DOCSLIB.ORG

Polysulfurating Reagent Design for Unsymmetrical Polysulfide Construction

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Polysulfurating Reagent Design for Unsymmetrical Polysulfide Construction ARTICLE DOI: 10.1038/s41467-018-04306-5 OPEN Polysulfurating reagent design for unsymmetrical polysulfide construction Xiao Xiao1, Jiahui Xue1 & Xuefeng Jiang 1,2,3 From life science to material science, to pharmaceutical industry, and to food chemistry, polysulfides are vital structural scaffolds. However, there are limited synthetic methods for unsymmetrical polysulfides. Conventional strategies entail two pre-sulfurated cross-coupling – 1234567890():,; substrates, R S, with higher chances of side reactions due to the characteristic of sulfur. Herein, a library of broad-spectrum polysulfurating reagents, R–S–S–OMe, are designed and scalably synthesized, to which the R–S–S source can be directly introduced for late-stage modifications of biomolecules, natural products, and pharmaceuticals. Based on the hard and soft acids and bases principle, selective activation of sulfur-oxygen bond has been accom- plished via utilizing proton and boride for efficient unsymmetrical polysulfuration. These polysulfurating reagents are highlighted with their outstanding multifunctional gram-scale transformations with various nucleophiles under mild conditions. A diversity of polysulfurated biomolecules, such as SS−(+)-δ-tocopherol, SS-sulfanilamide, SS-saccharides, SS-amino acids, and SSS-oligopeptides have been established for drug discovery and development. 1 Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China. 2 State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China. 3 State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. Correspondence and requests for materials should be addressed to X.J. (email: [email protected]) NATURE COMMUNICATIONS | (2018) 9:2191 | DOI: 10.1038/s41467-018-04306-5 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-04306-5 isulfide scaffolds, containing two covalently linked sulfur sulfide donor, mediating and regulating the release of hydrogen – atoms, are important molecular motifs in life science1 6, sulfide upon physiological activation (Fig. 1b)23, 24. From the D 7–15 16–18 pharmaceutical science , and food chemistry by materials perspective, organotrisulfides, such as dimethyl tri- − virtue of their unique pharmacological and physiochemical sulfide (DMTS) with a theoretical capacity of 849 mAhg 1, hold properties (Fig. 1a). Disulfide bonds, for instance, in biomolecules promise as high-capacity cathode materials for high-energy take multifaceted roles in various biochemical redox processes to rechargeable lithium batteries25. It should also be pointed out generate and regulate hormones, enzymes, growth factors, toxins, that trisulfides do exist in bioactive natural products from marine – and immunoglobulins for very homeostasis and bio-signaling invertebrates7, 26 28, such as the antitumor varacins A26 and the (e.g., metal trafficking); secondary and tertiary structures of anti-fungus outovirin C27. proteins are also well formed and stabilized via the disulfide Given the importance and predominance in pharmaceuticals – bridge2 5. In recent decades, potent bioactive natural products and other bioactive compounds of polysulfurated structures, it is and pharmaceuticals possessing sulfur–sulfur bonds have been always sought-after to develop general polysulfuration protocols discovered, such as the antifungal polycarpamine family7, the for synthetic purposes. Although typical methods for symmetrical anti-poliovirus epidithiodiketopiperazine (ETPs) family8, 9, disulfide preparation have been well developed29, the construc- romidepsin10, gliotoxin11, and some new histone deacetylase/ tion of unsymmetrical disulfides is still a challenging transfor- – methyltransferase inhibitors12, which, mechanism-wise, either mation due to the high reactivity of