Sustainable chemistry: how to produce better and more from less?

Sustainable chemistry: how to produce better and more from less?

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02006F, Perspective
P. Marion, B. Bernela, A. Piccirilli, B. Estrine, N. Patouillard, J. Guilbot, F. Jerome
This review describes the rapid evolution of chemistry in the context of a sustainable development of our society. Written in collaboration between scientists from different horizons, either from public organizations or chemical companies, we aim here at providing recommendations to accelerate the emergence of eco-designed products on the market.

Sustainable chemistry: how to produce better and more from less?

 Author affiliations

Abstract

The International Symposium on Green Chemistry (ISGC) organized in 2013, 2015 and 2017 has gathered many senior and young talented scientists from all around the world (2200 attendees in three editions), either from academia or industry. Through outstanding conferences, communications, debates, and round tables, ISGC has been the witness of the rapid evolution of chemistry in the context of a sustainable development of our societies, not only at the scientific and industrial levels but also on education, networking and societal aspects. This critical review synthesizes the different points of view and the discussions having taken place at ISGC and gives a general picture of chemistry, including few scientific disciplines such as catalysis, processes, resource management, and environmental impact, among others, within the framework of sustainable development. This critical review, co-authored by researchers from public organizations and chemical companies (small, medium and large industrial groups) provides criteria and recommendations which, in our view, should be considered from the outset of research to accelerate the emergence of eco-designed products on the market.

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Conclusions

Sustainable chemistry is the only mean to generate performant  products and long lasting  solutions able  to  generate  business  and  profit  for  chemical  industry.  Performance  is  the  best  systemic answer for customer needs and our societies. Defining  sustainable  chemistry  is,  however,  far  to  be  an  easy  task  because chemistry is a highly dynamic system. The sustainability of a value chain is for instance directly depending on the access  to energy (and above all to its origin – coal, gas, biomass…) and  on the supply of raw materials. In the current economic context,  it could be not so easy to predict what will be the best source of  energy or raw materials for a desired product in the future. The  development  of  predictive  tools  is  now  essential  and  will  represent probably one of the next scientific challenges in the coming years.  During the last 20 years, utilization of renewable feedstocks in  chemical processes has become a strategy of growing interest  but  it  definitely  does  not  guarantee  the  establishment  of  a  sustainable  chemistry.  Indeed,  in  some  cases,  it  is  more  sustainable to produce a chemical from a fossil carbon source  using decarbonized energy than the reverse. It is very important  to  distinguish  the  carbon  found  in  the  final  product  from  the  carbon content corresponding to the energy which is required  the  product  production  (going  from  raw  materials  to  manufacturing,  end  of  life,  etc.).  In  this  area,  the  concept  of biorefinery can help  to secure developments and  to minimize  investments  in  production  plant  by  mutualizing  facilities  and  R&D initiatives. Cooperation with local producers can also be a valuable  way  to  implement  new  bio‐based  products  while  favouring sustainable agricultural practices.  Whatever  the  raw materials  (renewable or  fossil), a complete  and systemic life cycle analysis of the whole chain value (from resources  to  manufacturing,  use  and  end  of  life)  must  be  performed because it gives us an accurate picture of the overall  economic,  environmental  and  societal  performances  of  a  product in an application for a defined market. In general, one should never forget that sustainable chemistry should help the  society to produce more and better (products).   Emergence of sustainable innovations on the market takes a lot  of  time  because  chemists  have  to  reinvent  chemistry.  To  achieve our  transition  to a sustainable society, we must  think  differently  and  bring  together  the  worlds  of  finance,  manufacturers, researchers and public authorities. The current  method of funding of research and innovation is not satisfying  yet because  too often based on  short‐term  projects and with  high Technology Readiness Level. Governments have to realize  that  this  funding  method  slows  down,  and  sometime  also  hampers, the emergence of future sustainable innovations.   Evolution of regulations with the aim of banning toxic, eco‐toxic  or  poor  biodegradable  products  is  an  important  driver  for  sustainable innovation. It is now seen and shared as a positive sign  providing  opportunities  to  develop  systemically  better  solutions  and  allowing  chemical  companies  advocating  sustainable development and products as a must to stay in the  competition.  As  examples,  ban  of  CFC,  replacement  of  chlorinated  or  other  toxic  solvents,  substitution  of  endocrine  disruptors lead to better solutions for the global benefit of our  societies.  Improving  public  perception  and  awareness  on  sustainable  chemistry is on the way but more efforts will be needed in the  future  to  definitely  contribute  to  the  emergence  of  eco‐ designed chemicals on the market.

