Nitrile Precursors Research Articles

Electron Transfer Reduction of Nitriles Using SmI2–Et3N–H2O: Synthetic Utility and Mechanism

The first general reduction of nitriles to primary amines under single electron transfer conditions is demonstrated using SmI2 (Kagan's reagent) activated with Lewis bases. The reaction features excellent functional group tolerance and represents an attractive alternative to the use of pyrophoric alkali metal hydrides. Notably, the electron transfer from Sm(II) to CN functional groups generates imidoyl-type radicals from bench stable nitrile precursors.

STRUCTURAL, ELECTRONIC AND OPTICAL PROPERTIES OF THIOPHENE AND THIENOTHIOPHENE CONTAINING DIKETO-PYRROLO-PYRROLES (DPPs) IN POLAR APROTIC SOLVENTS

Thiophene (T) and thienothiophene (TT) containing 2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione (DPP) compounds were prepared according to the succinic ester route from the corresponding heterocyclic nitrile precursors. As is typical of most DPP pigments, the new compounds showed high thermal stability and could be obtained in pure form as determined by elemental analysis. The bulk properties and molecular structure of the compounds were further characterized by thin film, powder XRD and solid state CP-MAS 13 C NMR. Density functional theory (DFT) and time-dependent (TD) DFT were employed to study the geometric and electronic structures of these molecules in the ground state. The optical properties were investigated by UV-Vis absorption and fluorescence spectroscopies in dimethylsulfoxide (DMSO) and N,N-dimethylacetamide (DMA), which revealed that the absorption maximum of the thiophene diketo-pyrrolo-pyrroles (TDPP) and thienothiophene diketo-pyrrolo-pyrroles (TTDPP) in solution were red shifted up to 25 nm and 60 nm, respectively, relative to Pigment Red 255 (PhDPP), while a new absorption band appeared at longer wavelengths in N-methyl pyrolidone (NMP) and N,N′-dimethylpropylene urea (DMPU) which is ascribed to solvent induced charge transfer (CT) complex. The molecular conformations and absorption spectra of TDPP and TTDPP were characterized by quantum chemical methods in order to better understand the observed behavior.

Forming tertiary organolithiums and organocuprates from nitrile precursors and their bimolecular reactions with carbon electrophiles to form quaternary carbon stereocenters.

The stereoselective formation of quaternary carbons is one of the most demanding challenges in organic synthesis.1 An especially direct way to construct such stereocenters would be to combine a prochiral tertiary organometallic and a carbon-centered electrophile (Figure 1A). However, this strategy is not mentioned in the numerous reviews of stereoselective synthesis of chiral quaternary carbons,1 and to our knowledge has never been employed in target-directed organic synthesis. This omission undoubtedly derives from the challenge in generating tertiary organometallic intermediates, particularly those containing three alkyl substituents.[2–4] We were recently drawn to explore this undeveloped approach for forming quaternary carbon stereocenters in the context of fashioning the demanding C8–C14 bond and the C8 quaternary stereocenter of rearranged spongian diterpenes such as aplyviolene (4) and dendrillolide A (5) by the reaction of tertiary organocuprate 1 and cyclopentenone 2. This coupling was anticipated to take place from the convex face of nucleophile 1 and from the face of 2 opposite the branched side chain (Figure 1B).[5]

Forming Tertiary Organolithiums and Organocuprates from Nitrile Precursors and their Bimolecular Reactions with Carbon Electrophiles to Form Quaternary Carbon Stereocenters

Forming Tertiary Organolithiums and Organocuprates from Nitrile Precursors and their Bimolecular Reactions with Carbon Electrophiles to Form Quaternary Carbon Stereocenters

Approaches to the Construction of Substituted 4-Amino-1H-pyrrol-2(5H)-ones

Fully substituted 4-aminopyrrolones are easily accessed via simple routes starting from imines, ketones, or α-bromophenyl acetonitriles. Imines were reacted with KCN/NH(4)Cl in aqueous ethanol to produce α-arylamino benzyl cyanides. On the other hand, ketones were transformed to the desired α-amino nitriles using a modified Strecker reaction. Then, α-amino nitrile precursors were allowed to react with a suitable acyl halide to produce the corresponding amides. Further treatment of these amides with ethanolic KOH converted them to highly substituted 4-amino-1H-pyrrol-2(5H)-one derivatives in moderate to excellent yields.

