On the Preparation of Aryl Nitriles Using Tosyl Cyanide

Rutan, K. J.; Heldrich, Frederick J.; Borges, Lawrence F.

doi:10.1021/jo00114a060

Cited by 19 publications

(9 citation statements)

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“…ortho-Lithiated 20 was highly unstable even at Ϫ78 ЊC and decomposed rapidly to an unidentified polar by-product (TLC). Quenching with DMF immediately after lithiation afforded benzonitrile 14 that was converted via (±)-23 into inhibitor (±)- 17. For the synthesis of (±)-18, aldehyde 21 was transformed into 1,3-dioxolane 24 that was ortho-lithiated and transformed with tosyl cyanide 22 into nitrile 25 and finally, by deprotection,…”

Section: Synthesismentioning

confidence: 99%

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pK_aand binding affinity and evidence for intermolecular C–F⋯CN interactions

et al. 2004

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The H-atoms of the phenylamidinium needle of tricyclic thrombin inhibitors, which interacts with Asp189 at the bottom of the selectivity pocket S1 of the enzyme, were systematically exchanged with F-atoms in an attempt to improve the pharmacokinetic properties by lowering the pK(a) value. Both the pK(a) values and the inhibitory constants K(i) against thrombin and trypsin were decreased upon F-substitution. Interestingly, linear free energy relationships (LFERs) revealed that binding affinity against thrombin is much more affected by a decrease in pK(a) than the affinity against trypsin. Surprising effects of F-substitutions in the phenylamidinium needle on the pK(a) value of the tertiary amine centre in the tricyclic scaffold of the inhibitors were observed and subsequently rationalised by X-ray crystallographic analysis and ab initio calculations. Evidence for highly directional intermolecular C-F...CN interactions was obtained by analysis of small-molecule X-ray crystal structures and investigations in the Cambridge Structural Database (CSD).

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Section: Synthesismentioning

confidence: 99%

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pK_aand binding affinity and evidence for intermolecular C–F⋯CN interactions

et al. 2004

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“…Tosyl cyanide (p-tolylsulfonyl cyanide, TsCN) has been used as a cyanating reagent in reactions with organometallic compounds [82], including phenylmagnesium bromide [83] and benzylzinc halides [84], and acts as a heterodienophile in Diels-Alder reactions [85,86]. However, reactions of 1 with TsCN in the presence of NaPF 6 were largely unsuccessful, with the desired monocyanovinylidene complex [Ru{C=C(Ph)CN}(PPh 3 ) 2 Cp]PF 6 being obtained in only ca.…”

Section: Selection Synthesis and Structure Of 1-cyano-4-dimethylaminmentioning

confidence: 99%

The synthesis, molecular and electronic structure of cyanovinylidene complexes

Long¹,

Brown²,

Man³

et al. 2012

Inorganica Chimica Acta

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“…For the synthesis of the hemithioindigo-based w-amino acids 1a and 1b, the Boc-protected aldehydes were prepared starting from 3-cyano-or 4-cyanobenzaldehyde. Protection of the aldehydes to give the dioxolanes 2a and 2b, 7,8 reduction to the benzylamines 3a and 3b, 7 Boc-pro-tection to the carbamates 4a and 4b, and removal of the acetal protecting group provided the N-Boc-protected aldehydes 5a and 5b in excellent overall yields (Scheme 1). For the synthesis of the meta-substituted w-amino acid 1b, the aldehyde 5b and the literature-known thioindoxyl carboxylic acid chloride 6 were condensed using 1% sodium hydroxide/tert-butyl alcohol (Scheme 2) as previously described by us.…”

Section: Figurementioning

confidence: 99%

Synthesis of Photoswitchable Hemithioindigo-Based ω-Amino Acids and Application in Boc-Based Peptide Assembly

Herre¹,

Steinle²,

Rück‐Braun³

2005

Synthesis

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Efficient procedures for the preparation of the N-Bocprotected aldehydes 5a and 5b are described which are valuable precursors for the synthesis of hemithioindigo-based w-amino acids and peptides.Driven by the development of new experimental techniques, the investigation and modulation of fast processes of peptide and protein folding gain increasing interest. 1 In addition, the reversible photocontrol of the conformation and activity of biomolecules is intensively being explored. 2,3 In an attempt to develop modular and tunable photoswitches for these applications, we are exploring the synthesis of novel hemithioindigo-derived compounds. 4,5 Our design is based on significant light-induced end-toend distance changes and changes in the dipole moment. Recently, we have demonstrated that a hemithioindigobased a-amino acid can be applied as a light switch for the photomodulation of ionic current through modified gramicidin ion channels. 6 Based on this promising approach, the Boc-protected hemithioindigo-derived pseudo-w-amino acids 1a and 1b (Figure 1) are developed in our laboratories for their incorporation into cyclic peptides. Figure 1So far, these pseudo-amino acids have been synthesized and used as valuable building blocks in the synthesis of diand tripeptides via Boc-based peptide assembly in solution.For the synthesis of the hemithioindigo-based w-amino acids 1a and 1b, the Boc-protected aldehydes were prepared starting from 3-cyano-or 4-cyanobenzaldehyde. Protection of the aldehydes to give the dioxolanes 2a and 2b, 7,8 reduction to the benzylamines 3a and 3b, 7 Boc-protection to the carbamates 4a and 4b, and removal of the acetal protecting group provided the N-Boc-protected aldehydes 5a and 5b in excellent overall yields (Scheme 1). For the synthesis of the meta-substituted w-amino acid 1b, the aldehyde 5b and the literature-known thioindoxyl carboxylic acid chloride 6 were condensed using 1% sodium hydroxide/tert-butyl alcohol (Scheme 2) as previously described by us. 4 These conditions provided the hemithioindigo 1b in 70% isolated yield and >95% purity after purification by chromatography on Florisil. Scheme 1In Boc-based solution-phase peptide synthesis, trifluoroacetic acid in combination with scavengers (e.g., H 2 O, DMS, ethanedithiol, phenols, cresols, thiocresols, or thioanisols) is commonly used for deprotection strategies. However, we found treatment with hydrogen chloride in dioxane to be superior. Thus, Boc-deprotection of the dipeptide 7 4 (Scheme 3), derived from 1a 4 by EDC coupling, was carried out with 4 M hydrogen chloride in dioxane (r.t.) and gave the hydrochloride 8 quantitatively after evaporation of the solvent. Scheme 2

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On the Preparation of Aryl Nitriles Using Tosyl Cyanide

Cited by 19 publications

References 0 publications

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pK_aand binding affinity and evidence for intermolecular C–F⋯CN interactions

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pK_aand binding affinity and evidence for intermolecular C–F⋯CN interactions

The synthesis, molecular and electronic structure of cyanovinylidene complexes

Synthesis of Photoswitchable Hemithioindigo-Based ω-Amino Acids and Application in Boc-Based Peptide Assembly

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On the Preparation of Aryl Nitriles Using Tosyl Cyanide

Cited by 19 publications

References 0 publications

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pKaand binding affinity and evidence for intermolecular C–F⋯CN interactions

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pKaand binding affinity and evidence for intermolecular C–F⋯CN interactions

The synthesis, molecular and electronic structure of cyanovinylidene complexes

Synthesis of Photoswitchable Hemithioindigo-Based ω-Amino Acids and Application in Boc-Based Peptide Assembly

Contact Info

Product

Resources

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A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pK_aand binding affinity and evidence for intermolecular C–F⋯CN interactions

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pK_aand binding affinity and evidence for intermolecular C–F⋯CN interactions