CN106946756B - A kind of high efficiency preparation method of sulfoxide sulfinyl urea series compound - Google Patents
A kind of high efficiency preparation method of sulfoxide sulfinyl urea series compound Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
Abstract
The invention discloses a kind of high efficiency preparation methods of sulfoxide sulfinyl urea series compound; this method is using sulfoxide sulfenimide and aralkyl acid azide as reaction substrate; it is set to carry out heating reaction under the conditions of without existing for any metallic element; reaction temperature is 70-100 DEG C; reaction time is 2 to 5 hours, efficiently obtained sulfoxide sulfinyl urea series compound.By means of the present invention, it can efficiently be made and contain sulfinyl carbamide compounds.This method chemo-selective is high, and substrate applicability is wide, easy to operate, the reaction time is short, and yield is high, unique by-product is nitrogen, is conducive to separating-purifying, product purity is high, is applicable to fairly large preparation.
Description
Technical field
The present invention relates to the nitrogen containing derivatives containing sulfoxide and urea structure skeleton, and in particular to a kind of sulfoxide sulfinyl urea system
The high efficiency preparation method of column compound.
Background technique
Sulfoxide sulfenimide is a kind of simultaneously containing sulphur oxygen and sulphur nitrogen double bond but the stable compound of chemical property, with sulfone
Class compound is compared, and the polarity of sulfenimide is bigger, can effectively improve the dissolubility of substance, and then constructs more complicated multiplicity
Useful molecule.Compound containing sulfenimide structure often has obviously biology or pharmaceutical activity.Such as base
In a kind of CDK inhibitor of the drug BAY1000394 of sulfenimide, it is used for the clinical treatment of advanced solid tumor cancer patient.
The drug AZD6738 of AstraZeneca (AstraZeneca) company exploitation is exactly having of constructing in sulfenimide structure basis
ATR kinase inhibitor (K.M.Foote, J.W.M.Nissink, P.Turner, the Morpholinopyrimidines and of effect
their use in therapy.AstraZeneca Patent WO 2011/154737A1,2011.).It is most recently successfully discovery
Methionine sulfoxide sulfenamide (MSO) be widely used in the heat such as the direct function dough reaction of organic asymmetric syntheses, C-H
Door research field.
Compound containing urea core skeleton structure is widely present in all kinds of natural products or has important biomolecule or medicine
In the active organic molecule of object, in addition, pesticide and materials science field also have a large amount of organic molecule to contain urea skeleton structure
((a)A.P.Kozikowski,J.Zhang,F.J.Nan,P.A.Petukhov,E.Grajkowska,J.T.Wroblewski,
T.Yamamoto,T.Bzdega,B.Wroblewska,J.H.Neale,J.Med.Chem.2004,47,1729.(b)
E.A.Terefenko,J.Kern,A.Fensome,J.Wrobel,Y.Zhu,J.Cohen,R.Winneker,Z.M.Zhang,
P.W.Zhang,Bioorg.Med.Chem.Lett.2005,15,3600.(c)Q.Li,T.M.Li,K.W.Woods,W.Z.Gu,
J.Cohen,V.S.Stoll,T.Galicia,C.Hutchins,D.Frost,S.H.Rosenberg,H.L.Sham,
Bioorg.Med.Chem.Lett.2005,15,2918.(d)I.Gallou,Org.Prep.Proced.Int.2007,39,
355.(e)A.Y.Guan,C.L.Liu,X.P.Yang,M.Dekeyser,Chem.Rev.2014,114,7079.(f)
S.J.Choi,J.L.Lee,Y.H.Lee,D.Y.Hwang,H.D.Kim,J.Appl.Polym.Sci.2011,121,3516.(g)
E.I.Pereira,F.B.Minussi,A.C.Bernardi,C.Ribeiro,J.Agric.Food Chem.2012,60,
5267).The discovery of Santella seminar, the molecule BMS-817399 containing such skeleton is a kind of CCR1 receptor of high-affinity
Antagonist has good curative effect to treatment inflammation especially rheumatic arthritis.
