ZSM-5分子筛催化苯与甲醇烷基化反应研究进展

我们综述了近年来苯和甲醇烷基化反应研究取得的进展.重点从ZSM-5催化剂的Si/Al、晶粒尺寸、改性等方面介绍了苯和甲醇烷基化催化剂的研究进展,总结并展望了苯和甲醇烷基化反应的研究方向,为ZSM-5分子筛催化剂的改性和苯-甲醇烷基化反应工艺创新提供参考.     

Synthesis and evaluation of 1,2,8, 8a-Tetrahydrocyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one, the parent alkylation subunit of CC-1065 and the duocarmycins: impact of the alkylation subunit substituents and its implications for DNA alkylation catalysis

The synthesis of 1,2,8,8a-tetrahydrocyclopropa[c]pyrrolo[3, 2-e]indol-4(5H)-one (CPI), the parent CC-1065 and duocarmycin SA alkylation subunit, is detailed. The parent CPI alkylation subunit lacks the C7 methyl substituent of the CC-1065 alkylation subunit and the C6 methoxycarbonyl group of duocarmycin SA, and their examination permitted the establishment of the impact of these natural product substituents. The studies revealed a CPI stability comparable to the CC-1065 alkylation subunit but which was 6x more reactive than the (+)-duocarmycin SA alkylation subunit, and it displayed the inherent reaction regioselectivity (4:1) of the natural products. The single-crystal X-ray structure of (+)-N-BOC-CPI depicts a near identical stereoelectronic alignment of the cyclopropane accounting for the identical reaction regioselectivity and a slightly diminished vinylogous amide conjugation relative to (+)-N-BOC-DSA suggesting that the stability distinctions stem in part from this difference in the vinylogous amide as well as alterations in the electronic nature of the fused pyrrole. Establishment of the DNA binding properties revealed that the CPI-based agents retain the identical DNA alkylation selectivities of the natural products. More importantly, the C6 methoxycarbonyl group of duocarmycin SA was found to increase the rate (12-13x) and efficiency (10x) of DNA alkylation despite its intrinsic lower reactivity while the CC-1065 C7 methyl group was found to slow the DNA alkylation rate (4x) and lower the alkylation efficiency (ca. 4x). The greater DNA alkylation rate and efficiency for duocarmycin SA and related analogues containing the C6 methoxycarbonyl is proposed to be derived from the extended length that the rigid C6 methoxycarbonyl provides and the resulting increase in the DNA binding-induced conformational change which serves to deconjugate the vinylogous amide and activate the alkylation subunit for nucleophilic attack. The diminished properties resulting from the CC-1065 C7 methyl group may be attributed to the steric impediment this substituent introduces to DNA minor groove binding and alkylation. Consistent with this behavior, the duocarmycin SA C6 methoxycarbonyl group increases biological potency while the CC-1065 C7 methyl group diminishes it.     

汽油烷基化脱硫反应中噻吩及其衍生物的烷基化性能

 研究了噻吩、2-甲基噻吩、3-甲基噻吩和 2,5-二甲基噻吩等硫化物与己烯进行烷基化反应的性能. 结果发现,它们进行一次烷基化反应的能力都比较强,在实验条件下转化率几乎都达到了100%. 但噻吩衍生物与己烯进行二次以至多次烷基化反应的能力则随着噻吩环上支链的增加逐渐减弱,原因可能来自噻吩衍生物继续进行烷基化反应的热力学条件不利,以及环上已有侧链的空间位阻效应. 噻吩衍生物发生深度烷基化反应能力的减弱导致了另外两个并行竞争反应芳烃烷基化和烯烃烷基化(聚合)的反应程度增强,表现为芳烃转化率和己烯聚合量的升高,以及各自二次烷基化产物相对含量的增加.     

