Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• ]. In addition, we have previously demonstrated the effective use of alkyl 3-bromo-3-nitroacrylates in the preparation of condensed furancarboxylates using potassium acetate as a catalyst [28][29][30]. The present study is aimed at developing methods for the synthesis of a wide range of condensed

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• existence in E configuration. Then, the spin system extends over two overlapping olefinic protons at δH 6.89 (H-6)/6.90 (H-7) proceeding to two olefinic protons at δH 6.38 (dd, J = 15.0, 11.0 Hz, H-8) and 6.56 (d, J = 15.0 Hz, H-9). In addition, the 1H–1H COSY spectrum of 1 (Figure 2) revealed another

• (Figure 2, Figure S10, Supporting Information File 1) that revealed key ROE correlations from H-2’ and H-3’ indicating their cofacial orientation whereas 3’-OH and 2’-NH are facing the opposite side of the molecule. In addition, further key ROE correlations were distinguished from H-11 to two methyl

• acid derivative named farinosone D. In addition, five known secondary metabolites were identified based on HRESIMS and detailed 1D/2D NMR spectroscopic analyses along with comparison with the reported literature. The isolated compounds were differentiated into two 2-pyridone derivatives farinosones A

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• reaction mixture. This step allows the oxidative addition of nickel on the aryl bromide 9 followed by the reductive elimination giving the desired product 11. Besides the innovative synthetic results obtained in this study, the authors underline a major advantage to switch to red light as it enables a

• . While transition metals such as copper, palladium, cobalt, and nickel are well-established in catalyzed cross-coupling reactions, J. Cornella et al. have highlighted the reactivity of main-group elements like bismuth, which can mimic transition-metal behavior through oxidative addition. In their recent

• study, the authors have developed a complementary ground-state- and excited-state-driven aryl oxidative addition platform based on an N,C,N-bismuthinidene complex, showing the unique capacity of this main-group element to engage in reactivity typically associated with d-block metals [21]. The study

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• . Diverse functionalized 3-substituted oxindole derivatives were successfully prepared in satisfactory yields and with high diastereoselectivity. In addition, the base-promoted dimerization of MBH carbonates of isatin afforded the ethylene-bridged bis(3-methylene)oxindole derivatives with nearly 4:1

• substitution products 5a–n in high yields (Scheme 2). The substituents showed a marginal effect on the yields. In addition, a secondary arylamine such N-methylaniline and aliphatic amine (n-butylamine) also gave the expected products 5m and 5n in satisfactory yields. It should be pointed out that no base

• used in the reaction, a direct Michael addition of the arylamine to the C=C bond of the maleimide unit and sequential elimination of carbon dioxide and tert-butoxide ion gives the intermediate B, which in turn undergoes an allylic rearrangement to afford the product 5. In this process, no extra

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• antiaromatic character of 2 compared to 1. The decrease of the oxidation potentials with increasing antiaromaticity in the neutral states is opposite to the case of aromatic oligomers [21], where molecules with greater aromatic character have higher oxidation potentials. In addition, in 1•+ and 12+ the charge

• theoretical Raman band at 1730 cm−1. FT-Raman spectra in CH2Cl2 (approx. 10−2 to 10−3 M) of: top) 1 (black), 1•+ (blue), and 12+ (red). Bottom) 2 (black), 2•+ (blue), and 22+ (red). Oxidations are carried out by stepwise addition of NOBF4 in CH2Cl2. Force constants for the CC stretching vibrational

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• to the diffusion mixing method is the slow dropwise addition of a reagent to the reaction mixture. However, in the latter case it is not possible to achieve uniform generation of active intermediates due to their formation in a local area, which accelerates unwanted side processes [19]. The results

• in a high yield in the presence of ʟ-proline could be explained by the efficient crotonic condensation of formaldehyde and acetylacetone (1), followed by the addition of the second equivalent of diketone 1 to the highly reactive methylidene intermediate. The mild reaction conditions (room temperature

