2-异丙基-1,3-二氢-4(1H)异喹啉酮及其衍生物的合成

异喹啉酮类化合物具有重要药理活性,本文在合成1,2,3,4-四氢-2-苄基异喹啉酮-4衍生物的基础上,参照Hinton方法制备2-异丙基-1,3-二氢-4(1H)异喹啉酮(1),用(1)进一步与芳醛、羟胺、酰氯及苯肼反应得到了相应的衍生物(3_a-6_e)。     

Bischler-Napieralski反应合成那可丁及其衍生物的立体化学

对通过Bischler-Napieralski反应制备的那可丁及其衍生物的立体选择性进行了研究. 以N-β-(3-甲氧基-4,5-亚甲二氧基苯基)乙基-6 ,7 -二甲氧基苯并呋喃酮-3-酰胺(1)和N-β-(3,4-亚甲二氧基苯基)乙基-6 ,7 -二甲氧基苯并呋喃酮-3-酰胺(2)为原料, 经Bischler-Napieralski反应和硼氢化钠还原制得五对苯酞类四氢异喹啉类化合物对映体3, 4a, 4b, 5a, 5b, 其中3和5a经氮甲基化反应得到外消旋的那可丁(α-narcotine)和白毛莨碱(b-hydrastine). 该法制得的苯酞类四氢异喹啉类化合物具有一定的立体选择性, 产物构型以赤式对映体为主, 中间产物二氢异喹啉环8位取代基的空间位阻将导致硼氢化钠还原时产生立体选择性.     

消旋防己诺林的全合成

本文报道由1-3'-溴4'-甲氧基)苄基-2-甲基-6-甲氧基-7-羟基-8-溴-1,2,3,4-四氢异喹啉(2)和1-(1'-羟基)苄基-2-甲基-6-甲氧基-7-羟基-1,2,3,4-四氢异喹啉(3)通过Ullmann反应合成了消旋防己诺林。     

苄基异喹啉生物碱Neolitacumonine、Mollinedine和Papaverine的全合成

研究了苄基异喹啉生物碱的一条新的通用合成路线.其关键步骤为1-苄基-3,4-二氢异喹啉的铜催化氧化芳构化串联反应.以胡椒醛或3,4-二甲氧基苯甲醛为起始原料,经8步反应,分别以42%、37%和37%的总收率实现了三个苄基异喹啉生物碱Neolitacumonine、Mollinedine和Papaverine的全合成.     

氢化喹啉及其芳(杂)环稠合衍生物的合成

通过环己二酮与β-二腈基苯乙烯的Michael加成得到2-氨基-3-氰基-4-芳基-5-氧代-1,4,5,6,7,8-六氢喹啉(1); 4-苯基六氢喹啉(1a)与环己二酮发生胺的加成缩合反应生成2-N-(3-氧代-1-环己烯基)氨基-3-氰基-4-苯基-5-氧代-1,4,5,6,7,8-六氢喹啉(2), 在碱性和氯化亚铜催化下进一步环合成4-苯基-5-氨基-二-(2-氧代环己烷)并[b,g]-1,3-二氢萘啶(3). 芳醛、α-萘胺和环己二酮在乙醇中共回流, 则一锅法完成9-芳基-5,6,7,8,9,10-六氢苯并[c]吖啶酮(4)的合成. 对合成中所涉及的化学反应机理进行了尝试性的讨论. 新化合物1a～4c均经IR, ¹H NMR 及元素分析证明其结构.     

5,6-二甲氧基-N-[(R)-4-甲氧基-2-(丙烯-2-基)-2,3-二氢苯并呋喃-5-基]-1,1a,2,7b-四氢环丙并[c]苯并吡喃-7b-基甲酰胺的合成与表征

鱼藤酮与氧硫叶立德反应得到关键中间体(5,6-二甲氧基-1,1a,2,7b-四氢环丙并[c]苯并吡喃-7b-基)[(R)-4-羟基-2-(丙烯-2-基)-2,3-二氢苯并呋喃-5-基]甲酮(2),2再通过醚化、肟化、贝克曼重排得到5,6-二甲氧基-N-[(R)-4-甲氧基-2-(丙烯-2-基)-2,3-二氢苯并呋喃-5-基]-1,1a,2,7b-四氢环丙并[c]苯并吡喃-7b-基甲酰胺(5),化合物的结构经1H NMR,MS和元素分析确认,采用单晶X射线衍射法确定化合物5的晶体结构.化合物5属于三斜晶系,P1空间群,晶胞参数:a=0.95772(5)nm,b=1.06591(6)nm,c=1.30112(7)nm,α=111.8460(10)°,β=109.8870(10)°,γ=93.0870°,V=1.13429(11)nm3,Z=2,Dc=1.281 g/cm3,μ(Mo Kα)=0.092 mm-1,F(000)=464.     

