CN108822037A - A kind of method of efficient high atom economy synthesis imidazolidine derivatives - Google Patents

A kind of method of efficient high atom economy synthesis imidazolidine derivatives Download PDF

Info

Publication number
CN108822037A
CN108822037A CN201810484753.2A CN201810484753A CN108822037A CN 108822037 A CN108822037 A CN 108822037A CN 201810484753 A CN201810484753 A CN 201810484753A CN 108822037 A CN108822037 A CN 108822037A
Authority
CN
China
Prior art keywords
reaction
imidazolidine derivatives
formula
alkyl
aryl
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.)
Granted
Application number
CN201810484753.2A
Other languages
Chinese (zh)
Other versions
CN108822037B (en
Inventor
周锡庚
张德兴
刘斌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fudan University
Original Assignee
Fudan University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Fudan University filed Critical Fudan University
Priority to CN201810484753.2A priority Critical patent/CN108822037B/en
Publication of CN108822037A publication Critical patent/CN108822037A/en
Application granted granted Critical
Publication of CN108822037B publication Critical patent/CN108822037B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention belongs to chemical technology field, specially a kind of method of efficient high atom economy synthesis imidazolidine derivatives.The present invention is incited somebody to action under rare-earth catalysis systemC‑Aryl‑N‑Allyl amidine generates imidazoline by intramolecular cyclization reaction.Raw material sources used in the method for the present invention are extensive or easily prepared, easy to operate and can synthesize imidazolidine derivatives in high yield in a mild condition, and the selectivity of reaction is high.

