Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• . Results and Discussion Our strategy for an efficient construction of (R) and (S)-N-(2,3-dihydroxypropyl)benzamide (6a) is outlined in Scheme 1. We envisioned that the opening of the phthalimide ring in (S)-3-(1,3-dioxoisoindolin-2-yl)-2-hydroxypropyl benzoate (5a) would afford the desired benzamide 6a

• was concentrated, and the crude mixture was directly used for column chromatography with 100% ethyl acetate. After column chromatographic purification, the product was isolated as a colorless liquid in 94% yield. (S)-N-(2,3-dihydroxypropyl)benzamide (6a): Viscous liquid: yield: 2.45 g (94%); IR (KBr

• [M + 1]; HRMS: calcd for C10H14NO3, 196.0967; found, 196.0974; HPLC: (Chiral PAK-1A (250 × 4.6 mm, column 5.0 u), 1.0 mL/min, 220 nm, n-hexane/IPA 80:20, ambient, 5 µL, retention times: 6.26 min, 100% ee; [α]D25 −12.44 (c 0.75, methanol). (R)-N-(2,3-dihydroxypropyl)benzamide (6b): Viscous liquid

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• . Importantly, 94 showed superior peak brain uptake (2.08% ID/g at 30 min) and faster brain washout than 58a in normal mice. Expanding on this 2-arylbenzoxazole scaffold, a series of benzamide-substituted 2-arylbenzoxazoles 95a–n was synthesized [71]. A representative synthesis of [123I]95e is shown (Scheme 8B

• target compound. SAR analysis of the compounds indicates that the benzamide moiety is favored at position 5 rather than 6 of the benzoxazole core in terms of binding affinity for Aβ plaques in vitro (Table 9). The best compound was 95e, which had a Ki value of 9.3 nM, but [123I]95e was unable to cross

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• benzophenone is tolerated on the benzamide ring with retention of the biological activity (3, Table 1) [23]. In addition to a PG, we needed a suitable linking functionality for attachment of a clickable acetylene group. Preliminary work (data not shown) established that an ether (versus amide) linker was

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• diastereoiomers; following column chromatography, the major diastereomer 22 was obtained in 70% yield, and was converted into the corresponding amino alcohol 23. The configuration of the amino alcohol 23 was determined by conversion into the corresponding benzamide and comparison with racemic and enantiomerically

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• substrates (Table 1). N-Benzyl-4-bromo-7-azainole (1-benzyl-4-bromo-1H-pyrrolo[2,3-b]pyridine, 1e) and benzamide (2a) were chosen as model substrates to find the suitable palladium-mediated coupling of amides with N-protected 4-bromo-7-azaindole 1. After extensive screening, we found that the combination of

• obtained (Table 1, entries 6 and 7). When tertiary ligand PCy3 (L4) was used as a ligand for the cross-coupling reaction no product formation was observed (Table, entry 5). Cross-coupling reaction of N-benzyl-4-bromo-7-azaindole (1e) and benzamide (2a) with other bases, e.g., K2CO3 and K3PO4, by using Pd

• conditions in dioxane [57]. The optimized reaction conditions worked well with benzamide (2a) (Table 2, entry 3) and phenylsulfonamide (2b) (Table 2, entry 4) to obtained a good yield. A cyclic secondary amide (lactam) 2c also reacted efficiently (Table 2, entry 5). The methodology works equally well with 2

On the control of secondary carbanion structure utilising ligand effects during directed metallation

• Andrew E. H. Wheatley,
• Jonathan Clayden,
• Ian H. Hillier,
• Alison Campbell Smith,
• Mark A. Vincent,
• Laurence J. Taylor and
• Joanna Haywood

Beilstein J. Org. Chem. 2012, 8, 50–60, doi:10.3762/bjoc.8.5

• towards the study of the competition between the ortho and lateral deprotonation of 2-alkylated benzamide substrates. Hence, 2-ethylated analogues of 1-H and 2-H (3-H and 4-H, respectively; Scheme 2) have been treated with t-BuLi in the presence of either PMDTA (N,N,N′,N″,N″-pentamethyldiethylenetriamine