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Below  we  provide  a  bulleted  list  to  summarize  the  main  recommendations that are, in our views, essential for designing sustainable products.  (1) Products  design  &  Manufacture:  For  the  intended  application, sustainable chemicals must imperatively bring a  global  benefit,  created  by  a  scientific  or  technological  breakthrough,  while  minimizing  risks.  They  should  also  generate profit to emerge on the market. Products should  be  produced  according  to  the  12  principles  of  green  chemistry. In addition, their end of life should be integrated  at the outset of research,  (2) Resources: They should be available for future generations  and  should  have  low  environmental  impact  (protecting  endangered species, deforestation, erosion of biodiversity,  contamination of natural resources, global warming, etc.), it  should  make  progress  the  societal  development  of  concerned area (sharing any benefits with local producer, no  child  labour,  help  developing  countries,  etc.)  and  their  utilization  should not destabilise other  supply  chains. Non  edible raw material, a return to the idea of ‘localness’ and  the need for closeness should be preferred,  (3) Process:  The  ideal  process  would  be  a  low  Capex  or  a  progressive  Capex  process and  should  be energy‐efficient,  not  use  solvents,  be  without  effluents,  should  limit  the  number of reactional and purification steps and should be  developed  rapidly  to  limit  the  associated  risks  and  costs.  Efforts  are  still  needed  for  miniaturisation  of  equipment,  intensification and development of continuous reactors,  (4)  Energy:  The  chemical  industry  is  also  energy  intensive.  Although  less  than  10%  of  fossil  carbon  is  used  for  the  manufacture of chemicals, finding decarbonized sources of  energy  is  mandatory  to  avoid  the  depletion  of  carbon  reserves  and  price  increase  and  to  ensure  that  future  generations  will  have  access  to  the  same  resource  in  the  same amount,   (5)  Life cycle assessment: it should be assessed in all cases, the  earlier the better, by preferring a ‘cradle to grave’ approach. It should give an accurate picture of the overall economic,  environmental and societal performances of a product in an  application for a defined market,  (6)  Education:  we  should  improve  public  awareness  and  perception  on  sustainable  chemistry  to  facilitate  the  acceptation of sustainable products by the consumer. More  education  programs  should  be  launched  in  the  future  not  only to reassure the consumer but also to create a pool of  students  better  armed  to  tackle  the  future  challenges  of  (sustainable)  chemistry.  The  rapid  development  of  digital  tools should be helpful to address this issue,  (7) Network: we should prefer working in an open innovation  mode  by  bringing  together  the  worlds  of  finance,  manufacturers,  researchers  and  public  authorities  to  accelerate the emergence of eco‐designed chemicals on the  market. Networks  should enable local  players  to adapt  to  changes  in  their  environment  while  optimising  their  economic and environmental efficiency,  (8)  Funding:  A  good  balance  between  funding  to  applied  research and basic research must be addressed in order to continuously  generate  scientific  innovation.  However,  public authorities must  realise  that societal challenges are  more  important  than  the  short  term  financial  challenges  faced  by  businesses.  The  current  model  of  our  economy  based  on  rapid  profitability  is  unfortunately  not  well  adapted  for  these  advances  since  long‐term  investments  will be needed for a more sustainable development of our  society,  (9)  Legislation & Regulation: it should facilitate the emergence  of sustainable chemicals by banning harmful chemicals  for  the  human  health  and  the  environment,  even  those  nowadays  generating  substantial  profits.  The  registration  process  of  improved  sustainable  chemicals  by  the  concerned agencies should be quicker than now to speed up  their integrations on the market,  (10)  Predictive  methods:  the  development  of  tools  to  accurately  predict  the  technical  and  application  performances, the economic efficiency, the environmental  and societal performance of a  targeted product should be  developed  to  limit  the  risks  and  costs  associated  with  potential  failure  and  to  reassure  the  investors.  It  is  also  urgent  to  develop  these  tools  for  chemicals  that  are  intended to be dispersed in nature.
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Increasing global access to the high-volume HIV drug nevirapine through process intensification

New Drug Approvals

Increasing global access to the high-volume HIV drug nevirapine through process intensification

Green Chem., 2017, 19,2986-2991
DOI: 10.1039/C7GC00937B, Paper
Jenson Verghese, Caleb J. Kong, Daniel Rivalti, Eric C. Yu, Rudy Krack, Jesus Alcazar, Julie B. Manley, D. Tyler McQuade, Saeed Ahmad, Katherine Belecki, B. Frank Gupton
Fundamental elements of process intensification were applied to generate efficient batch and continuous syntheses of the high-volume HIV drug nevirapine.

