1 PSS Monomer and eagent Chemistry Chemistry Frank J. Feher, aquel Terroba, en-zhi Jin, Sabine Lücke, Frank Nguyen, ichard Brutchey and Kevin D. Wyndham Department of Chemistry UCI Irvine, CA
2 Acknowledgements Coworkers (recent past) Daravong Soulivong ichard Baldwin Collaborators Joseph Lichtenhan (Hybrid Plastics LLC) Joseph Schwab (Hybrid Plastics LLC) Shawn Phillips (AFL - Edwards AFB) Joseph Ziller (UCI Crystallography) John Greaves (UCI Mass Spec Facility) Andre Lee (Michigan State) Funding National Science Foundation Air Force esearch Laboratory (Edwards AFB) Los Alamos National Laboratory Hybrid Plastics LLC National Institute of Standards & Technology Advanced Technology Program
3 utline for this Presentation Introduction Polyhedral oligosilsesquioxanes (PSS) as precursors to hybrid hybrid inorganic/organic polymers verview of advances in PSS synthesis to date New methods for synthesizing PSS monomers Selective cleavage of -- in fully condensed [ 3/2 ] n frameworks Manipulation of functional groups General synthetic methods Conclusions verview of PSS synthesis - past, present and future
4 Polyhedral ligosilsesquioxanes X 3 H 2 solvent [ 3/2 ] n Scott (1946), Barry & Gilkey (50 s), Sprung & Guenther (50 s), Brown & Vogt (60 s), lsson (60 s), lsson (60 s), Frye (70 s), Voronkov & Lavrentyev (70 s-80 s), Klemperer (1985), Feher Feher (1986), Agaskar (1989), Calzaferri (1987), Weidner (1989), Bassindale (1993), Marsmann Marsmann (1995), Laine (1996), thers... = H, Me, vinyl, small alkyls, aryls, (CH 2 ) 3 X, 3
5 Synthesis of lsesquioxanes Cl 3 H 2 acetone 3-36 months ~ 70% yield H H H H H 60% 15% 25% Brown, Vogt J. Am. Chem. Soc. 1965, 87, Feher, Newman, Walzer J. Am. Chem. Soc. 1989, 111, Feher, Budzichowski, Blanski, Weller, Ziller rganometallics 1991, 10, 2526.
6 lsesquioxanes as Precursors to Inorganic/rganic Hybrid Materials H H X X X X Lichtenhan (Edwards Air Force Base) & Feher (UCI) Hybrid Plastics LLC (Fountain Valley, CA) Phillips (Edwards AFB), Lee (MSU), Mather (UConn), Hsiao (SUNY), Coughlin Coughlin (UMass)
7 Highly Desirable Transformations H or 1 or H H H or H H or H H Any reaction that selectively introduces functionality!!!
8 Cleavage of by Strong Acid X X excess HX HX = HBF 4 Me 2 or CF 3 S 3 H Net esult: X X High yield at high conversion!
9 Four Disilanols from and CF 3 S 3 H H H H H H H H H Feher, Soulivong, Nguyen Chem. Commun. 1998, Methodology is not general and reactions do not scale up well.
10 Potential outes to (Me) 3 H <H> (Me) 3 H Ph(Me) 3 is readily available. Hydrogenation of Ph to to is known. 3/2 H n <H> 3/2 H n Ph can be prepared prepared in ~100% yield. yield can be prepared prepared in >85% yield. yield. Ph Ph Ph Ph Ph Ph Ph Ph <H> Basic u catalysts available for arene hydrogenation ne pot synthesis of from Ph(Me) 3?