Description

A kind of method of efficient high atom economy synthesis imidazolidine derivatives
Technical field
The invention belongs to chemical technology fields, and in particular to a method of synthesis imidazolidine derivatives.
Background technique
Substituted imidazoline ring is the important structural unit of numerous natural products and drug molecule.This kind of compound is both important Organic synthesis intermediate, and prepare the key precursor of the functional materials such as imidazoline salt.In addition, they be also important it is organic Heterocyclic ligand and organic micromolecule catalyst.Therefore, it is organic for developing new efficient high selectivity substituted imidazoline method Eternal important project in synthesis.
It in existing technology of preparing, uses using allyl amidine as raw material, prepares imidazoles by aoxidizing ring amidification reaction method Quinoline derivant.Document（J. Am. Chem. Soc., 2011,133,13942-13945 and Org. Lett., 2012, 14, 5342-5345）It reports using allyl amidine as raw material, under copper catalyst system, with PhI (OAc)2Reaction, is prepared into To the method for substituted imidazoline.Document（Angew. Chem. Int. Ed. 2011, 50, 5678-5681）Document report, Equally under copper catalyst system, allyl amidine and oxygen carry out alkene amidino groups/oxidation/cyclization, and corresponding mesh is prepared Mark product.Document（J. Am. Chem. Soc., 2012, 134, 3679-3682）Report Aerobic [3+2]- Annulation reaction method, under CuI catalyst system（The oxygen of 1 atm）Oxidative cyclization reaction occurs, imidazoles is prepared Quinoline derivant.
The method condition of above-mentioned synthesis imidazolidine derivatives is harsher, needs using oxidant and a large amount of inorganic base, Reaction temperature is high, easily initiation side reaction, Atom economy and substrate poor compatibility, not energy-efficient, environmentally friendly, post-processes relatively complicated.
Summary of the invention
The object of the present invention is to provide a kind of raw material simplicity to be easy to get, and reaction condition is mild, can synthesize substitution miaow in high yield The method of oxazoline derivative.
Its feature is reaction selectivity height and 100% Atom economy；Same substrate sets out, and can be prepared different from it The product of its method.
The method of synthesis imidazolidine derivatives provided by the invention, includes the following steps：
Under nitrogen protection, under rare-earth catalysis system, with formula（Ⅰ）Shown compound is raw material, passes through intramolecular N-H key and alkene The addition reaction of hydrocarbon, is prepared imidazolidine derivatives, and structural formula is（Ⅱ）It is shown；Its reaction equation is：
In above-mentioned formula, R1It is aryl or heteroaryl；R2It is C1-8Alkyl, aryl or heteroaryl； R3It is C1-4Alkyl； R4It is C1-4 Alkyl or aryl；
Wherein, the aryl is unsubstituted or with 1-3 substituent group selected from the group below：C1-4Alkyl, C1-4Alkoxy or Person's halogen；
The rare earth catalyst is Y [N (SiMe3)2]3Or Sm [N (SiMe3)2]3。
Preparation formula（Ⅱ）Shown compound, is calculated with molar ratio：Formula（I）Compound/rare earth catalyst is 1/0.01- 0.15。
Preparation formula（Ⅱ）Shown compound, reaction temperature are 0-60 DEG C.
Preparation formula（Ⅱ）Shown compound, reaction time 0.5-24 h.
The present inventor passes through long-term thoroughgoing and painstaking research, it was found that a kind of reaction pattern of completely new unsaturated amidine, it can be by One step of amidine is converted into polysubstituted imidazolidine derivatives.Compared with existing process route, the present invention is had the following advantages that：
1）Raw material（Formula（Ⅰ）Compound）Simplicity is easy to get；
2）Reaction condition is mild, and reaction selectivity is strong, product yield high, 100% Atom economy, preparation process and product separation Purification is easy, strong flexibility, is suitable for preparing various substituted imidazole quinoline derivants；
3）Reaction condition is easy, without additional additive；
4）Establish the new reaction pattern of amidino groups substituted olefine.
The imidazolidine derivatives quality being prepared using the method for the present invention is high, high income；Can be prepared with it is existing The different product of method.It realizes and imidazoline is synthesized with the addition reaction of alkene by a step intramolecular N-H key under temperate condition Derivative.
Specific embodiment
Below by embodiment, the invention will be further described, but embodiment is not intended to limit protection scope of the present invention.
Embodiment 1
The preparation of Isosorbide-5-Nitrae-dimethyl -2- benzylimidazoline, structural formula are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl benzene carbon amidine is added（0.5 mmol）With catalyst Y [N (SiMe3)2]3(10 Mol%), N- methacrylic amine（1 mL）, 25 DEG C of 12 h of reaction, product separation yield 96%.
