such as lower structure：
Wherein, R ", R " ' it is arbitrarily to be selected from the virtue that carbon atom number is 6-20 after methyl, ethyl and various ways replace
Base, the alkyl that carbon atom number is 1-10, R " groups can be with R " ' group is consistent, also can be inconsistent, digital n is within 1-4
Arbitrary integer.
In above-mentioned benzo 1, the preparation method of -4 ketone acetal compound of 3- bioxin, the solvent is dichloro
Methane, chloroform, methanol, ethyl acetate, monochloro methane, carbon tetrachloride, dichloroethanes, tetrahydrofuran, ether, acetonitrile, first
It is benzene, benzene, dimethylbenzene, ethylene glycol, polyethylene glycol, glycol dimethyl ether, glycol monoethyl ether, methyl tertiary butyl ether(MTBE), ethyl alcohol, different
The mixture of any one or more solution in propyl alcohol, the tert-butyl alcohol, dimethyl sulfoxide (DMSO) or mixed solution with water.Preferentially make
Solvent is any one in dichloromethane, chloroform, methanol, ethyl alcohol or ethyl acetate.
Compared with prior art, the present invention has the advantages that：The method substrate spectrum of the present invention is wide, operation letter
List and mild condition, product are easily isolated, and reaction is relatively rapid, in high yield, metal catalytic are not necessarily to, so as to avoid in product
Metal residual, the advantages that process green is friendly.Used substrate and catalyst are wanted in the reaction simultaneously without special
It asks, is that can be obtained with buy cheap or facile syntheesis, so as to make the compound library of the molecule greatly be widened,
Realize the efficient green synthesis of target compound.
Specific implementation mode
Specific example is given to the present invention below to be described further：
Embodiment 1：2- (2- carbonyls propyl) -2- phenyl -4- hydrogen-benzo [the d] [synthesis of 1,3] bioxin -4- ketone：
The structural formula of this is as follows：
Into salicylic acid (0.3mmol) and the dichloromethane solution (2mL) of 4- phenyl -3- crotonylenes -one (0.3mmol),
Nafoxidine (10mol%) is instilled under stirring condition, (25 DEG C) reactions of room temperature are overnight.Reaction solution be spin-dried for after by column layer
Analysis purifying obtains target product 2- (2- carbonyls propyl) -2- phenyl -4- hydrogen-benzo [d] [1,3] bioxin -4- ketone：
77.08mg yield：91%, yellow oily liquid.1H NMR(400 MHz,CDCl3)δ:7.81 (dd, J=7.8,1.6Hz,
1H), 7.52 (ddd, J=7.6,7.1,1.5Hz, 3H), 7.32 (ddd, J=9.7,5.5,2.4Hz, 3H), 7.12 (d, J=
8.3Hz, 1H),7.07–6.99(m,1H),3.38–3.20(m,2H),2.32(s,3H).13C NMR(101 MHz,CDCl3)δ:
202.39,160.47,155.93,138.59,136.70,129.84,129.48, 128.83,126.30,123.23,
117.40,114.61,105.60,55.32,31.85.HR-MS: C17H14O4,[M+Na]+, Calcd.:305.0787, Found:
305.0784
Embodiment 2：The bromo- 2- of 7- (2- carbonyls propyl) -2- phenyl -4- hydrogen-benzo [the d] [conjunction of 1,3] bioxin -4- ketone
At
To the methanol solution (2mL) of 4- bromination salicylic acids (0.3mmol) and 4- phenyl -3- crotonylenes -one (0.3mmol)
In, morpholine (20mol%) is instilled under stirring condition, (25 DEG C) reactions of room temperature are overnight.Reaction solution passes through column chromatography after being spin-dried for
Purifying obtains the bromo- 2- of target product 7- (2- carbonyls propyl) -2- phenyl -4- hydrogen-benzo [d] [1,3] bioxin -4- ketone：
80.19mg yield：74%, yellow oily liquid.1H NMR (400MHz,CDCl3)δ:7.68 (d, J=8.4Hz, 1H),
7.49 (dd, J=7.8,1.5Hz, 2H), 7.39-7.32 (m, 4H), 7.19 (dd, J=8.4,1.7Hz, 1H), 3.28 (d, J=
3.2Hz,2H),2.31(s,3H).13C NMR(101MHz,CDCl3)δ:201.91,159.81, 156.20,138.12,
131.13,130.94,129.72,128.99,126.90,126.24, 120.73,113.47,106.07,55.04,
31.84.HR-MS:C17H13O4Br,[M+Na]+, Calcd.:382.9889,Found:382.9884.
