Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• synthesis of N-alkylcarboxyspiropyrans (e.g., C4SP) involves N-alkylation of 2,3,3-trimethylindolenine (1) with a bromoalkanoic acid or ester 2, isolation of the resulting indolium salt 3 or treatment with base to generate the exo-methylene enamine 4, then condensation with the appropriate salicylaldehyde 5

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• invented an unprecedented effect of salicylaldehyde, one of the A3 coupling partners, which could lead to the formation of propargylamine, an important pharmaceutical building block, in the absence of any metal catalyst and under mild conditions. The role of the hydroxy group in ortho position of

• salicylaldehyde has been explored, which presumably activates the Csp–H bond of the terminal alkyne leading to the formation of propargylamines in good to excellent yields, thus negating the function of the metal catalyst. This observation is hitherto unknown, tested for a variety of salicylaldehyde, amine and

• acetylene, established as a general protocol, and is believed to be of interest for synthetic chemists from green chemistry. Keywords: A3 coupling; metal-catalyst-free; propargylamine; salicylaldehyde; terminal alkyne; Introduction Propargylamines are important synthetic intermediates for the preparation

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• conversion of aldehydes to vinyl iodides, and has seen widespread implementation in organic synthesis. The reaction is usually noted for its high (E)-selectivity; however, herein we report the highly (Z)-selective Takai olefination of salicylaldehyde derivatives. Systematic screening of related substrates

• standard) for a larger scale reaction. Unsubstituted salicylaldehyde (12) was chosen for this experiment, as it contains the core structure present in all the examples above, and gives approximately equal amounts of the (E)- and (Z)-products (Scheme 5). Initially, low recovery of material was observed

• )-selectivity. Additionally, with careful design of substrates, synthetic routes utilising (Z)-selective Takai olefinations can now be considered, a strategy which has been hitherto unprecedented. A control experiment showed that, in the presence of 0.5 equivalents of salicylaldehyde, benzaldehyde was converted

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• b) [24]. Similarly, treatment of 2a with salicylaldehyde furnished the 3-sulfonyl-2H-chromene derivative 4 in 69% yield (Scheme 1, path c) [24]. The formation of allenyl sulfone 5 and propargyl sulfone 6 in the reaction of 2a with cesium carbonate indicated that 5 is an intermediate in the above

• -mentioned reactions (Scheme 1, path d) [24]. The facile cyclocondenzation of salicylaldehyde with 2a (Scheme 1, path c) prompted us to explore analogous annulation reactions for the synthesis of functionalized chromene derivatives. The biological activities exhibited by many 4H-chromene derivatives provided

• salicylaldehyde and Cs2CO3 and d) reaction of 2a with Cs2CO3. Base-mediated cyclization reaction of o-hydroxychalcone 7a and 2-bromoallyl sulfone 2a. Preparation of ortho-hydroxychalcones 7a–i. Synthesis of 4H-chromenes via base-mediated reactions of 7a–i and 2a,b. Reaction conditions: 7a–i (0.25 mmol), 2a,b

Robust bifunctional aluminium–salen catalysts for the preparation of cyclic carbonates from carbon dioxide and epoxides

• Yuri A. Rulev,
• Zalina Gugkaeva,
• Victor I. Maleev,
• Michael North and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2015, 11, 1614–1623, doi:10.3762/bjoc.11.176

• -(tert-butyl)salicylaldehyde (5) [24][25][26][27]. 5-N,N-Dimethylamino-3-(tert-butyl)salicylaldehyde (6) was prepared directly from 5, using a literature procedure [28][29]. The salen ligand 7 was then obtained in high yield by condensation with (R,R)-cyclohexanediamine, according to a known technique

• complex in situ, as shown in Scheme 4. High activities for this type of dinuclear complexes have been reported before [31]. In order to prove the bifunctional nature of our catalysts, aluminium complex 10 was prepared (Scheme 3) using 3,5-di-(tert-butyl)salicylaldehyde as a starting material. It was found

Fluoride-driven ‘turn on’ ESPT in the binding with a novel benzimidazole-based sensor

• Kai Liu,
• Xiaojun Zhao,
• Qingxiang Liu,
• Jianzhong Huo,
• Bolin Zhu and
• Shihua Diao

