Neutral Amine Research Articles

Effect of Nucleophile Deprotonation on SuFEx: Synthesis of Sulfonamides

In a quest for efficient SuFEx-type transformations we studied reactions of amines with 4-fluorobenzenesulfonyl fluoride. The substrate may react by fluoride substitution at the aromatic ring (SNAr) and at the sulfonyl group (SuFEx). Analysis of the reaction course revealed that deprotonation of N-nucleophile controls the reaction course: neutral amines in DMF attack at the aromatic ring, whereas amine anions, generated in equilibrium with LiHMDS in toluene, favor sulfonyl substitution. Using the base-promoted conditions we synthesized a set of substituted sulfonamides in high yields.

Structural Elucidation of Ubiquitin via Gas-Phase Ion/Ion Cross-Linking Reactions Using Sodium-Cationized Reagents Coupled with Infrared Multiphoton Dissociation.

Accurate structural determination of proteins is critical to understanding their biological functions and the impact of structural disruption on disease progression. Gas-phase cross-linking mass spectrometry (XL-MS) via ion/ion reactions between multiply charged protein cations and singly charged cross-linker anions has previously been developed to obtain low-resolution structural information on proteins. This method significantly shortens experimental time relative to conventional solution-phase XL-MS but has several technical limitations: (1) the singly deprotonated N-hydroxysulfosuccinimide (sulfo-NHS)-based cross-linker anions are restricted to attachment at neutral amine groups of basic amino acid residues and (2) analyzing terminal cross-linked fragment ions is insufficient to unambiguously localize sites of linker attachment. Herein, we demonstrate enhanced structural information for alcohol-denatured A-state ubiquitin obtained from an alternative gas-phase XL-MS approach. Briefly, singly sodiated ethylene glycol bis(sulfosuccinimidyl succinate) (sulfo-EGS) cross-linker anions enable covalent cross-linking at both ammonium and amine groups. Additionally, covalently modified internal fragment ions, along with terminal b-/y-type counterparts, improve the determination of linker attachment sites. Molecular dynamics simulations validate experimentally obtained gas-phase conformations of denatured ubiquitin. This method has identified four cross-linking sites across 8+ ubiquitin, including two new sites in the N-terminal region of the protein that were originally inaccessible in prior gas-phase XL approaches. The two N-terminal cross-linking sites suggest that the N-terminal half of ubiquitin is more compact in gas-phase conformations. By comparison, the two C-terminal linker sites indicate the signature transformation of this region of the protein from a native to a denatured conformation. Overall, the results suggest that the solution-phase secondary structures of the A-state ubiquitin are conserved in the gas phase. This method also provides sufficient sensitivity to differentiate between two gas-phase conformers of the same charge state with subtle structural variations.

Dual Tunability for Uncatalyzed N-Alkylation of Primary Amines Enabled by Plasma-Microdroplet Fusion.

The fusion of non-thermal plasma with charged microdroplets facilitates catalyst-free N-alkylation for a variety of primary amines, without halide salt biproduct generation. Significant reaction enhancement (up to >200×) is observed over microdroplet reactions generated from electrospray. This enhancement for the plasma-microdroplet system is attributed to the combined effects of energetic collisions and the presence of reactive oxygen species (ROS). The ROS (e.g., O2•-) act as a proton sink to increase abundance of free neutral amines in the charged microdroplet environment. The effect of ROS on N-alkylation is confirmed through three unique experiments: (i) utilization of radical scavenging reagent, (ii) characterization of internal energy distribution, and (iii) controls performed without plasma, which lacked reaction acceleration. Establishing plasma discharge in the wake of charged microdroplets as a green synthetic methodology overcomes two major challenges within conventional gas-phase plasma chemistry, including the lack of selectivity and product scale-up. Both limitations are overcome here, where dual tunability is achieved by controlling reagent concentration and residence time in the microdroplet environment, affording single or double N-alkylated products. Products are readily collected yielding milligram quantities in eight hours. These results showcase a novel synthetic strategy that represents a straightforward and sustainable C-N bond-forming process.