11 Base-Mediated Cleavage of -- 35% aq Et 4 NH THF H H H H H H H H H High Yield to Disilanol, High Conversion and General
12 Proposed Mechanism H H Cleavage with retention of stereochemistry at (strong nucleophile and poor poor leaving group) H H H + from H 2
13 Proposed Mechanism H H H H H H H H + H H H H + H H H H H H H H 2 H + (H)3 H H
14 Current State of the Art i-bu(me) 3 (< $3.50 per pound) >95% yield >95% yield H H H aq Et 4 NH THF reflux >80% yield H H aq Et 4 NH THF 0 C >95% yield = i-bu utlook for the future: The cost of PSS monomers should become comparable to the cost of bulk silanes (X 3 ).
15 Practical oute to PSS Monomers H H H X Cl 3 Et 3 N X pre-1999: = cyclopentyl or cyclohexyl now: cyclopentyl, cyclohexyl, isobutyl (all work well on large scale) p-tolyl (very promising) Manufacturing costs have dropped by 2 orders of magnitude.
16 Practical oute to PSS Monomers H H = i-bu ethyl vinyl c-c 5 H 9 c-c 6 H 11 p-tolyl C 3 H 6 NHBoc Z MeCl 2 Et 3 N / CDCl 3 25 C Z MeCl 2 Et 3 N / CDCl 3 25 C Me Me H = = i-bu vinyl c-c 5 H 9 = i-bu c-c 5 H 9 c-c 6 H 11
17 Practical oute to PSS Monomers H H HBF 4 Me 2 BF 3 Et 2 F F = i-bu, ethyl, vinyl, c-c 5 H 9, c-c 6 H 11, p-tolyl H 2 N 1. Li 2. workup N NH 2 = = i-bu c-c 5 H 9 c-c 6 H 11
18 Methyl-Substituted PSS Me Me Me Me Me Me aq Et 4 NH THF modest yield Me Me Me H H H Me Me Me Me Me Me Modest quantities available. Properties can be evaluated. The potential of methyl-substituted substituted PSS can assessed. Me Me Me Me Me Me Me
19 Spherosilicates as Feedstocks? TES or 2 4 NH spherosilicate solutions TMSCl [(TMS) 3/2 ] n n = 6,8,10 TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS TMS D. Hoebbel, I. Hasegawa, P. A. Agaskar, P. G. Harrison,. M. Laine, & others Weidner, Zeller, Deubzer, Frey USP 5,047,492 (1991 to Wacker Chemie)
20 Spherosilicates as Feedstocks TMS TMS TMS TMS TMS TMS H /H 2 low T TMS H TMS H TMS H H TMS TMS TMS Yields for both reactions are quantitative. Both products are extremely soluble in organic solvents, and both have resisted crystallization. (vinyl)me 2 Cl TMS TMS TMS TMS TMS TMS = Me 2 (vinyl)
21 Spherosilicates as Feedstocks TMS H TMS H TMS H H TMS TMS TMS Ph(H)3 THF 20 C TMS TMS TMS Ph H H H TMS TMS TMS Z-Cl 3 Modest quantities available. Properties can be evaluated. Potential can assessed. TMS TMS Ph TMS TMS TMS TMS
22 Three Approaches to Polyfunctional PSS Direct Synthesis From Monomers ZX 3 Z (Z = polymerizable group) X 3 + ZZ 3 Z n (8-n) Partial Functionalization of Highly Functionalized PSS Z n (8-n) 8 12 Stoichiometric eactions of Lightly Functionalized PSS X n (8-n) 8 12 Z n (8-n) (H) ClMe 2 Z (Me 2 Z) 3
23 Pendant Group Modifications X 8 T 8 Y 8 T 8 There are 21 possible species! There are 22 possible species!
24 mulation of X to Y (assuming that all sites are equally reactive) reactive) 1 eq 2 eq 3 eq 4 eq Time NTE: The same product distributions can be produced by random co-condensation of X Cl 3 and Y Cl 3.