Green Chemistry

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Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C-C coupling reactions

Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C-C coupling reactions

Green Chem., 2017, 19,2931-2935
DOI: 10.1039/C7GC00789B, Communication
O. N. Chupakhin, A. V. Shchepochkin, V. N. Charushin
A simple and efficient electrochemical method for the synthesis of asymmetrical bi(het)aryls through direct functionalization of the C(sp2)-H bond in azaaromatics with fragments of (hetero)aromatic nucleophiles has been developed

From the journal:

Green Chemistry

Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C–C coupling reactions

Abstract

The synthesis of asymmetrical bi(het)aryls through direct functionalization of the C(sp2)–H bond in azaaromatics with fragments of (hetero)aromatic nucleophiles has first been carried out under electrochemical oxidative conditions. This versatile method for C–C bond formation between two aryl fragments can be realized under very mild potential-controlled oxidative conditions, and it does require neither incorporation of any halogen atoms or other leaving groups, nor the use of metal catalysts. The use of the electrochemical SHN methodology for modification of azaaromatic compounds has first been demonstrated.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC00789B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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Synthesis of compounds 3a-d

The potassium tert-butoxide (0.55 mmol), corresponding phenols 2a-d (0.55 mmol) and acetonitrile (10mL) were added to electrochemical cell under argon atmosphere. The reaction mixture was stirred at room temperature for 15 min. Then 10-methylacridinium tetrafluoroborate 1 (0.5 mmol, 140 mg) was added to the reaction mixture, and stirred at room temperature for 1 h. The supporting electrolyte (40 mL) was placed in the anode and in the cathode cell compartment (10 mL). Finally, the acetic acid (1 mmol, 57 μL) was placed in the anode cell compartment. Electrolysis was carried out at a controlled potential (reference electrode Ag/AgNO3). Upon passing 2.1F of electricity (for a two-electron process), the electrolysis was stopped, the solvent was distilled off in vacuum from the anolyte, the residue was washed with 30 ml of ether and 10 ml of water. The residue was recrystallized from water and dried on air. 9-(4-Hydroxy-3,5-dimethyl-phenyl)-10-methyl-acridinium tetrafluoroborate (3a) Orange needles. 195 mg (98%). The product was identified as a compound 3a by comparing its 1H NMR spectra with its given in the literature. Satisfactory elemental analysis for C, H and N were obtained for compound 3a; none of the experimentally found percentages deviated from the theoretical values by more than 0.3%.2

1H NMR (500 MHz, [D6]DMSO): δ 9.09 (s, 1H), 8.82 (d, 2H, J=9.2 Hz), 8.45-8.42 (m, 2H), 8.12-8.10 (m, 2H), 7.94-7.91 (m, 2H), 7.16 (s, 2H), 4.90 (s, 3H), 2.33 (s, 6H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ 161.5, 155.2, 141.1, 138.2, 130.3, 130.1, 127.6, 125.7, 124.8, 123.5, 119.0, 38.8, 16.6 ppm.

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Cp2TiCl: An Ideal Reagent for Green Chemistry?

 Abstract Image

The development of Green Chemistry inevitably involves the development of green reagents. In this review, we highlight that Cp2TiCl is a reagent widely used in radical and organometallic chemistry, which shows, if not all, at least some of the 12 principles summarized for Green Chemistry, such as waste minimization, catalysis, safer solvents, toxicity, energy efficiency, and atom economy. Also, this complex has proved to be an ideal reagent for green C–C and C–O bond forming reactions, green reduction, isomerization, and deoxygenation reactions of several functional organic groups as we demonstrate throughout the review.

Cp2TiCl: An Ideal Reagent for Green Chemistry?

 Department of Chemical Engineering, Escuela Politécnica Superior, University of Sevilla, 41011 Sevilla, Spain
 Organic Chemistry, ceiA3, University of Almería, 04120 Almería, Spain
§ Petrochemical Engineering, Universidad de las Fuerzas Armadas-ESPE, 050150 Latacunga, Ecuador
 Department of Organic Chemistry, Faculty of Science, University of Granada, 18071 Granada, Spain
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.7b00098
*E-mail: arosales@us.es.

http://pubs.acs.org/doi/10.1021/acs.oprd.7b00098

Synthesis and Properties of Cp2TiCl

Cp2TiCl is a single-electron-transfer (SET) complex that can be easily prepared from commercial and nontoxic Cp2TiCl2  by using economic and nontoxic reductants such as Mn or Zn. In solution, Cp2TiCl is in an equilibrium between mononuclear and dinuclear species. It has recently been reported that the stoichiometric metal reductant can be replaced by an organic reducing agent.
Figure

Although Cp2TiCl is not a renewable feedstock, it is important to say that this SET is a good alternative to them because it is obtained from nonhazardous materials and also because titanium is one of the most abundant and safe transition metals on Earth

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ChemSpider 2D Image | Titanocene dichloride | C10H10Cl2Ti