Synthesis and Characterisation of α‐Glycosyloxyamides Derived from Cyanogenic Glycosides

After exposure to oxidative stress, the leaves of some cyanogenic plants contain primary α-glycosyloxyamides with structures corresponding to their original cyanogenic glycosides. The aim of this study was to prepare such amides from their nitrile precursors and to characterise the new substances in order to facilitate their early identification in forthcoming studies. Methods - A simple but highly specific method is described for the in-vitro synthesis of the amides from their nitrile glycoside precursors using the Radziszewski reaction with hydrogen peroxide and a single-step purification of the reaction product. A TLC method is presented for the preliminary and fast identification of the α-glycosyloxyamides. Following this procedure, seven representative α-glycosyloxyamides, five of them new, were obtained and analytically characterised by means of (1) H, (13) C NMR and ATR-IR spectroscopy, highlighting the differences from their respective nitrile glycoside precursors. Thus, α-glycosyloxyamides can be obtained in sufficient amounts and purity to serve as references for further studies on the catabolism of cyanogenic glycosides and the detoxification of cyanogenic foodplants using the new aspect of nitrile hydrolysis with (endogenous) hydrogen peroxide.

Radical formation of amino acid precursors in interstellar regions? Ser, Cys and Asp

It is proposed that the glycine precursor NH(2)CH(2)CN may be synthesised in interstellar dust clouds by the radical combination reactions NH(2)˙ + ˙CH(2)CN → NH(2)CH(2)CN (ΔG = -302 kJ mol(-1)) and/or NH(2)CH(2)˙ + ˙CN → NH(2)CH(2)CN (ΔG = -414 kJ mol(-1)). All calculations at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31+G(d) level of theory. This paper extends that concept to radical/radical coupling reactions to form Ser, Cys and Asp precursor nitriles. The hydrogen abstraction process NH(2)CH(2)CN + HO˙→ NH(2)˙CHCN + H(2)O (ΔG = -130 kJ mol(-1)) is suggested to precede the radical coupling reactions NH(2)˙CHCN + R˙→ NH(2)CHRCN (R˙ = ˙CH(2)OH, ˙CH(2)SH and ˙CH(2)CN) to form nitrile precursors of the amino acids Ser, Cys and Asp. These three reactions are all favourable (ΔG = -240, -227 and -223 kJ mol(-1)). The radical species ˙CH(2)NH(2), ˙CH(2)OH, ˙CH(2)SH and ˙CH(2)CN are shown to be stable for the microsecond timeframe by a combination of theoretical calculations and the experimental mass spectrometric neutralization/reionization procedure.

1,2,4-Triazoles: Synthetic approaches and pharmacological importance. (Review)

The synthetic routes of 1,2,4-triazole compounds as well as their pharmacological properties have been described. The review focuses intensively on two methods: cycloaddition reaction in the syntheses of various 1,5-dialky-1H-1,2,4-triazole derivatives from the reactive cumulenes with the nitrile precursors as well as the microwave irradiation method.

Synthesis and applications of alkylated C-sugars as peptide bioconjugates

Permethylated C-sugars affect the stability and solubility of their carbohydrate precursors and may represent an important group of bioconjugates. When properly functionalized, these units can be appended to the N- and C-termini or to the side chains of peptides or other therapeutic candidates. In this report, we describe the synthesis of an amine-functionalized alkylated mannose derivative and confirm the configuration by determining the X-ray crystal structure of its nitrile precursor. An acid functionalized counterpart, when attached to the N-terminus of a NR box peptide analog, improved binding to estrogen receptor β (ERβ) but not to ERα.

