AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2690-1897/198
College of Chemistry and Material Science, Shandong Agricultural University, Taian 271018, P. R. China
*Corresponding Author: Nan Lu, College of Chemistry and Material Science, Shandong Agricultural University, Taian 271018, P. R. China.
Citation: Nan Lu, Chengxia Miao, (2024), Theoretical investigation on Rh (III)-catalyzed cascade reaction of N-alkoxycarbamoyl indole with CF3–ynone to synthesize pyr-rolo[1,2-a] indole based on C−H activation, J, Surgical Case Reports and Images, 7(5); DOI:10.31579/2690-1897/198
Copyright: © 2024, Nan Lu. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 10 June 2024 | Accepted: 17 June 2024 | Published: 26 June 2024
Keywords: C-H activation; N-alkoxycarbamoyl; directing group; migratory insertion; rhodacycle
The mechanism is investigated for Rh(III)-catalyzed cascade reaction of N-alkoxycarbamoyl indole with CF3–ynone and cascade transformation to cycloheptenone fused indole. The former contains cleavage of carbamoyl and indoyl bond giving five-membered rhodacycle via reversible CMD process, triple bond insertion into Rh−C after ynone coordination with Rh(III), proto-demetalation assisted by one HCl, extra MeOH embed into carbonyl determined to be rate-limiting, complex divided into indole and N-alkoxycarbamoyl unit, N-nucleophilic addition affording pyrrolo[1,2-a]indole and Rh(III) recover with second HCl. The latter is composed of rate-limiting Friedel−Crafts acylation initiated by ester cleavage forming MeOH and seven-membered cyclic ketone, the long range relay of H transfer arriving at α-C of indole, and β-elimination after dehydration. The positive solvation effect is suggested by decreased absolute and activation energies in solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.
Pyrrolo[1,2-a]indoles are privileged members pharmaceutically. As important natural products, they are also powerful molecules with antibacterial, antinociceptive, anti-inflammatory, and antitumor activities [1-3]. Among many representative examples, the derivatives with trifluoromethyl (CF3) unit are especially sought-after in fields of biochemical, agrochemical, medicinal, and material sciences. Thus the synthesis of CF3-pyrrolo[1,2-a]indole has received wide interest in recent years [4]. Many protocols could enable construction of carbon−carbon or carbon−heteroatom bond via photoredox, cascade, and transition-metal (TM)-catalyzed C−H bond activation (CHA) [5-7]. In this aspect, Yu developed the selective synthesis of dihydropyrimido[1,6-a]indol-1(2H)-ones via Rh(III)-catalyzed [3 + 3] or [4 + 2] C−H annulation [8]. Chen achieved Rh(III)-catalyzed selective olefination of N-carboxamide indoles with unactivated olefins via internal oxidation at room temperature [9]. Duan reported divergent synthesis of trifluoromethyl-substituted (dihydro)-pyrimidoindolones via Rh(III)-catalyzed C−H activation/annulation of N-carbamoylindoles with CF3-imidoyl sulfoxonium ylides [10].
With wide application and rich reactivity in organic synthesis, CF3-ynones were utilized creatively as coupling partners (CPs) for CHA reaction [11]. For example, 2,4-diaryl-6-trifluoromethylated pyridines was synthesized regioselectively through copper-catalyzed cyclization of CF3-ynones and vinyl azides [12]. With anilines, 2-trifluoromethylquinolines was obtained through rhodium-catalysed redox-neutral [3 + 3] annulation [13]. Based on multiple bond activation, CF3-tethered indazole derivatives was achieved via solvent-dependent selective synthesis [14]. Wang found cascade C(sp2)−H and C(sp3)−H bond cleavage in unusual reaction of 1-phenylpyrazolidinones toward diazonaphthalen-2(1H)-ones [15]. Shen got fluorinated pyridopyrimidinone in Rh(III)-catalyzed simultaneous [3 + 3]/[5 + 1] annulation of 1-arylpyrazolidinones with gem-difluorocyclopropenes [16]. Song applied unsymmetrical relay C−H alkenylation and [2 + 2] cycloaddition of N-arylsydnones with allenyl acetates to access quinoline-fused cyclobutanes [17]. There were also [4 + 1 + 1] annulation of N-aryl amidines with diazo homophthalimides and O2, simultaneous indole construction and aryl introduction from 2-alkenylanilines and diazonaphthalen-2(1H)-ones and cascade reactions of N-nitrosoanilines with iodonium ylides leading to pyranone-tethered indazoles or carbazoles [18-20].