25 PSS with an Average of Three Epoxides Vinyl Cl 3 (+ other isomers & homologs) Vinyl is readily available in pure state Extent of epoxidation evaluated by 1 H NM spectroscopy Product distribution is believed to be random statistical mixture (~25% tetra, 10-15% tri, 10-15% penta, 5-10% di, 5-10% hexa)
26 PSS with an Average of Three Epoxides Cl 3 + Cl 3 H 2 mixed T-resin cat. H * n (8-n) 8 12 *Cl 3 n Cl 3 (8-n) random statistical mixture Excellent overall yield peracetic acid Product distribution set by ratio of Cl 3 Cl 3 to *Cl 3 (0 100%) Isomorphous substitution of */? Product distribution can be analyzed by ultra-high resolution 29 NM (+ other isomers/homologs)
27 mulated vs Experimental 29 NM Spectra mulation assumes: andom statistical /* mple additivity rules are valid efs: , * , * edge effect: ~8 Hz face diagonal effect: 1.5 Hz body diagonal effect: 0 Hz b a δ 1 + 3e 1 + 2f 1 d c δ 2 + 2e 2 δ 2 + e 2 δ 2 + 2f 2
28 Polyaminosilsesquioxanes H 2 NCH 2 CH 2 CH 2 (Me) 3 HCl MeH ClH 3 NCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 NH 3 Cl ClH 3 NCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 NH 3 Cl ClH 3 NCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 NH 3 Cl ClH 3 NCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 NH 3 Cl NM, MALDI-TF Wacker-Chemie ( 91 US Patent) claims free amine, but no details provided Independently rediscovered by. M. Laine (Michigan) Starting materials are inexpensive eadily available in LAGE quantities
29 eactions with Electrophilic eagents eagent X Isolated Yield (%) ε-caprolactone benzoyl chloride maleic anhydride HN HN HN H H 64 = CH 2 CH 2 CH 2 NH 2 allyl isocyanate HN NH 90 phosgene N=C= = CH 2 CH 2 CH 2 X CH 2 /HPPh 2 N PPh 2 37 PPh 2
30 lsesquioxane Sugarballs NH 2 NH 2 H H H H H H NH 2 H H H H H H H H H 2 N NH 2 H 2 N H 2 N NH 2 N H H H lactonolactone H H H galactose residue H maltonolactone NH 2 NH 2 H H H N H H H H H H glucose residue H H
31 Selective Binding to Lectins Time (minutes) Inhibitor (µm) I ) Concanavalin A (Con A) Turbidity Experiment Glucose Specific (reversed by addition of D-maltose) II ) Competitive Inhibition of HepG2 (ASGP)/ 125 I-ASM Galactose Specific cta-glucosyl PSS cta-galactosyl PSS D cta-aminopropyl PSS
32 te-specific Drug Delivery NH NH NH HN HN NH NH NH HN HN HN HN NH HN NH HN Targeting Groups Bioactive Group or Tag
33 Summary Fully-condensed PSS frameworks are attractive precursors to precursors to useful compounds. Cleavage of many frameworks is both favorable and remarkably selective. selective. Intermediates are versatile precursors to PSS monomers. Many highly functionalized frameworks are now available. Efforts to develop fundamental chemistry of PSS have paid big paid big dividends. Many fundamental chemical problems have been solved. Many reactions are amenable to scale up. Prospects for continued development are excellent.
34 Considering that Where is the Market for Polyhedral lsesquioxanes (PSS)? and are nearly 3/4 of the Earth s crust. Starting materials are readily available: X 3 Many PSS frameworks (e.g., ) can be prepared in high yield. yield. Physical characteristics should be useful: optically transparent hydrolytically stable good UV/thermal stability good insulators desirable chemical and mechanical properties licones (i.e., [ 2 ] n ) and silicates (i.e., [ 2 ] n ) are each multibillion multibillion dollar businesses.
35 There are Markets Everywhere! The potential of PSS has been unrealized because the chemistry of PSS has been relatively undeveloped. ecent developments in PSS chemistry provide provide ways to capture this potential.