• adducts of the Diels–Alder (i.e., I) and the hetero-Diels–Alder reaction (i.e., II), or adducts resulting from the addition of a second equivalent of CH acid to the crotonic condensation product (i.e., III). Apparently ʟ-proline played an essential role as catalyst in this three-component reaction. Using

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• additional redox reagents to the reaction, making this method a valuable addition to the synthesis of disulfides. Furthermore, this approach can be extended to the synthesis 3-sulfenylchromones, thereby broadening its application. Results and Discussion Reaction conditions were optimized using sodium p

• ]. Control experiments were performed for the 3-thioflavone formation process. It was found that without the addition of sodium p-toluenesulfinate, 3a was converted to 4H-chromen-4-one (3aa) in high yield (reaction 3 in Scheme 5). When 3aa and 1a were used as substrates, product 4a could be obtained in high

• whether the reaction proceeded through a free radical mechanism, different free radical inhibitors were added to the reaction (reaction 7, Scheme 5). The addition of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) resulted in complete inhibition of the reaction, while BHT (2,6-di-tert-butyl-4-methylphenol

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• replacing the rotor pyridyl group of a hydrazone switch with a phenyl group afforded long-lived negative photochromic compounds [49]. In addition, Hecht and co-workers reported that the thermal stability of indigos can be tuned by N-functionalization [50][51]. They revealed that the introduction of electron

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• example, substrates with a bromine atom occupying the 4-position and a methoxy group at the 7-position could be successfully converted into the target products (3s and 3t). In addition, doubly substituted benzimidazoles (3u–w), as well as the single imidazole (3x), were also found to be applicable. This

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• ]. In addition, carbonyldiimidazole-based heteroannulations via MCRs have been reported, giving access to drug like scaffolds [21][22][23][24]. However, their employment in C1 chemistry should and could be advanced. Herein, we point out formamide as an alternative relevant building block for C1

• synthesis was efficient and rapid as the final adducts could be isolated only by precipitation. In addition, the reactions were performed in a parallel setup using custom-made metal blocks. Specifically, thienopyrimidine and thienopyrimidone derivatives exhibit a range of biological activities, i.e

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• dioxazolone 7. Subsequently, nitrene insertion of INT-12 into the Cu–C bond, forms INT-13, which then undergoes isomerization and protodemetalation, followed by catalyst regeneration, as suggested by the DFT calculations. Finally, the nucleophilic addition of the amine to the electrophilic intermediate INT-15

• slightly diminished reactivity (23c and 23d). In addition, poor reactivity was observed with dioxazolones bearing thiophene, implying that the undesired coordination of sulfur to copper reduces the reactivity (23e). Despite the reduced reactivity, excellent enantioselectivity was still maintained. Moreover

• copper catalyst, providing the vinyl copper intermediate INT-30. This intermediate then undergoes oxidative addition to the N–O bond of the dioxazolone to generate INT-31. Subsequently, decarboxylative reductive elimination occurs, forming the copper imidate INT-32. The active copper species is

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• . We expect this information to be useful for the rational application of the CF2H group in drug development and molecular design. Previous quantum mechanical calculations revealed that the CF2H···O binding energy (ΔE) ranges from 1.0 kcal/mol to 5.5 kcal/mol [14][15][18][21]. In addition, as measured

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• cooperative intermolecular forces. Zinc ion-induced coordination with the macrocycle and a terpyridinium derivative enabled orthogonal polymerization, as revealed by 1H NMR, DLS, and TEM techniques. In addition, viscosity measurements showed a transition from oligomers to polymers at the critical

• molar ratio observed in ESI experiments. These inspiring results prompted us to further examine the interaction between host H1 and G1 by 1H NMR spectroscopy. Our prior experience with cyclo[6]aramide has confirmed binding to the cationic guest [49]. Indeed, addition of compound H1 to the guest solution

• /or π-stacking interactions, conferring the characteristic 2:2 constitutional stoichiometry onto this host–guest complex. In addition, there were eight C–H···O interactions between the hydrogen atoms of G1 and the nearby pyridinium group of H2, with distances of 2.2–3.5 Å, and two C–H···O interactions

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• through oxidative addition, followed by transmetalation and reductive elimination, to obtain the desired product. Throughout the catalytic cycle, the catalyst undergoes conversion between [M]n and [M]n+2 (Figure 1) [11]. However, using alkyl electrophiles as coupling partners in cross-coupling reactions

• remains a significant challenge owing to the high energy barrier required for oxidative addition and facile β-hydride elimination [12]. The development of radical approaches facilitated by transition-metal catalysis has provided a promising solution to overcome the limitations of conventional coupling

• olefin addition reactions [20] conducted by various research groups, contributed to this area of research. Recently, the coupling reactions of C(sp3)-based electrophiles were explored using dual photoredox and copper catalysis, achieving selective radical coupling reactions involving alkyl halides [21

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• ]benzofuran (3fa) in 81% yield. Next, we explored the mechanism of the coupling reactions between 2-fluorobenzofurans 1 and arylboronic acids 2. Because these reactions proceed under mild conditions despite involving aromatic C–F bond activation [19], direct oxidative addition of C–F bonds is unlikely (Scheme

•  5, path a). Instead, the reactions are thought to proceed through a formal oxidative addition involving nickelacyclopropane intermediates E [15][16][17][38][39], which are generated from 2-fluorobenzofurans 1 and zero-valent nickel species (Scheme 5). Following β-fluorine elimination, this results

• in a formal oxidative addition to form benzofuranylnickel(II) fluorides F, which then undergo transmetallation with arylboronic acids 2 to produce intermediates G (Scheme 5, path b). Alternatively, a direct transition from E to G via transition state H is also possible (Scheme 5, path c). Ultimately

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• emerged among copper catalysts because it can act as a precursor to triflic acid in addition to a powerful copper-catalytic effect. Indeed, Cu(OTf)2 has proven to be an excellent surrogate for triflic acid compared with other metal triflates because it is inexpensive and exhibits high activity with low

• or radical (Figure 1). The latter is typically operative when the reaction is carried out under oxidative conditions, usually in the presence of O2 and TEMPO, involving the formation of radical species through single-electron transfer (SET) from a copper catalyst to a precursor. Subsequent addition

• . Among various Lewis acids, only Cu(OTf)2 in combination with TMSCN was effective or a valuable alternative was the use of acetone cyanohydrin combined with a catalytic amount of TEA (5 mol %). The mechanism involves the formation of an imine facilitating the addition of the nitrile group. Among the

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• organocatalytic Michael addition to alkynals 2 (Scheme 1) [18]. The authors identified the Jørgensen–Hayashi-type catalyst C1 as the most efficient organocatalyst. In this way, a range of axially chiral styrenes were obtained in high yields and enantiomeric purities. The reaction was based on an iminium

• activation, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

• intermediate Int-9. As the assumed rate-determining step the intramolecular nucleophilic addition takes place, followed by further cyclization and finally, release of the organocatalyst to form the axially chiral product 9. Various aryl-substituted indolines 9 were obtained in good yields and high enantiomeric

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• demonstrated their ability to form round vesicles and some tubular shapes, the pursuit of asymmetric structures, such as the stomatocyte, presents a novel challenge and opportunity in the field [16][17]. The stomatocyte shape would be an excellent addition because of its demonstrated suitability for nanomotor

• fabrication [18]. The necessary shape transformation for achieving this morphology is primarily driven by changes in osmotic pressure. Initially achieved through dialysis and later by the addition of PEG solution [1][18], the process involves deflating the polymeric vesicle, prompting it to bend and adopt the

• stomatocyte configuration. Several critical factors contribute to this transformation. Firstly, the application of osmotic pressure which must be sufficiently robust. This control is notably easier with the addition of PEG, as it swiftly creates a substantial osmotic gradient [19]. Secondly, the vesicle's

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• crucial role in the synthesis of phenethylamine analogues via this method. Dithering before the addition of the copper solution leads to the formation of Micheal adducts, which decrease the product yields. This phenomenon is due to the nature of β-nitrostyrenes, displaying considerable delocalization

• towards the nitro group, which makes them highly susceptible to Michael addition [34]. While being stirred with the borohydride, the substrate progressively forms an α-carbanion in the newly formed nitroalkane, which ultimately leads to Michael addition to the nitrostyrene. Furthermore, studies to

• extraction process and copper(II) removal. However, the addition of DETA led to decreased yields and a deterioration of the phase separation. It was observed that using a 20% aqueous sodium hydroxide solution, instead of 35%, negatively impacted phase separation, making the extraction process more time

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• ][2]. In addition, machine-guided optimization has emerged as a promising framework to obtain reaction conditions that perform optimally for single- or multiple-target objectives, enabling researchers to explore diverse solution spaces and uncover the optimal conditions that strike a balance between

• consonant and/or conflicting targets. In addition, the incorporation of lab robotics into chemical synthesis has enabled the development of closed-loop optimization platforms capable of executing optimization campaigns rapidly with minimal human intervention, relieving experimenters from labor-intensive

• constraints of parallel reactors that share the same MTP. In addition, challenges arise when standard MTP-based reaction vessels are used at a temperature near the solvent's boiling point, as this labware is not enclosed or able to cool the top of the reaction vessel to facilitate reflux conditions. Although

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• Scholl reaction conditions. The structure of 3 was confirmed with single crystal X-ray crystallography, as detailed later. In addition, another product with a molecular ion peak of 1695.9115 in the high-resolution mass spectrum (Supporting Information File 1, Figure S6) was isolated in trace amounts

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• 2–7 was performed by NMR spectroscopy, which confirmed the synthetic outcomes (Figures S1–S11, Supporting Information File 1). The structures of compounds 7 were further confirmed by HRMS and IR analyses (Figures S12–S18, Supporting Information File 1). In addition, the chemical structure of 7-H was

• charge transfer, as indicated by the λmax value of 342 nm. In addition, the effect of solvent polarity on the UV−vis absorption was studied with 7-H (Figure 2b). The spectra show that there is no significant difference in the absorption bands in different solvents, indicating that the polar environment

• induced by the stronger electron-donating feature of the carbazole substituent located on the donor carbazole group. In addition, we tested the emission wavelength of 7-H in different solvents (Figure 3b) and found that the maximum is redshifted gradually with increasing solvent polarity, which indicates

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• ) ligand 4 were reported by Cowley and co-workers in 2010 [14]. In addition to heterocyclic fluoranthene analogues, highly oxygenated benzo[j]fluoranthenes are commonly encountered fungal natural products with important biological activities [15]. Bulgarein (5) is an example of such a benzo[j]fluoranthene

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• benziodoxolone was generated in situ, via a reaction of chlorobenziodoxolone with sulfinate salts, followed by the addition of amines or hydrazines, respectively. On the follow-up on our research, we envisaged to extend the diversity of BBX reagents as electrophilic amine reagents and investigated their

• lengths and angles fall within the expected range for similar compounds [31]. Later, the β-sulfinyl esters 4 were prepared by Michael addition reaction of thiols and α,β-unsaturated esters [32], followed by oxidation of the corresponding sulfides 3 using two different oxidizing agents (oxone and m-CPBA

• ) [32][33]. To investigate the reactivity of the BBXs in this electrophilic amination reaction, the generated compound 4 was subjected to a retro-Michael addition to produce the sulfenate anion intermediate, followed by the addition of BBX 2. Based on our experience with HIRs, the reaction of 2 with

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

• tertiary amide on the same position. Alternatively, the use of a double Boc-protected Dha resulted in a rather low yield of compound 25 (32%), while varying one Boc-protecting group with a Cbz-protecting group increased the yield substantially to 86% for compound 26. In addition, the use of a cyclic, N-Cbz

• slight increase in chemical yield. Giese reaction: Radical addition on olefins with an electron-withdrawing group (EWG) followed by a HAT or SET and protonation; halogen-atom transfer: (a) tin-mediated XAT, (b) XAT initiated by a photocatalyst (PC) and mediated by boranes (B), silanes (Si) or alkylamines