Since directing group (DG) is required to guarantee regioselectivity of CHA reaction, N-alkoxylcarbamoyl indoles are important substrates containing easily removable or readily transformable DG [21]. Many advantages have been shown for Rh(III)-catalyzed oxidative [4+2] annulation of 2-arylquinoxalines, 2-aryl-2H-indazoles with allyl alcohols and switchable β-C(sp2)–H alkenylation of acyclic enamides [22,23]. In this context, a breakthrough was Wang’s [2 + 3] annulation of N-alkoxycarbamoyl indole with CF3-ynone catalyzed by [RhCp*Cl2]2 [24]. This novel method was also appliable to prepare cycloheptenone fused indole skeleton with remarkable biological activities [25]. Although this was the first example with N-alkoxycarbamoyl as effective DG for C2−H functionalization, many problems still puzzledand there was no report about detailed mechanistic study explaining the indispensable N-alkoxycarbamoyl group. Why the envisioned indole fused diazepine was not obtained and how unexpected pyrrolo-[1,2-a]indole product was yielded? What is the relation between C−H bond activation and N-alkoxycarbamoyl unit? How the acid-promoted cascade transformation gives cycloheptenone fused indole? To solve these questions in experiment, an in-depth theoretical study was necessary for this strategy leading to diverse functionalized pyrrolo[1,2-a]indole derivatives.
The geometry optimizations were performed at the B3LYP/BSI level with the Gaussian 09 package [26,27]. The mixed basis set of LanL2DZ for Rh and 6-31G(d) for non-metal atoms [28-32] was denoted as BSI. Different singlet and multiplet states were clarified with B3LYP and ROB3LYP approaches including Becke's three-parameter hybrid functional combined with Lee−Yang−Parr correction for correlation [33-39]. The nature of each structure was verified by performing harmonic vibrational frequency calculations. Intrinsic reaction coordinate (IRC) calculations were examined to confirm the right connections among key transition-states and corresponding reactants and products. Harmonic frequency calculations were carried out at the B3LYP/BSI level to gain zero-point vibrational energy (ZPVE) and thermodynamic corrections at 353 K and 1 atm for each structure in methanol. The solvation-corrected free energies were obtained at the B3LYP/6-311++G(d,p) (LanL2DZ for Rh) level by using integral equation formalism polarizable continuum model (IEFPCM) in Truhlar’s “density” solvation model [40-42] on the B3LYP/BSI-optimized geometries.
As an efficient method obtaining bond and lone pair of a molecule from modern ab initio wave functions, NBO procedure was performed with Natural bond orbital (NBO3.1) to characterize electronic properties and bonding orbital interactions [43,44]. The wave function analysis was provided using Multiwfn_3.7_dev package [45] including research on frontier molecular orbital (FMO) and Mayer bond order (MBO).
The mechanism was explored for (a) Rh(III)-catalyzed cascade reaction of N-alkoxycarbamoyl indole 1a with CF3–ynone 2 leading to pyrrolo[1,2-a]indole 3a (b) cycloheptenone fused indole 4b from pyrrolo[1,2-a]indole acetate 3b (Scheme 1). Illustrated by black arrow of Scheme 2a, initially, Rh(III)-catalyzed carbamoyl N2-H bond and indoyl C1−H bond cleavage of 1a gives five-membered rhodacycle I via two steps of reversible CMD process. After the removal of two HCl, the coordination of triple bond of 2 with Rh(III) of I furnishes intermediate II, from which the following migratory insertion of activated triple bond into Rh−C bond generates III. Next assisted by one additional HCl, proto-demetalation of III affords intermediate IV, which forms intermediate i5 involving H-bond after the addition of an extra MeOH molecule to carbonyl group. Then, the N-alkoxycarbamoyl unit embeded in i5 is removed to give V and VI. Subsequently, V undergoes concerted proton transfer and intramolecular N-nucleophilic addition to afford product 3a(red arrow). Meanwhile with a second HCl, proto-demetalation of VI gives methyl methoxycarbamate (VII) and regenerates Rh(III) catalyst (blue arrow).