Beilstein J. Org. Chem. 2015, 11, 563–567, doi:10.3762/bjoc.11.61

• selectively fluorescence enhancement for fluoride by ESPT. Importantly, BIP displayed a fluoride-selective fluorescence response with a wider linear range from 0.04 to 1.2 μM. Results and Discussion BIP was synthesized by the condensation of 2-aminobenzimidazole and 4-(dimethylamino)salicylaldehyde according

• neutral and anionic guest may contribute to design more efficient anion chemosensors. Experimental Synthesis of compound 1: 4-(Dimethylamino)salicylaldehyde was synthesized according to the literature [15][16] with little modification. POCl3 (4.0 mL, 43.2 mmol) was added dropwise to dry DMF (21.0 mL

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• methylenedioxyphenyl groups in ketone 8 would be added by sequential addition of aryllithiates to both the carbonyl and aldehyde groups, derived from the terminal alkene, of a homoallylic carboxylic acid derivative 9. Our route to ketone 8 began from salicylaldehyde (10) which underwent a Horner–Wadsworth–Emmons

• and 2 provides clues to the relative stereochemistry of all substituents on the natural products. The route developed allows easy introduction of alternate aryl substituents at the C-10 and C-11 positions, whilst replacing salicylaldehyde 10 with a more functionalised aldehyde could allow for the

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• , Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.10.320 Abstract The switchable three-component reactions of 5-amino-3-methylisoxazole, salicylaldehyde and N-aryl-3-oxobutanamides under different conditions were studied and discussed. The unexpected influence of the aryl substituent in N-aryl-3

• ; catalysis; chemoselectivity; heterocycle; multicomponent reaction; ultrasonication; salicylaldehyde; Introduction Generally, considerable interest in heterocyclic compounds is due to their key role in biological processes in nature and biological activity. In particular, condensed heterocycles bearing a

• hydroxyaryl group as well as tricyclic nitrogen-containing heterocycles derived from salicylaldehyde have been reported as anticancer [1], antihypertensive agents [2], neuropeptide Y antagonists [3], and calcium channel blockers [4]. Fused azoloazines containing carboxamide substituents also exhibit a broad

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• triaminoguanidinium chloride (1, TAG-Cl) and salicylaldehyde, ring-substitued derivatives thereof [2][3][4][5] and 3-(hydroxyimino)pentane-2,4-dione [6] to prepare 1,2,3-tris(iminyl)guanidines; as multidentate chelating ligands they form complexes with several metal ions giving rise to various supramolecular

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• so as to optimize the Raman signal intensity. The apparatus is shown in Figure 1b. Testing the interface: The synthesis of 3-acetylcoumarin As our first reaction for study, we selected the piperidine-catalyzed synthesis of 3-acetylcoumarin (1) from salicylaldehyde with ethyl acetoacetate (Scheme 1

• determine whether we could observe spectroscopically a slug of the coumarin passing through the flow cell. The Raman spectrum of 1 (Figure 2) exhibits strong Raman-active stretching modes at 1608 cm−1 and 1563 cm−1 while the salicylaldehyde and ethyl acetoacetate starting materials exhibit minimal Raman

• intervals using the EZ Raman software provided with the instrument. The data was then exported to Excel for processing. Typical procedure for monitoring the formation of 3-acetylcoumarin (1) Performing the reaction: Into a 50 mL volumetric flask was added salicylaldehyde (6.106 g, 50 mmol, 1 equiv) and

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

• Rajesh Munirathinam,
• Roberto Ricciardi,
• Richard J. M. Egberink,
• Jurriaan Huskens,
• Michael Holtkamp,
• Herbert Wormeester,
• Uwe Karst and
• Willem Verboom

Beilstein J. Org. Chem. 2013, 9, 1698–1704, doi:10.3762/bjoc.9.194

• , using gallium(III) triflate, required a reaction time of 8 h in refluxing acetonitrile to obtain the corresponding nitrile 10 in 87% yield. In case of 2-hydroxy-1-naphthaldehyde oxime (6) [22] (Table 2, entry 4) and salicylaldehyde oxime (7) [18] (Table 2, entry 5) dehydration happened between the ortho

• salicylaldehyde oxime (7, Table 2, entry 5), the conversions were determined by following the decrease in the absorbance at 353 nm (ε353 = 8360 L·mol−1·cm−1) and 310 nm (ε310 = 4820 L·mol−1·cm−1), respectively; the corresponding oxazoles 11 and 12 showed no absorbance in that region. With 4-nitrobenzaldehyde