Experimental Enthalpy of Formation of Isonitrile from Collision-Induced Dissociation Threshold Energy Measurements

The enthalpy of formation of HNC is determined using collision-induced dissociation threshold measurements with protonated nitriles. The average value obtained using five different nitrile precursors is 49.7 ± 2.9 kcal/mol, which agrees with the previously reported experimental value after accounting for revisions in the proton affinity scale. While the main dissociation pathway for all ions is found to be simple cleavage, the protonated propionitrile and acrylonitrile ions also dissociate by formation of HCNH+ formed by intramolecular proton transfer.

Synthesis of15N-Labelled D-Isovaline and α-Aminoisobutyric Acid

[15N]-D-isovaline was prepared from DL-[α-15N]-α-aminoisovaleramide by enzymatic resolution with Mycobacterium neoaurum. The 15N-isotope was introduced during the Strecker synthesis of its precursor, e.g. aminoisovaleronitrile. Attempts to prepare the amino nitrile precursor of [15N]-α-aminoisobutyric acid (Aib) led to a poor yield and loss of the label. Significantly, improved results were obtained when a cosolvent is present during formation of aminoisobutyronitrile.

Biosynthesis of brominated tyrosine metabolites by Aplysina fistularis.

The biosynthesis of brominated tyrosine metabolites by the marine sponge Aplysina fistularis was investigated. [U-14C]-L-Tyrosine, [U-14C]-L-3-bromotyrosine, and [U-14C]-L-3,5-dibromotyrosine were incorporated into both dibromoverongiaquinol [1] and aeroplysinin-1 [2], and [methyl-14C]methionine was specifically incorporated into the O-methyl group group of 2. [Methyl-14C]-L-O-methyltyrosine, [methyl-14C]-L-3,5-dibromo-O-methyltyrosine, and several putative nitrile precursors were not incorporated into 1 or 2.

Simple Synthetic Approach to Arylacetic NsaiasviaTosMIC Procedure

Abstract Preparation of 1-methylpyrrole-2-acetonitrile, 1-methyl-5-(4-methylbenzoyl) pyrrole-2-acetonitrile and 2-(6-methoxy-2-naphthyl)propionitrile by treatment of 1-methylpyrrole-2-carboxaldehyde, 1-methyl-5-(4-methylbenzoyl)pyrrole-2-carboxaldehyde and, respectively, 6-methoxy-2-acetylnaphthalene with tosylmethylisocyanide (TosMIC) is described. This one-step synthetic procedure is very useful to obtain the nitrile precursors of tolmetin and naproxen, two clinically important non-steroidal antiinflammatory agents (NSAIAs).

An efficient general route to furo-, pyrido- and thieno-[d][2]benzazepines via Pd0 catalysed cross coupling reactions and nitrile ylide cyclisations

The cyclisation of diene-conjugated nitrile ylides of the general type 1, in which the conjugated system consists of a benzene ring and a five- or a six-membered heterocyclic ring, provides an effective route to fully unsaturated heterocyclo[d][2]benzazepines. The combination of this cyclisation with a direct route to the nitrile ylide precursors via Pd0 catalysed cross-coupling gives an efficient general synthetic route to these systems from readily available starting materials.