Displayed by black arrow of Scheme 2b, the cascade transformation is initiated by intramolecular Friedel−Crafts acylation of 3b along with ester cleavage at 120 °C. The dissociated alkoxy group and hydrogen of benzene ring forming MeOH molecule leaves after the generation of seven-membered cyclic ketone A. Then, one hydrogen atom of methylene undergoes two times of proton migration arriving active α-C of indole, from which hydroxyl bonds with the eliminated β-H forming H2O molecule to complete dehydration and the formation of desired product 4b. The schematic structures of optimized TSs in Scheme 2 were listed by Figure 1. The activation energy was shown in Table 1 for all steps. Supplementary Table S1, Table S2 provided the relative energies of all stationary points. According to experiment, the Gibbs free energies in methanol solution phase are discussed here.
Scheme 1 (a) Rh(III)-catalyzed cascade reaction of N-alkoxycarbamoyl indole 1a with CF3–ynone 2 leading to pyrrolo[1,2-a]indole 3a (b) cycloheptenone fused indole 4b from pyrrolo[1,2-a]indole acetate 3b.
Scheme 2 Proposed reaction mechanism of (a) cascade reaction of 1a with 2 leading to 3a catalyzed by Cp*RhCl2 (b) 4b from 3b. TS is named according to the two intermediates it connects.
(a)
(b)
Figure 1. Relative Gibbs free energy profile in solvent phase starting from complex (a) i0, II, i3, i4, V, i7 (b) 3b, A (Bond lengths of optimized TSs in Å).
| TS | ΔG≠gas | ΔG≠sol |
| ts-i01 | 21.3 | 12.7 |
| ts-i12 | 22.4 | 26.9 |
| ts-IIIII | 14.5 | 12.0 |
| ts-i3IV | 23.0 | 26.6 |
| ts-i45 | 33.8 | 32.6 |
| ts-i56 | 19.6 | 20.1 |
| ts-i78 | 16.1 | 12.9 |
| ts-V3a | 48.6 | 41.5 |
| ts-3bin1 | 47.0 | 42.3 |
| ts-Ain2 | 38.6 | 32.5 |
| ts-in23 | 2.8 | 1.7 |
| ts-in34 | 33.6 | 31.9 |
Table 1 The activation energy (in kcal mol−1) of all reactions in gas and solvent
3.1 Reversible CMD process
Initially, the CMD process between 1a and Cp*RhCl2 proceeds via ts-i01 as step 1 with the activation energy of 12.7 kcal mol−1 relative to the starting point i0 endothermic by 3.6 kcal mol−1 (black dash line of Figure 1a). Promoted by one Cl ligand of Rh(III) catalyst, the carbamoyl N1 is deprotonated as depicted by the transition vector including the transfer of H1 from N1 to Cl1 and coordination of Rh to N1 (1.1, 1.8, 2.17 Å). When H1-Cl1 is formed, Rh-N1 is also bonded in resultant intermediate i1.
From i1, the reactive indoyl α-C1 is deprotonated by another Cl ligand of Rh(III) catalyst forming a second H2-Cl2 molecule, which occurs via ts-i12 with activation energy of 26.9 kcal mol−1 endothermic by 19.4 kcal mol−1 leading to i2 in step 2. The transition vector contains concerted motion of C1···H2···Cl2 and cooperated Rh···C1 approaching (1.32, 1.67, 2.12 Å) (Figure S1a). The accomplish of Rh-C1 coordinated bond gives five-membered rhodacycle I along with two HCl in i2. Although barriers of this two steps are mediate at 80 °C in experiment, both endothermic indicates disfavorable process in thermodynamics, which echoes the prediction of reversible CMD by experiment.
3.2 Triple bond migratory insertion, proto-demetalation and methanol embed
After the removal of two HCl, an intermediate II is furnished via the coordination of ynone to Rh(III) and taken as new starting point for subsequent step 3. The migratory insertion of activated triple bond into Rh−C1 bond takes place via ts-IIIIIwith activation energy of 12.0 kcal mol−1 affording III exothermic by -17.4 kcal mol−1. Clearly III is stable with the new seven-membered ring. The transition vector corresponds to the elongation of C2-C3 triple bond to double one, cleavage of Rh···C1 and simultaneous linkage of C1···C2, Rh···C3 (1.28, 2.10, 2.15,2.07 Å) (Figure S1b).