Microwave-assisted solid-phase synthesis of pseudopeptides containing reduced amide bond

Procedures were developed for reducing the reaction time and improving the yield of reductive alkylation in solid phase pseudopeptide synthesis by utilizing microwave irradiation. We chose dipeptides containing the reduced amide bond ψ[CH₂NH] as a model system and optimized the microwave assisted reductive alkylation reaction in solid phase pseudopeptide synthesis using Fmoc chemistry. Under the optimized condition, the reductive alkylation reaction used for incorporating the reduced amide bond into the dipeptides was completed in only 8.5 min, whereas the normal reductive alkylation reaction required a total of 300 min. The purity and yield of the various dipeptides containing the reduced amide bond synthesized in this way are better than those achieved using the reductive alkylation method without microwave irradiation. We chose α helical peptides, which are known as a difficult sequence to synthesize, and incorporated the reduced amide bond by the microwave-assisted reductive alkylation reaction. We successfully synthesized pseudopeptides containing the reduced amide bond as a major product by using the novel microwave-assisted method, whereas the same products were obtained as a minor product when using the reductive alkylation method without microwave irradiation.     

KF/Al2O3‐Mediated N‐Alkylation of Amines and Nitrogen Heterocycles and S‐Alkylation of Thiols

KF/Al₂O₃ efficiently catalyzes N‐alkylation of heterocyclic, primary, and secondary amines and S‐alkylation of thiols with a variety of alkyl halides. The N‐alkylation and S‐alkylation adducts were produced in good to excellent yields and in short times.     

有机杂化介孔Beta分子筛的合成及在苯甲醇烷基化反应中的应用

针对沸石分子筛在苯甲醇和三甲基苯的烷基化催化反应应用中存在催化活性低及微孔孔道内大量苯甲醇自醚化副反应导致产物选择性低这一难题, 通过引入等级孔结构提高外比表面积和有机杂化修饰封堵微孔孔道的双重策略, 在大幅提升可接触的外表面活性中心数量的同时有效降低苯甲醇进入微孔孔道内发生自醚化副反应, 开发出具有高反应活性及烷基化产物选择性的有机杂化介孔Beta分子筛材料, 大幅度提升了其对苯甲醇和三甲基苯的烷基化反应的催化活性和产物的选择性, 使苯甲醇的转化率从66.8%提升到了99.7%, 烷基化产物的选择性从14.8%提高到50.7%. 本工作为开发高活性及高选择性的烷基化催化剂提供了新的思路.     

Iron salt-catalyzed cascade type one-pot double alkylation of indole with vinyl ketones

Indole was reacted with vinyl ketones in the presence of 5-8 mol % of iron (II) tetrafluoroborate or iron (III) perchlorate to give 2,3-dialkylated products; initial alkylation took place at 3-position on the indole ring and subsequent alkylation occurred at 2-position. It was found that the first alkylation proceeded very quickly, while the reaction rate of the second alkylation was very slow. Using this, cascade type synthesis of 2,3-dialkylated-indoles has been accomplished using iron (III)salt as catalyst.     

Alkylation kinetics of proteins in preparation for two-dimensional maps: a matrix assisted laser desorption/ionization-mass spectrometry investigation

All existing protocols for protein separation by two-dimensional (2-D) gel electrophoresis require the full reduction, denaturation, and alkylation as a precondition for an efficient and meaningful separation of such proteins. Existing literature provides a strong evidence to suggest that full reduction and denaturation can be achieved in a relatively short time; the same thing, however, can not be said for the alkylation process, which the present study shows that more than 6 h are required for a complete alkylation. We have used matrix assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS) to monitor protein alkylation by iodoacetamide over the period 0-24 h at pH 9. The present, fast and specific MS method provided clear indication on the extent and speed of alkylation which reached approximately 70% in the first 2 min, yet the remaining 30% resisted complete alkylation up to 6 h. The use of sodium dodecyl sulfate (SDS) during the alkylation step resulted in a strong quenching of this reaction, whereas 2% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) exerted a much reduced inhibition. The implications of the present measurements on 2-D gel analysis in particular and proteomics in general are discussed.     