Dual Tunability for Uncatalyzed N‐Alkylation of Primary Amines Enabled by Plasma‐Microdroplet Fusion

AbstractThe fusion of non‐thermal plasma with charged microdroplets facilitates catalyst‐free N‐alkylation for a variety of primary amines, without halide salt biproduct generation. Significant reaction enhancement (up to >200×) is observed over microdroplet reactions generated from electrospray. This enhancement for the plasma‐microdroplet system is attributed to the combined effects of energetic collisions and the presence of reactive oxygen species (ROS). The ROS (e.g., O2⋅−) act as a proton sink to increase abundance of free neutral amines in the charged microdroplet environment. The effect of ROS on N‐alkylation is confirmed through three unique experiments: (i) utilization of radical scavenging reagent, (ii) characterization of internal energy distribution, and (iii) controls performed without plasma, which lacked reaction acceleration. Establishing plasma discharge in the wake of charged microdroplets as a green synthetic methodology overcomes two major challenges within conventional gas‐phase plasma chemistry, including the lack of selectivity and product scale‐up. Both limitations are overcome here, where dual tunability is achieved by controlling reagent concentration and residence time in the microdroplet environment, affording single or double N‐alkylated products. Products are readily collected yielding milligram quantities in eight hours. These results showcase a novel synthetic strategy that represents a straightforward and sustainable C−N bond‐forming process.

Corrosion in Crude Oil Distillation Units (CDUs) and a Study of Reducing Its Rates by Changing Chemical Injection Sites

The injection of chemicals is one of the most important treatment steps used to reduce the effect of corrosion factors in crude oil distillation units in oil refineries. As a result of the availability of suitable conditions for the formation of the main corrosion agents, namely acids (HCI, H2S). It has become necessary to neutralize the effect of these factors in distillation units and towers by changing the sites of adding chemicals, where oil refineries use anti_ corrosion film and caustic soda (NaOH) as well as neutral amine to control and limit the effect of chloride ion, iron rates, salts and the (PH) values. As a result, the research paper is interested in developing a study of adding and changing chemical injection areas (points) of adding chemicals, especially (caustic soda and neutralizer amine) at different specific points, and as it is well known, crude oil passes through a number of different heat exchangers to raise its temperature in preparation for refining. It was found that changing the addition of the neutral amine in the striper tower area of the kerosene section (drops that are returned to the main refinery tower) has a significant effect in controlling the stabilization of pH values between (5.5-6.5) and reducing the iron ion concentration at a rate of (1% ppm), While the injection of caustic soda depends on the temperatures of the crude oil, so it is changed into two lines. The first is before the heat exchangers, that is, when the temperature of the crude oil is (20-35) c̊, and the second line is after the crude oil reaches the temperature (65-90) c̊, it has a significant effect in reducing the concentration of the chloride ion at a rate of (1-5 ppm) present in the form of chloride salts dissolved in the crude oil.

Nuclear Magnetic Resonance Analysis of Hydrothermal Reactions of Ethyl- and Octylamine in Sub- and Supercritical Water

Hydrothermal reactions of aliphatic amines have recently gained importance in relation to the application of amines as film-forming corrosion inhibitors for steam-water cycles. The kinetics and mechanism of the hydrothermal reactions of ethylammomiun cation (EtAH+) and n-octylammonium cation (OctAH+) were studied for comparison with the corresponding neutral amines to elucidate their reaction products and pathways at sub- and supercritical temperatures of 300-400 °C as model reactions of aliphatic ammonium cations. We analyzed the reaction of 13C-15N-labeled EtAH+ using NMR spectroscopy and revealed that the initial hydrolysis to ethanol, known as the main path, is followed by the elimination reaction producing ethene and the disproportionation reaction giving diethylammonium cation. The OctAH+ yields octene and octanol, each of which isomerizes to thermodynamically more stable species as the major products. Comparisons were made between the reactions of the neutral amines and ammonium cations to highlight their different reactivity. The hydrolysis, alkene formation, and dehydration of alcohols to alkenes were all found to be accelerated at low pH. The formation of low-molecular-weight organic acids such as acetic acid and formic acid was not observed. These results indicate that the corrosion protection effect of film-forming amines will be maintained under practical conditions with pH values as high as around 9 to 10, and hence side reactions involving byproducts will be suppressed.