The introduction of an additional HCl makes starting point denoted as i3 for the following step 4 via ts-i3IV with a barrier of 26.6 kcal mol−1 exothermic by -23.1 kcal mol−1delivering intermediate IV. Assisted by HCl, this proto-demetalation includes protonation and ring opening at C3. That is H3···C3 bonding and Rh···C3 breaking suggested by the transition vector, which also contains the afore required departure of Cl3-H3 and the after formation of Rh-Cl3 (1.51, 2.15, 1.50, 2.60 Å) (Figure S1c). The heat release of this two steps effectively pulls the entire reaction process thermodynamically.
From IV, the addition of an extra MeOH generates i4 as starting point of next step 5. The MeOH is divided into alkoxy MeO and proton H two parts and inserted to C5-O1 carbonyl group. This step proceeds via ts-i45 with activation energy of 32.6 kcal mol−1 endothermic by 25.5 kcal mol−1 yielding reactive intermediate i5. The transition vector is composed of remarkable O2···H4 fracture, extension of C5-O1 bond from double to single and bonding of C5···O2, O1···H4 (1.51, 1.33, 2.04, 1.05 Å) (Figure S1d). Here i5 is active involving the embedded N-alkoxycarbamoyl unit and O1-H4···N2 H-bond ready for the following split into two parts.
3.3 N-alkoxycarbamoyl unit remove, intramolecular N-nucleophilic addition and Rh(III) recover
Then i5 is removed into indole and N-alkoxycarbamoyl unit two parts denoted as V and VI respectively.The step 6 takesplace via ts-i56 with activation energy of 20.1 kcal mol−1 forming stable i6 exothermic by -7.4 kcal mol−1. According to the transition vector, the atomic motion predicts asynchronous complicated process of the prior N2···C5 dissociation, laggered O1···H4···N2 proton giving and the resulting C5···O1 shortened from single to double (2.07,1.10, 2.25, 1.34 Å) (Figure S1e). Since this step is key to the product generation and catalyst recover simultaneously, the low barrier and heat release confirms the advantage from both kinetics and thermodynamics, which verifies the efficiency of this novel reaction pattern theoretically.
Subsequently via ts-V3a, V undergoes intramolecular N-nucleophilic addition followed by concerted proton transfer producing 3a (red dash line of Figure 1a). The activation energy of step 7 is 41.5 kcal mol−1 relative to V exothermic by -8.2 kcal mol−1. Without Rh(III) catalyst, this barrier becomes somewhat high yet capable to overcome under 80 °C inexperiment. The detailed motion can be demonstrated by the transition vector (Figure S1f). That is N-nucleophilic attack of N2 to C4, proton H4 transferring from N2 to O3 and subsequent stretching of C4-O3 from double to single (1.59, 1.20, 1.44, 1.32 Å). The functionalized pyrrolo[1,2-a]indole is achieved as the ring closing of five-membered pyrrole.
Meanwhile a second H5-Cl4 is required for Rh(III) catalyst regeneration in step 8 via ts-i78 with activation energy of 12.9 kcal mol−1exothermic by -9.1 kcal mol−1 generating i8 binding RhCp*Cl2 and VII (blue dash line of Figure 1a). The transition vector of this second protodemetalation is about coordination shift from of N1···Rh to Rh···Cl4 and proton H5 given by Cl4 to N1 (2.22, 2.60, 1.81, 1.11 Å).
Under the promotion of Rh(III), the MeOH embed into carbonyl group via ts-i45 is determined to be rate-limiting. This clarifies why N-alkoxycarbamoyl group is indispensable for C−H bond activation in experiment. Furthermore, the product generation and catalyst recover are both favorable thermodynamically. To highlight the idea of feasibility for changes in electron density and not molecular orbital interactions are responsible of the reactivity of organic molecules, quantum chemical tool Multiwfn was applied to analyze of electron density such as MBO results of bonding atoms and contribution of atomic orbital to HOMO of typical TSs (Table S3, Figure S2). These results all confirm the above analysis.