Role of the countercation in diastereoselective alkylations of pyramidalized bicyclic serine enolates. An easy approach to alpha-benzylserine

The use of a chiral serine equivalent as an excellent chiral building block has been demonstrated in the synthesis of alpha-benzylserine through a diastereoselective lithium enolate alkylation reaction and subsequent acid hydrolysis. The role of a coordinating countercation (lithium) in the alkylation reaction has been investigated. Theoretical studies have been performed in order to elucidate the stereochemical outcome of the alkylation process, which occurs with total retention of configuration.     

Efficient asymmetric synthesis of novel gastrin receptor antagonist AG-041R via highly stereoselective alkylation of oxindole enolates

An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.     

Novel tricyclic diamines 3. Synthesis of 1,4-diazaadamantane

Synthesis of the previously unreported 1,4-diazaadamantane is described. The overall strategy involves complete saturation of a flat, aromatic heterocycle, appropriate functionalization and intramolecular double alkylation. The alkylation takes place via an iminophosphorane under anhydrous conditions, which produced superior results vs. alkylation of the corresponding primary amine.     

Visible Light‐Induced Decarboxylative Alkylation of Heterocyclic Aromatics with Carboxylic Acids via Anthocyanin as a Photocatalyst

A visible light‐induced decarboxylative alkylation of heterocyclic aromatics with aliphatic carboxylic acids was developed by using anthocyanins as a photocatalyst under mild conditions. A series of alkylated heterocyclic compounds were obtained in moderate to good yields by using the metal‐free decarboxylative coupling reaction under blue light. This strategy uses cheap and readily available carboxylic acids as alkylation reagents with good functional group tolerance and environmental friendliness. It is worth noting that this is the first time that anthocyanin has been used to catalyze the Minisci‐type C?H alkylation. The mechanism of decarboxylation alkylation was studied by capturing the adduct of alkyl radical and hydroquinone, thus confirming a radical mechanism. This protocol provides an alternative visible light‐induced decarboxylative alkylation for the functionalization of heterocyclic aromatics.     

Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland-Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation sequence: scope and applications of organocatalytic biomimetic reductions

A practical and novel organocatalytic chemo- and enantioselective process for the cascade synthesis of highly substituted 2-alkyl-cyclohexane-1,3-diones and Wieland-Miescher (W-M) ketone analogs is presented via reductive alkylation as a key step. First time, we developed the one-step alkylation of dimedone and 1,3-cyclohexanedione with aldehydes and Hantzsch ester through an organocatalytic reductive alkylation strategy. Direct combination of l-proline-catalyzed cascade Knoevenagel/hydrogenation and cascade Robinson annulation of CH acids (dimedone and 1,3-cyclohexanedione), aldehydes, Hantzsch ester, and methyl vinyl ketone furnished the highly functionalized W-M ketone analogues in good to high yields and with excellent enantioselectivities. Many of the reductive alkylation products show a direct application in pharmaceutical chemistry.     

Reactions of unsaturated acid halides—IV: Competitive friedel-crafts acylations and alkylations of monohalogenobenzenes by the bifunctional cinnamoyl chloride

Aluminium chloride-catalysed acylations and alkylations of monohalogenobenzenes with cinnamoyl chloride has been studied. Under strictly homogeneous conditions, alkylation was increasingly favoured relative to acylation as the primary reaction along the series: benzene <fluorobenzene<bromobenzene<chlorobenzene. Changing to heterogeneous conditions (excess catalyst with CS₂ as diluent) preserved this order but primary alkylation was relatively enhanced. The addition of nitrobenzene to the homogeneous reaction restrained alkylation more than acylation.Primary acylation may be followed by alkylation giving asymmetrical 1,3,3-triarylpropan-1-ones but the possibility that these are formed by alkylation followed by acylation is ruled out. These ketones may subsequently undergo α,β-ketonic fission.Primary alkylation may be followed by cycliacylation producing 3-arylindan-l-ones with the halogeno substituent at the side-chain aryl group and this observation rules out their alternative mode of formation, cyclialkylation of the primary acylation product.An example of a para → meta bromine shift is discussed.     