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• benzamide 56 with sec-BuLi/TMEDA (1.05 equiv, 3 h, −78 °C) and addition of the resulting organolithium agent to 65 was presumed to form the alkoxide 66. In situ treatment of 66 with t-BuLi induced bromine–lithium exchange and cyclization of organolithium species 67 to a product that was believed to be 68

• detailed in the isolation paper [90][91]. An unexpected problem materialized when the foregoing sequence was transposed to the case of topopyrone B, the synthesis of which required the execution of the same operations starting with benzamide 57. Surprisingly, this material resisted deprotonation under

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• Ar–CO axis as a chiral “aide-mémoire” for translating the configuration of the starting amino acid into the configuration of the product. We have previously employed benzamide and naphthamide Ar–CO axes in “chiral memory” processes [52][53]. Kouklovsky reported the enantioselective alkylation of

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• of DMSO-d6 at δ 2.50 ppm for 1H (297.801 MHz) and δ 39.50 ppm for 13C (76.190 MHz), while 15N (30.188 MHz) chemical shifts were referenced relative to external benzamide (δ 103.55 ppm). Individual resonances were assigned on the basis of their chemical shifts, signal intensities, multiplicity of

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• (eluent:hexane/EtOAc 3:1) to give 64 as a pale yellow oil (300 mg, 73%). (S)-N-{1-[1-(tert-Butyldimethylsiloxy)ethyl]-2-methoxy-3-oxo-but-1-enyl}benzamide (64) 1H NMR (500 MHz, CDCl3) δ 0.07, 0.11, 0.88 (3 s, 3H, 3H, 9H, OTBS), 1.46 (d, J = 6.4 Hz, 3H, 2’’-H), 2.32 (s, 3H, 4’-H), 3.51 (s, 3H, OMe), 5.33 (q, J

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• the intramolecular photocycloaddition of a cinnamoylamide and a benzamide moiety (Scheme 32) [97]. This reaction is very efficient and leads to high yields of the bicyclo[2.2.2]octadiene derivative. In this example, the cinnamoylamide is sensitized by benzil to its triplet excited-state. The proposed

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• the starting material (Scheme 8). In this reaction, compound 25 was readily hydrolyzed to afford the β-ketonitrile derivative, i.e., 4-(1-cyano-2-oxoethyl)benzamide 26 which reacted efficiently with hydrazines to give the corresponding 5-aminopyrazoles 27. Subsequent cleavage from the resin afforded 5

• , imidazo[1,2-b]pyrazol-2-ones. Synthesis of 5-amino-3-(pyrrol-2-yl)pyrazole-4-carbonitrile. Synthesis of N-(1,3-diaryl-1H-pyrazol-5-yl)benzamide. Synthesis of 3,7-bis(arylazo)-6-methyl-2-phenyl-1H-imidazo[1,2-b]pyrazoles. Synthesis of 3,5-diaminopyrazole. Synthesis of 5-amino-4-cyanopyrazole and 5-amino-3

Self-assembly and semiconductivity of an oligothiophene supergelator

• Pampa Pratihar,
• Suhrit Ghosh,
• Vladimir Stepanenko,
• Sameer Patwardhan,
• Ferdinand C. Grozema,
• Laurens D. A. Siebbeles and
• Frank Würthner

Beilstein J. Org. Chem. 2010, 6, 1070–1078, doi:10.3762/bjoc.6.122

• (dodecyloxy)benzamide (6). Compound 4 (2.94 mmol) was dissolved in 5 mL dry CH2Cl2 and cooled in an ice-bath. To this cold solution, 4 mL triethylamine was added slowly. The resulting mixture was ice-cooled for an additional 10 minutes and then a solution of compound 5 in 10 mL dry CH2Cl2 was added dropwise

