The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• (Table 1, entry 7) to completion, it was found that heating the monolith resulted in the production of an impurity, at 29.7% conversion by 1H NMR (with 64.5% conversion to the bromide). This was identified as 1-(chloromethyl)-4-iodobenzene, i.e., the starting material underwent chlorination rather than

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• acids) [76][77][78] also catalyzed the chlorination of β-ketoesters with N-chlorosuccinimide or N-chlorosulfonamides as halogenating agents [43]. The Lewis acid catalyzed halogenations of β-ketoesters present an interesting alternative to either radical or neutral noncatalyzed reaction modes. Catalytic

• (Table 3). Results for either fluorination (→6-F) with F–TEDA or the more soluble reagent NFSI (N-fluorobenzenesulfonimide) and NCS (N-chlorosuccinimide) for chlorination [43] (→6-Cl) are displayed in Table 3. Above ambient temperature, increasing temperatures give lower selectivity (Table 3, entries 1–3

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• yield, as well as the sPLA2 inhibitor 123, in a short reaction sequence (Scheme 19) [46]. Using TMPMgCl·LiCl (41), it is possible to prepare fully substituted indoles, such as 128 (Scheme 20) [47]. Thus, starting from the aniline 124, an ortho-directed chlorination with N-chlorosuccinimide at 90 °C

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• replaced by an N-acylated amide which is suggested to mimic the C-terminus of angiotensin II [49]. The imidazole ring of losartan, an antihypertensive and angiotensin II blocker is formed in a condensation reaction between valeroamidine 160 and dihydroxyacetone [50]. It was found that direct chlorination

• of the imidazole 162 also forms the dichlorination product 164 (as shown in Scheme 33) with formaldehyde as a by-product which proved difficult to suppress and made purification of the reaction mixture problematic. Hence, a sequence involving silyl protection, chlorination and deprotection was

A two step synthesis of a key unit B precursor of cryptophycins by asymmetric hydrogenation

• Benedikt Sammet,
• Mathilde Brax and
• Norbert Sewald

Beilstein J. Org. Chem. 2011, 7, 243–245, doi:10.3762/bjoc.7.32

• tolerated. Both the methoxy and the chloro substituent are required for full biological activity [1][2][3][4]. The previously published synthetic route to unit B precursor 4 involves a three-step modification of D-tyrosine by chlorination, protecting group introduction and double methylation followed by a

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• chains have been limited to trifluoromethylated compounds. This was due to the unique preparation (at that time) of such compounds by means of two consecutive reaction steps: the chlorination of the side chain followed by replacement of the chlorine atoms by fluorine. This procedure enabled only the

• chlorination with only minor amounts of bis-(CF3S) products (Scheme 12). Aryl magnesium [78] and -mercury [79] compounds have been employed for the introduction of CF3S groups. Such reactions proceed in ether or THF at low temperatures; however, the yields of aryltrifluoromethyl sulfides do not exceed 50–60

Synthesis of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide – a tailor-made photoinitiator for dental adhesives

• Norbert Moszner,
• Iris Lamparth,
• Jörg Angermann,
• Urs Karl Fischer,
• Frank Zeuner,
• Thorsten Bock,
• Robert Liska and
• Volker Rheinberger

Beilstein J. Org. Chem. 2010, 6, No. 26, doi:10.3762/bjoc.6.26

• . The identity of compound 4 was established by an independent synthesis of the compound from 2-(allyloxy)ethanol and 3-(chloromethyl)-2,4,6-trimethylbenzoyl chloride 3, prepared by chlorination of 3-(chloromethyl)-2,4,6-trimethylbenzoic acid with thionyl chloride. In the third step, the

• in acetonitrile (10−3 mol/L). DSC-plot of a mixture of Bis-GMA (42 wt %), UDMA (37 wt %), TEGDMA (21 wt %) and the PI WBAPO or BAPO. Bisacylphosphine oxide with improved solubility in polar solvents. Etherification of 3-(chloromethyl)-2,4,6-trimethylbenzoic acid and chlorination of 1. Rearrangement

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• , lower toxicity, and the fact that only stoichiometric amounts of water are generated as the side product the FC alkylation with benzyl-, allyl- and propargyl alcohols presented a first and important step toward an environmental friendly process. In 1986, Uemura et al. investigated the chlorination of

• authors explained this observation with a chlorination of 1-phenylethanol 1 and subsequent FC alkylation of the formed benzyl chloride and toluene. However, more surprisingly the reaction yield could be improved to 93% if only catalytic amounts (10 mol%) of TeCl4 were present (Scheme 3) [2]. Although the