S–S bond30 40. In general, the sequester enzyme-cofactor zinc or generate highly reactive elec- synthesis of unsymmetrical disulfides can be achieved via an SN2 trophiles to induce DNA strand scission. When it comes to process between a thiol and a prefunctionalized thiol with leaving – antibody-drug conjugates (ADC), the disulfide bond has also group32 38. Alternatively, one can employ either two different been extensively utilized as a linker to deliver the active drug into kinds of thiols with unavoidable formation of homocoupling – the targeted cell after cleavage upon internalization of ADC19 22. byproducts39 or two distinct symmetrical disulfides with the use Due to the higher intracellular concentration of free thiols (glu- of rhodium(I) by Yamaguchi group40. Based on our continuous – tathione) than in the bloodstream, the sulfur–sulfur bonds can be research in organic sulfur chemistry41 48, comproportionation selectively cleaved in the cytoplasm of cancer cell, thereby between two distinct inorganic sulfur sources was utilized for achieving the specified release of cytotoxic molecules. Notably, unsymmetrical disulfides syntheses49. However, the strategy of disulfide compounds in allium species plants can not only aforementioned methods introduces disulfide bonds from two demonstrate vasorelaxation activity, but also inhibit ADP- different kinds of sulfur-containing substrates, requiring more – induced platelet aggregation16 18. synthetic steps and leading to side-reactions due to both reactive – Tri-sulfides have recently received considerable attention. To thio-derivatives (Fig. 2a)30 40, 49. We intend to develop metho- cite the allium-derived diallyl trisulfide (DATS) as an example, it dology which can introduce the RSS source with one disulfurating serves as a gasotransmitter precursor and an excellent hydrogen reagent at a later stage so as to provide great compatibility and a b Disulfide: Me Me Trisulfide: O O NMe2 Me N H S MeO O NH O S S S S S S S S O S Me S Me MeO NH Me S R NH S S S S O Polycarpamine B S Me Me R = O DATS Protein structure Polycarpamine C Istodax (gasotransmitter DMTS R = S (electrode material) (romidepsin) H2S donors) (anti-fungus) Life Science Natural Products Pharmaceuticals Life Science Materials Science S Cytotoxic S OMe molecule O MeO OMe Allicin MeO S S (hypolipidemic, OH OHO S Linker H S hypotensive) S S N S S Attachment site S S NMe OH NH2 S OH O O Z-ajoene Outovirin C Varacins A (anti-thrombotic) (anti-fungus) (antitumor) Antibody Antibody Drug Conjugates (ADC) Food Chemistry Natural Products Fig. 1 Significant polysulfides. a The importance of disulfide scaffolds in life science, natural products, pharmaceuticals, antibody drug conjugates, and food chemistry. b Functional trisulfide molecules 2 NATURE COMMUNICATIONS | (2018) 9:2191 | DOI: 10.1038/s41467-018-04306-5 | www.nature.com/naturecommunications NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-04306-5 ARTICLE several possibilities of polysulfuration. Hydropersulfide (RSSH) acetyl masked disulfurating nucleophiles and organometallic seems to be a prime disulfurating reagent, though it is unstable reagents (Fig. 2b)52. owing to its high reactivity50, 51. Two sulfur atoms were suc- Nevertheless, there is a large demand for a universal dis- cessfully introduced in one step via oxidative cross-couplings of ulfurating reagent, which is compatible with diverse coupling a Disulfuration via two sulfur sources: 2 1 2 Two functionalized "sulfur" S R (1) R S + R S R1 S b Direct disulfuration via masked strategy: Nucleophilic reagent: 1 Oxidative cross-coupling 1 S Mask (2) (Mask1 = Ac) R S Metal cat. δ– S Nu R1 S Electrophilic reagent: S Mask2 Umpolung 1 (3) (Mask2 = ?) R S δ+ Metal free c This work: electrophilic disulfuration BR / H+ Cat. Nu S S OMe Nu H 3 S 1 R1 S + R1 S + R Nu + δ Nu = C, N, S Challenge: Solution: The same main group, similar electronic effect HSAB Electronic effect S Mask i) Umpolung R1 S ii) Selective S-O cleavage Lewis base Fig. 2 Strategies for polysulfide construction. a Traditional methodologies for unsymmetrical disulfide syntheses. b Masked strategy for disulfuration. c Electropilic disulfurating reagent for polysulfuration Table 1 Optimization of polysulfide reagentsa,b Entry CuSO4 (mol%) Ligand (mol%) PhI(OPiv)2 (equiv) Temp (°C) Time (h) Yields (%) 1c 10 bpy (10) 2.5 25 11 31 2d 10 bpy (10) 2.5 25 11 ND 3 10 bpy/ phen (10) 2.5 25 11 50/53 4 10 L1 (10) 2.5 25 11 77 5 10 L2/L3/L4 (10) 2.5 25 11 70/63/68 6 10 L1 (10) 2.5 20 13 86 7 5 L1 (10) 2.5 20 13 86 8 2.5 L1 (10) 2.5 20 13 79 9 5 L1 (5) 2.5 20 13 76 10 5 L1 (10) 2.2 20 13 88 11 5 L1 (10) 1.9 20 13 65 a Conditions: 1d (0.2 mmol, 1 equiv), CuSO4·5H2O, Ligand, Li2CO3 and PhI(OPiv)2 were added to MeOH (2 mL) at 20 °C for 13 h bIsolated yields c PhI(OAc)2 was instead of PhI(OPiv)2 d PhI(OTFA)2 was instead of PhI(OPiv)2 NATURE COMMUNICATIONS | (2018) 9:2191 | DOI: 10.1038/s41467-018-04306-5 | www.nature.com/naturecommunications 3 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-04306-5 Table 2 The scope of polysulfurating reagentsa,b a 1 (5 mmol, 1 equiv), CuSO4·5H2O (0.0125 mol, 0.125 mol%), L1 (0.025 mol, 0.25 mol%), Li2CO3 (5 mmol, 1 equiv) and PhI(OPiv)2 (11 mmol, 2.2 equiv) were added to MeOH (10 mL) at 20 °C for 15 h bIsolated yields c1 (10 mmol, 1 equiv) and MeOH (10 mL) were used partners without transition-metal catalysis. The umpolung strat- PhI(OAc) as oxidant (Table 1, entry 1). The bulky iodonium salt − + 2 egy, replacement of acetyl (RSS ) with methoxyl (RSS ) group, PhI(OPiv)2 was the oxidant of choice in this conversion (Table 1, will afford the precursor of persulfide cation (Fig. 2c). Originating entries 1–3). Systematic investigations of ligands showed that 4,7- from the same main group, sulfur and oxygen possess similar diphenyl-1,10-phenanthroline helped to increase the yield of 2d electronic effect, which imposes a great challenge for selective to 77% (Table 1, entries 3–5).
Load more

Recommended publications
  • Vulcanization & Accelerators
    Vulcanization & Accelerators Vulcanization is a cross linking process in which individual molecules of rubber (polymer) are converted into a three dimensional network of interconnected (polymer) chains through chemical cross links(of sulfur). The vulcanization process was discovered in 1839 and the individuals responsible for this discovery were Charles Goodyear in USA and Thomas Hancock in England. Both discovered the use of Sulfur and White Lead as a vulcanization system for Natural Rubber. This discovery was a major technological breakthrough for the advancement of the world economy. Vulcanization of rubbers by sulfur alone is an extremely slow and inefficient process. The chemical reaction between sulfur and the Rubber Hydrocarbon occurs mainly at the C = C (double bonds) and each crosslink requires 40 to 55 sulphur atoms (in the absence of accelerator). The process takes around 6 hours at 140°C for completion, which is uneconomical by any production standards. The vulcanizates thus produced are extremely prone to oxidative degradation and do not possess adequate mechanical properties for practical rubber applications. These limitations were overcome through inventions of accelerators which subsequently became a part of rubber compounding formulations as well as subjects of further R&D. Following is the summary of events which led to the progress of ‘Accelerated Sulfur Vulcanization'. Event Year Progress - Discovery of Sulfur Vulcanization: Charles Goodyear. 1839 Vulcanizing Agent - Use of ammonia & aliphatic ammonium derivatives: Rowley. 1881 Acceleration need - Use of aniline as accelerator in USA & Germany: Oenslager. 1906 Accelerated Cure - Use of Piperidine accelerator- Germany. 1911 New Molecules - Use of aldehyde-amine & HMT as accelerators in USA & UK 1914-15 Amine Accelerators - Use of Zn-Alkyl Xanthates accelerators in Russia.
    [Show full text]
  • 1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, in Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study
    molecules Article 1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study Danuta Branowska 1, Zbigniew Karczmarzyk 1,*, Ewa Woli ´nska 1, Waldemar Wysocki 1, Maja Morawiak 2 , Zofia Urba ´nczyk-Lipkowska 2 , Anna Bielawska 3 and Krzysztof Bielawski 3 1 Faculty of Exact and Natural Sciences, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland; [email protected] (D.B.); [email protected] (E.W.); [email protected] (W.W.) 2 Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland; [email protected] (M.M.); zofi[email protected] (Z.U.-L.) 3 Medical University of Bialystok, Department of Medicinal Chemistry and Drug Technology, J. Kilinskiego 1, 15-089 Bialystok, Poland; [email protected] (A.B.); [email protected] (K.B.) * Correspondence: [email protected]; Tel.: +48-25-643-1017 Received: 24 March 2020; Accepted: 14 May 2020; Published: 16 May 2020 Abstract: In this study, we synthesized novel sulfonamides with a 1,2,4-triazine moiety according to pharmacophore requirements for biological activity. All the synthesized compounds were tested in vitro to verify whether they exhibited anticancer activity against the human breast cancer cell lines MCF-7 and MDA-MB-231. Among them, two most active ones, having IC50 values of 50 and 42 µM, respectively, were found to show higher anticancer activity than chlorambucil used as the reference in the in vitro tests. In addition, two other compounds, which had IC50 values of 78 and 91 µM, respectively, exhibited a similar level of activity as chlorambucil.
    [Show full text]
  • THE CHEMISTRY of SULFENIMIDES by Barbara Ann Orwig a Thesis
    THE CHEMISTRY OF SULFENIMIDES by Barbara Ann Orwig A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfilment of the requirements for the degree of Master of Science Department of Chemistry McGill University Montreal, P.Q. Canada May 1971 @) Barbara Ann Orwig 1972 Dedicated to My Parents Il Thanx Il i ACKNOWLEDGEMENTS 3l MY thanks to Dr. D.F.R. Gilson for the p nmr spectra, to Victor Yu for the A-60 nmr spectra, and to Peter Currie for the mass spectra. For helpful discussions and worthwhile suggestions l thank David Ash 1 Errol Chang 1 and John Gleason. For his guidance and help as my research director l thank Dr. David N. Harpp. And to Elva and Hermann Heyge go special thanks for their help and for "putting up wi th œil. TABLE OF CONTENTS Page ACKNOWLEDGEMENTS i INTRODUcrION 1 EXPERIMENTAL SECTION 22 RESULTS AND DISCUSSION 42 TABLES 1 Preparation of Sulfenyl Chlorides 72 2 Preparation of N-(alkyl/aryl thio)phthalimides 73 3 Desulfurization Reactions of N-(alkyl/aryl thio)phthalimides 76 4 Mass Spectra of N-(alkyl/aryl thio)phthalimides 77 FIGURES (Spectra) 78 - 87 BIBLIOGRAPHY 88 INTRODUcrION AND BACKGROUND Sulfenic acids Cl), in which sulfur exists in its R-S-OH l lcwest oxidation state, are highly lmstable compolmds and only a few l have been isolated. The derivatives of sulfenic acid {~.> however, are generally isolable and usually stable. 2 R-S-Y 2 When Y is -NH ' -~HR, or -NR ' the resulting class of compolmds is 2 2 ter.med sulfenamides.
    [Show full text]
  • United States Patent Office
    3,454,590 United States Patent Office Patented July 8, 1969 2 3,454,590 New compounds that can be produced by the process BENZOTHAZO-LE-2-SULFNAMIDES are benzothiazole-2-sulfinamides where R and R in the Alan Jeffrey Neale, Llangollen, Wales, and Terence above formula each represent an aliphatic or cyclo James Rawlings, Penicuik, Scotland, assignors to aliphatic group and the total number of carbon atoms Monsanto Chemicals Limited, London, England, in R and R' is at least four, and sulfinamides where R a British company No Drawing. Filed June 1, 1967, Ser. No. 642,717 and R are linked to form a saturated cyclic system with Claims priority, application Great Britain, June 17, 1966, the nitrogen atom. 27,184/66 The invention includes a process in which a new com nt. C. C07d 91/44, 29/34 pound as defined above is employed as an accelerator U.S. CI. 260-306.6 3 Claims O for the Vulcanization of rubber. Sulfinamides that can be produced by oxidation of the corresponding sulfenamides in the process defined above ABSTRACT OF THE DISCLOSURE can also be obtained by reaction of a benzothiazole-2-sul finyl halide with an appropriate amine. In particular, sul This disclosure is benzothiazole-2-sulfinamides of the 5 finamides in which the sulfinamide grouping is represented formula by the formula: S N R R C-S-N -s-N Né y 20 R. can be obtained by reaction of the sulfinyl halide with where R and R' are each an aliphatic or cycloaliphatic an amine having the formula HNRR.
    [Show full text]
  • UNDERSTANDING SULFUR BASED REDOX BIOLOGY THROUGH ADVANCEMENTS in CHEMICAL BIOLOGY by THOMAS POOLE a Dissertation Submitted to T
    UNDERSTANDING SULFUR BASED REDOX BIOLOGY THROUGH ADVANCEMENTS IN CHEMICAL BIOLOGY BY THOMAS POOLE A Dissertation Submitted to the Graduate Faculty of WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Chemistry May 2017 Winston-Salem, North Carolina Approved By: S. Bruce King, Ph.D., Advisor Leslie B. Poole, Ph.D., Chair Patricia C. Dos Santos, Ph.D. Paul B. Jones, Ph.D. Mark E. Welker, Ph.D. ACKNOWLEDGEMENTS First and foremost I would like to thank professor S. Bruce King. His approach to science makes him an excellent role model that I strive to emulate. He is uniquely masterful at parsing science into important pieces and identifying the gaps and opportunities that others have missed. I thank him for the continued patience and invaluable insight as I’ve progressed through my graduate studies. This work would not have been possible without his insight and guiding suggestions. I would like to thank our collaborators who have proven invaluable in their support. Cristina Furdui has provided the knowledge, context, and biochemical support that allowed our work to be published in esteemed journals. Leslie Poole has provided the insight into redox biology and guidance towards appropriate experiments. I thank my committee members, Mark Welker and Patricia Dos Santos who have guided my graduate work from the beginning. Professor Dos Santos provided the biological perspective to evaluate my redox biology work. In addition, she helped guide the biochemical understanding required to legitimize my independent proposal. Professor Welker provided the scrutinizing eye for my early computational work and suggested validating the computational work with experimental data.
    [Show full text]
  • Recent Advances in Sulfur–Nitrogen Bond Formation Via Cross-Dehydrogenative Coupling Cite This: RSC Adv.,2018,8, 18456 Reactions
    RSC Advances View Article Online REVIEW View Journal | View Issue Recent advances in sulfur–nitrogen bond formation via cross-dehydrogenative coupling Cite this: RSC Adv.,2018,8, 18456 reactions Fatemeh Alsadat Hosseini Nasab,a Leila Zare Fekri,b Aazam Monfared,b *c b Received 12th January 2018 Akram Hosseinian and Esmail Vessally Accepted 12th April 2018 This focus-review surveys literature methods for the construction of sulfur–nitrogen bonds through cross- DOI: 10.1039/c8ra00356d dehydrogenative coupling reactions between thiols and N–H compounds with a particular emphasis on the rsc.li/rsc-advances mechanistic aspects of the reactions. The literature has been surveyed until the end of 2017. 1. Introduction 2 with trade name Topamax is a promising anticonvulsant medicine available in a number of countries worldwide. The 8 Needless to say, organosulfur compounds play a very important drug is also used for migraine prevention in adults. Folpet 3 is Creative Commons Attribution-NonCommercial 3.0 Unported Licence. role in various elds such as organic synthesis, materials a fungicide used for broad-spectrum control of fungal patho- 9 science, agriculture, and medicinal chemistry.1–4 Among them, gens. Sulfoxaor 4 is an insecticide with a sulfoximine motif, compounds bearing sulfur–nitrogen bonds are important this compound is very active against a wide range of sap-feeding 10 building blocks in a variety of biologically active substances. For insect pests and widely used around the world. Thus, instance, sultiame 1 (Fig. 1) with brand name Ospolot is construction of biologically and synthetically important sulfur– a synthetic sulfa-based drug marketed worldwide for the treat- nitrogen bonds is one of the essential transformations in ment of epilepsy.5,6 The drug works by reducing the activity of organic synthesis.
    [Show full text]
  • 2-Nitrophenylsulfenyl Chloride Into New Compounds with Potential Pesticidal Activity
    Synthesis and transformation of 4-dichloromethylsulfonyl-2-nitrophenylsulfenyl... 5 Pestycydy/Pesticides, 2009, (1-4), 5-14. ISSN 0208-8703 Synthesis and transformation of 4-dichloromethylsulfonyl- 2-nitrophenylsulfenyl chloride into new compounds with potential pesticidal activity Zbigniew OCHAL, Wojciech BIAŁKOWSKI and Łukasz BANACH Warsaw University of Technology, Faculty of Chemistry, 3 Noakowskiego St., 00-664 Warsaw, Poland e-mail: [email protected] Abstract: The synthesis of 4-dichloromethylsulfonyl-2-nitrophenylsulfenyl chloride and its transformation into new compounds with promising pesticidal activity is reported. The title compounds were obtained by a three-step synthesis, starting from 4-dichloromethylchlorophenyl sulfone. It was nitrated and then subjected to the SNAr reaction with sodium disulfide to give proper diphenyl disulfide, which was next chlorinated by chlorine. The obtained phenylsulfenyl chloride was transformed into sulfenamide derivatives by reactions with amines. Keywords: 4-chlorophenyldichloromethyl sulfone, sulfenyl chloride, sulfenamides, pesticides INTRODUCTION Some sulfenamide derivatives are known as the non-systemic fungicides widely used to control foliage and fruit diseases of tomatoes, coffee berry, potato and many other fruits and vegetables [1, 2]. Galactofuranosyl-N,N-dialkyl sulfenamides displayed an antimycobacterial activity [3]. Some N-sulfenyl heterocycles are effective sulfenylating agents of aromatic amines [4]. In addition, they are the important intermediates in many reactions, promising in the prodrug technologies [5, 6]. On the other hand, it is well known that chemical compounds with chloromethyl groups show an interesting biological activity [1]. We have proved in our previous investigations that chloro- and dichloromethylsulfonyl 6 Z. Ochal, W. Białkowski, Ł. Banach groups in aromatic compounds were favorable to pesticidal activities [7-11].
    [Show full text]
  • United States Patent Office Patented Apr
    3,658,828 United States Patent Office Patented Apr. 25, 1972 2 3,658,828 R R UNSYMMETRICAL DIALKYL THAZOLE / SULFENAMIDES T-S -N-ce John Joseph D'Amico, Akron, Ohio, assignor to R3 Monsanto Company, St. Louis, Mo. 5 wherein T is benzothiazolyl or substituted benzothiazolyl, No Drawing. Filed Nov. 19, 1969, Ser. No. 878,243 where the substituents are chloro, bromo, fluoro, iodo, ni Int, C. C07d 91/44 tro or lower alkoxy, R is tertiary-alkyl of 4-12 carbon U.S. C. 260-306.6A 5 Claims atoms, R2 and R3 are alkyl of 1-8 carbon atoms or to gether with the carbon atom to which they are attached O form cycloalkyl of 5-8 carbon atoms. ABSTRACT OF THE DISCLOSURE Examples of tertiary-alkyl radicals suitable for the prac Unsymmetrical dialkyl thiazole sulfenamides of the tice of this invention are tertiary-butyl, tertiary-amyl, formula tertiary-hexyl, tertiary-octyl, tertiary-nonyl, tertiary-decyl and tertiary-dodecyl. A tertiary-alkyl radical has its first 5 carbon atom linked to three other carbon atoms. The aliphatic groups from which R2 and R can be Selected include alkyl groups containing from 1-8 car bon atoms having straight or branched chains, for ex wherein T is benzothiazolyl or substituted benzothiazolyl, ample, methyl, ethyl, propyl, isopropyl, butyl, secondary where the substituents are chloro, bromo, fluoro, iodo, 20 butyl, amyl, hexyl and octyl. Cyclopentyl, cyclohexyl and nitro or lower alkoxy, R is tertiary-alkyl of 4-12 carbon cyclooctyl are examples of radicals when R2 and R3 to atoms, R2 and R3 are alkyl of 1-8 carbon atoms or to gether with the carbon to which they are attached form gether with the carbon atom to which they are attached cycloalkyl.
    [Show full text]
  • Insight Into Vulcanization Mechanism of Novel Binary Accelerators for Natural Rubber*
    Chinese Journal of Polymer Science Vol. 32, No. 8, (2014), 1077−1085 Chinese Journal of Polymer Science © Chinese Chemical Society Institute of Chemistry, CAS Springer-Verlag Berlin Heidelberg 2014 Insight into Vulcanization Mechanism of Novel Binary Accelerators for * Natural Rubber Shu-yan Yanga, Zhi-xin Jiab**, Lan Liub, Wei-wen Fub, De-min Jiab and Yuan-fang Luob a Chemical Industrial Cleaner Production and Green Chemical R&D Center of Guang Dong Universities, Dongguan University of Technology, Dongguan 523808, China b College of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China Abstract A novel TU derivative, N-phenyl-N′-(γ-triethoxysilane)-propyl thiourea (STU), is prepared and its binary accelerator system is investigated in detail. Compared to the control references, the optimum curing time of NR compounds with STU is the shortest, indicating a more nucleophilic reaction occurs. The Py-GC/MS results present that the phenyl iso- thiocyanate fragment still remains in the NR/STU compounds with or without extracting treatment, but no silane segment can be found in the vulcanizate with extracting treatment. Vibrations of C＝S, NH and aromatic ring in FTIR experiments and a new methyne carbon peak, as well as the peaks of phenyl group of STU, in the solid state 13C-NMR experiments are found in the NR/STU vulcanizate with extracting treatment. Moreover, the crosslinking density of vulcanizates with STU evolves to lower level, indicating the sulfur atom of STU does not contribute to the sulfur crosslinking. Therefore, a new vulcanization kinetic mechanism of STU is propounded that the thiourea groups can graft to the rubber main chains as pendant groups by chemical bonds during the vulcanization process, which is in accordance with the experimental observations quite well.
    [Show full text]
  • An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols Or Nitrogen-Sulfur Bonds, but Not Both
    An apparent binary choice in biochemistry: mutual reactivity implies life chooses thiols or nitrogen-sulfur bonds, but not both The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Petkowski, Janusz J., William Bains, and Sara Seager, "An apparent binary choice in biochemistry: mutual reactivity implies life chooses thiols or nitrogen-sulfur bonds, but not both." Astrobiology 19, 4 (March 2019): p. 579-613 doi 10.1089/AST.2018.1831 ©2019 Author(s) As Published 10.1089/AST.2018.1831 Publisher Mary Ann Liebert Inc Version Final published version Citable link https://hdl.handle.net/1721.1/124665 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. ASTROBIOLOGY Volume 19, Number 4, 2019 Hypothesis Article ª Mary Ann Liebert, Inc. DOI: 10.1089/ast.2018.1831 An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols or Nitrogen-Sulfur Bonds, but Not Both Janusz J. Petkowski,1 William Bains,2 and Sara Seager1,3 Abstract A fundamental goal of biology is to understand the rules behind life’s use of chemical space. Established work focuses on why life uses the chemistry that it does. Given the enormous scope of possible chemical space, we postulate that it is equally important to ask why life largely avoids certain areas of chemical space. The nitrogen-sulfur bond is a prime example, as it rarely appears in natural molecules, despite the very rich N-S bond chemistry applied in various branches of industry (e.g., industrial materials, agrochemicals, pharmaceu- ticals).
    [Show full text]
  • UNITED STATES PATENT OFFICE 2,421,352 SUBSTITUTED TOCARBAMO SULFENAMOES Philip T
    Patiented May 27, 1947 242,352 UNITED STATES PATENT OFFICE 2,421,352 SUBSTITUTED TOCARBAMO SULFENAMOES Philip T. Paul and Byron A. Hunter, Naugatuck, Conn., assignors to United States Rubber Com pany, New York, N. Y., a corporation of New Jersey No Drawing. Original application March 9, 1944, Serial No. 525,774. Divided and this applica tion April 26, 1944, Serial No. 532,881 5 Claims. (C. 260-551) 2 . This invention relates to new chemical com phatic groups (saturated or unsaturated) such pounds which are useful as vulcanization accel as methyl, ethyl, propyl, methallyl, amyl, hexyl, erators in the Vulcanization of rubbers, both nat allyl, butyl, benzyl, lauryl, etc., exemplified by ural and synthetic, such as Hevea brasiliensis N',N'-dimethyl thiocarbamo sulfenamide, N',N'- and Various polymerS Such as butadiene-styrene 5 diethyl thiocarbamo sulfenamide, N',N'-dipropyl copolymer, butadiene - acrylonitrile copolymer, thiocarbamosulfenamide, N',N'-dimethallylthio isoprene-isobutylene copolymer, etc. carbamo sulfenamide, N',N'-diamyl thiocarbamo This application is a division of our copending sulfenamide, N',N'-dihexyl thiocarbamo Sulfen application Serial No. 525,774, filed March 9, 1944. amide, N',N'-diallyl thiocarbamo sulfenamide, The new class of rubber vulcanization accel O N',N' - dibutyl thiocarbamo sulfenamide, N'- erators are N,N'-disubstituted thiocarbamo Sul methyl N-benzyl thiocarbamo sulfenamide, N'- fenamides in which the sulfenamide nitrogen is ethyl N-benzyl thiocarbamo Sulfenamide, N',N'- directly attached to each of
    [Show full text]
  • Sulfur Vulcanization of Natural Rubber for Benzothiazole Accelerated Formulations: from Reaction Mechanisms to a Rational Kinetic Model
    Y 592 03-R-19 8/18/03 3:21 PM Page 592 SULFUR VULCANIZATION OF NATURAL RUBBER FOR BENZOTHIAZOLE ACCELERATED FORMULATIONS: FROM REACTION MECHANISMS TO A RATIONAL KINETIC MODEL PRASENJEET GHOSH,+ SANTHOJI KATARE,PRIYAN PATKAR JAMES M. CARUTHERS,* VENKAT VENKATASUBRAMANIAN SCHOOL OF CHEMICAL ENGINEERING,PURDUE UNIVERSITY WEST LAFAYETTE, IN 47906-1283 KENNETH A. WALKER CHEMICAL PRODUCTS BUSINESS UNIT,CATERPILLAR,INC. P.O. BOX 400, MOSSVILLE,IL 61552-4000 ABSTRACT The chemistry of accelerated sulfur vulcanization is reviewed and a fundamental kinetic model for the vulcaniza- tion process is developed. The vulcanization of natural rubber by the benzothiazolesulfenamide class of accelerators is studied, where 2-(morpholinothio) benzothiazole (MBS) has been chosen as the representative accelerator. The reaction mechanisms that have been proposed for the different steps in vulcanization chemistry are critically evaluated with the objective of developing a holistic description of the governing chemistry, where the mechanisms are consistent for all reaction steps in the vulcanization process. A fundamental kinetic model has been developed for accelerated sulfur vul- canization, using population balance methods that explicitly acknowledge the polysulfidic nature of the crosslinks and various reactive intermediates. The kinetic model can accurately describe the complete cure response including the scorch delay, curing and the reversion for a wide range of compositions, using a single set of rate constants. In addition, the concentration profiles of all the reaction intermediates as a function of polysulfidic lengths are predicted. This detailed information obtained from the population balance model is used to critically examine various mechanisms that have been proposed to describe accelerated sulfur vulcanization.
    [Show full text]