Total Synrhesis of the Amaryllidaceae Alkaloid (±)-Epielwesine. The Importance of Vinylsilane Stereochemistry in Iminium Ion-Vinylsilane Cyclizations

(±)-Epielwesine (9) was prepared in an efficient and completely stereocontrolled fashion in six steps and 28% overall yield from commercially available 3,4-methylenedioxyphenylacetonitrile (15a). The key step is acid promoted cyclization of the (Z)-vinylsilane-iminium cation (13) to construct the cis-3a-arylhexahydroindole (12) in 95% yield. The Z stereochemistry of the vinylsilane is critical to the success of the iminium ion-vinylsilane cyclization, a result that establishes the importance of hyperconjugative electron release from the β-C-Si σ bond in stabilizing the cyclization transition state. A method for the convenient preparation of Δ 1 -pyrrolines (3,4-dihydro-2H-pyrroles) or Δ 1 -piperideines (3,4,5,6-tetrahydropyridines) from nitrile precursors is also provided

Synthesis of a tritium labeled tetrafluoro‐substituted aryl azide photoaffinity labeling agent for chloride channels. Application of [3H]‐sodium borohydride‐cobalt chloride to tritium labeling

Abstract5‐Nitro‐2‐[N‐3‐(4‐azido‐2,3,5,6‐tetrafluorophenyl)‐propylamino]‐benzoic acid (FAzNPPB), a photoaffinity analog of the potent epithelial chloride channel blocker 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid (NPPB) has been prepared in five steps from commercially available 4‐amino‐2,3,5,6‐tetrafluorobenzonitrile. The main feature of this synthesis was the use of NaBH4‐CoCl2 to convert an aryl‐substituted alkenyl nitrile precursor to the corresponding alkyl amine. The feasibility of this approach and the stoichiometry were developed by model work with cinnamonitrile. Using sodium borotritide‐cobalt chloride, [3H]‐FAzNPPB (specific activity 13.9 mCi/mmol, radiochemical purity >99%) was prepared in three steps from (E)‐4‐amino‐2,3,5,6‐tetrafluorocinnamonitrile.

ChemInform Abstract: Bis(trimethylsilyl)amide as Nitrile Precursor.

Chemischer InformationsdienstVolume 17, Issue 29 Preparative Organic Chemistry ChemInform Abstract: Bis(trimethylsilyl)amide as Nitrile Precursor. B. RIGO, B. RIGOSearch for more papers by this authorC. LESPAGNOL, C. LESPAGNOLSearch for more papers by this authorM. PAULY, M. PAULYSearch for more papers by this author B. RIGO, B. RIGOSearch for more papers by this authorC. LESPAGNOL, C. LESPAGNOLSearch for more papers by this authorM. PAULY, M. PAULYSearch for more papers by this author First published: July 22, 1986 https://doi.org/10.1002/chin.198629126Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume17, Issue29July 22, 1986 RelatedInformation

Bis (trimethylsilyl) amide as nitrile precursor

Bis (trimethylsilyl) amides are converted into nitriles with high yields when they are treated wich a catalyst (tetrabutylammonium fluoride, Lewis acids or iron phthalocyanine).

Chiral Induction in Originally Racemic Amino Acids via 5‐Acyl and 5‐Acyloxyaminooxazoles

AbstractA variety of chiral 2,4‐disubstituted‐5‐trifluoroacetamido‐,5‐carbobenzyloxyamino, and 5‐β,β,β,‐trichloroethoxycarbonylaminooxazoles have been prepared from diamide, dipeptide, or amide nitrile precursors. Conversion to their (poly)amide equivalents via a deacylation/hydration sequence is described. The extent of induction of chirality realized upon ring opening in each case is determined by HPLC.

Evidence that linamarin and lotaustralin, the two cyanogenic glucosides of Trifolium repens L., are synthesized by a single set of microsomal enzymes controlled by the Ac/ac locus

A microsomal fraction from Trifolium repens L. shoots of genotype Ac Ac has been used in the study of the biosynthesis of the two glucosides, linamarin and lotaustralin. It was demonstrated that it is likely that one set of enzymes is responsible for the biosynthesis of both hydroxynitriles from their respective amino acid precursors. The nitrile precursor of linamarin, 2-methylpropane nitrile appears to be used much less effectively than the oxime precursor. The results are discussed in relation to the role of the Ac/ac locus in the genetic control of cyanogenic glucoside biosynthesis, and in relation to results obtained with Linum usitatissimum.