Palladium- catalyzed cross coupling reactions of 4-bromo- 6H-1,2-oxazines

• Reinhold Zimmer,
• Elmar Schmidt,
• Michal Andrä,
• Marcel-Antoine Duhs,
• Igor Linder and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2009, 5, No. 44, doi:10.3762/bjoc.5.44

• chlorination of 6H-1,2-oxazines 1a,b by addition of chlorine and subsequent base-induced dehydrochlorination. The expected 4-chloro-6H-1,2-oxazines 6a,b were obtained in good yields. In analogy to the aforementioned bromination, the chlorination of 3-phenyl-6H-1,2-oxazine 1a also led to dihalogenation

• . HRMS (80 eV, 40 °C) m/z calcd for C12H1179Br2NO2: 358.9157; found: 358.9160. Chlorination of 6H-1,2-oxazine 1b, typical procedure Chlorine gas was passed into diethyl ether (28 mL) at −30 °C until the solution became dark yellow. Then, 6H-1,2-oxazine 1b (0.200 g, 1.00 mmol) was added and the reaction

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• also employed in a similar flow system for the asymmetric α-chlorination of acid chlorides (Scheme 7) [31][32]. This cinchona alkaloid derivative served the dual purpose of dehydrohalogenation and asymmetric induction, and was found to be reusable at least up to 100 times, after regeneration each time

• by flushing with a solution of i-PrNEt2 in THF. A diastereoselective synthesis of the metalloproteinase inhibitor BMS-275291 24 was developed using this column-based flow approach, with this α-chlorination reaction as a key step (Scheme 7) [32]. The Michael addition of indanone 26 to methyl vinyl

• flow. Asymmetric synthesis of ß-lactams. α-Chlorination of acid chlorides in flow. Asymmetric Michael reaction in continuous flow. Enantioselective addition of Et2Zn to benzaldehyde using monolithic chiral amino alcohol. Continuous-flow hydrolytic dynamic kinetic resolution of epibromohydrin (32

Synthesis of methylenebisamides using CC- or DCMT- activated DMSO

• Qiang Wang,
• Lili Sun,
• Yu Jiang and
• Chunbao Li

Beilstein J. Org. Chem. 2008, 4, No. 51, doi:10.3762/bjoc.4.51

• on the chlorination [10] and etherification [11] of benzyl alcohols and from other references [12][13][14], we believe the reaction between 2,4,6-trichloro[1,3,5]triazine (cyanogen chloride, or CC) and DMSO produces a reactive sulfonium salt intermediate. Therefore, it was of interest to study the

Ru-catalyzed dehydrogenative coupling of carboxylic acids and silanes - a new method for the preparation of silyl ester

• Guo-Bin Liu and
• Hong-Yun Zhao

Beilstein J. Org. Chem. 2008, 4, No. 27, doi:10.3762/bjoc.4.27

• chlorination of silanes, either with chlorine gas [7] or with hydrochloric acid under Pd/C catalysis [25][26], the synthesis of silyl esters from the corresponding silanes requires two reaction steps. Some newer synthetic protocols to silyl esters have been developed and a lot of literature focuses itself on

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• works well with electron-deficient anisoles cannot be applied to anisole itself. In fact, halogen attack on the phenyl ring proceeds more easily than radical chlorination of the methyl group. Louw and Franken could show that with elemental chlorine, photostimulated in refluxing tetrachloromethane

• , essentially trichloromethylanisole is obtained [20]. The fluorination of the trichloromethyl ether succeeds then easily as shown above. The chlorination/fluorination sequence described above can be simplified by producing the trichloromethyl aryl ethers without isolation and through in situ conversion into

• developed an approach based on the readily accessible, although highly toxic aryl chlorothionoformates 1. They can be cleanly converted by chlorination into trichloromethyl aryl ethers [17]. This step is then followed by fluorination using antimony trifluoride and a catalytic amount of antimony

Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

• John W. Hull Jr.,
• Duane R. Romer,
• David E. Podhorez,
• Mezzie L. Ash and
• Christine H. Brady

Beilstein J. Org. Chem. 2007, 3, No. 23, doi:10.1186/1860-5397-3-23

• /debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of

• thiophene ring without isolation of the tribromo intermediate 6. The final low-melting acid chloride 1 was readily purified by vacuum distillation on a 250 g laboratory scale to remove a small amount of tar and gave 1 as a light-yellow colored product. Vapor Phase Chlorination Studies. Routes to 3,4,5

• from 2-chloromethyl-3,4,5-trichlorothiophene. [21] However, since 2-thiophenecarbonitrile 20 was commercially available, we investigated the vapor phase chlorination of this starting material as a potential convenient manufacturing route to 3 that could be carried out on a multi-Kg scale (Scheme 3