Synergistic Extraction of Ga(III) from Chloride Solution by Mixture of Cyanex 272 and Alamine 336

Aming to select a suitable system for the synergistic solvent extraction of Ga(III), solvent extraction (SX) experiments were carried out by using acidic organo-phosphorous extractants, namely P204, P507 and Cyanex 272, and their mixtures with neutral extractants (TBP, N503) or amine extractants (Alamine 336). Among the studied mixtures, a remarkable synergistic effect for Ga(III) extraction was resulted by the combination of Cyanex 272 and Alamine 336 and the maximal synergistic enhancement coefficient reached 3.11. Compared to the single Cyanex 272, higher equilibrium pH values were observed when mixture of Cyanex 272 and Alamine 336 was employed. The extraction of hydrogen ions by Alamine 336 during the reaction was considered to be responsible for the synergistic extraction, and thus the the extraction of Ga(III) by Cyanex 272 was promoted. Finally, the synergistic extraction stoichiometry of mixture of Cyanex 272 and Alamine 336 for Ga(III) was projected by slope analysis. Ga(OH)A2 was resulted to be the composition of extracted complexes.

Li vs Na: Divergent Reaction Patterns between Organolithium and Organosodium Complexes and Ligand-Catalyzed Ketone/Aldehyde Methylenation.

Organosodium chemistry is underdeveloped compared with organolithium chemistry, and all the reported organosodium complexes exhibit similar, if not identical, reactivity patterns to their lithium counterparts. Herein, we report a rare organosodium monomeric complex, namely, [Na(CH2SiMe3)(Me6Tren)] (1-Na) (Me6Tren: tris[2-(dimethylamino)ethyl]amine) stabilized by a tetra-dentate neutral amine ligand Me6Tren. Employing organo-carbonyl substrates (ketones, aldehydes, amides, ester), we demonstrated that 1-Na features distinct reactivity patterns compared with its lithium counterpart, [Li(CH2SiMe3)(Me6Tren)] (1-Li). Based on this knowledge, we further developed a ligand-catalysis strategy to conduct ketone/aldehyde methylenations, using [NaCH2SiMe3]∞ as the CH2 feedstock, replacing the widely used but hazardous/expensive C═O methylenation methods, such as Wittig, Tebbe, Julia/Julia-Kocieński, Peterson, and so on.

Liquid Dynamics Determine Transition Metal-N-Heterocyclic Carbene Complex Formation.

The mechanism of metal-N-heterocyclic carbene (NHC) complex formation from imidazolium salts in the presence of weak bases was investigated through theoretical methods. Quantum chemical calculations revealed that the two bases considered here, sodium acetate and trimethylamine, both facilitate complex formation. In contrast to previous experiments, these calculations indicated a slightly lower barrier with the amine. Molecular dynamics simulations showed that the ionic nature of the [AuCl2 ]- and imidazolium ions, as well as the sodium acetate base keep these species associated in the reaction mixture through ion pairing. This pre-association of the components produces those clusters that are essential for the metal complex formation reaction. The neutral amine, however, remains mostly separated from the other reaction partners, making it a significantly less effective base.

Novel Synergistic Catalysis by Ethylcarbodiimide Hydrochloride Salt and CuI Towards Morita‐Baylis‐Hillman Reaction

AbstractMorita Baylis‐Hillman (MBH) reaction of various aldehydes, bearing electron‐releasing as well as electron‐withdrawing groups with acrylonitrile and methyl acrylate as electron‐deficient alkene is reported herein. The cornerstone of the reaction is the utilization of EDC.HCl (a salt) as a novel catalyst, salt gets converted into neutral tertiary amine in the presence of CuI for the synthesis of MBH adduct. Excellent product yield (up to 99 %), ambient reaction conditions, shorter reaction time, and no side product formation are the salient features of the envisaged synthetic protocol.

Highly selective separation of C3H6/C3H8 within hierarchical metal–organic CuxOy@HP–Cu–BTCs

Two critical characteristics for gas adsorption and separation are the porosity and open metal sites of adsorbents. The Cu–BTC (BTC = benzene–1,3,5–tricarboxylate) structure was tailored using a template synthesis technique to increase the separation performance for C3H6/C3H8 mixtures. The three hierarchical porous frameworks, CuxOy@HP–Cu–BTC, synthesized using a cationic surfactant (cetyltrimethylammonium bromide (CTAB)), a neutral organic amine (N,N–dimethyltetradecylamine (N,N)), and an anionic surfactant (sodium dodecylbenzene sulfonate (SDBS)) as the template, CuxOy@HP–Cu–BTC(SDBS) exhibited the best performance, with a C3H6 adsorption capacity of 6.679 mmol g−1, which was significantly greater than that of C3H8 (5.721 mmol g−1). CuxOy@HP–Cu–BTC(SDBS) has an ideal ultra–microporous structure that encloses C3H6 molecules precisely while rejecting slightly bigger C3H8 molecules, and C3H6 interacts strongly with unsaturated metal sites through particular π–Cu bonds. According to the ideal adsorbed solution theory (IAST), the adsorption selectivity of C3H6/C3H8 was 63.322, which is more than that of the reference adsorbent Cu–BTC. Additionally, the breakthrough studies shown that CuxOy@HP–Cu–BTC(SDBS) has a good dynamic performance for the effective separation of the C3H6/C3H8 mixture.

Amine Volatilization from Herbicide Salts: Implications for Herbicide Formulations and Atmospheric Chemistry.

Amines are frequently included in formulations of the herbicides glyphosate, 2,4-D, and dicamba to increase herbicide solubility and reduce herbicide volatilization by producing herbicide-amine salts. Amines, which typically have higher vapor pressures than the corresponding herbicides, could potentially volatilize from these salts and enter the atmosphere, where they may impact atmospheric chemistry, human health, and climate. Amine volatilization from herbicide-amine salts may additionally contribute to volatilization of dicamba and 2,4-D. In this study, we established that amines applied in herbicide-amine salt formulations undergo extensive volatilization. Both dimethylamine and isopropylamine volatilized when aqueous salt solutions were dried to a residue at ∼20 °C, while lower-vapor pressure amines like diglycolamine and n,n-bis-(3-aminopropyl)methylamine did not. However, all four amines volatilized from salt residues at 40-80 °C. Because amine loss typically exceeded herbicide loss, we proposed that neutral amines dominated volatilization and that higher temperatures altered their protonation state and vapor pressure. Due to an estimated 4.0 Gg N/yr applied as amines to major U.S. crops, amine emissions from herbicide-amine salts may be important on regional scales. Further characterization of worldwide herbicide-amine use would enable this contribution to be compared to the 285 Gg N/yr of methylamines emitted globally.

Elucidating Solution-State Coordination Modes of Multidentate Neutral Amine Ligands with Group-1 Metal Cations: Variable-Temperature NMR Studies.

Multidentate neutral amine ligands play vital roles in coordination chemistry and catalysis. In particular, these ligands are used to tune the reactivity of Group-1 metal reagents, such as organolithium reagents. Most, if not all, of these Group-1 metal reagent-mediated reactions occur in solution. However, the solution-state coordination behaviors of these ligands with Group-1 metal cations are poorly understood, compared to the plethora of solid-state structural studies based on single-crystal X-ray diffraction (SCXRD) studies. In this work, we comprehensively mapped out the coordination modes with Group-1 metal cations for three multidentate neutral amine ligands: tridentate 1,4,7-trimethyl-1,4,7-triazacyclononane (Me3TACN), tetradentate tris[2-(dimethylamino)ethyl]amine (Me6Tren), and hexadentate N,N′,N″-tris-(2-N-diethylaminoethyl)-1,4,7-triaza-cyclononane (DETAN). The macrocycles in the Me3TACN and DETAN are identified as the rigid structural directing motif, with the sidearms of DETAN providing flexible “on-demand” coordination sites. In comparison, the Me6Tren ligand features more robust coordination, with the sidearms less likely to undergo the decoordinating–coordinating equilibrium. This work will provide a guidance for coordination chemists in applying these three ligands, in particular, the new DETAN ligand to design metal complexes which suit their purposes.

Late Transition Metal Catalysts with Chelating Amines for Olefin Polymerization

Polyolefins are the most consumed polymeric materials extensively used in our daily life and are usually generated by coordination polymerization in the polyolefin industry. Olefin polymerization catalysts containing transition metal–organic compound combinations are undoubtedly crucial for the development of the polyolefin industry. The nitrogen donor atom has attracted considerable interest and is widely used in combination with the transition metal for the fine-tuning of the chemical environment around the metal center. In addition to widely reported olefin polymerization catalysts with imine and amide donors (sp2 hybrid N), late transition metal catalysts with chelating amine donors (sp3 hybrid N) for olefin polymerization have never been reviewed. In this review paper, we focus on late transition metal (Ni, Pd, Fe, and Co) catalysts with chelating amines for olefin polymerization. A variety of late transition metal catalysts bearing different neutral amine donors are surveyed for olefin polymerization, including amine–imine, amine–pyridine, α-diamine, and [N, N, N] tridentate ligands with amine donors. The relationship between catalyst structure and catalytic performance is also encompassed. This review aims to promote the design of late transition metal catalysts with unique chelating amine donors for the development of high-performance polyolefin materials.

Reaction of Chlorine Dioxide with Saturated Nitrogen-Containing Heterocycles and Comparison with the Micropollutant Behavior in a Real Water Matrix.

Chlorine dioxide (ClO2) is a very selective oxidant that reacts with electron-rich moieties such as activated amines and thus can degrade specific N-containing micropollutants. N-containing heterocycles (NCHs) are among the most frequent moieties of pharmaceuticals. In this study, the reactions of ClO2 with ritalinic acid and cetirizine, two abundant micropollutants, and model compounds representing their NCH moiety were investigated. The pH-dependent apparent reaction rates of all NCHs with ClO2 were measured and modeled. This model showed that neutral amines are the most important species having reaction rates between 800 and 3200 M-1 s-1, while cationic amines are not reactive. Ritalinic acid, cetirizine, and their representative model compounds showed a high stoichiometric ratio of ≈5 moles ClO2 consumption per degraded ritalinic acid and ≈4 moles ClO2 consumption per degraded cetirizine, respectively. Investigation of chlorine-containing byproducts of ClO2 showed that all investigated NCHs mostly react by electron transfer and form above 80% chlorite. The reactions of the model compounds were well comparable with cetirizine and ritalinic acid, indicating that the model compounds indeed represented the reaction centers of cetirizine and ritalinic acid. Using the calculated apparent reaction rate constants, micropollutant degradation during ClO2 treatment of surface water was predicted for ritalinic acid and cetirizine with -8 to -15% and 13 to -22% error, respectively. The results indicate that in ClO2-based treatment, piperidine-containing micropollutants such as ritalinic acid can be considered not degradable, while piperazine-containing compounds such as cetirizine can be moderately degraded. This shows that NCH model compounds could be used to predict micropollutant degradation.

Micelle-mediated assembly of metals in Ag@MnOx/m-SiO2 for reinforced antimicrobial activity and photothermal water evaporation

The increasing complexity of environmental pollution posed a higher requirement for the development of environment-governed functional materials. Herein, to achieve desired synergy and multiple functionalities of eco-friendly nanomaterials, a micelle-mediated metal assembly strategy was proposed to integrate plasmonic Ag nanoparticles into MnOx modified mesoporous silica hosts by metal-modified neutral dodecyl amine surfactant, correspondingly, a multifunctional mesoporous Ag@MnOx/m-SiO2 (AMSs) nanocomposite was obtained. The characterization results revealed that the introduction of Mn and alteration in the amount of Ag mediated the formation of a special mesostructure and nanometric morphology of the silica host. Bearing a low Ag loading (r.t. of Ag/Mn = 1/2), ultrafine Ag nanoparticles were embedded in the inner core of mesoporous silica nanospheres. While assembly with a higher Ag concentration affected the morphology of the obtained AMSs and resulted in rich Ag nanoparticles on the exterior surface of mesoporous silica. By this strategy, ultrafine Ag nanoparticles and well-dispersed amorphous MnOx species were coupled into the mesoporous silica to reach a special configuration and integrated functionality. The obtained AMSs-3 can effectively inactivate bacteria (E. coli, S. aureus, and P. aeruginosa) with a prolonged inhibitory effect, rapidly reduce harmful nitrophenol, as well as photothermally assist water evaporation (evaporation rate of 1.51 kg m−2 h−1, receiver efficiency of 87%). This work provides versatile environment-governing functional nanomaterials for both highly effective antimicrobial and environmental remediation.

Dissipative Acid-Fueled Reprogrammable Supramolecular Materials

Smart materials reversibly changing properties in response to a stimuli are promising for a broad array of applications. In this article, we report the use of trichloroacetic acid (TCA) as fuel to create new types of time-controlled materials switching reversibly from a gel to a solution (gel-sol-gel cycle). Applying various neutral amines as organogelators, TCA addition induces amine protonation, switching the system to a solution, while TCA decarboxylation over time enables a return to the initial gel state. Consequently, the newly obtained materials possess interesting time-dependent properties applied in the generation of remoldable objects, as an erasing ink, as chiroptical switches, or for the generation of new types of electrical systems.

Engineering of corrosion product-polymer hybrid layers for enhanced CO2 corrosion protection of carbon steel part two: Computational investigation and surface characterisation

Carbon dioxide internal corrosion of carbon steel pipelines remains a major issue that is typically mitigated via the addition of corrosion inhibitors. In specific operational environments, a protective natural corrosion product layer known as iron carbonate (FeCO 3 ) can evolve on internal pipeline walls, providing comparable corrosion inhibitionefficiency to that achieved from surfactants. However, in some instances, incomplete corrosion product coverage can initiate localised corrosion. In our previous work, we demonstrated the ability of Poly (allylamine hydrochloride) (PAH) to act synergistically with FeCO 3 when the corrosion product exhibits partial coverage of ×65 carbon steel surfaces in an aqueous CO 2 corrosion environment. In this work, we employ density functional theory (DFT) to show that PAH is able to coordinate with both FeCO 3 and the bare carbon steel surface, producing a FeCO 3 -PAH hybrid structure. The surface and chemical properties of a naturally formed FeCO 3 and the FeCO 3 -PAH hybrid layers are characterised employing scanning electron microscopy (SEM) coupled with focused ionic beam (FIB), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD) and X-ray photoelectron spectroscopy (XPS). • The PAH molecules adsorb onto the carbon steel surface and corrosion product (FeCO 3 ) via chemisorption and physisorption. • The PAH molecules interact with FeCO 3 through coordination and hydrogen bonding producing a hybrid layer. • The PAH centres of interaction with film-free carbon steel and FeCO 3 film are protonated and neutral amine groups. • The crystal structure and layer thickness of FeCO 3 and FeCO 3 -PAH hybrid layers are characterised and compared.

Headgroup interaction effects in mixed fatty acid-alkyl amine monolayers

The impact of headgroup interactions in binary mixed monolayers comprised of fatty acids and alkyl amine-based surfactants has been investigated with a view towards understanding molecular pair formation at the air-water interface. Monolayers consisting of equimolar mixtures of cationic Stearyltrimethylammonium bromide with myristic acid (STAB/MA), and nominally neutral octadecyl amine with myristic acid (ODA/MA) were studied using a combination of Langmuir monolayer methods. Measurements support the formation of molecular pairs between STAB and MA in monolayers, which was not observed for the ODA/MA mixture. By studying the effect of subphase pH, measurements suggest hydrogen bonding between the headgroups and surrounding water significantly impacts film structure for the mixed systems. Notably, at pH 3.5, similarities in film morphology for the STAB/MA and the ODA/MA were observed, indicating that subphase pH can be used to enhance pair formation. This lower pH promoted the formation of phase-separated domains with LE and LC features and changed the kinetic stability of the monolayers. These works clarify the fundamental importance of headgroup interactions, hydrogen-bond formation and chemical structures in regulating intermolecular pair formation, an issue that has been largely unreported and underappreciated in the literature to date. This information can provide guidance on important intermolecular interaction considerations that must be taken into account for applied systems.

Proton‐transfer‐induced in situ defect passivation for highly efficient wide‐bandgap inverted perovskite solar cells

AbstractWide‐bandgap (≥1.68 eV) inverted perovskite solar cells (PSCs) have been recognized as promising top component cells on the commercial crystalline silicon cell to surpass its Shockley–Queisser efficiency limit. However, the power conversion efficiency (PCE) is dramatically limited by the huge open‐circuit voltage (VOC) loss. Herein, we propose a proton‐transfer‐induced in situ defect passivation strategy to reduce the nonradiative recombination to minimize the VOC loss. Specifically, a liquid‐form neutral amine, 3,4,5‐trifluorobenzylamine (TFBA) was added into ethyl acetate (EA) as anti‐solvent for the film preparation, which induces proton‐transfer from the formamidinium (FA) and methylammonium (MA) in the perovskite precursors to the TFBA. The protonated TFBA exhibits a gradient distribution near the surface of the perovskite film, achieving in situ defect passivation. As a result, TFBA‐based 1.68 eV‐bandgap inverted PSCs afforded a PCE of 20.39%, one of the highest for cells with this bandgap. Meanwhile, due to the strong interaction between TFBA and the perovskite film, the mixed‐halide perovskites demonstrate much better photostability. Our findings offer an effective strategy to passivate defects in PSCs.image