Embodiment 3：7- methyl -2- (2- carbonyls propyl) -2- phenyl -4- hydrogen-benzo [d] be [1,3] bioxin -4- ketone
Synthesis
To the tetrahydrofuran solution of 4- cresotinic acids (0.3mmol) and 4- phenyl -3- crotonylenes -one (0.3mmol)
In (2mL), piperidines (5mol%) is instilled under stirring condition, (25 DEG C) reactions of room temperature are overnight.Reaction solution passes through column after being spin-dried for
Chromatographic purifying obtains target product 7- methyl -2- (2- carbonyls propyl) -2- phenyl -4- hydrogen-benzo [d] [1,3] bioxin -4-
Ketone：66.62mg yield：75%, colourless oil liquid.1H NMR(400MHz,CDCl3)δ:7.73 (dd, J=8.2,
0.7Hz,1H),7.54–7.48 (m,2H),7.37–7.29(m,3H),6.62–6.52(m,2H),3.86(s,3H),3.25
(q, J=14.5Hz, 2H), 2.32 (s, 3H)13C NMR(101MHz,CDCl3)δ:202.62, 166.49,160.32,
157.83,138.82,131.44,129.42,128.82,126.11, 110.85,107.23,105.54,101.31,55.83,
55.39,31.87.HR-MS:C18H1604, [M+Na]+,Calcd.:319.0941,Found:319.0939
Embodiment 4：2- (2- carbonyls propyl) -2- phenyl -4- hydrogen-naphtho- [the d] [synthesis of 1,3] bioxin -4- ketone.
Chloroform to 3- hydroxy-2-naphthoic acids (0.3mmol) and 4- phenyl -3- crotonylenes -one (0.3mmol) is molten
In liquid (2mL), N- Methylethyls amine (20mol%) is instilled under stirring condition, (25 DEG C) reactions of room temperature are overnight.Reaction solution
It purifies by column chromatography to obtain target product 2- (2- carbonyls propyl) -2- phenyl -4- hydrogen-naphtho- [d] [1,3] bis- Evil after being spin-dried for
English -4- ketone：88.75mg yield：89%, yellow oily liquid.1H NMR(400MHz,CDCl3)δ8.46(s,1H),7.78
(dd, J=18.5,8.3Hz, 2H), 7.59-7.52 (m, 3H), 7.49 (s, 1H), 7.40 (dd, J=11.2,3.9Hz, 1H),
7.33–7.29(m,1H),7.29–7.22(m,2H),3.44–3.22(m,2H),2.36 (s,3H).13C NMR(101MHz,
CDCl3)δ:202.52,160.99,151.00,138.82, 137.61,132.61,129.80,129.68,129.46,
129.19,128.87,127.00, 126.53,125.67,114.64,113.34,105.68,55.51,31.89.HR-MS:
C21H1604, [M+Na]+,Calcd.:355.0941,Found:355.0935
Embodiment 5：[the synthesis of 1,3] bioxin -4- ketone of 2- (2- carbonyls propyl) -4- hydrogen-benzo [d]
To the ethyl acetate solution of salicylic acid (0.3mmol) and 4- trimethylsilyl -3- crotonylenes -one (0.3mmol)
In (2mL), nafoxidine formic acid (proline) (15mol%) is instilled under stirring condition, (25 DEG C) reactions of room temperature are overnight.