The method for thering is lot of documents to report compound of the synthesis containing urea structure at present, such as: the phosgenation of arylamine is formed
Isocyanate intermediate, then reacted with another molecular amine and can construct urea structure；The coupling of aryl halide and metal cyanides is anti-
Can should efficiently construct urea structure (I.Tkatchenko, R.Jaouhari, M.Bonnet, G.Dawkins, S.Lecolier,
France Patent FR2575467,1986；U.S.Patent 4,749,806,1988.)；And the aryl of catalyzing by metal palladium
Halides synthesize with carbon monoxide and the triflated cross-coupling reaction for closing object and replace carbamide compound etc.
(E.V.Vinogradova,B.P.Fors,S.L.Buchwald,J.Am.Chem.Soc.2012,134,11132.).It is above this
A little methods provide many alternative approach for synthesis urea derivative.
However, by literature survey it was found that the above method is not particularly suited for the synthesis urea of sulfinyl containing sulfoxide series
Compound.Its reason may be sulfoxide sulfenamide due to containing S=O and S=N double bond, these unsaturated bonds in structure simultaneously
It is unstable, strong acid-base or it is transition metal-catalyzed under conditions of be easy to happen conversion.The synthesis sulfoxide sulfenyl urea being currently known
Method only have an example, i.e. Johnson et al. is in report in 1972 using sulfenimide and isocyanates as originating instead
Object is answered, addition reaction occurs under drastic conditions and obtains sulfoxide sulfenyl urea (Johnson, C.R. for the two；Haake,M.；
Schroeck,C.W.J.Am.Chem.Soc.1970,92,6594-6598.).The shortcoming of this reaction is that condition is more severe
It carves, in addition, isocyanate chemical property also less stable, hypertoxic character, and is easy hydrolytic spoilage, need pre-synthesis and severe
It is stored under conditions of quarter.
Based on the characteristic in terms of potent biology or pharmaceutical activity natural possessed by urea skeleton, having in conjunction with sulfinyl
Rich and varied reactivity in chemical machine, it is believed that developing new synthetic method synthesis sulfoxide sulfenyl carbamide compounds has
Realistic meaning in terms of highly important theoretical research value and industrial production.In addition, such compound, which also helps, synthesizes it
The natural products or drug molecule of the more complicated structure of sulfenamide containing sulfoxide of his structure, thus living for subsequent lead drug
Property molecule high flux screening provide convenience.Based on this, the present invention is directed to a kind of without the highly selective of metal catalytic by development
Coupling reaction uses acyl azide more stable and cheap and easy to get in structure to replace traditional isocyanates as original
Material, reacts under the reaction condition of heating, and acid azide can occur removing nitrogen in situ in a solvent and obtain high reaction work
Property nitrogen Cabbeen intermediate, then occur Ku Ertisi (Curtius) rearrangement reaction, resulting intermediate again with sulfoxide sulfenyl
Amine reacts, and synthesizes to high efficiency, high chemo-selective the urea series compound of sulfenyl containing sulfoxide.The method of the present invention need not appoint
What metallic element is as catalyst or reaction promoter, to all kinds of groups such as halogen (fluorine, chlorine, bromine, iodine), unsaturated alkenyl base
Group, the sensitive groups such as cyano, ester group, nitro have good compatibility, these groups itself have good reactivity, because
Further conversion can occur by other organic chemical reactions for this products therefrom, thus in 1- sulfinyl -3- phenyl
More functional groups are introduced on urea skeleton.Reaction only needs acetonitrile that can react as solvent, and unique by-product is nitrogen, right
It is high in most of convenient functionality's reaction yield, up to 100% quantitative yield, separation and purification operation is greatly facilitated,
Thus there are very superior industrial production potentiality.
Summary of the invention
It is an object of that present invention to provide a kind of high efficiency preparation method of sulfoxide sulfinyl urea series compound, the present invention
Method chemo-selective it is high, substrate applicability is wide, reaction condition is simple, easy to operate, catalyst economics, at low cost, secondary
Product is few, product purity is high, convenient for separating-purifying, be applicable to fairly large preparation.
The invention is realized in this way in organic solvent, using sulfenimide and benzoyl nitrine as reaction
Substrate reacts 2 to 5 hours under conditions of 70-100 DEG C, can efficiently obtain product sulfoxide sulfinyl urea series compound.