Titanocene dichloride

  • Molecular FormulaC10H10Cl2Ti
  • Average mass248.959 Da
1271-19-8 [RN]
Di(2,4-cyclopentadiénide) de dichlorotitane(2+) [French] [ACD/IUPAC Name]
Dichlorotitanium(2+) di(2,4-cyclopentadienide) [ACD/IUPAC Name]
Dichlortitan(2+)di(2,4-cyclopentadienid) [German] [ACD/IUPAC Name]
Titanocene dichloride [Wiki]
Titanocene dichloride
Titanocene dichloride
Ball-and-stick model of titanocene dichloride
Sample of titanocene dichloride
Names
IUPAC name

Dichloridobis(η5-cyclopentadienyl)titanium
Other names

titanocene dichloride, dichlorobis(cyclopentadienyl)titanium(IV)
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.013.669
PubChem CID
RTECS number XR2050000
Properties
C10H10Cl2Ti
Molar mass 248.96 g/mol
Appearance bright red solid
Density 1.60 g/cm3, solid
Melting point 289 °C (552 °F; 562 K)
sl. sol. with hydrolysis
Structure
Triclinic
Dist. tetrahedral
Hazards
R-phrases(outdated) R37R38
S-phrases(outdated) S36
NFPA 704
Flammability (red): no hazard code Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g., calcium Special hazards (white): no code

NFPA 704 four-colored diamond

Related compounds
Related compounds
Ferrocene
Zirconocene dichloride
Hafnocene dichloride
Vanadocene dichloride
Niobocene dichloride
Tantalocene dichloride
Molybdocene dichloride
Tungstenocene dichloride
TiCl4
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Titanocene dichloride is the organotitanium compound with the formula (η5-C5H5)2TiCl2, commonly abbreviated as Cp2TiCl2. This metallocene is a common reagent in organometallic and organic synthesis. It exists as a bright red solid that slowly hydrolyzes in air.[1]Cp2TiCl2 does not adopt the typical “sandwich” structure like ferrocene due to the 4 ligands around the metal centre, but rather takes on a distorted tetrahedral shape.[2] It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as a chemotherapy drug.[3]

Preparation

The standard preparations of Cp2TiCl2 start with titanium tetrachloride. The original synthesis by Geoffrey Wilkinson and Birmingham uses sodium cyclopentadienide[4] is still commonly used:

2 NaC5H5 + TiCl4 → (C5H5)2TiCl2 + 2 NaCl

The reaction is conducted in THF. Workup sometimes washing with hydrochloric acid to convert hydrolysis derivatives to the dichloride. Recrystallization from toluene forms acicular crystals.

Cp2TiCl2 can also be prepared by using freshly distilled cyclopentadiene rather than its sodium derivative:

2 C5H6 + TiCl4 → (C5H5)2TiCl2 + 2 HCl

This reaction is conducted under a nitrogen atmosphere and by using THF as solvent. The product is purified by soxhlet extractionusing toluene as solvent.[5]

The complex is pseudotetrahedral. Each of the two Cp rings are attached as η5 ligands.

Applications in organic synthesis

Cp2TiCl2 is a generally useful reagent that effectively behaves as a source of Cp2Ti2+. A large range of nucleophiles will displace chloride. Examples:

Application in preparing sulfur allotropes[edit]

Titanocene dichloride is used to prepare titanocene pentasulfide, a precursor to unusual alloptropes of sulfur:

Li2S5 + (C5H5)2TiCl2 → (C5H5)2TiS5 + LiCl

Structure of pentasulfur-The resulting pentasulfur-titanocene complex is allowed to react with polysulfur dichloride to give the desired cyclosulfur of in the series:[10]

Reactions

Cp2TiCl2 undergoes anion exchange reactions, e.g. to give the pseudohalides. With NaSH and with polysulfide salts, one obtains the sulfido derivatives Cp2Ti(SH)2 and Cp2TiS5.

One Cp ligand can be removed from Cp2TiCl2 to give tetrahedral CpTiCl3. This conversion can be effected with TiCl4 or by reaction with SOCl2.[11]

Reduction with zinc gives the dimer of bis(cyclopentadienyl)titanium(III) chloride in a solvent-mediated chemical equilibrium:[12][13]

N-RB equilibrium.jpg

Ti(II) derivatives

Cp2TiCl2 is a precursor to many TiII derivatives, though titanoce itself, TiCp2, is so highly reactive that it rearranges into a TiIII hydride dimer and has been the subject of much investigation.[14][15] This dimer can be trapped by conducting the reduction of titanocene dichloride in the presence of ligands; in the presence of benzene, a fulvalene complex, μ(η55-fulvalene)-di-(μ-hydrido)-bis(η5-cyclopentadienyltitanium), can be prepared and the resulting solvate structurally characterised by X-ray crystallography.[16] The same compound had been reported earlier by a lithium aluminium hydride reduction[17] and sodium amalgam reduction[18] of titanocene dichloride, and studied by 1H NMR[19] prior to its definitive characterisation.[14][15]

“Titanocene” is not Ti(C5H5)2, but rather this isomer with a fulvalene dihydride structure.[15][16]

Reductions have been investigated using Grignard reagent and alkyl lithium compounds. More conveniently handled reductants include Mg, Al, or Zn. The following syntheses demonstrate some of the compounds that can be generated by reduction of titanocene dichloride in the presence of π acceptor ligands:[20]

Cp2TiCl2 + 2 CO + Mg → Cp2Ti(CO)2 + MgCl2
Cp2TiCl2 + 2 PR3 + Mg → Cp2Ti(PR3)2 + MgCl2
Cp2TiCl2 + 2 Me3SiCCSiMe3 + Mg → Cp2TiMe3SiCCSiMe3 + MgCl2

With only one equivalent of reducing agent, TiIII species such as Cp2TiCl result.

Alkyne and benzyne derivatives of titanocene are well known.[21] One family of derivatives are the titanocyclopentadienes.[22]

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the Pauson–Khand reaction).[23] A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.[24]

Reduction of titanocene dichloride in the presence of conjugated dienes such as 1,3-butadiene gives η3-allyltitanium complexes.[25] Related reactions occur with diynes. Furthermore, titanocene can catalyze C-C bond metathesis to form asymmetric diynes.[22]

Derivatives of (C5Me5)2TiCl2

Many analogues of Cp2TiCl2 are known. Prominent examples are the ring-methylated derivatives (C5H4Me)2TiCl2 and (C5Me5)2TiCl2. The ethylene complex (C5Me5)2Ti(C2H4) can be synthesised by Na reduction of (C5Me5)2TiCl2 in the presence of ethylene. The Cp compound has not been prepared. This pentamethylcyclopentadienyl (Cp*) species undergoes many reactions such as cycloadditions of alkynes.[21]

Medicinal research

Titanocene dichloride was investigated as an anticancer drug.[26] In fact, it was both the first non-platinum coordination complex and the first metallocene to undergo a clinical trial.[3]The mechanism by which it acts is not fully understood; however, it has been conjectured that its activity might be attributable to the compound’s interactions with the protein transferrin.[3][27]