Reaction solution purifies to obtain target product 2- (2- carbonyls propyl) -4- hydrogen-benzo [d] [1,3] bis- Evil by column chromatography after being spin-dried for
English -4- ketone：45.78mg yield：75%, colourless oil liquid.1H NMR(400MHz,CDCl3)δ:8.00 (dd, J=7.8,
1.5Hz, 1H), 7.70-7.54 (m, 1H), 7.25-7.16 (m, 1H), 7.06 (d, J=8.3Hz, 1H), 6.09 (t, J=
5.2Hz, 1H), 3.23 (dd, J=6.9,5.2Hz, 2H), 2.32 (s, 3H)13C NMR(101 MHz,CDCl3)δ:202.30,
161.63,158.06,136.40,130.32,123.73,116.71, 114.38,97.92,47.16,31.13.HR-MS:
C11H1004,[M+Na]+,Calcd.:229.0471, Found:229.0454
Embodiment 6：2- (2- carbonyls propyl) -2- butyl -4- hydrogen-naphtho- [the d] [synthesis of 1,3] bioxin -4- ketone
Into salicylic acid (0.3mmol) and the acetonitrile solution (2mL) of 3- crotonylenes -one (0.3mmol), under stirring condition
Piperazine (20mol%) is instilled, (25 DEG C) reactions of room temperature are overnight.Reaction solution purifies to obtain target product 2- by column chromatography
(2- carbonyls propyl) -2- butyl -4- hydrogen-benzo [d] [1,3] bioxin -4- ketone：64.53mg yield：82%.Colorless oil
Liquid.1H NMR(400MHz,CDCl3)δ:8.00 (dd, J=7.8,1.6Hz, 1H), 7.61 (ddd, J=8.3,7.5,
1.7Hz, 1H), 7.17 (tt, J=8.6,4.3Hz, 1H), 7.02 (d, J=8.3Hz, 1H), 3.17-3.05 (m, 2H), 2.26
(s, 3H), 2.08 (ddd, J=14.3,7.8,5.0Hz, 2H), 1.38-1.23 (m, 4H), 0.90 (t, J=7.3Hz, 3H)13C
NMR(101MHz,CDCl3)δ:203.07,160.50–159.72, 155.40,136.80,129.76,123.08,117.31,
113.45,107.10,49.32, 36.40,31.86,25.23,22.38,13.85.HR-MS:C15H1804,[M+Na]+,
Calcd.: 285.1097,Found:285.1085
Other substrates and catalyst are expanded lists * with yield to impinging upon in following table：
* reaction condition：Substrate 1=0.3mmol, substrate 2=0.3mmol, solvent volume=2mL, under room temperature (25
DEG C) be stirred to react overnight.
The method for showing to provide through the invention by the embodiment of above-mentioned offer, can it is simple, green, be efficiently synthesized
Benzo 1,3- bioxin -4- ketone acetal compounds, this method have of low cost, easy to operate, mild condition, reaction fast
Speed, high yield, convenient separation, without metallic pollution the advantages that.
Claims (7)
1. a kind of benzo 1, the preparation method of -4 ketone acetal compound of 3- bioxin, it is characterised in that：With salicylic acid or phenyl ring
Salicylic acid after upper substitution, with the 3- alkynyl -2- butanone after substitution as reaction substrate, using secondary-amine compound as catalysis
Agent, in solvent environment, via the cascade reaction approach of the double Michael additions of catalysis, one kettle way obtains the benzo 1,3- of racemization
- 4 ketone acetal compound of bioxin.
2. benzo 1 as described in claim 1, the preparation method of -4 ketone acetal compound of 3- bioxin, which is characterized in that institute
The molecular formula for stating -4 ketone acetal compound of benzo 1,3- bioxin is：
Wherein：
Substituent R1For the substituted group of one or more hydrogen on aromatic rings Ar, the group is selected from fluorine, chlorine, bromine, iodine, trifluoro
Methyl, alkoxy that naphthenic base that alkyl that carbon atom number is 1-10, carbon atom number are 1-10, carbon atom number are 1-10, carboxyl,
Ester group-COOR, amide groups-CONH2Or the aryl that-CONHR or-CONRR ', hydroxyl, nitro, carbon atom number are 6-20, and tool
There are one or multiple secondary substituent groups above-mentioned group；It is described secondary substituent group be selected from carbon atom number be 6-20 aryl, carbon
Alkoxy, trifluoromethyl, nitro, hydroxyl and the halogen group that alkyl that atomicity is 1-10, carbon atom number are 1-10；R and
R ' be selected from carbon atom number be 6-20 aryl, carbon atom number be 1-10 alkyl；
Substituent R2The alkyl for being 1-10 for carbon atom number, carbon atom number are the aryl and one or more hydrogen of 6-20
The above-mentioned group replaced by secondary substituent group；It is described secondary substituent group be selected from carbon atom number be 6-20 aryl, carbon atom number
For the alkyl of 1-10, carbon atom number be 1-10 alkoxy, trifluoromethyl, nitro, amino, carbon atom number be 1-10 substitution amine
Base, hydroxyl and halogen group；
Substituent R3For hydrogen, carbon atom number is the alkyl of 1-10, and carbon atom number is the alkoxy of 1-10, and carbon atom number is 6-20's
Aryl, the aryloxy group that carbon atom number is 6-20 and the above-mentioned group that one or more hydrogen is replaced by secondary substituent group；
The secondary substituent group is arbitrarily to be derived from alkyl, carbon atom number that aryl, carbon atom number that carbon atom number is 1-20 are 1-10 to be
The alkoxy of 1-10, trifluoromethyl, nitro, amino, substituted amido, hydroxyl and the halogen group that carbon atom number is 1-10.
3. benzo 1 as described in claim 1, the preparation method of -4 ketone acetal compound of 3- bioxin, which is characterized in that institute
The molar ratio for stating salicylic acid and 3- alkynyl -2- butanone is 1:1, the dosage of secondary amine class catalyst is the amount of salicylic substance
1~20%.
4. benzo 1 as described in claim 1, the preparation method of -4 ketone acetal compound of 3- bioxin, which is characterized in that institute
State secondary amine class catalyst be nafoxidine, indoline, tetrahydroquinoline, 1,2- dihydroquinoline, morpholine, piperidines, piperazine, pyrazoles and
The above-mentioned secondary amine that pyrazolidine, oxazolidines or one or more hydrogen are substituted with a substituent；The substituent group includes hydroxyl, carboxyl,
Ester group-COOR, amide groups-CONH2Or the alkyl that-CONHR or-CONRR ', carbon atom number are 1-10, carbon atom number are 1-10's
Alkoxy, carbon atom number are the aryl of 6-20, and carbon atom number is that the aryloxy group of 6-20 and one or more hydrogen are taken by secondary
For the above-mentioned group of base substitution；It is described secondary substituent group be carbon atom number be 6-20 aryl, carbon atom number be 6-20 fragrant oxygen
Base, the alkyl and halogen group, carboxyl, hydroxyl, amino, trifluoromethyl, trimethyl silicon substrate, triethyl group silicon that carbon atom number is 1-10
Base, tributyl silicon substrate, trimethylsiloxy group, triethyl group siloxy, tributyl siloxy or azido；R that this place is mentioned and
R ' be selected from carbon atom number be 6-20 aryl, carbon atom number be 1-10 alkyl.
5. benzo 1 as described in claim 1, the preparation method of -4 ketone acetal compound of 3- bioxin, which is characterized in that institute
It further includes such as lower structure to state secondary amine class catalyst：
Wherein, R ", R " ' it is arbitrarily to be selected from the aryl, carbon that carbon atom number is 6-20 after methyl, ethyl and various ways replace
Atomicity is the alkyl of 1-10, and R " groups can be with R " ' group is consistent, also can be inconsistent, digital n is arbitrary whole within 1-4
Number.
6. benzo 1 as described in claim 1, the preparation method of -4 ketone acetal compound of 3- bioxin, which is characterized in that institute
The solvent stated is dichloromethane, chloroform, methanol, ethyl acetate, monochloro methane, carbon tetrachloride, dichloroethanes, tetrahydrochysene furan
It mutters, ether, acetonitrile, toluene, benzene, dimethylbenzene, ethylene glycol, polyethylene glycol, glycol dimethyl ether, glycol monoethyl ether, methyl- tert
The mixture of any one or more solution in butyl ether, ethyl alcohol, isopropanol, the tert-butyl alcohol, dimethyl sulfoxide (DMSO) is mixed with water
Close solution.
7. benzo 1 as claimed in claim 6, the preparation method of -4 ketone acetal compound of 3- bioxin, which is characterized in that institute
The solvent stated is preferably any one in dichloromethane, chloroform, methanol, ethyl alcohol or ethyl acetate.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2194080A1 (en) * | 1995-12-28 | 1997-06-29 | Kun-Tai Kim | Novel process for preparing 2,6-di(4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid oxime ester derivatives |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2194080A1 (en) * | 1995-12-28 | 1997-06-29 | Kun-Tai Kim | Novel process for preparing 2,6-di(4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid oxime ester derivatives |
Non-Patent Citations (3)
| Title |
|---|
| NIRANJAN PANDA ET AL.: "Synthesis of Isocoumarins via Silver(I)-Mediated Annulation of Enol Esters", 《J. ORG. CHEM.》 * |
| VIJAY K. TRIPATHI ET AL.: "Addition of Nitrogen-, Oxygen-, and Sulphur-containing Nucleophiles to Aryl Ethynyl Ketones", 《J.C.S. PERKIN I》 * |
| 上海第一医学院等合编: "《药物合成反应》", 30 June 1985, 化学工业出版社 * |
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