1H NMR (400 MHz, CDCl3): δ 7.54-7.53 (m, 2H), 7.38-7.37 (m, 3H), 4.18- 4.09 (m, 1H), 3.57 (t, J = 8.0, 1H), 2.98 (t, J = 8.0 Hz, 1H), 2.76 (s, 3H), 1.32 (d, J = 6.6 Hz, 3H).。
Embodiment 2
The preparation of Isosorbide-5-Nitrae-dimethyl -2- p-methylphenyl imidazoline, structural formula are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl is added to methyl benzene carbon amidine（0.5 mmol）With catalyst Y [N (SiMe3)2]3(8 mol%), N- methacrylic amine（1 mL）, 25 DEG C of 12 h of reaction, product separation yield 85%.
1H NMR (400 MHz, CDCl3): δ 7.45-7.43 (m, 2H), 7.20-7.18 (m, 2H), 4.17- 4.08 (m, 1H), 3.57 (t, J = 9.5 Hz, 1H), 2.97 (t, J = 8.7 Hz, 1H ), 2.77 (s, 3H), 2.36 (s, 3H), 1.32 (d, J = 6.6 Hz, 3H).。
Embodiment 3
The preparation of Isosorbide-5-Nitrae-dimethyl -2- rubigan imidazoline, structural formula are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl is added to fundal（0.5 mmol）With catalyst Y [N (SiMe3)2]3 (10 mol%), N- methacrylic amine（1 mL）, 25 DEG C of 10 h of reaction, product separation yield 92%.
1H NMR (400 MHz, CDCl3): δ 7.50-7.48 (m, 2H), 7.38-7.36 (m, 2H), 4.18- 4.08 (m, 1H), 3.58 (t, J = 9.5 Hz, 1H), 2.98 (t, J = 8.8 Hz, 1H), 2.76 (s, 3H), 1.32 (d, J = 6.6 Hz, 3H).。
Embodiment 4
Preparation of the Isosorbide-5-Nitrae-dimethyl -2- to iodophenyl imidazoline, structural formula are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl is added to iodobenzene amidine（0.5 mmol）With catalyst Y [N (SiMe3)2]3 (10 mol%), N- methacrylic amine（1 mL）, 25 DEG C of 12 h of reaction, product separation yield 89%.
1H NMR (400 MHz, CDCl3): δ 7.74-7.72 (m, 2H), 7.30-7.27 (m, 2H), 4.17- 4.07 (m, 1H), 3.57 (t, J = 9.5 Hz, 1H), 2.97 (t, J = 8.8 Hz, 1H), 2.75 (s, 3H), 1.31 (d, J = 6.6 Hz, 3H).。
Embodiment 5
The preparation of 3- (Isosorbide-5-Nitrae-dimethyl -4,5- dihydro -1H- imidazoles -2- alkenyl) pyridine, structural formula are as follows：
Under nitrogen protection, raw material 3-N- allyl-N- picoline amidine is added（0.5 mmol）With catalyst Y [N (SiMe3)2]3 (10 mol%), N- methacrylic amine（1 mL）, 25 DEG C of 12 h of reaction, product separation yield 75%.
1H NMR (400 MHz, CDCl3) δ 8.79-8.78 (m, 1H), 8.66-8.64 (m, 1H), 7.91- 7.88 (m, 1H), 7.37-7.33 (m, 1H), 4.22-4.12 (m, 1H), 3.63 (t, J = 9.6 Hz, 1H), 3.03 (t, J = 8.8 Hz, 1H), 2.80 (s, 3H), 1.34 (d, J = 6.6 Hz, 3H).。
Embodiment 6
The preparation of 1- allyl -4- methyl -2- benzylimidazoline, chemical structure are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl benzene carbon amidine is added（0.5 mmol）With catalyst Y [N (SiMe3)2]3(8 Mol%), N, N- diallylamine（1 mL）, 25 DEG C of 10 h of reaction, product separation yield 80%.
1H NMR (400 MHz, CDCl3): δ 7.55-7.53 (m, 2H), 7.39-7.36 (m, 3H), 5.79- 5.70 (m, 1H), 5.24-5.15 (m, 2H), 4.22-4.13 (m, 1H), 3.73-3.55 (m, 3H), 2.99 (dd, J = 9.1, 8.3 Hz, 1H), 1.33 (d, J = 6.6 Hz, 3H).。
Embodiment 7
The preparation of 1- cyclohexyl -4- methyl -2- benzylimidazoline, chemical structure are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl benzene carbon amidine is added（0.5 mmol）With catalyst Y [N (SiMe3)2]3(5 Mol%), N- cyclohexyl allyl amine（1 mL）, 25 DEG C of 10 h of reaction, product separation yield 83%.
1H NMR (400 M, CDCl3): δ 7.48-7.46 (m, 2H), 7.39-7.36 (m, 3H), 4.16- 4.07 (m, 1H), 3.61-3.57 (m, 1H), 3.31-3.23 (m, 1H), 3.02 (t, J = 8.6 Hz, 1H), 1.72-1.64 (m, 3H), 1.59-1.56 (m, 2H), 1.45-1.34 (m, 2H), 1.29 (d, J = 6.6 Hz, 3H), 1.15-0.98 (m, 3H).。
Embodiment 8
The preparation of 1- benzyl -4- methyl -2- benzylimidazoline, chemical structure are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl benzene carbon amidine is added（0.5 mmol）With catalyst Sm [N (SiMe3)2]3 (6 Mol%), N- benzyl allyl amine（1 mL）, 25 DEG C of 10 h of reaction, product separation yield 95%.
1H NMR (400 MHz, CDCl3): δ 7.61-7.59 (m, 2H), 7.3 7-7.31 (m, 5H), 7.27-7.22 (m, 3H), 4.33-4.13 (m, 3H), 3.51 (t, J = 8.0 Hz, 1H), 2.92 (t, J = 8.0 Hz, 1H), 1.31 (d, J = 4.0 Hz, 3H).。
Embodiment 9
The preparation of 1- benzyl -2- phenyl -4,4- methylimidazole quinoline, chemical structure are as follows：
Under nitrogen protection, raw material N- allyl-N- methyl benzene carbon amidine is added（0.5 mmol）With catalyst Y [N (SiMe3)2]3 (5 Mol%), N- benzyl -2- methyl -2- propylene -1- amine（1 mL）, 25 DEG C of 12 h of reaction, product separation yield 89%.
1H NMR (400 MHz, CDCl3): δ 7.61-7.58 (m, 2H), 7.37-7.32, (m, 5H), 7.27-7.22 (m, 3H), 4.28 (s, 2H), 3.13 (s, 2H), 1.31 (s, 6H).。
Finally, it should be noted that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although ginseng It is described the invention in detail according to preferred embodiment, those skilled in the art should understand that, it can be to invention Technical solution is modified or replaced equivalently, and without departing from the spirit and scope of the technical solution of the present invention, should all be covered In scope of the presently claimed invention.