1-(2-炔丙基)-7,8-二氢喹啉-2,5(1H,6H)-二酮的合成

以1,3-环己二酮为原料,依次经亚胺化反应、Michael加成-环化反应、烷基化反应合成了含有端基炔的喹啉酮衍生物——1-(2-炔丙基)-7,8-二氢喹啉-2,5(1H,6H)-二酮,其结构经1H NMR,HR-MS和2D NMR确证。     

用"点击化学"法合成新型他克林-四氢异喹啉异二联体

从2-氯乙胺盐酸盐出发,经叠氮化与缩合反应制得9-(叠氮基乙基氨基)-1,2,3,4-四氢吖啶类衍生物(4a～4c);以6-庚炔-1-醇为原料,利用微波反应合成了2-(6.庚炔基)-6,7-二甲氧基-1-苯基-1,2,3,4-四氢异喹啉(7);4与7通过"点击化学"法合成了三个乙酰胆碱酯酶抑制剂-3个他克林-四氢异喹啉...     

4-(5-喹啉-3-基-四氮唑-2-基)丁胺的合成

三苯基膦钯催化3-溴喹啉完成氰化取代制得3-氰喹啉(1);1与叠氮化钠经[2+3]环加成合成了3-(2H-四氮唑-5-基)喹啉(2);2与N-(4-溴丁基)邻苯二甲酰亚胺反应制得2-[4-(5-喹啉-3-基-四氮唑-2-基)丁基]异吲哚-1,3-二酮(3);3经肼解合成了4-(5-喹啉-3-基-四氮唑-2-基)丁胺(4...     

简法合成二氢茉莉酮酸甲酯和二氢新茉莉酮酸甲酯

以环戊二烯为原料,先合成了环戊-2-烯酮(1),(1)经过Michael加成反应得到3-酮-环戊基乙酸甲酯(4)。再经过Aldol缩合反应和催化氢化,得到二氢茉莉酮酸甲酯和二氢新茉莉酮酸甲酯。     

Heterocyclic monomers via reissert chemistry

An AA bisphenolic monomer ( 13 ), an AB activated fluoro‐phenolic monomer ( 14 ), and an AB₂ alcohol‐diester monomer precursor ( 17 ), all based on the isoquinoline nucleus, were prepared using Reissert compound chemistry. Additionally, model reactions established the efficiency of condensation of isoquinoline Reissert compounds with dihaloalkanes, providing evidence of the potential of this reaction to produce high molecular weight polymers, which was subsequently realized. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

An unusual reaction of a Reissert compound involving alkylation,rearrangement, SNAr and SET processes

Reaction of isoquinoline Reissert compound 1 with NaH and then isopropyl iodide in DMF at 22?°C led to four isolated products. Ketone 3 is the expected product of the well-known rearrangement of the intermediate Reissert anion. Cyano lactam 4 results from S_NAr intramolecular displacement of the fluoride ion from the activated aroyl moiety of the anion. Isopropyl lactam 5 is proposed to result from a SET (single electron transfer) process via formation of the radical anion of 4, subsequent loss of the cyanide ion, and coupling of the resultant radical with isopropyl radicals formed via copper used to “stabilize” the alkyl iodide. The expected alkylated product 2 is also formed via a SET process involving electron transfer from the Reissert anion to 4, leading to the Reissert radical. Use of “non-stabilized” bromide or iodide led to 3 and 4, but did not produce 2 or 5.     

Synthesis and Crystal Structure of 3-Phenyl-10b-benzyl-1,10b-dihydroimdazo[5,1-a]isoquinoline

Praziquantel, 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one, is a novel antiparasitic drug possessing one chiral center.[1] In the study of structure-activity relationship of praziquantel we were interested in its structural modification. 1-Benzyl Reissert compound of isoquinoline is required as starting materials for the synthesis of praziquantel analogues with modified chiral centers. On the other hand, we want to know what could be obtained when 1-benzyl Reissert compounds were exposed to high pressure catalytic hydrogenation. In this paper we report the results in the hydrogenation of 1-benzyl Reissert compound.     

Synthesis of heterocyclic monomers via Reissert chemistry

The chemistry of Reissert compounds has been used to synthesize activated difluorotetraketone monomers containing two coupled isoquinolyl moieties, linked at either the 1,1′‐ or 4,4′‐positions. These monomers offer routes to novel families of poly(heteroarylene ether)s. New 4,4′‐coupled bis(Reissert compound) 9 containing 4,4′‐diketo moieties failed to afford the desired difluorotetraketo monomer upon attempted rearrangement. However, analogous bis(Reissert compound) 19 containing 4,4′‐dibenzyl units did so, via aldehyde condensation, hydrolysis of the intermediate ester and oxidation of the four benzylic moieties to keto groups; thus the novel difluorotetraketone monomer 10 was prepared. Novel bis(Reissert compound)s 24 , 28 , and 35 were synthesized from diacid chlorides and 4‐(p‐fluorobenzyl)isoquinoline. Rearrangement of 24 to the diketone 29 , followed by oxidation of the 4‐benzyl moieties resulted in difluorotetraketone monomer 30 containing a 1,1′‐linked bisisoquinoline. The 1,1′‐linked bis(isoquinolylfluorodiketo) monomer 38 , isomeric with 10 , was prepared from 4‐(p‐fluorobenzyl) Reissert compound 36 by condensation with terephthaldehyde, ester hydrolysis to diol 37 , and oxidation. In the course of this effort, a number of new isoquinoline Reissert compounds were synthesized as model systems. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3856–3867, 2010     