Reaction formula is as follows:
Wherein R1、R2、R3For the groups such as H or various alkyl, alkoxy, naphthenic base, alkenyl, alkynyl, silicon substrate or various contain
The aryl of the various electron-withdrawing groups such as fluorine, chlorine, bromine, iodine, ester group, nitro, cyano, amide groups is powered containing alkyl, alkoxy etc.
Aryl or heterocyclic group such as furyl, thienyl, pyridyl group of son etc..
Wherein the organic solvent is acetonitrile.
The beneficial effects of the present invention are: reacting without other any metallic elements as catalyst or promotor, reaction
It is carried out under the conditions of completely existing for no metal；The molal quantity ratio of reactant sulfenimide and benzoyl nitrine is 1:
1.05 can carry out very wellly, and thus reaction embodies the high efficiency of reactant；The yield of reaction is high, and unique by-product
Object is nitrogen, is advantageous to separating-purifying, and thus also embodying reaction has Atom economy and environment friendly；Due to producing
Object has good compatibility for halogen (fluorine, chlorine, bromine, iodine), unsaturated alkenyl group, the sensitive groups such as cyano, ester group, nitro
Property, these groups itself have good reactivity, therefore products therefrom can be occurred by other organic chemical reactions
Further conversion constructs the compound of some other novel structure of sulfonylurea containing sulfoxide therefore in biological medicine, pesticide
There is extraordinary application prospect with fields such as material science.
Detailed description of the invention
Fig. 1 is the general structure of products therefrom sulfoxide sulfinyl urea series compound according to the method for the present invention.
Specific embodiment
Embodiment one:
4- methoxybenzoyl base nitrine (63.7mg, 0.36mmol) is dissolved in organic solvent acetonitrile under air atmosphere
In (1mL), the acetonitrile (1mL) of diphenyl sulfenimide (65.1mg, 0.3mmol) is added drop-wise in magnetic stirring apparatus at 80 DEG C
In solution, the reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through fast
Fast column chromatography for separation obtains pure product 1- sulfinyl -3- phenylurea compounds 3a.Yield: 96%.It is product 3a below
Nuclear magnetic resonance experiment data:
1H NMR (400MHz, d6-DMSO) δ 9.50 (s, 1H), 8.03 (d, J=6.8Hz, 4H), 7.63 (d, J=
7.7Hz, 6H), 7.42 (d, J=8.6Hz, 2H), 6.81 (d, J=8.2Hz, 2H), 3.68 (s, 3H)
13C NMR(100MHz,d6-DMSO)δ157.3,154.8,140.6,133.8,130.2,127.9,120.4,
120.0,114.2,55.6.
Embodiment two:
4- methyl benzoyl nitrine (58mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere,
In acetonitrile (1mL) solution that 80 DEG C are added drop-wise to diphenyl sulfenimide (65.1mg, 0.3mmol) in magnetic stirring apparatus,
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash column
Analyse the product 1- sulfinyl -3- phenylurea compounds 3b for separating pure.Yield: 91%.Be below product 3b nuclear-magnetism it is total
Vibration experimental data:
1H NMR (400MHz, d6-DMSO) δ 9.55 (s, 1H), 8.03 (d, J=7.1Hz, 4H), 7.71-7.59 (m,
6H), 7.39 (d, J=8.3Hz, 2H), 7.02 (d, J=8.1Hz, 2H), 2.21 (s, 3H)
13C NMR(100MHz,d6-DMSO)δ157.3,140.5,138.2,133.8,131.1,130.2,129.4,
128.0,118.6,20.8.
Embodiment three:
Benzoyl nitrine (882mg, 6mmol) is dissolved in organic solvent acetonitrile (10mL) under air atmosphere, at 80 DEG C
It is added drop-wise in magnetic stirring apparatus in acetonitrile (10mL) solution of diphenyl sulfenimide (1.085g, 5mmol), in air atmosphere
The reaction was continued 3 hours under enclosing, and is monitored with TLC plate to complete reaction in reaction process.Post-processing is separated by rapid column chromatography
Pure product 1- sulfinyl -3- phenylurea compounds 3c, yield: 87%.It is the nuclear magnetic resonance experiment number of product 3c below
According to:
1H NMR (400MHz, d6-DMSO) δ 9.65 (s, 1H), 8.04 (d, J=7.2Hz, 4H), 7.69-7.62 (m,
6H), 7.52 (d, J=8.0Hz, 2H), 7.22 (t, J=7.7Hz, 2H), 6.93 (t, J=7.2Hz, 1H)
13C NMR(100MHz,d6-DMSO)δ157.4,140.7,140.5,133.9,130.2,129.0,128.0,
122.3,118.6.
Example IV:
4- fluoro benzoyl nitrine (59.4mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere,
In acetonitrile (1mL) solution that 80 DEG C are added drop-wise to diphenyl sulfenimide (65.1mg, 0.3mmol) in magnetic stirring apparatus,
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash column
Analyse the product 1- sulfinyl -3- phenylurea compounds 3d for separating pure.Yield: 86%.Be below product 3d nuclear-magnetism it is total
Vibration experimental data:
1H NMR (400MHz, d6-DMSO) δ 9.74 (s, 1H), 8.04 (d, J=7.0Hz, 4H), 7.70-7.61 (m,
6H), 7.54-7.50 (m, 2H), 7.06 (t, J=8.8Hz, 2H)
13C NMR(100MHz,d6-DMSO)δ157.4,140.4,137.1,133.9,130.2,127.9,120.1,
115.6,115.4.
Embodiment five:
4- chlorobenzene formacyl nitrine (65.2mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere,
In acetonitrile (1mL) solution that 80 DEG C are added drop-wise to diphenyl sulfenimide (65.1mg, 0.3mmol) in magnetic stirring apparatus,
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash column
Analyse the product 1- sulfinyl -3- phenylurea compounds 3e for separating pure.Yield: 78%.Be below product 3e nuclear-magnetism it is total
Vibration experimental data:
1H NMR (400MHz, d6-DMSO) δ 9.81 (s, 1H), 8.04 (d, J=7.2Hz, 4H), 7.70-7.62 (m,
6H), 7.54 (d, J=8.8Hz, 2H), 7.27 (d, J=8.8Hz, 2H)
13C NMR(100MHz,d6-DMSO)δ157.4,140.3,139.7,133.9,130.3,128.9,127.9,
125.9,120.1.
Embodiment six:
4- iodobenzoyl nitrine (98.3mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere,
In acetonitrile (1mL) solution that 80 DEG C are added drop-wise to diphenyl sulfenimide (65.1mg, 0.3mmol) in magnetic stirring apparatus,
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash column
Analyse the product 1- sulfinyl -3- phenylurea compounds 3f for separating pure.Yield: 83%.Be below product 3f nuclear-magnetism it is total
Vibration experimental data:
1H NMR (400MHz, d6-DMSO) δ 9.80 (s, 1H), 8.03 (d, J=7.2Hz, 4H), 7.70-7.62 (m,
6H), 7.55 (d, J=8.6Hz, 2H), 7.36 (d, J=8.7Hz, 2H)
13C NMR(100MHz,d6-DMSO)δ157.4,140.6,140.3,137.6,133.9,130.3,127.9,
120.9,85.3.
Embodiment seven:
2- naphthoyl nitrine (71mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere, at 80 DEG C
It is added drop-wise in magnetic stirring apparatus in acetonitrile (1mL) solution of diphenyl sulfenimide (65.1mg, 0.3mmol), in air
The reaction was continued under atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing is separated by rapid column chromatography
Obtain pure product 1- sulfinyl -3- phenylurea compounds 3g.Yield: 96%.It is the nuclear magnetic resonance experiment of product 3g below
Data:
1H NMR (400MHz, d6-DMSO) δ 9.90 (s, 1H), 8.18 (s, 1H), 8.08 (d, J=7.1Hz, 4H), 7.79
(d, J=8.4Hz, 2H), 7.72-7.58 (m, 8H), 7.41 (t, J=7.2Hz, 1H), 7.33 (t, J=7.2Hz, 1H)
13C NMR(100MHz,d6-DMSO)δ157.7,140.4,138.4,134.1,133.9,130.3,129.6,
128.6,128.0,127.8,127.5,126.7,124.4,120.1,114.0.
Embodiment eight:
4- nitro acid azide (69.1mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere,
80 DEG C are added drop-wise in acetonitrile (1mL) solution of diphenyl sulfenimide (65.1mg, 0.3mmol) in magnetic stirring apparatus, in
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through rapid column chromatography
The product 1- sulfinyl -3- phenylurea compounds 3h for separating pure.Yield: 67%；It is the nuclear magnetic resonance of product 3h below
Experimental data:
1H NMR (400MHz, d6-DMSO) δ 10.36 (s, 1H), 8.14 (d, J=9.2Hz, 2H), 8.06 (d, J=
7.2Hz,4H),7.76-7.64(m,8H).
13C NMR(100MHz,d6-DMSO)δ157.5,147.3,141.6,139.9,134.1,130.3,127.9,
125.4,118.0.
Embodiment nine:
3- chlorobenzene formacyl nitrine (65.2mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere,
In acetonitrile (1mL) solution that 80 DEG C are added drop-wise to diphenyl sulfenimide (65.1mg, 0.3mmol) in magnetic stirring apparatus,
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash chromatography
The product 1- sulfinyl -3- phenylurea compounds 3i for separating pure.Yield: 87%；It is the nuclear magnetic resonance of product 3i below
Experimental data:
1H NMR (400MHz, d6-DMSO) δ 9.90 (s, 1H), 8.04 (d, J=7.0Hz, 4H), 7.71-7.63 (m,
7H), 7.39 (d, J=8.2Hz, 1H), 7.25 (t, J=8.1Hz, 1H), 6.99-6.97 (m, 1H)
13C NMR(100MHz,d6-DMSO)δ157.5,142.3,140.2,134.0,133.5,130.7,130.3,
127.9,122.0,117.9,117.0.
Embodiment ten:
4- methoxybenzoyl base nitrine (63.7mg, 0.36mmol) is dissolved in organic solvent acetonitrile under air atmosphere
In (1mL), 4,4- dichlorophenyl sulfenimide (85.8mg, 0.3mmol) is added drop-wise in magnetic stirring apparatus at 80 DEG C
In acetonitrile (1mL) solution, the reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Afterwards
Handle the product 1- sulfinyl -3- phenylurea compounds 3j for separating pure by flash chromatography.Yield: 68%；It is below
The nuclear magnetic resonance experiment data of product 3j:
1H NMR (400MHz, d6-DMSO) δ 9.59 (s, 1H), 8.03 (s, 4H), 7.72 (d, J=5.3Hz, 4H), 7.41
(d, J=6.8Hz, 2H), 6.80 (s, 2H), 3.69 (s, 3H)
13C NMR(100MHz,d6-DMSO)δ156.9,155.0,139.2,139.0,133.6,130.4,130.0,
120.1,114.2,55.6.
Embodiment 11:
4- methoxybenzoyl base nitrine (63.7mg, 0.36mmol) is dissolved in organic solvent acetonitrile under air atmosphere
In (1mL), 4,4- dimethyl diphenyl sulfenimide (73.5mg, 0.3mmol) is added drop-wise in magnetic stirring apparatus at 80 DEG C
Acetonitrile (1mL) solution in, the reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.
Post-process the product 1- sulfinyl -3- phenylurea compounds 3k for separating pure by flash chromatography.Yield: 95%；Below
It is the nuclear magnetic resonance experiment data of product 3k:
1H NMR (400MHz, d6-DMSO) δ 9.43 (s, 1H), 7.87 (d, J=7.9Hz, 4H), 7.41 (d, J=
8.5Hz, 6H), 6.80 (d, J=8.4Hz, 2H), 3.68 (s, 3H), 2.35 (s, 6H)
13C NMR(100MHz,d6-DMSO)δ157.4,154.8,144.2,137.9,134.0,130.6,127.8,
120.0,114.2,55.6,21.4.
Embodiment 12:
Benzoyl nitrine (1.764g, 12mmol) is dissolved in organic solvent acetonitrile (20mL) under air atmosphere, 80
It DEG C is added drop-wise in magnetic stirring apparatus in acetonitrile (20mL) solution of ethenylphenyl sulfenimide (1.67g, 10mmol), in
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash chromatography point
From product 1- sulfinyl -3- phenylurea compounds 3l that must be pure.Yield: 80%；It is the nuclear magnetic resonance reality of product 3l below
Test data:
1H NMR(400MHz,d6-DMSO)δ9.56(s,1H),8.01-7.98(m,2H),7.79-7.70(m,3H),
7.54 (d, J=7.7Hz, 2H), 7.29-7.22 (m, 3H), 6.95 (t, J=7.3Hz, 1H), 6.44-6.33 (m, 2H)
13C NMR(100MHz,d6-DMSO)δ157.5,140.8,138.9,138.2,134.0,130.1,129.5,
128.9,128.0,122.3,118.6.
Embodiment 13:
4- methoxybenzoyl base nitrine (63.7mg, 0.36mmol) is dissolved in organic solvent acetonitrile under air atmosphere
In (1mL), the acetonitrile of ethenylphenyl sulfenimide (50.1mg, 0.3mmol) is added drop-wise in magnetic stirring apparatus at 80 DEG C
In (1mL) solution, the reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing
The product 1- sulfinyl -3- phenylurea compounds 3m for separating pure by flash chromatography.Yield: 99%；It is product below
The nuclear magnetic resonance experiment data of 3m:
1H NMR (400MHz, d6-DMSO) δ 9.41 (s, 1H), 8.00 (d, J=7.3Hz, 2H), 7.80-7.71 (m,
3H), 7.44 (d, J=8.9Hz, 2H), 7.29-7.22 (m, 1H), 6.85 (d, J=9.0Hz, 2H), 6.43-6.32 (m, 2H),
3.73(s,3H).
13C NMR(100MHz,d6-DMSO)δ157.4,154.8,139.0,138.3,133.9,130.1,129.3,
128.0,120.0,114.1,55.6.
Embodiment 14:
2- naphthoyl nitrine (71mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere, at 80 DEG C
It is added drop-wise in magnetic stirring apparatus in acetonitrile (1mL) solution of ethenylphenyl sulfenimide (50.1mg, 0.3mmol), in
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash chromatography point
From product 1- sulfinyl -3- phenylurea compounds 3n that must be pure.Yield: 87%；It is the nuclear magnetic resonance reality of product 3n below
Test data:
1H NMR (400MHz, d6-DMSO) δ 9.73 (s, 1H), 8.17 (s, 1H), 8.00 (d, J=7.3Hz, 2H),
7.79-7.68 (m, 6H), 7.58-7.55 (m, 1H), 7.41 (t, J=7.5Hz, 1H), 7.35-7.23 (m, 2H), 6.44-6.32
(m,2H).
13C NMR(100MHz,d6-DMSO)δ157.7,138.9,138.5,138.1,134.1,134.0,130.2,
129.6,128.5,128.0,127.8,127.5,126.7,124.4,120.2,114.0.
Embodiment 15:
Benzoyl nitrine (1.764g, 12mmol) is dissolved in organic solvent acetonitrile (20mL) under air atmosphere, 80
It DEG C is added drop-wise in magnetic stirring apparatus in acetonitrile (20mL) solution of aminomethyl phenyl sulfenimide (1.55g, 10mmol), in sky
The reaction was continued 3 hours under atmosphere is enclosed, and is monitored with TLC plate to complete reaction in reaction process.Post-processing is separated by flash chromatography
Obtain pure product 1- sulfinyl -3- phenylurea compounds 3o.Yield: 93%；It is the nuclear magnetic resonance experiment of product 3o below
Data:
1H NMR (400MHz, d6-DMSO) δ 9.37 (s, 1H), 8.02 (d, J=7.3Hz, 2H), 7.77-7.67 (m,
3H), 7.50 (d, J=7.7Hz, 2H), 7.20 (t, J=7.9Hz, 2H), 6.91 (t, J=7.3Hz, 1H), 3.50 (s, 3H)
13C NMR(100MHz,d6-DMSO)δ158.0,140.9,134.0,133.9,129.9,128.9,127.6,
122.1,118.7,43.9.
Embodiment 16:
4- methoxybenzoyl base nitrine (63.7mg, 0.36mmol) is dissolved in organic solvent acetonitrile under air atmosphere
In (1mL), the acetonitrile of aminomethyl phenyl sulfenimide (46.5mg, 0.3mmol) is added drop-wise in magnetic stirring apparatus at 80 DEG C
In (1mL) solution, the reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing
The product 1- sulfinyl -3- phenylurea compounds 3p for separating pure by flash chromatography.Yield: 99%；It is product below
The nuclear magnetic resonance experiment data of 3p:
1H NMR(400MHz,d6-DMSO)δ9.24(s,1H),8.05-8.03(m,2H),7.80-7.70(m,3H),
7.44 (d, J=9.0Hz, 2H), 6.83 (d, J=9.0Hz, 2H), 3.72 (s, 3H), 3.51 (s, 3H)
13C NMR(100MHz,d6-DMSO)δ157.9,154.7,140.1,134.1,133.8,129.9,127.6,
120.1,114.1,55.6,43.9.
Embodiment 17:
2- naphthoyl nitrine (71mg, 0.36mmol) is dissolved in organic solvent acetonitrile (1mL) under air atmosphere, at 80 DEG C
It is added drop-wise in magnetic stirring apparatus in acetonitrile (1mL) solution of ethenylphenyl sulfenimide (46.5mg, 0.3mmol), in
The reaction was continued under air atmosphere 3 hours, is monitored with TLC plate to complete reaction in reaction process.Post-processing passes through flash chromatography point
From product 1- sulfinyl -3- phenylurea compounds 3q that must be pure.Yield: 96%；It is the nuclear magnetic resonance reality of product 3q below
Test data:
1H NMR (400MHz, d6-DMSO) δ 9.63 (s, 1H), 8.17 (s, 1H), 8.05 (d, J=7.4Hz, 2H),
7.78-7.69 (m, 6H), 7.58-7.55 (m, 1H), 7.41 (t, J=7.5Hz, 1H), 7.32 (t, J=7.4Hz, 1H), 3.53
(s,3H).
13C NMR(100MHz,d6-DMSO)δ158.2,139.9,138.6,134.1,133.9,129.9,129.5,
128.4,127.8,127.7,127.4,126.6,124.2,120.2,113.9,43.9.
Claims (3)
1. a kind of preparation method of sulfoxide sulfinyl urea series compound, it is characterised in that: in organic solvent, using sub- sulphur
Acid imide and acid azide react 2-5 hours at 70-100 DEG C as reaction substrate, obtain product sulfoxide sulfinyl urea system
Column compound, reaction formula are as follows:
Wherein, R1For H or alkyl, alkoxy, naphthenic base, alkenyl, alkynyl, silicon substrate, or containing alkyl, alkoxy, fluorine, chlorine, bromine, iodine,
Ester group, nitro, cyano or amide groups aryl or furyl, thienyl, pyridyl group；
R2For aryl or furyl, thiophene containing alkyl, alkoxy, fluorine, chlorine, bromine, iodine, ester group, nitro, cyano or amide groups
Base, pyridyl group；
R3For aryl or furyl, thiophene containing alkyl, alkoxy, fluorine, chlorine, bromine, iodine, ester group, nitro, cyano or amide groups
Base, pyridyl group.
2. the preparation method of sulfoxide sulfinyl urea series compound according to claim 1, it is characterised in that: described
Organic solvent is acetonitrile.
3. the preparation method of sulfoxide sulfinyl urea series compound according to claim 1, it is characterised in that: sulfenyl
The molal quantity ratio of imines and acid azide is 1:1.05.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1307271A (en) * | 1970-06-25 | 1973-02-14 | Shell Int Research | Sulphoximine derivatives and their use in herbicidal compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1307271A (en) * | 1970-06-25 | 1973-02-14 | Shell Int Research | Sulphoximine derivatives and their use in herbicidal compositions |
Non-Patent Citations (2)
| Title |
|---|
| Rearrangement processes in the mass spectra of N-substituted sulfoximines;Whittle,C.P. 等;《Organic Mass Spectrometry》;19740430;第9卷(第4期);第422-434页 * |
| 基于三氮唑类化合物的金属卡宾形成反应研究进展;黄家翩 等;《有机化学》;20160318;第36卷;第1555-1563页 * |
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