离子液体中异丁烷/2-丁烯烷基化反应机理研究

以复合离子液体[Et_3NH]Cl-AlCl_3-CuCl为催化剂,在连续搅拌釜式反应器中进行了异丁烷与2-丁烯烷基化反应;利用氘代异丁烷同位素示踪法研究了催化反应机理。结果表明,在离子液体中异丁烷烷基化的反应诱导期较短;三甲基戊烷产物主要源于异丁烷的自烷基化、丁烷/丁烯的直接烷基化以及C_(12)~+中间体的裂化反应,而大部分二甲基己烷是仲丁基碳正离子与丁烯加成的产物。     

丝光沸石催化愈创木酚选择性烷基化反应的研究

本文研究了氢型丝光沸石催化愈创木酚(1)与莰烯(2)的选择性烷基化反应. 该烷基化反应产物萜基愈创木酚(3～6)中含5-异莰基愈创木酚(3a)25.0%, 经氢化, 氢解得萜基环己醇混合物, 含人造檀香主要成份反式-3-异莰基环己醇(7a)23.0%. 通过IR, ^1H NMR 和MS鉴定了烷基化产物色谱图中的5个主要化合物.     

超临界流体状态下的异构烷烃与烯烃烷基化反应

成功地应用固体酸催化剂在超临界反应条件下进行了异构烷烃与丁烯的烷基化反应。在超临界反应条件下,固体酸催化剂在１４００ｈ的反应以后,仍保持１００％的烯烃转化率。探索出一个解决固体酸催化剂在烷基化反应中极易失活的有效方法。探讨了超临界流体抑制固体酸催化剂结炭失活的机制和烷基化反应中选择超临界反应条件的规律。     

Total Synthesis of (-)-Tetrahydropalmatine via Chiral Formamidine Carbanions: Unexpected Behavior with Certain Ortho-Substituted Electrophiles

A method has been developed by alkylation of chiral lithioformamidines to construct protoberberine alkaloids with a C(9) and C(10) D-ring substitution pattern. This ring pattern was established using an ortho-substituted hydroxymethylbenzene electrophile protected as a silyl ether to ultimately provide (-)-tetrahydropalmatine in 88% ee. Additionally, we have discovered limitations with ortho-substituted electrophiles in the asymmetric formamidine alkylation. These electrophiles have the potential to disrupt the lithium formamidine chelate and cause the selectivity in the alkylation to be uncharacteristically low. The total synthesis of (+/-)-canadine and (-)-tetrahydropalmatine along with the limitations to the formamidine alkylation technology are delineated herein.     

Structural characterization of melphalan modified 2′-oligodeoxynucleotides by miniaturized LC-ES MS/MS

In this study a miniaturized LC coupled to electrospray tandem mass spectrometry was used to analyze modifications originating from the interaction between the chemotherapeutic agent melphalan and 2'-oligodeoxynucleotides. Low energy CAD product ion spectra gave information about the specificity of melphalan alkylation with regard to certain DNA sequences. These data can be very useful to estimate the risk in the development of secondary leukaemia as a result of a melphalan cure. In the study of the interaction between melphalan and d(GG), differentiation could be made between alkylation on the 5'-side and alkylation on the 3'-side, because of the presence or absence of the alkylated w1 fragment in the low energy CAD spectra. In the other di-mers alkylation specificity for the different bases could be observed. Melphalan alkylation occurs in the sequence G > A > C > T. The study of the alkylated d(GGGG) revealed the presence of mainly 5'-end alkylation. Furthermore studies were performed which investigated other melphalan treated di-, tetra-, hepta-, and octa-mers.