References

  1. Jump up^ Budaver, S., ed. (1989). The Merck Index (11th ed.). Merck & Co., Inc.
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  3. Jump up to:a b c Roat-Malone, R. M. (2007). Bioinorganic Chemistry: A Short Course (2nd ed.). John Wiley & Sons. pp. 19–20. ISBN 978-0-471-76113-6.
  4. Jump up^ Wilkinson, G.; Birmingham, J.G. (1954). “Bis-cyclopentadienyl Compounds of Ti, Zr, V, Nb and Ta”. J. Am. Chem. Soc. 76 (17): 4281–4284. doi:10.1021/ja01646a008.
  5. Jump up^ Birmingham, J. M. (1965). “Synthesis of Cyclopentadienyl Metal Compounds”. Adv. Organometal. Chem. 2: 365–413. doi:10.1016/S0065-3055(08)60082-9.
  6. Jump up^ Payack, J. F.; Hughes, D. L.; Cai, D.; Cottrell, I. F.; Verhoeven, T. R. (2002). “Dimethyltitanocene”Org. Synth. 79: 19.
  7. Jump up^ Claus, K.; Bestian, H. (1962). “Über die Einwirkung von Wasserstoff auf einige metallorganische Verbindungen und Komplexe”. Justus Liebigs Ann. Chem. 654: 8. doi:10.1002/jlac.19626540103.
  8. Jump up^ Herrmann, W.A. (1982). “The Methylene Bridge”. Adv. Organomet. Chem20: 159–263. doi:10.1016/s0065-3055(08)60522-5.
  9. Jump up^ Straus, D. A. (2000). “μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium”. Encyclopedia of Reagents for Organic Synthesis. London: John Wiley.
  10. Jump up^ Housecroft, Catherine E.; Sharpe, Alan G. (2008). “Chapter 16: The group 16 elements”. Inorganic Chemistry (3rd ed.). Pearson. p. 498. ISBN 978-0-13-175553-6.
  11. Jump up^ Chandra, K.; Sharma, R. K.; Kumar, N.; Garg, B. S. (1980). “Preparation of η5-Cyclopentadienyltitanium Trichloride and η5-Methylcyclopentadienyltitanium Trichloride”. Chem. Ind. – London44: 288–289.
  12. Jump up^ Manzer, L. E.; Mintz, E. A.; Marks, T. J. (1982). “Cyclopentadienyl Complexes of Titanium(III) and Vanadium(III)”. Inorg. Synth. 21: 84–86. doi:10.1002/9780470132524.ch18.
  13. Jump up^ Nugent, William A.; RajanBabu, T. V. “Transition-metal-centered radicals in organic synthesis. Titanium(III)-induced cyclization of epoxy olefins”. J. Am. Chem. Soc. 110 (25): 8561–8562. doi:10.1021/ja00233a051.
  14. Jump up to:a b Wailes, P. C.; Coutts, R. S. P.; Weigold, H. (1974). “Titanocene”. Organometallic Chemistry of Titanium, Zirconium, and Hafnium. Organometallic Chemistry. Academic Press. pp. 229–237. ISBN 9780323156479.
  15. Jump up to:a b c Mehrotra, R. C.; Singh, A. (2000). “4.3.6 η5-Cyclopentadienyl d-Block Metal Complexes”. Organometallic Chemistry: A Unified Approach (2nd ed.). New Delhi: New Age International Publishers. pp. 243–268. ISBN 9788122412581.
  16. Jump up to:a b Troyanov, Sergei I.; Antropiusová, Helena; Mach, Karel (1992). “Direct proof of the molecular structure of dimeric titanocene; The X-ray structure of μ(η55-fulvalene)-di-(μ-hydrido)-bis(η5-cyclopentadienyltitanium)·1.5 benzene”. J. Organomet. Chem. 427 (1): 49–55. doi:10.1016/0022-328X(92)83204-U.
  17. Jump up^  Antropiusová, Helena;  Dosedlová, Alena;  Hanuš, Vladimir; Karel,  Mach (1981). “Preparation of μ-(η55-Fulvalene)-di-μ-hydrido-bis(η5-cyclopentadienyltitanium) by the reduction of Cp2TiCl2 with LiAlH4 in aromatic solvents”. Transition Met. Chem. 6 (2): 90–93. doi:10.1007/BF00626113.
  18. Jump up^ Cuenca, Tomas; Herrmann, Wolfgang A.; Ashworth, Terence V. (1986). “Chemistry of oxophilic transition metals. 2. Novel derivatives of titanocene and zirconocene”. Organometallics5 (12): 2514–2517. doi:10.1021/om00143a019.
  19. Jump up^ Lemenovskii, D. A.; Urazowski, I. F.; Grishin, Yu K.; Roznyatovsky, V. A. (1985). “1H NMR Spectra and electronic structure of binuclear niobocene and titanocene containing fulvalene ligands”. J. Organomet. Chem. 290 (3): 301–305. doi:10.1016/0022-328X(85)87293-4.
  20. Jump up^ Kuester, Erik (2002). “Bis(5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium”. Encyclopedia of Reagents for Organic Synthesis. John Wiley. doi:10.1002/047084289X.rn00022.
  21. Jump up to:a b Buchwald, S.L.; Nielsen, R.B. (1988). “Group 4 Metal Complexes of Benzynes, Cycloalkynes, Acyclic Alkynes, and Alkenes”. Chem. Rev. 88 (7): 1047–1058. doi:10.1021/cr00089a004.
  22. Jump up to:a b Rosenthal, U.; et al. (2000). “What Do Titano- and Zirconocenes Do with Diynes and Polyynes?”. Chem. Rev. 33 (2): 119–129. doi:10.1021/ar9900109.
  23. Jump up^ Hicks, F. A.; et al. (1999). “Scope of the Intramolecular Titanocene-Catalyzed Pauson-Khand Type Reaction”. J. Am. Chem. Soc. 121 (25): 5881–5898. doi:10.1021/ja990682u.
  24. Jump up^ Kablaoui, N. M.; Buchwald, S. L. (1998). “Development of a Method for the Reductive Cyclization of Enones by a Titanium Catalyst”. J. Am. Chem. Soc. 118 (13): 3182–3191. doi:10.1021/ja954192n.
  25. Jump up^ Sato, F.; Urabe, Hirokazu; Okamoto, Sentaro (2000). “Synthesis of Organotitanium Complexes from Alkenes and Alkynes and Their Synthetic Applications”. Chem. Rev. 100(8): 2835–2886. PMID 11749307doi:10.1021/cr990277l.
  26. Jump up^ WO 2004005305, Knox, R. J. & P. C. McGowan, “Metallocenes as Anti-Tumour Reagents”, issued 2004
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Further reading