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• been studied extensively under a variety of Brønsted/Lewis acid catalyzed conditions [35], most of these conditions failed to facilitate a 6-endo cyclization where salicylaldehyde (or any electron-donating aldehyde such as 4-dimethylaminobenzaldehyde) was used as a source of aldehyde [1][22]. Even

• and results are summarized in Table 2. Tryptamine (1) reacted well with aldehydes with both electron-donating and electron-withdrawing substituents to furnish 1,2,3,4-tetrahydro-β-carboline 3. It is interesting to note that salicylaldehyde (2g) and 4-dimethylaminobenzaldehyde (2h) produced the desired

• cyclized products 3g and 3h, respectively, when condensed with tryptamine (1) in the presence of cyanuric chloride. It is reported in the literature that the condensation of electron-donating aldehydes, such as salicylaldehyde with tryptophan methyl ester or tryptamine in acidic media, provided the 6-endo

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

• condensation between the bromo-substituted salicylaldehyde (137) and α-brominated 4-nitroacetophenone (138) to form the benzofuran core (Scheme 9E). Nitro reduction followed by methylation gave 139, and radiolabeling gave 126. This compound showed good affinity for Aβ1-42 aggregates (Ki = 6.6 nM). Secondary

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• -triphenylporphyrin using SnCl2 under acidic conditions [41][42]. Firstly, meso-(4-aminophenyl)porphyrin 1 was reacted with salicylaldehyde or 5-chlorosalicylaldehyde in the presence of La(OTf)3 as a Lewis acid catalyst in toluene under reflux to afford the corresponding iminoporphyrins 2 and 3, which on reduction by

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• aminoindolizines, 2-(aminomethyl)indoles, imidazopyridines, butenolides and 1,2-dihydroisoquinoline derivatives, respectively, combining these two approaches successfully. Along the same lines, we investigated a reaction between ethoxyacetylene, pyrrolidine and salicylaldehyde in the presence of a transition-metal

• the assistance of the work reported by Patil et al. [24][32]). Initial condensation of pyrrolidine with salicylaldehyde 1 produced iminium intermediate A. The addition of copper ethoxyacetylide, formed on the reaction of ethoxyacetylene with Cu, to the iminium intermediate A yielded propargylamine

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• Ishmael B. Masesane Zelalem Yibralign Desta Department of Chemistry, University of Botswana, Private Bag 00704, Gaborone, Botswana 10.3762/bjoc.8.244 Abstract The reported methodologies for the synthesis of chromane derivatives through the reaction of salicylaldehyde and enolates are discussed

• . The enolates and their equivalents involved in the reactions discussed in this article were derived from ketones, nitroalkanes, malononitrile and α,β-unsaturated compounds. Keywords: acetophenone; chromane; enolates; malononitrile; Michael addition; salicylaldehyde; Introduction The chromane

• ][16][17]. Among the reported methodologies for the synthesis of chromane derivatives, the reaction of salicylaldehyde and enolates or their equivalents has gained a prominent position. The key features of the synthesis of chromane derivatives by the reaction of salicylaldehyde and enolates are

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• -Michael addition followed by aza-Baylis–Hillman reaction by means of an iminium-allenamine activation strategy. Later on, the same authors [49] in 2011 reported a similar tandem reaction (abnormal Baylis–Hillman) between 2-alkynals 5 and salicylaldehyde derivatives 1 catalyzed by proline derivatives

• reaction of salicylaldehyde derivatives 10 and α,β-unsaturated cyclic ketones 11. Using chiral pyrrolidine XI as organocatalyst and 2-nitrobenzoic acid as additive, the reaction of salicylaldehydes and α,β-unsaturated cyclic ketones afforded the corresponding tetrahydroxanthones 12 with moderate yields (up

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• indole 9 (Scheme 7) [18][19]. Only aryl aldehydes are able to perform the reaction, but the yields as reported by both groups are very good. Besides the usual reaction between indolines and aldehydes, both groups also found that intermolecular hydride transfer occurred when salicylaldehyde was employed