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• and new reactivity from simple, readily made starting materials. We have used cyclisations of benzamide-stabilised carbanions, for example, to give bicyclic functionalised indolinones as intermediates in the synthesis of the neuroactive amino acids [22][23][24][25][26][27][28][29][30][31][32], while

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

• drastic reaction conditions [19][22]. In this paper, we report the reaction of amides with DMSO activated by CC or 2,4-dichloro-6-methoxy[1,3,5]triazine (DCMT) [24]. Results and Discussion Initially, we chose CC as the activation reagent and benzamide as a model substrate to optimize the reaction

• amides: considerable amounts of by-products were formed, probably due to the greater nucleophilicity of the aliphatic amides. In order to improve the yield of aliphatic amides, less active DCMT was used as activating reagent instead of CC. We also optimized the reaction conditions using benzamide as a

• these experiments, a possible mechanism [6][23][25] is shown in Scheme 5. Intermediate 1 reacted with amides by two pathways. When the reaction of benzamide and CC-activated DMSO was carried out in chloroform, S,S-dimethyl-N-benzoylsulfilimine (4) was isolated as a major product, most probably formed by

The enantiospecific synthesis of (+)-monomorine I using a 5-endo- trig cyclisation strategy

• Malcolm B. Berry,
• Donald Craig,
• Philip S. Jones and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2007, 3, No. 39, doi:10.1186/1860-5397-3-39

• protecting groups. The full evolution of the 5-endo-trig cyclisation-based pyrrolidine methodology will be described in a future publication. Key to the successful synthesis of (+)-monomorine I was the use of the N-(benzoyl)aminosulfone 11 (Scheme 3). Benzamide 11 could be prepared from N-(diphenylphosphinyl

Synthesis of phosphorothioates using thiophosphate salts

• Babak Kaboudin and
• Fatemeh Farjadian

Beilstein J. Org. Chem. 2006, 2, No. 4, doi:10.1186/1860-5397-2-4

• chlorides. Reaction of ammonium O,O'-diethyl thiophosphate with benzoyl chloride, as a model compound, in acetonitrile gave benzamide as the major product (Scheme 5). Benzoyl chloride reacts with ammonia (from ammonium O,O'-diethyl thiophosphate) faster than anion O,O'-diethyl thiophosphate to give

• benzamide. All efforts for solving this problem failed and in all cases benzamide was obtained as the major product. We decided to replace this ammonium ion with a triethyl ammonium ion and then to study the reaction of new salt with benzoyl chloride. Triethylammonium O,O'-diethyl thiophosphate was obtained

EcoScale, a semi- quantitative tool to select an organic preparation based on economical and ecological parameters

• Koen Van Aken,
• Lucjan Strekowski and
• Luc Patiny

Beilstein J. Org. Chem. 2006, 2, No. 3, doi:10.1186/1860-5397-2-3

• benzoic acid [24] Synthesis of benzamide [25] Synthesis of benzamide using HMDS [26] The penalty points to calculate the EcoScale The penalty points for example 1 The penalty points for example 2 The penalty points for example 3 The penalty points for example 4

Total syntheses of oxygenated brazanquinones via regioselective homologous anionic Fries rearrangement of benzylic O-carbamates

• Glaucia Barbosa Candido Alves Slana,
• Mariângela Soares de Azevedo,
• Rosângela Sabattini Capella Lopes,
• Cláudio Cerqueira Lopes and
• Jari Nobrega Cardoso

Beilstein J. Org. Chem. 2006, 2, No. 1, doi:10.1186/1860-5397-2-1

• conjecture that, barring the competitive [1,2]–Wittig rearrangement, and one-pot route, 3 → 4 → 1, may be established in a direct manner without resort to DoM-derived benzamide intermediate, thereby establishing new carbonyl dianion equivalency 4 (see Scheme 1). We now report the versatility of this strategy