3.4 Cycloheptenone fused indole formation
In view of another product 4b attractive biologically, the cascade transformation from 3b is also explored as is displayed by black arrow of Scheme 2b. Without the effective Rh(III), the whole process demands higher 120 °C especially the initial intramolecular Friedel−Crafts acylation via ts-3bin1. The activation energy of step 1 is 42.3 kcal mol−1 relative to the starting point 3b endothermic by 14.1 kcal mol−1 (black dash line of Figure 1b). As acyl donor, the ester bond C6···O3 breaks and the bonding C6···C7 replaces H6 on benzene ring. The dissociated alkoxy MeO3 group combines with H6 and leaves as a methanol MeOH molecule. This can be illustrated in detail by the transition vector (1.68, 2.29, 1.57, 1.08 Å) (Figure S1g).
After the removal of MeOH, a seven-membered cyclic ketone A is located as new starting point of the following three steps. Then one hydrogen atom H7 of methylene undergoes two times of proton migration arriving active α-C of indole. From A, H7 moves from to C8 to C10 via ts-Ain2 with activation energy of 32.5 kcal mol−1 endothermic by 2.0 kcal mol−1 in step 2 and again from C10 to C1 via ts-in23 with low activation energy of 1.7 kcal mol−1 in step 3 leading to in3 exothermic by -0.9 kcal mol−1. Two transition vectors are both simple corresponding to C8···H7···C10 and C10···H7···C1 (1.71, 1.15, 1.19, 1.64 Å) respectively (Figure S1h, Figure S1i). Obviously, this long range relay mechanism of H transfer is feasible at 120 °C. Therefore the carbocation case proposed by experiment may be not necessary.
With C1-H7 in hand, the final β-elimination together with dehydration occurs via ts-in34 in step 4 with a barrier of 31.9 kcal mol−1 exothermic by -3.6 kcal mol−1delivering in4. The transition vector is composed of a third proton H7 transfer from C1 to O4, C4···O4 separation forming H2O molecule (1.37, 1.36, 1.85 Å) (Figure S1j). When H2O is lost from in4, the desired 4b is obtained with new C3-C4 double bond. The Friedel−Crafts acylation is rate-limiting for cycloheptenone fused indole formation. All barriers are readily to overcome under high temperature of experiment.
Our DFT calculations provide the first theoretical investigation on Rh(III)-catalyzed cascade reaction of N-alkoxycarbamoyl indole with CF3–ynone. The cleavage of carbamoyl and indoyl bond gives five-membered rhodacycle via two steps of reversible CMD process. The triple bond is inserted into Rh−C after ynone coordination with Rh(III) and removal of two HCl. After proto-demetalation assisted by one HCl, an extra MeOH is embedded into carbonyl group determined to be rate-limiting. forming N-alkoxycarbamoyl unit The complex is then removed into two parts of indole and N-alkoxycarbamoyl unit indispensable for C−H activation. The intramolecular N-nucleophilic addition of the former affords product pyrrolo[1,2-a]indole and Rh(III) is recovered with a second HCl from the latter both favorable in thermodynamics.
For cascade transformation to cycloheptenone fused indole without catalyst, the rate-limiting intramolecular Friedel−Crafts acylation is initiated by ester cleavage forming MeOH molecule and seven-membered cyclic ketone. The long range relay of H transfer arriving at α-C of indole is feasible via two steps. The last β-elimination is achieved after dehydration of one H2O molecule. All barriers are readily to overcome under high temperature of experiment. The positive solvation effect is suggested by decreased absolute and activation energies in MeOH solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.
Supplementary data available: [Computation information and cartesian coordinates of stationary points; Calculated relative energies for the ZPE-corrected Gibbs free energies (ΔGgas), and Gibbs free energies (ΔGsol) for all species in solution phase at 353 K.]
Conceptualization, Nan Lu; Methodology, Nan Lu; Software, Nan Lu; Validation, Nan Lu; Formal Analysis, Nan Lu; Investigation, Nan Lu; Resources, Nan Lu; Data Curation, Nan Lu; Writing-Original Draft Preparation, Nan Lu; Writing-Review & Editing, Nan Lu; Visualization, Nan Lu; Supervision, Chengxia Miao; Project Administration, Chengxia Miao; Funding Acquisition, Chengxia Miao. All authors have read and agreed to the published version of the manuscript.
This work was supported by National Natural Science Foundation of China (21972079) and Key Laboratory of Agricultural Film Application of Ministry of Agriculture and Rural Affairs, P.R. China.
The authors declare no conflict of interest.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