Stereochemistry of alkylated isoquinoline Reissert compounds

A series of alkylated isoquinoline Reissert compounds (2-acyl-1-alkyl-1,2-dihydroisoquinoline-1-nitriles) with either 3-H (3) or 3-CH₃ (4) substituents was examined by ¹H, ¹³C, and ¹⁹F NMR spectroscopies and X-ray crystallography. In all cases the trans-amide conformation, with reference to the carbonyl oxygen and the 3-position of the isoquinoline ring, exists exclusively in the solid state, and predominates in solution. As expected the 1-alkyl groups (isopropyl, isobutyl, benzyl) are nearly pseudo-axial or axial in all cases. In N-aroyl compounds the larger ortho-aroyl substituent lies syn to the 1-alkyl moiety in nine of the 11 cases, as revealed by X-ray crystallographic studies. In solution NMR results show that atropisomerism about the Ar/CO bond is usually rapid at room temperature, but slow at −50 °C and usually favors the syn isomer. CH?π interactions of the 3-methyl protons of 4 with the N-aroyl moieties appear to influence the atropisomerism.     

Synthesis of new fused isoquinolines via reissert compounds

Reissert compounds 2 derived from isoquinoline, chloroformates and TMS‐cyanide were alkylated in position 1. The resulting alkylation products 3 as well as the precursors 2 reacted with Grignard reagents affording imidazoisoquinolines 4, 5, 7 and 8 by addition to the cyano group and Grignard reduction or by twofold addition to the cyano group, respectively. In both cases the alcohol of the 2‐alkoxycarbonyl moiety was eliminated by attack of the N‐atom at the carbonyl carbon atom. Under acid conditions, 1‐benzylated Reissert compound 3h cyclised by attack of the resulting N‐acyliminium C‐atom at the o‐position of the benzyl ring to form tetracyclic 1,3‐bridged tetrahydroisoquinolines 10 and 11. Bromocyclisation of 1‐allyl‐2‐menthyloxycarbonyl‐substituted Reissert compounds 3b, c led to tricyclic dibromo products 12, in which the menthol moiety was split off and addition to the enamine double bond occurred. A 2‐menthyloxycarbonyl group in Reissert compounds 2a and 3 failed to exert an asymmetric induction in all cases.     

Nature of reissert analogs derived from N,N-dialkyl and N,N-diaryl carbamoyl chlorides

Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method. Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.     

5-羟基-3,4-二氢异喹啉-1-酮的合成

以异喹啉为起始原料,经成盐、磺化得异喹啉-5-磺酸(3),3与熔融的氢氧化钠和氢氧化钾反应得1,5-二羟基异喹啉(4),以5%Pd-C为催化剂还原4得5-羟基-3,4-二氢异喹啉-1-酮(1),总收率47.6%。1的结构经1H NMR和MS确证。     

Novel tricyclic heterocycles (benzopyrrocolines) arising via carbanion attack on a nitrile function

A new reaction of 2-n-alkanoyl-1,2-dihydroisoquinaldonitriles 1 (isoquinoline Reissert compounds) has been discovered. As previously reported reaction of the conjugate bases of Reissert compounds with alkyl halides yields the corresponding 1-alkyl derivatives 2 . However, compounds 2 , R = n-alkyl, with only a catalytic amount of bases form the enolate ion, which attacks the neighboring nitrile functionality to produce directly in the same reaction vessel excellent yields of benzopyrrocoline derivatives 5-10 . The nmr spectrum reveals a solvent dependent tautomeric equilibrium between ketoeneamine ( a ) and ketoimine ( b ) forms. Unlike compounds 2 the double bonds of the pyridine ring of compounds 7 and 8 were readily reduced with hydrogen. Thus, n-alkanoyl Reissert compounds afford a convenient route to the corresponding benzopyrroco-lines.     

Chemical modification of polymers. VII. Condensation of polymeric aldehydes with the anion of an isoquinoline reissert compound

The anion of the isoquinoline Reissert compound, 2-benzoyl-1,2-dihydroisoquinaldonitrile, reacts with polymeric aldehydes in essentially complete conversion, leading to polymeric esters containing isoquinoline moieties. These can be completely hydrolyzed to the corresponding alcohols. The reactivity of the Reissert anion toward polymeric halides and aldehydes is rationalized on the basis of its moderate hardness.