IR of Titanocene dichloride

MS of Titanocene dichloride

HNMR of Titanocene dichloride

ESR of Titanocene dichloride

ESR

MORE……………

Introduction

Natural product synthesis is an exigent test for newly developed methodologies. Within this context, Rajanbabu and Nugent reported a series of seminal papers about the potential role of Cp2TiCl as a new tool in organic synthesis.1 Soon afterwards, Gansäuer’s group published a collection of relevant papers where a substoichiometric version of this protocol was developed.2Those results were especially important in the development of the corresponding asymmetric reactions using chiral titanocene(III) complexes.3 After these inspiring works, titanocene(III) complexes, essentially titanocene(III) chloride (Cp2TiCl), have recently emerged as a powerful tool in organic synthesis. They are soft single-electron-transfer (SET) reagents capable of promoting different kinds of reactions, such as homolytic epoxide4 and oxetane5 openings, Barbier-type reactions,6 Wurtz-type reactions,7 Reformatsky-type reactions,8 reduction reactions,9 and pinacol coupling reactions (Scheme 1).10

image file: c3qo00024a-s1.tif
Scheme 1 General reactivity of Cp2TiCl.

Image result for Titanocene chloride

From a practical point of view, titanocene(III) complexes can be prepared and stored. Nevertheless, they are usually highly oxygen-sensitive compounds. Interestingly, they can be easily prepared in situ by simply stirring the corresponding titanocene(IV) precursor and manganese or zinc dust. Another key characteristic of the titanocene(III) chemistry is that whatever the reaction in which it is involved, a catalytic cycle can be closed. In that case, a titanocene(IV) regenerating agent and an electron source, such as manganese or zinc dust, are required. Although some of them have been described in the literature, only two are commonly used: the simple combination of trimethylsilyl chloride and 2,4,6-collidine for aprotic reaction conditions11 and 2,4,6-collidinium hydrochloride for aqueous conditions (see Scheme 2).2

image file: c3qo00024a-s2.tif
Scheme 2 Catalytic cycles in titanocene(III) chemistry.

http://pubs.rsc.org/en/Content/ArticleHtml/2014/QO/c3qo00024a

Conclusions

Titanocene(III)-mediated radical processes have been applied to the synthesis of natural products of diverse nature. Beyond simple functional group interconversions, radical cyclizations, mainly from epoxides, have demonstrated their utility to yield (poly)cyclic natural skeletons, which are valuable synthons in organic synthesis. This radical approach has in many cases resulted in better yields and stereoselectivities than the cationic equivalents. In particular, the synthesis at room temperature of stereodefined terpenic skeletons without enzymatic assistance is remarkable. In this context, the main limitation of this bioinspired approach is, in fact, its extraordinary stereoselectivity, which avoids obtaining cis-fused decalins and/or substituents in axial positions. Such stereochemistry is present in many interesting natural terpenes. On the other hand, as can be seen in the first part of the review, the diverse reactivity of titanocene(III) complexes derives in some functional group incompatibilities. It is expected that in near future judicious designs of new titanocene(III) complexes can resolve this drawback. In any case, the evolution of the applications of titanocene(III) in natural product synthesis suggests that these reagents can be a matter of choice in the arsenal of a synthetic organic chemist.

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Green Synthesis of Veratraldehyde Using Potassium Promoted Lanthanum–Magnesium Mixed Oxide Catalyst

 Abstract Image

Veratraldehyde is an important chemical used in perfumery, agrochemical, and pharmaceutical industries. Current processes of manufacture of veratraldehyde use homogeneous catalysts, which make them highly polluting, creating problems of disposal of effluents and product purity. In the current work, veratraldehyde was synthesized from O-alkylation of vanillin with an environmentally benign reagent, dimethyl carbonate. A series of potassium loaded La2O3–MgO were prepared by the incipient wetness impregnation method, and their performance was evaluated vis-à-vis MgO, La2O3, La2O3–MgO, and a series of 1–4 wt % K/La2O3–MgO. All catalysts were characterized by different techniques, such as N2 adsorption/desorption, XRD, TGA-DSC, FT-IR, CO2-TPD, and SEM techniques. The effect of different loadings (1–4 wt %) of potassium on La2O3–MgO was studied, among which 2 wt % K/La2O3–MgO showed the best activity and selectivity due to high dispersion of potassium and high basicity in comparison with the rest. The activity of 2 wt % K/La2O3–MgO in O-methylation of vanillin with dimethyl carbonate (DMC) was closely associated with basicity. Various parameters were studied to achieve the maximum yield of the desired product. The maximum conversion was found with catalyst loading of 0.03 g/cm3 and mole ratio of vanillin and DMC of 1:15 at 160 °C in 2 h. The reaction follows pseudo-first-order kinetics for the O-methylation of vanillin. The energy of activation was found to be 13.5 kcal/mol. Scale-up was done using the kinetic model to observe that the process could be scaled up using the process parameters. The overall process is clean and green.

Figure

Green Synthesis of Veratraldehyde Using Potassium Promoted Lanthanum–Magnesium Mixed Oxide Catalyst

Department of Chemical Engineering, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga Mumbai-400 019, India
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.7b00127
*E-mail: gd.yadav@ictmumbai.edu.in, Phone: +91-22-3361-1001, Fax: +91-22-3361-1020; +91-22-3361-1002.

Conclusion


Synthesis of veratraldehyde using a catalytic green process is desirable in today’s environmentally conscious world. Therefore, a new process was devised in this work using a novel catalyst using mixed metal oxides. Different loadings of potassium promoted on La2O3–MgO (1–4 wt %) catalysts were synthesized and characterized by various techniques. The activity of catalyst was studied in the reaction of vanillin with DMC for the synthesis of veratraldehyde in comparison with several other catalysts, such as MgO, La2O3, La2O3–MgO, 1 wt % K/La2O3–MgO, 2 wt % K/La2O3–MgO, 3 wt % K/La2O3–MgO, and 4 wt % K/La2O3–MgO. Potassium promoted mixed oxides showed much higher catalytic activity than the corresponding pure La2O3–MgO mixed oxide, due to an increase in moderate, strong, superbasic sites. Moreover, loading of potassium on La2O3–MgO changes the structural properties, such as pore volume and surface area, and it gives higher conversion toward the desired product. Two wt % K/La2O3–MgO is the best and gives 96% of conversion at mole ratio 1:15 of vanillin to DMC and 0.03 g/cm3 catalyst loading at 160 °C. By using this catalyst, we studied various parameters systematically to establish kinetics. The catalyst is reusable up to four cycles. The energy of activation for O-methylation of vanillin was found to be 13.5 kcal/mol. A scale up was also attempted. Experimental and theoretical values matched very well. The process is green and clean.
Jayaram Molleti
Institute Of Chemical Technology
Department of Chemical Engineering, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga Mumbai-400 019, India
Image result
Prof. GD Yadav, Vice-Chancellor, ICT, Mumbai
*E-mail: gd.yadav@ictmumbai.edu.in, Phone: +91-22-3361-1001, Fax: +91-22-3361-1020; +91-22-3361-1002.
Institute Of Chemical Technology
Department of Chemical Engineering, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga Mumbai-400 019, India

Is water a suitable solvent for the catalytic amination of alcohols?

Is water a suitable solvent for the catalytic amination of alcohols?

Green Chem., 2017, 19,2839-2845
DOI: 10.1039/C7GC00422B, Paper
Johannes Niemeier, Rebecca V. Engel, Marcus Rose
The catalytic aqueous-phase amination of biogenic alcohols with solid catalysts is reported for future development of renewable amine value-added chains.

Green Chemistry

Is water a suitable solvent for the catalytic amination of alcohols?

Abstract

The catalytic conversion of biomass and biogenic platform chemicals typically requires the use of solvents. Water is present already in the raw materials and in most cases a suitable solvent for the typically highly polar substrates. Hence, the development of novel catalytic routes for further processing would profit from the optimization of the reaction conditions in the aqueous phase mainly for energetic reasons by avoiding the initial water separation. Herein, we report the amination of biogenic alcohols in aqueous solutions using solid Ru-based catalysts and ammonia as a reactant. The influence of different support materials and bimetallic catalysts is investigated for the amination of isomannide as a biogenic diol. Most importantly, the transferability of the reaction conditions to various other primary and secondary alcohols is successfully proved. Hence, water appears to be a suitable solvent for the sustainable production of biogenic amines and offers great potential for further process development.

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Selective hydrogenation of N-heterocyclic compounds using Ru nanocatalysts in ionic liquids

Selective hydrogenation of N-heterocyclic compounds using Ru nanocatalysts in ionic liquids

Green Chem., 2017, 19,2762-2767
DOI: 10.1039/C7GC00513J, Communication
Hannelore Konnerth, Martin H. G. Prechtl
N-Heterocyclic compounds have been tested in the selective hydrogenation catalysed by small 1-3 nm sized Ru nanoparticles (NPs) embedded in various imidazolium based ionic liquids (ILs).

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC00513J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

From the journal:

Green Chemistry

Selective hydrogenation of N-heterocyclic compounds using Ru nanocatalysts in ionic liquids

Abstract

N-Heterocyclic compounds have been tested in the selective hydrogenation catalysed by small 1–3 nm sized Ru nanoparticles (NPs) embedded in various imidazolium based ionic liquids (ILs). Particularly a diol-functionalised IL shows the best performance in the hydrogenation of quinoline to 1,2,3,4-tetrahydroquinoline (1THQ) with up to 99% selectivity.

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