Synthesis of polyfunctional secondary amines by the addition of functionalized zinc reagents to nitrosoarenes

Addition of functionalized aryl, heteroaryl or adamantyl zinc reagents to various nitroso-arenes in the presence of magnesium salts and LiCl in THF produces after a reductive work-up with FeCl2 and NaBH4 in ethanol the corresponding polyfunctional secondary amines in high yields

Recent Methods for Synthesis of Coumarin Derivatives and Their New Applications

Coumarin (2H-1-benzopyran-2-one) and its heterocyclic derivatives are widely used as lactone scaffolds used by innovative methods for the preparation of heterocyclic molecules. Nowadays, significant biological activities, as well as properties of unique nature coumarin derivatives, have played an important role in the development of novel drugs. This chapter entitles numerous methods of one-pot construction of coumarin derivatives, together with well-known name reactions and other type reactions as well, in the presence of various metal-based homogenous and heterogeneous catalyst system. Coumarin is one of the very important heterocycles and its analogs like natural product and pharmaceutically active drug molecules are extracted/isolated from a plants, animals, and microbes. Coumarin precursors have a wide range of biological activities Hence, the synthesis of coumarins and their heterocyclic analogs have become among the most interesting compound over the last many years in the growth of improved synthetic methodologies to form different types of functional groups that are present in coumarins derivatives. The synthesis of coumarins enabled by current approaches and their most recent bio-applications are discussed in this book chapter. Corresponding complex heterocycles-based coumarin analogs are produced from substituted alkyne substrates and other starting materials as well

N-Heterocyclic Carbene Triazolium Salts Containing Brominated Aromatic Motifs: Features and Synthetic Protocol

In this work, we provide a brief overview of the role of N-aryl substituents on triazolium N-heterocyclic carbene (NHC) catalysis. This synopsis provides context for the disclosed synthetic protocol for new chiral N-heterocyclic carbene (NHC) triazolium salts with brominated aromatic motifs. Incorporating brominated aryl rings into NHC structures is challenging, probably due to the substantial steric and electronic influence these substituents exert throughout the synthetic protocol. However, these exact characteristics make it an interesting N-aryl substituent, because the electronic and steric diversity it offers could find broad use in organometallic- and organo-catalysis. Following the synthetic reaction by NMR guided the extensive modification of a known protocol to enable the preparation of these challenging NHC pre-catalysts

Lewis-acid mediated acetamidation of <i style="">N</i>-protected bromomethylindoles

327-334A facile ZnBr2-mediated acetamidation of various types of N-protected 2/3-bromomethylindoles is reported. Upon interaction of bromomethylindoles with acetonitrile in the presence of anhydrous ZnBr2 at reflux followed by aqueous work up led to the isolation of respective acetamidomethylindoles in good yields

Studies on Lewis-acid mediated domino reaction of <i style="">N</i>-protected bromomethylindoles with arenes/heteroarenes

843-857A systematic study on Lewis-acid mediated domino reaction of N-protected 2/3-bromomethylindoles with various types of arenes and heteroarenes is reported

A facile preparation of methyl indolylacetates <i style="">via</i> Stille carbonylation of <i style="">N</i>-protected bromomethylindoles

858-864A systematic study on carbonylation of N-protected bromomethylindoles using different types of Pd catalyst and bases under Stille condition has been explored. Carbonylation of bromomethylindoles in the presence of methyl/ethyl alcohol led to the formation of the corresponding esters in reasonable yields

Case Series of Prolonged Febrile Illness in Pediatric Age Group: A Diagnostic Challenge

Background: Fever is defined as a rectal temperature of 100.4oF or more. It is a physiologic response characterized by an elevation of body temperature above normal variation. Fever is one of the common causes of medical consultation in children, responsible for 15%–25% of consultations in Pediatrics practice. Children with prolonged fever worry their parents and are a diagnostic challenge to pediatricians. Persistence of fever raises clinical queries towards diagnosis, especially in patients without identifiable focus. Children with a temperature of more than 38°C (100.4°F) recorded by a healthcare professional without any determined reason after at least 8 days of evaluation should be classified as having a “fever of unknown origin”. Most fevers with unknown causes usually have atypical presentations of common illnesses.  Case Presentation: We reviewed the case records of 9 children admitted to our pediatric ward with prolonged fever episodes from December 2021 to October 2022. They were diagnostic challenges for clinicians. In our cases, 2 children had scrub typhus, 1 was diagnosed with acute lymphoblastic leukemia, and 1 had multidrug-resistant typhoid fever. However, 2 patients remained with a fever of unknown origin. Three children were found to have coinfections and diagnosed with enteric fever with other coinfections like dengue, leptospirosis, and urinary tract infection. Cases 1, 2, and 9 had persistent fever despite appropriate antibiotics therapy based on sensitivity patterns, hence a significant diagnosis challenge. Cases 3 and 6 had initial diagnostic deviations due to their atypical presentations, and both cases were diagnosed as scrub typhus. After extensive evaluation, case 4 was diagnosed as malignancy (acute lymphoblastic leukemia). Cases 5 and 7 posed a diagnostic challenge: The causes were not found after extensive evaluation, and there was persistent fever after 10 days of admission. Hence, they were diagnosed as “fever of unknown origin”. Conclusions: A complete history and detailed examination are essential in evaluating pediatric illnesses. We have found that there might be deviators during disease evolution. We should not settle with a single diagnosis until a good clinical response is achieved and also consider alternative diagnoses or coinfections. Common causes of prolonged fever should be ruled out first. Coinfections should also be considered if there is no clinical response to treatment in a patient. A practical, systematic, and stepwise approach can be helpful with the assessment and management of prolonged fever in the pediatric age group

Synthesis of Substituted Adamantylzinc Reagents Using a Mg-Insertion in the Presence of ZnCl₂ and Further Functionalizations

The LiCl-mediated Mg-insertion in the presence of ZnCl₂ allows an efficient synthesis of adamantylzinc reagents starting from the corresponding functionalized tertiary bromides. The highly reactive adamantylzinc species readily undergo a broad variety of functionalizations such as Negishi cross-couplings, Cu­(I)-catalyzed acylations and allylations, and 1,4-addition reactions leading to the expected products in excellent yields. Furthermore, the adamantyl moiety could be introduced as α-substituent in terthiophene, increasing its solubility due to the higher lipophilicity and the prevention of π-stacking

Rerouting an Organocatalytic Reaction by Intercepting its Reactive Intermediates

Reactive intermediates are key to halting and promoting chemical transformations, however due to their elusive nature, they are seldom harnessed for reaction design. Herein, we describe studies aimed at stabilizing reactive intermediates in the N-heterocyclic carbene (NHC) catalytic cycle, which enabled fully shutting down the known benzoin coupling pathway, while rerouting its intermediates toward deuteration. The reversible nature of NHC catalysis and the selective stabilization of reaction intermediates facilitated clean hydrogen-deuterium exchange reactions of aromatic aldehydes by D2O, even for challenging electron withdrawing substrates. The addition of catalytic amounts of phenyl boronic acid was used to further stabilize highly reactive intermediates and mitigate the formation of benzoin coupling by-products. The mechanistic understanding at the foundation of this work resulted in unprecedented mild conditions with base and catalyst loadings as low as 0.1 mol%, and a scalable deuteration reaction applicable to a broad substrate scope with outstanding functional group tolerance. More importantly, adopting this approach enabled the construction of a machine-learning derived guideline for identifying the appropriate catalyst and conditions for different substrates based on a logistic regression classification model. Experimental studies combined with machine learning and computational methods shed light on the non-trivial mechanistic underpinnings of this reaction