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• intramolecular aldol reaction of O-acetonyl-salicylaldehydes was described by our research group (Scheme 3) [10]. We envisaged that this 5-enolexo aldolization could be utilized to construct the 1,3-diol moiety of smyrindiol, if a coumarin derivative of the O-acetonyl-salicylaldehyde were to be used. The

• salicylaldehyde (Scheme 6). The total synthesis of smyrindiol is depicted in Scheme 7. Firstly, the O-acetonyl-salicylaldehyde 13, as the substrate for the aldol reaction, was synthesized in five steps. Iodination of commercially available 2,4-dihydroxybenzaldehyde (9) with iodine monochloride in acetic acid [11

• monoprotected salicylaldehyde 12 with 1-bromo- or chloroacetone under basic conditions led to side products due to a subsequent base-catalyzed aldol reaction. For this reason, the alkylation was conducted under basic conditions with 2-methoxyallyl bromide as a masked acetonylating reagent. Hydrolysis of the

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines

• Luca Banfi,
• Andrea Basso,
• Valentina Cerulli,
• Valeria Rocca and
• Renata Riva

Beilstein J. Org. Chem. 2011, 7, 976–979, doi:10.3762/bjoc.7.109

• noting that the Mitsunobu reaction is not effective on unprotected salicylaldehyde. 2,3-Dihydrobenzo[f][1,4]oxazepines similar to 5a,b have been previously prepared, but through less general routes [22][23][24]. Compounds 5a,b were reacted with a series of isocyanides and carboxylic acids to give, in

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• ; methylenedioxy-bearing; one-pot; quinoline-3-carboxylic acid; salicylaldehyde; Introduction Heterocyclic systems containing a quinoline nucleus are an important group of compounds in medicinal chemistry, and are ubiquitous sub-structures associated with biologically active natural products [1][2][3][4]. Some

• present on the salicylaldehyde. These reactions were found to be very complex and we could not separate and obtain any of the desired products in appreciable yields in these cases. Instead, intractable complex mixtures were observed on TLC. To illustrate the reaction mechanism, the formation of 3a is

• )-6,7-methylenedioxyquinoline-3-carboxylic acids 3a–h A mixture of ethyl 2-chloromethyl-6,7-methylenedioxyquinoline-3-carboxylate (5) (0.5 mmol, 0.147 g), the corresponding salicylaldehyde or 2-hydroxy-1-naphthaldehyde (0.5 mmol) and anhydrous K2CO3 (2.5 mmol, 0.400 g) was stirred in refluxing CH3CN (12

Prediction of reduction potentials from calculated electron affinities for metal-salen compounds

• Sarah B. Bateni,
• Kellie R. England,
• Anthony T. Galatti,
• Handeep Kaur,
• Victor A. Mendiola,
• Alexander R. Mitchell,
• Michael H. Vu,
• Benjamin F. Gherman and
• James A. Miranda

Beilstein J. Org. Chem. 2009, 5, No. 82, doi:10.3762/bjoc.5.82

• condensation of the appropriate substituted salicylaldehyde with ethylenediamine. The reaction was allowed to reflux for 2 h before the crude salen ligand was recrystallized in 95% ethanol. Each salen ligand was characterized by IR and NMR spectroscopy. Second, the appropriate metal acetate and the salen

Novel base catalysed rearrangement of sultone oximes to 1,2-benzisoxazole- 3-methane sulfonate derivatives

• Veera Reddy Arava,
• Udaya Bhaskara Rao Siripalli,
• Vaishali Nadkarni and
• Rajendiran Chinnapillai

Beilstein J. Org. Chem. 2007, 3, No. 20, doi:10.1186/1860-5397-3-20

• )-one-2,2-dioxide Y = H), an obvious precursor for 5, was reported by Timoney et al., in an overall yield of ~30% [1] via the cyclisation of the methanesulfonate of salicylaldehyde followed by oxidation (Scheme 4). Results and discussion In order to prepare 6 in better yield, we choose methyl salicylate

• methanesulfonate of salicylaldehyde. Preparation of 1,2-benzoxathiin-4(3H)-one-2,2-dioxides. Preparation of sultone oximes. Preparation of 3-alkyl-1,2-benzisoxazole derivatives. Synthesis of zonisamide from 1,2-benzisoxazole-3-methane-sulfonate. Compounds 6a-i prepared. Compounds 5a-i prepared. Compounds 10a-i