Claims (3)

1. a kind of method of efficient high atom economy synthesis imidazolidine derivatives, which is characterized in that the specific steps are：
Under nitrogen protection, under rare-earth catalysis system, with formula（Ⅰ）Shown compound is raw material, passes through intramolecular N-H key and alkene The addition reaction of hydrocarbon, is prepared polysubstituted imidazolidine derivatives, and structural formula is（Ⅱ）It is shown；Its reaction equation is：
In formula, R1It is aryl or heteroaryl；R2It is C1-8Alkyl, aryl or heteroaryl；R3It is C1-4Alkyl；R4It is C1-4Alkyl or virtue Base；Wherein, the aryl is unsubstituted or with 1-3 substituent group selected from the group below：C1-4Alkyl, C1-4Alkoxy or Person's halogen；
The rare earth catalyst is Y [N (SiMe3)2]3Or Sm [N (SiMe3)2]3。
2. the method according to claim 1, wherein being calculated with molar ratio：Formula（Ⅰ）Compound/rare earth catalyst For 1/0.01-0.15.
3. the method according to claim 1, wherein reaction temperature be 0-60 DEG C, reaction time 0.5-24 h。
CN201810484753.2A 2018-05-20 2018-05-20 Method for efficiently synthesizing imidazoline derivative with high atom economy Active CN108822037B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810484753.2A CN108822037B (en) 2018-05-20 2018-05-20 Method for efficiently synthesizing imidazoline derivative with high atom economy

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810484753.2A CN108822037B (en) 2018-05-20 2018-05-20 Method for efficiently synthesizing imidazoline derivative with high atom economy

Publications (2)

Publication Number Publication Date
CN108822037A true CN108822037A (en) 2018-11-16
CN108822037B CN108822037B (en) 2021-08-20

Family

ID=64148925

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810484753.2A Active CN108822037B (en) 2018-05-20 2018-05-20 Method for efficiently synthesizing imidazoline derivative with high atom economy

Country Status (1)

Country Link
CN (1) CN108822037B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113773244A (en) * 2021-04-06 2021-12-10 复旦大学 Method for removing ketone fragment in nitrogen heterocyclic compound substituent

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
DEXING ZHANG ET AL.: "Intramolecular alkene hydroamination and degradation of amidines: divergent behavior of rare earth metal amidinate intermediates", 《CATAL. SCI. TECHNOL.》 *
HUI CHEN ET AL.: "anti-Selective aminofluorination of alkenes with amidines mediated by hypervalent iodine(III) reagents", 《ORG. BIOMOL. CHEM.》 *
HUI CHEN ET AL.: "Diastereoselective Aminooxygenation and Diamination of Alkenes with Amidines by Hypervalent Iodine(III) Reagents", 《ORGANIC LETTERS》 *
LONGCHENG HONG ET AL.: "Ln[N(SiMe3)2]3-Catalyzed Cross-Diinsertion of C≡N/C≡C into an N-H Bond: Facile Synthesis of 1,2,4-Trisubstituted Imidazoles from Propargylamines and Nitriles", 《CHEM. EUR. J.》 *
SHUJIAN HUANG ET AL.: "Cycloamidination of Aminoalkenes with Nitriles: Synthesis of Substituted 2-Imidazolines and Tetrahydropyrimidines", 《ANGEWANDTE COMMUNICATIONS》 *
STEPHEN SANJAYA ET AL.: "Copper-Catalyzed Aminooxygenation of N‑Allylamidines with PhI(OAc)2", 《ORGANIC LETTERS》 *
北京大学《大学基础化学》编写组: "《大学基础化学》", 30 June 2003, 高等教育出版社 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113773244A (en) * 2021-04-06 2021-12-10 复旦大学 Method for removing ketone fragment in nitrogen heterocyclic compound substituent
CN113773244B (en) * 2021-04-06 2024-03-22 复旦大学 Method for removing ketone fragment in nitrogen heterocyclic compound substituent

Also Published As

Publication number Publication date
CN108822037B (en) 2021-08-20

Similar Documents

Publication Publication Date Title
AU2008241602B2 (en) A new process for the manufacturing of the compound 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile 701
CN107973779B (en) Preparation method of N- (2-pyridine/pyrimidine-based) indole derivative
CN109354583B (en) Chiral 3, 4-dihydro-2 (1H) -quinolinone compound and preparation method thereof
Zhou et al. Facile synthesis of unnatural β-germyl-α-amino amides via Pd (ii)-catalyzed primary and secondary C (sp3)–H bond germylation
CN110437124B (en) Preparation method of indoloquinone derivative
Ackermann et al. Palladium-catalyzed sequential indole synthesis using sterically hindered amines
CN108822037A (en) A kind of method of efficient high atom economy synthesis imidazolidine derivatives
Casaschi et al. Palladium catalysed tandem cyclisation–anion capture. Part 7: Synthesis of derivatives of α-amino esters, nitrogen heterocycles and β-aryl/heteroaryl ethylamines via in situ generated vinylstannanes
Shaikh et al. An efficient alkynylation of 4-thiazolidinone with terminal alkyne under C–H functionalisation
CN112047871A (en) Preparation method of indole compound
CN113045530B (en) Method for preparing naphthopyran compounds by ruthenium catalysis
Mukherjee et al. Facile synthesis of functionalized 6-cyano-2-oxa-7-azabicyclo [4.1. 0] hept-3-en-1-yl acetates: a catalyst free approach to access the pyran fused 2-acetoxy-NH-aziridines
CN105237481B (en) A kind of method of rare earth catalyst synthesis 1,4,5,6- tetrahydropyrimidinederivatives derivatives
CN113200905A (en) Chiral indolone derivative and synthesis method thereof
JP2004537405A (en) Palladium catalyst
CN109265403A (en) A kind of synthetic method of benzimidazole and its derivative
Brielles et al. Diethylzinc/CuII-mediated alkylation of aromatic amines and related compounds
CN105001163A (en) Tetra-substituted imidazole synthesis method
Radhika et al. Cu (ii)-catalyzed C–N coupling of 2-aminobenzothiazoles with boronic acids at room temperature
CN104059063A (en) Preparation method of 7,7-difluoro-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridine and derivatives of 7,7-difluoro-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridine
KR101580821B1 (en) Development of a New Synthetic Method for Quinazolinones via Aerobic Oxidation in dimethylsulfoxide
CN109651344A (en) A kind of benzofuran triarylmethane class compound and its green catalysis synthetic method
CN109369515A (en) A kind of synthetic method for the carbocyclic derivatives that unsaturated double-bond replaces
CN105218451A (en) A kind of method of narrowing of rare earth catalyst ring Reactive Synthesis imidazolidine derivatives
JP5277699B2 (en) Method for producing benzoxazole compound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant