CN105949144B - The method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization - Google Patents
The method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization Download PDFInfo
- Publication number
- CN105949144B CN105949144B CN201610316838.0A CN201610316838A CN105949144B CN 105949144 B CN105949144 B CN 105949144B CN 201610316838 A CN201610316838 A CN 201610316838A CN 105949144 B CN105949144 B CN 105949144B
- Authority
- CN
- China
- Prior art keywords
- compound
- nitrogen heterocycle
- aromatic nitroso
- heterocycle propane
- cyclization
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 aromatic nitroso compound Chemical class 0.000 title claims abstract description 84
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 35
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000001294 propane Substances 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000007363 ring formation reaction Methods 0.000 title claims abstract description 17
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 43
- 238000010719 annulation reaction Methods 0.000 claims abstract description 11
- 230000004913 activation Effects 0.000 claims abstract description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 150000001348 alkyl chlorides Chemical class 0.000 claims abstract description 5
- 230000000977 initiatory effect Effects 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims abstract description 4
- 150000003751 zinc Chemical class 0.000 claims abstract description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 11
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 8
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000011592 zinc chloride Substances 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 235000005074 zinc chloride Nutrition 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- UUWYUBKTWPLKKD-UHFFFAOYSA-N 1-methyl-4-propylsulfonylbenzene Chemical class CCCS(=O)(=O)C1=CC=C(C)C=C1 UUWYUBKTWPLKKD-UHFFFAOYSA-N 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 48
- 125000004122 cyclic group Chemical group 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 58
- 239000000047 product Substances 0.000 description 52
- 239000012043 crude product Substances 0.000 description 22
- NLRKCXQQSUWLCH-UHFFFAOYSA-N nitrosobenzene Chemical compound O=NC1=CC=CC=C1 NLRKCXQQSUWLCH-UHFFFAOYSA-N 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000001819 mass spectrum Methods 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 229910002651 NO3 Inorganic materials 0.000 description 6
- 238000006352 cycloaddition reaction Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 0 CCCC([C@](CC(*C)C(C)C1)C1(CC)[*+](*C)*C1[C+]C1)=*(C)CC Chemical compound CCCC([C@](CC(*C)C(C)C1)C1(CC)[*+](*C)*C1[C+]C1)=*(C)CC 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 238000007142 ring opening reaction Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- NTEIHBXTIUTKMM-UHFFFAOYSA-N [O-][N+](c1c(C2ON2c2ccccc2)cccc1)=O Chemical compound [O-][N+](c1c(C2ON2c2ccccc2)cccc1)=O NTEIHBXTIUTKMM-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000005213 imbibition Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D273/01—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having one nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The invention discloses a kind of method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization; it is that initiation material is made with the nitrogen heterocycle propane compound of p-toluenesulfonyl activation; make nucleopilic reagent using aromatic nitroso compound, annulation is carried out with aziridine in alkyl chloride varsol under the effect of zinc class lewis promoters.Course of reaction of the present invention is simple, mild condition, and cyclic method has extensive universality, and the aziridine and aromatic nitroso compound of different structure can obtain higher yield.
Description
Technical field
The present invention relates to a kind of method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization, belong to organic conjunction
Into technical field.
Background technology
Nitrogen heterocycle propane compound is building block and intermediate important in organic synthesis, is present in many natural products
In, there is good antiviral, antitumor and other bioactivity.A series of important reactions can occur for aziridine, such as
Ring-opening reaction, cycloaddition reaction, reduction and elimination reaction etc..Its cycloaddition reaction can be used for synthesis five yuan or six-membered cyclic chemical combination
Thing, and then many is synthesized with bioactivity and in the medication chemistry industry extremely compound with application prospect.
It is of common occurrence for nucleopilic reagent and the report of aziridine ring-opening reaction, but people are for azacyclo- third
The research enthusiasm of alkane correlated response does not subtract still, and in these numerous reactions, aziridine cycloaddition reaction is increasingly
Arouse people's interest；Wherein aziridine carbon-carbon bond easily occurs under lewis acidic catalysis breaks to form 1,3- dipoles
The corresponding target production of cycloaddition reaction generation occurs for the dipolarophile bodies such as body, the middle physical efficiency and alkene, alkynes, aldehyde, ketone or imines
Thing.
In summary, although the research of aziridine cycloaddition reaction achieves certain progress, but aromatic nitroso
So far there are no for the relevant report of compound and nitrogen heterocycle propane compound cycloaddition reaction；Therefore, the reaction condition of green is found
Especially with the reaction condition of cheap and simple catalyst come complete that aromatic nitroso compound and aziridine carry out into
Ring reacts, so that reaction is easily operated, environmental protection, product yield high, is worth people further to go to explore and find.
The content of the invention
The present invention is intended to provide with different structure nitrogen heterocycle propane compound cyclization occurs for a kind of aromatic nitroso compound
The method of reaction.
The invention provides a kind of method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization, with to toluene
Sulfonyl activating nitrogen heterocycle propane compound is initiation material, using aromatic nitroso compound as nucleopilic reagent, the party
Method is under zinc class lewis promoters action condition, and in alkyl chloride varsol, nitrogen heterocycle propane compound is carried out
Annulation.
In the above method, the aromatic nitroso compound has following general structure：
In formula, R represents H, alkyl, halogen, nitro or aryl.
In the above method, the nitrogen heterocycle propane compound of the tosyl activation has following general structure：
In formula, X represents H, C1~C20Alkyl, halogen, nitro,
Wherein, R1Represent H, methyl, methoxyl group or halogen.
The annulation of aromatic nitroso compound and nitrogen heterocycle propane compound is as follows：
In the above method, the zinc class lewis promoters are one kind in zinc chloride, zinc nitrate or zinc iodide, are promoted
The mol ratio of agent and nitrogen heterocycle propane compound is (1~10): 10.
In the above method, the alkyl chloride varsol be dichloromethane, chloroform or 1,2- dichloroethanes in one kind, chlorine
Dosage for alkane is 2~12mL/mmol nitrogen heterocycle propane compounds.
Above-mentioned reaction is carried out in chlorinated paraffin solvent system, because chloralkane has certain water imbibition, cruelly
The dew easy moisture absorption in atmosphere, and make system carry micro moisture, therefore, further research are reacted to the tolerance of water particularly
It is important.Use additionReacted in the chloralkane of molecular sieve, compared with the reaction for being added without molecular sieve, reaction rate
All there is no significant difference with yield, illustrate that above-mentioned reaction has good tolerance for micro water.
In the above method, the nitrogen heterocycle propane compound of p-toluenesulfonyl activation and aromatic nitroso compound
Mol ratio is 3: (1~12).Further, the nitrogen heterocycle propane compound and aromatic nitroso of the p-toluenesulfonyl activation
The mol ratio of compound is 2: (1~4).
In the above method, the annulation is carried out at 20~90 DEG C.Further, the annulation is 20~70
Carried out at DEG C.
The present invention is to make initiation material with the nitrogen heterocycle propane compound of p-toluenesulfonyl activation, and p-toluenesulfonyl is made
For electron-withdrawing substituent, the cloud density on azacyclo- can be reduced, makes it easily by nucleopilic reagent attack.After annulation
P-toluenesulfonyl on product can remove using conventional method, be not the emphasis that the present invention describes, therefore the present invention is to it
It is not explained.
Nucleopilic reagent is made with aromatic nitroso compound the invention provides one kind, in zinc chloride, zinc nitrate or zinc iodide
Under the conditions of accelerator in chlorinated paraffin solvent system, to the method for nitrogen heterocycle propane compound cyclization, the letter of this method division operation
Single, reaction condition is gently outer, has further the advantage that：
1) reaction makees accelerator using zinc chloride, zinc nitrate or zinc iodide, and reaction cost is relatively low；
2) solvent chloralkane is environment-friendly, reacts strong particularly valuable to the tolerance of water；
3) the cyclic method of the present invention has extensive universality, to the aziridine and aromatic nitroso of different structure
Compound annulation can obtain higher yield；
Therefore, there is very strong practical application valency as a kind of new nitrogen heterocycle propane compound cyclization method, the present invention
Value.
Embodiment
The present invention is further illustrated below by embodiment, but is not limited to following examples.
The various nitrogen heterocycle propane compounds of p-toluenesulfonyl activation be shown below is in different aromatic nitrosos
The lower embodiment for carrying out annulation of compound effect.
Embodiment 1：
Aziridine 0.22mmol, aromatic nitroso compound 2a of the structural formula as shown in 1a are added in test tube
0.24mmol, 0.132mmolZnCl2, 1,2- dichloroethanes 0.8mL, it is heated to stirring reaction 6h at 25 DEG C.Crude product is through silica gel
Column chromatography obtains cyclic product, and structural formula carries out sign to product as shown in 3a in table 1, using nuclear magnetic resonance and confirms production
The structure of thing.
The aziridine 1a of table 1 and aromatic nitroso compound 2a reaction
3a White solid；mp 156-157℃；1H NMR(400MHz,CDCl3), δ=7.47-7.52 (m, 6H),
7.77-7.79(m,2H),7.93(s,1H),8.39-8.41(m,2H)ppm。
Embodiment 2：
Aziridine 0.34mmol, aromatic nitroso compound 2b of the structural formula as shown in 1a are added in test tube
0.3mmol, 0.17mmol Zn (NO3)2, chloroform 1.5mL, stirring reaction 6h at 35 DEG C is heated to, through extracting, washing and dry
Crude product.Crude product by silica gel chromatography post purifies to obtain cyclic product, structural formula as shown in 3b in table 2, using nuclear magnetic resonance and
High resolution mass spectrum carries out characterizing the structure for confirming product to product.
The aziridine 1a of table 2 and aromatic nitroso compound 2b reaction
3b White solid；mp 108-110℃；1H NMR(600MHz,CDCl3), δ=2.44 (s, 3H), 7.27-
7.32 (m, 2H), 7.34-7.36 (m, 1H), 7.39 (d, J=9Hz, 1H), 7.49-7.50 (m, 3H), 7.58 (s, 1H), 8.36-
8.37(m,2H)ppm；13C NMR(100MHz,CDCl3):δ=17.1,123.4,126.7,128.7,128.8,129.4,
130.4,130.9,131.5,131.8,137.6,148.7ppm；Calcd for C14H13NO+H 212.1075,found
212.1069。
Embodiment 3：
Aziridine 0.4mmol, aromatic nitroso compound 2c of the structural formula as shown in 1a are added in test tube
0.4mmol, 0.2mmol ZnI2, 1,2- dichloroethanes 2.5mL, stirring reaction 9h at 25 DEG C is heated to, through extracting, washing and do
It is dry to obtain crude product.Crude product by silica gel chromatography post is purified to obtain cyclic product, and structural formula is total to as shown in 3c in table 3 using nuclear-magnetism
Shake and product is carried out to characterize the structure for confirming product.
The aziridine 1a of table 3 and aromatic nitroso compound 2c reaction
3c White solid；mp 84-85℃；1H NMR(600MHz,CDCl3), δ=2.44 (s, 3H), 7.26 (d, J
=7.8Hz, 1H), 7.36 (t, J=7.8Hz, 1H), 7.46-7.50 (m, 3H), 7.54-7.55 (m, 1H), 7.61 (s, 1H),
7.90(s,1H),8.39-8.40(m,2H)ppm。
Embodiment 4：
Aziridine 0.35mmol, aromatic nitroso compound 2d of the structural formula as shown in 1a are added in test tube
0.36mmol, 0.14mmolZnCl2, dichloromethane 2.5mL, stirring reaction 2h at 45 DEG C is heated to, through extracting, washing and dry
Obtain crude product.Crude product by silica gel chromatography post purifies to obtain cyclic product, and structural formula is as shown in 3d in table 4, using nuclear magnetic resonance
Product is carried out to characterize the structure for confirming product.
The aziridine 1a of table 4 and aromatic nitroso compound 2d reaction
3d White solid；mp 112-114℃；1H NMR(600MHz,CDCl3), δ=2.41 (s, 3H), 7.25 (d,
J=12.0Hz, 2H), 7.46-7.48 (m, 3H), 7.65 (d, J=12.6Hz, 2H), 7.90 (s, 1H), 8.38-8.40 (m, 2H)
ppm。
Embodiment 5：
Aziridine 0.22mmol, aromatic nitroso compound 2e of the structural formula as shown in 1a are added in test tube
0.25mmol, 0.154mmolZnCl2, 1,2- dichloroethanes 1.5mL, stirring reaction 6h at 25 DEG C is heated to, through extracting, washing
With dry crude product.Crude product by silica gel chromatography post purifies to obtain cyclic product, and structural formula is as shown in 3e in table 5, using core
Magnetic resonance and high resolution mass spectrum carry out characterizing the structure for confirming product to product.
The aziridine 1a of table 5 and aromatic nitroso compound 2e reaction
3e White solid；mp 88-89℃；1H NMR(600MHz,CDCl3), δ=7.42-7.47 (m, 2H), 7.51
(t, J=3.6Hz, 3H), 7.68 (dt, J=7.2,1.8Hz, 1H), 7.83 (t, J=1.8Hz, 1H), 7.91 (s, 1H), 8.39-
8.40(m,2H)ppm；13C NMR(100MHz,CDCl3):δ=120.0,122.4,128.8,129.3,130.2,130.3,
130.3,131.4,135.0,149.9ppm.Calcd for C13H10ClNO+H 232.0529,found 232.0528。
Embodiment 6：
Aziridine 0.2mmol of the structural formula as shown in 1a, aromatic nitroso compound are added in test tube
2f0.26mmol 0.16mmolZn (NO3)2, dichloromethane 2.0mL, stirring reaction 10h at 25 DEG C is heated to, through extracting, washing
With dry crude product.Crude product by silica gel chromatography post purifies to obtain cyclic product, and structural formula is as shown in 3f in table 6, using core
Magnetic resonance and high resolution mass spectrum carry out characterizing the structure for confirming product to product.
The aziridine 1a of table 6 and aromatic nitroso compound 2f reaction
3f White solid；mp 158-159℃；1H NMR(400MHz,CDCl3), δ=7.44-7.49 (m, 5H),
7.73 (d, J=8.8Hz, 2H), 7.91 (s, 1H), 8.38-8.40 (m, 2H) ppm；13C NMR(100MHz,CDCl3):δ=
123.1,128.8,129.2,129.3,130.4,131.3,134.7,135.8,147.4ppm；Calcd for C13H10ClNO+
H 232.0529,found232.0529。
Embodiment 7：
Aziridine 0.5mmol, nitrosobenzene 2a 0.4mmol of the structural formula of table 7 as shown in 1b are added in test tube,
0.15mmolZn(NO3)2, chloroform 2.0mL is heated to stirring reaction 25h at 40 DEG C, and crude product by silica gel chromatography post purifies to obtain
Cyclic product, structural formula carry out sign to product as shown in 4b in table 7, using nuclear magnetic resonance and high resolution mass spectrum and confirm product
Structure.
The aziridine 1b of table 7 and nitrosobenzene 2a reaction
4b White solid；mp 114-115℃；1H NMR(400MHz,CDCl3), δ=7.48-7.58 (m, 5H),
7.62 (t, J=7.88Hz, 1H), 7.83 (dd, J=4.0,2.0Hz, 2H), 7.89-7.91 (m, 1H), 7.94 (d, J=
8.2Hz, 1H), 8.06 (d, J=8.2Hz, 1H), 8.69 (s, 1H), 9.76 (d, J=7.4Hz, 1H) ppm；13C NMR
(100MHz,CDCl3):δ=30.9,121.7,122.0,125.7,125.8,126.0,127.1,129.3,129.5,130 .0,
149.9ppm；MS(ESI):Calcd for C17H13NO+H 248.1075,found 248.1067。
Embodiment 8：
Aziridine 0.5mmol, nitrosobenzene 2a of the structural formula of table 8 as shown in 1c are added in round-bottomed flask
0.6mmol, 0.125mmolZn (NO3)2, chloroform 3.5mL, it is heated to stirring reaction 15h at 60 DEG C, crude product by silica gel chromatography post
Purifying obtains cyclic product, and structural formula carries out sign card as shown in 4c in table 8, using nuclear magnetic resonance and high resolution mass spectrum to product
The real structure of product.
The aziridine 1c of table 8 and nitrosobenzene 2a reaction
4c White solid；mp 113-115℃；1H NMR(400MHz,CDCl3), δ=7.27 (d, J=8.0Hz,
1H), 7.45-7.57 (m, 6H), 7.72 (d, J=8.2Hz, 1H), 7.84-7.90 (m, 5H), 7.97-8.02 (m, 2H), 8.08
(s,1H),9.45(s,1H)ppm；13C NMR(100MHz,CDCl3):δ=129.1,129.5,130.4,130.5,130.8,
131.0,132.0,132.1,132.3,132.9,136.1,137.3,137.4,152.1ppm；MS(ESI):Calcd for
C17H13NO+H 248.1075,found 248.1070。
Embodiment 9：
Aziridine 0.9mmol, nitrosobenzene 2a of the structural formula of table 9 as shown in 1d are added in round-bottomed flask
0.95mmol, 0.54mmolZnCl2, chloroform 6.5mL is heated to stirring reaction 25h at 50 DEG C, and crude product by silica gel chromatography post is pure
Change obtains cyclic product, and structural formula carries out sign confirmation as shown in 4d in table 9, using nuclear magnetic resonance and high resolution mass spectrum to product
The structure of product.
The aziridine 1d of table 9 and nitrosobenzene 2a reaction
4d White solid；mp 77-78℃；1H NMR(400MHz,CDCl3), δ=7.35-7.44 (m, 2H),
7.47-7.53 (m, 4H), 7.78-7.81 (m, 2H), 8.43 (s, 1H), 9.52 (d, J=8.0,1.6Hz, 1H) ppm；13C NMR
(100MHz,CDCl3):δ=121.9,127.2,128.4,129.2,129.3,129.6,130.2,130.5,131.5,
135.6,149.5ppm；MS(ESI):Calcd for C13H10ClNO+H 232.0529,found 232.0528。
Embodiment 10：
Aziridine 1.2mmol, nitrosobenzene 2a of the structural formula of table 10 as shown in 1e are added in round-bottomed flask
1.2mmol, 0.6mmolZnI2, chloroform 2.5mL, it is heated to stirring reaction 10h at 60 DEG C, the purifying of crude product by silica gel chromatography post
Cyclic product is obtained, structural formula carries out sign confirmation as shown in 4e in table 10, using nuclear magnetic resonance and high resolution mass spectrum to product
The structure of product.
The aziridine 1e of table 10 and nitrosobenzene 2a reaction
4e White solid；mp 83-84℃；1H NMR(400MHz,CDCl3), δ=7.38-7.43 (m, 2H),
7.48-7.49 (m, 3H), 7.75-7.77 (m, 2H), 7.90 (s, 1H), 8.15 (d, J=7.2Hz, 1H), 8.56 (s, 1H) ppm
；13C NMR(100MHz,CDCl3):δ=121.7,123.0,127.1,128.4,129.1,129.8,130.0,130.8,
132.2,133.2,134.7,149.0ppm；MS(ESI):Calcd for C13H10ClNO+H 232.0529,found
232.0532。
Embodiment 11：
Aziridine 0.3mmol, nitrosobenzene 2a of the structural formula of table 11 as shown in 1f are added in test tube
0.28mmol, 0.21mmolZn (NO3)2, chloroform 1.5mL, it is heated to stirring reaction 24h at 50 DEG C, crude product by silica gel chromatography post
Purifying obtains cyclic product, and structural formula carries out sign to product as shown in 4f in table 11, using nuclear magnetic resonance and confirms product
Structure.
The aziridine 1f of table 11 and nitrosobenzene 2a reaction
4f ellowish oil；1H NMR(400MHz,CDCl3), δ=7.35-7.44 (m, 2H), 7.46-7.53 (m,
4H), 7.77-7.81 (m, 2H), 8.43 (s, 1H), 9.52 (dd, J=8.0,2.0Hz, 1H) ppm.
Embodiment 12：
Aziridine 0.4mmol, nitrosobenzene 2a of the structural formula of table 12 as shown in 1g are added in test tube
0.44mmol, 0.16mmolZnI2, 1,2- dichloroethanes 3.0mL, stirring reaction 24h at 60 DEG C is heated to, crude product is through silica gel
Column chromatography obtains cyclic product, and structural formula is entered as shown in 4g in table 12 using nuclear magnetic resonance and high resolution mass spectrum to product
Row characterizes the structure for confirming product.
The aziridine 1g of table 12 and nitrosobenzene 2a reaction
4g Yellowish oil；1H NMR(400MHz,CDCl3), δ=2.45 (s, 3H), 7.35 (dd, J=5.6,3,
6Hz, 2H), 7.46-7.51 (m, 4H), 7.75 (dd, J=7.6,1.6Hz, 2H), 8.07 (s, 1H), 9.34-9.38 (m, 1H)
ppm；13C NMR(100MHz,CDCl3):δ=20.0,121.0,122.0,126.5,128.0,128.4,129.0,130.0,
130.4,130.9,132.1,137.1ppm；MS(ESI):Calcd for C14H13NO+H 212.1075,found
212.1070。
Embodiment 13：
Aziridine 0.5mmol, nitrosobenzene 2a of the structural formula of table 13 as shown in 1h are added in test tube
0.48mmol, 0.4mmolZnCl2, 1,2- dichloroethanes 3.5mL, stirring reaction 16h at 70 DEG C is heated to, crude product is through silica gel
Column chromatography obtains cyclic product, and structural formula is entered as shown in 4h in table 13 using nuclear magnetic resonance and high resolution mass spectrum to product
Row characterizes the structure for confirming product.
The aziridine 1h of table 13 and nitrosobenzene 2a reaction
4h Yellowish oil；1H NMR(400MHz,CDCl3), δ=2.43 (s, 3H), 7.28 (d, J=7.6Hz,
1H), 7.36 (t, J=8.0Hz, 1H), 7.46-7.51 (m, 3H), 7,76-7.78 (m, 2H), 7.89 (s, 1H), 8.10 (d, J=
7.6Hz,1H),8.32(s,1H)ppm；13C NMR(100MHz,CDCl3):δ=21.6,127.1,127.6,127.9,128.5,
129.0,129.8,136.5,137.0,138.9.5,143.3,151.5ppm；MS(ESI):Calcd for C14H13NO+H
212.1075,found 212.1079。
Embodiment 14：
Aziridine 0.6mmol, nitrosobenzene 2a of the structural formula of table 14 as shown in 1i are added in round-bottomed flask
0.5mmol, 0.3mmol ZnCl2, chloroform 4.0mL, it is heated to stirring reaction 7h at 70 DEG C, the purifying of crude product by silica gel chromatography post
Cyclic product is obtained, structural formula carries out sign confirmation as shown in 4i in table 14, using nuclear magnetic resonance and high resolution mass spectrum to product
The structure of product.
The aziridine 1i of table 14 and nitrosobenzene 2a reaction
4i White solid；mp 80-81℃；1H NMR(400MHz,CDCl3), δ=2.42 (s, 3H), 7.29 (d, J
=8.4Hz, 2H), 7.44-7.51 (m, 3H), 7.77 (dd, J=8.4,2.0Hz, 2H), 7.89 (s, 1H), 8.29 (d, J=
8.0Hz,2H)ppm；13C NMR(100MHz,CDCl3):δ=20.2,127.2,127.8,128.0,128.4,129.3,
129.7,129.8,136.3,137.2,143.4,149.3ppm；MS(ESI):Calcd for C14H13NO+H 212.1075,
found 212.1079。
Embodiment 15：
Aziridine 0.35mmol, nitrosobenzene 2a of the structural formula of table 15 as shown in 1j are added in test tube
0.3mmol, 0.35mmolZn (NO3)2, 1,2- dichloroethanes 1.5mL, stirring reaction 7h at 25 DEG C is heated to, crude product is through silica gel
Column chromatography obtains cyclic product, and structural formula is entered as shown in 4j in table 15 using nuclear magnetic resonance and high resolution mass spectrum to product
Row characterizes the structure for confirming product.
The aziridine 1j of table 15 and nitrosobenzene 2a reaction
4j White solid；mp 79-81℃；1H NMR(600MHz,CDCl3), δ=7.51 (t, J=3.6Hz, 3H),
7.57 (t, J=8.4Hz, 1H), 7.76-7.81 (m, 3H), 8.09 (d, J=3.0Hz, 1H), 8.60 (s, 1H), 9.38 (d, J=
7.8Hz,1H)ppm；13C NMR(150MHz,CDCl3):δ=66.3,124.7,127.5,127.9,131.2,132.2,
132.4,133.3,133.5,136.4,150.5,152.2ppm；MS(ESI):Calcd for C13H10N2O3+H 243.0770,
found 243.0769。
Embodiment 16：
Aziridine 0.5mmol, nitrosobenzene 2a of the structural formula of table 16 as shown in 1k are added in test tube
0.52mmol, 0.15mmol ZnCl2, chloroform 3.0mL is heated to stirring reaction 7h at 70 DEG C, and crude product by silica gel chromatography post is pure
Change obtains cyclic product, and structural formula carries out sign card as shown in 4k in table 16, using nuclear magnetic resonance and high resolution mass spectrum to product
The real structure of product.
The aziridine 1k of table 16 and nitrosobenzene 2a reaction
4k White solid；mp 39-40℃；1H NMR(400MHz,CDCl3), δ=7.51-7.53 (m, 3H), 7.66
(t, J=7.9Hz, 1H), 7.78-7.81 (m, 2H), 8.09 (s, 1H), 8.28 (d, J=8.2Hz, 1H), 8.79 (d, J=
8.2Hz,1H),9.21(s,1H)ppm；13C NMR(100MHz,CDCl3):δ=124.5,128.7,134.7,137.4,
189.8ppm；MS(ESI):Calcd for C13H10N2O3+H 243.0770,found 243.0760。
Embodiment 17：
Aziridine 0.5mmol, nitrosobenzene 2a of the structural formula of table 17 as shown in 1l are added in round-bottomed flask
0.6mmol, 0.3mmol ZnCl2, chloroform 4.0mL, it is heated to stirring reaction 6h at 70 DEG C, the purifying of crude product by silica gel chromatography post
Cyclic product is obtained, structural formula carries out characterizing the structure for confirming product as shown in 4l in table 17, using nuclear magnetic resonance to product.
The aziridine 1l of table 17 and nitrosobenzene 2a reaction
4l White solid；mp 60-61℃；1H NMR(400MHz,CDCl3), δ=6.76 (d, J=7.9Hz, 1H),
7.20 (d, J=7.8Hz, 1H), 7.39-7.43 (m, 2H), 7.49-7.53 (m, 3H), 7.84-7.91 (m, 2H), 8.09 (s,
1H)ppm。
Claims (9)
1. the method for aromatic nitroso compound and nitrogen heterocycle propane compound cyclization, the azacyclo- activated with p-toluenesulfonyl
Propane compounds are initiation material, and nucleopilic reagent is used as using aromatic nitroso compound, it is characterised in that：This method is in zinc
Under class lewis promoters action condition, in alkyl chloride varsol, annulation is carried out to nitrogen heterocycle propane compound；
The structural formula of gained target compound is as follows：
In formula, R represents H, alkyl, halogen, nitro or aryl.
2. the method for aromatic nitroso compound according to claim 1 and nitrogen heterocycle propane compound cyclization, its feature
It is：The aromatic nitroso compound has following general structure：
In formula, R represents H, alkyl, halogen, nitro or aryl.
3. the method for aromatic nitroso compound according to claim 1 and nitrogen heterocycle propane compound cyclization, its feature
It is：The nitrogen heterocycle propane compound of the tosyl activation has following general structure：
In formula, X represents H, C1~C20Alkyl, halogen, nitro,
Wherein, R1Represent H, methyl, methoxyl group or halogen.
4. the method for aromatic nitroso compound according to claim 1 and nitrogen heterocycle propane compound cyclization, its feature
It is：The zinc class lewis promoters are one kind in zinc chloride, zinc nitrate or zinc iodide, accelerator and aziridine
The mol ratio of compound is (1~10): 10.
5. the method for aromatic nitroso compound according to claim 1 and nitrogen heterocycle propane compound cyclization, its feature
It is：The alkyl chloride varsol is one kind in dichloromethane, chloroform or 1,2- dichloroethanes, and the dosage of chloralkane is
2~12mL/mmol nitrogen heterocycle propane compounds.
6. the method for aromatic nitroso compound according to claim 1 and nitrogen heterocycle propane compound cyclization, its feature
It is：The nitrogen heterocycle propane compound of the p-toluenesulfonyl activation and the mol ratio of aromatic nitroso compound are 3: (1~
12)。
7. the method for aromatic nitroso compound according to claim 6 and nitrogen heterocycle propane compound cyclization, its feature
It is：The nitrogen heterocycle propane compound of the p-toluenesulfonyl activation and the mol ratio of aromatic nitroso compound are 2: (1~
4)。
8. the method for aromatic nitroso compound according to claim 1 and nitrogen heterocycle propane compound cyclization, its feature
It is：The annulation is carried out at 20~90 DEG C.
9. the method for aromatic nitroso compound according to claim 8 and nitrogen heterocycle propane compound cyclization, its feature
It is：The annulation is carried out at 20~70 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610316838.0A CN105949144B (en) | 2016-05-12 | 2016-05-12 | The method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610316838.0A CN105949144B (en) | 2016-05-12 | 2016-05-12 | The method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105949144A CN105949144A (en) | 2016-09-21 |
| CN105949144B true CN105949144B (en) | 2018-02-02 |
Family
ID=56911392
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610316838.0A Expired - Fee Related CN105949144B (en) | 2016-05-12 | 2016-05-12 | The method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105949144B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103910657A (en) * | 2014-04-11 | 2014-07-09 | 太原理工大学 | Ring opening method of aziridine compounds |
| CA2972294C (en) * | 2014-12-24 | 2018-09-25 | National Institute Of Biological Sciences, Beijing | Necrosis inhibitors |
| CN105461651B (en) * | 2015-11-18 | 2018-02-02 | 太原理工大学 | A kind of method using ketoxime to nitrogen heterocycle propane compound cyclization |
-
2016
- 2016-05-12 CN CN201610316838.0A patent/CN105949144B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN105949144A (en) | 2016-09-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Molecular iodine-catalyzed and air-mediated tandem synthesis of quinolines via three-component reaction of amines, aldehydes, and alkynes | |
| Du et al. | Regio‐and Stereoselective Construction of Highly Functionalized 3‐Benzazepine Skeletons through Ring‐Opening Cycloamination Reactions Catalyzed by Gold | |
| Wang et al. | Ortho-Hydroxylative ipso-Cyclization of N-arylpropiolamide | |
| CN108033922B (en) | Preparation method of 3-acyl quinoxalinone derivative | |
| Rao et al. | Chemoselective and stereospecific iodination of alkynes using sulfonium iodate (i) salt | |
| Xiao et al. | Diversified Construction of Chromeno [3, 4‐c] pyridin‐5‐one and Benzo [c] chromen‐6‐one Derivatives by Domino Reaction of 4‐Alkynyl‐2‐oxo‐2H‐chromene‐3‐carbaldehydes | |
| CN102659494B (en) | Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound | |
| CN106349147A (en) | Synthetic method of pyrrole derivatives | |
| CN105153083B (en) | Preparation method for polysubstituted furan compound | |
| CN105949144B (en) | The method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization | |
| CN106518887A (en) | Method for establishing tetrahydroquinoline spiro framework under catalyst-free condition | |
| Compain et al. | Selective anti-Markovnikov cyclization and hydrofluorination reaction in superacid HF/SbF5: A tool in the design of nitrogen-containing (fluorinated) polycyclic systems | |
| CN106046002B (en) | A kind of synthetic method of pyridine-imidazole simultaneously [1,2,3] triazoloquinoline class compound | |
| CN112028848A (en) | Method for preparing isoxazoline | |
| CN115477627B (en) | Polysubstituted 2-furanone compound and synthesis method thereof | |
| CN108558785B (en) | 5-aryl-2-arylseleno-1, 3-oxazole compound and preparation method thereof | |
| CN105968068B (en) | A kind of method of aromatic nitroso compound and nitrogen heterocycle propane compound cyclization | |
| CN112479898B (en) | Divalent manganese catalyzed arylamine ortho-olefination reaction method | |
| CN104817483B (en) | A kind of pair of carbonyl Benzazole compounds and its synthetic method | |
| CN108047128A (en) | A kind of method for synthesizing (E) -2- methyl 4-phenyl -6- styryl substituted pyridine compounds | |
| CN108314642A (en) | A kind of synthetic method of 2- picolines class compound | |
| CN108314649B (en) | Synthetic method of 6-phenylphenanthridine compound | |
| CN112028873A (en) | Method for preparing N- (2-quinoline) -2-ketone compound under mild condition | |
| CN106674108B (en) | Process for preparing 3-iminoisoquinoline-1, 4-dione derivatives | |
| Guo et al. | Efficient Synthesis of Tetrahydroquinolines from the Reaction of Aldehyde, Aniline, and Alkene under the In Situ Redox of SnCl2 and FeCl3 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180202 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |