sonochemistry: ultrasound applications in organic ... - The Stoltz Group

DEFINING THE LAWS OF SONOCHEMISTRYA specific nature of sonochemistry is suggested Ando etal JCSCC, 1984, p439BrKCN/Al 2 O 3CN83% 76%+ regioisomersSTIRREDSONOLYSEDSonication seems to obey some rules of its own• An empirical systemization of sonochemistry has been published (Luche, J.L. Advances in Sonochemistry, Vol3,1993, p 85 and TL, 1990, 4125)• Effects are both chemical and mechanicalRULE 1Reactions that proceed via radical or radical ion intermediates are most likely to be sonochemically influencedRULE 2In heteregenous systems, reactions proceeding via ionic intermediates can be stimulated by mechanical effects.Usually the effect is comparable to efficient mixingRULE 3Heterogenous reactions with mixed mechanisms (radical and ionic). These may be enhanced in a convergent way(chemically for the radical and mechanical for the ionic) or a switch may occur where the radical pathway is enhancedand "change" the reaction productsFactors affecting sonochemical reactions: frequency, power, reaction temperature (low temperature can lead tohigher reaction rates!), overpressure, solventSONOCHEMICAL REACTIONS IN ORGANIC SYNTHESISHOMOGENOUS REACTIONS - Have received less attention for sonochemical activationKinetic StudiesON 3)))N C OPorter etal. JACS, 1938, 1497Enhanced initial rateHydrolysisO 2 NOOR+H 2 O)))35 o CROOH+O 2 NOHKristol etal. TL, 1981,90714-15% enhancementindependentof R group(CH 3 ) 3 C-ClH 2 O/ Ethanol)))(CH 3 ) 3 C-OH+ HClMason etal. Ultrasonics Int. '85Proc., Butterworth, U.K., 839• Effect of ultrasound increased with EtOH content with a maximum effect at 50% w/w• Rates of reaction under sonolysis increased as temp was reduced from 20 o C to 10 o C

Sonolysis of some solvents may occur: H 2 O, CCl 4 , CHCl 3 . We can take advantage of this in synthesisSonoisomerizationCO 2 MeR• X•CO 2 Me- X•MeO 2 CElpiner etal. Nature, 1965, 945CO 2 Me)))XCO 2 MeCO 2 MeR-XA Variation of the Hunsdiecker Reaction (Dauben etal. JOC, 1989, 6101)NOSROCl 3 C• X•)))10 - 15 min, 33 o CCl 3 C-XNSCCl 3 + CO 2+R•X•R-ClCleavage of the Tin Hydrogen bondOHOIPhR 3 SnHO 2))) 0-20 o COPhNakamura, E. JACS, 1991, 898084%The radical nature of some reactions is compromised by attached R groupsHOPOROR+R'R'NR')))R'R'R'HNOPOR ORHubert C. etalJOC, 1995, 1488>90% yield in 1.5 h w/ R = EtNo rate enhancement w/ R = C 16 H 31Sonolysis of Iron CarbonylsOOOHFe 2 (CO) 9)))23 o C, 30 min(OC) 3 FeO60 atm COOOLey, S.V etal.J. Organomet. Chem.1985, C17, 28570%Milder Conditions, Enhanced Rates for the Heck Reaction (Cheng, J etal. Bull. Inst. Chem. Acad. Sin. 1989, 9)ICO 2 MePd(PPh 3 ), NEt 3CH 3 CN, C 6 H 6CO 2 Me50 o C, 6h, 76% (sonication)80 o C, 24h, 71% (thermal)Pauson-Khand Annulation is Accelerated by Sonication (J. Organomet. Chem. 1988, 233)OCo(CO) 3HCo(CO) 3+OBu 3 PO, hexane)))Ph

CARBON-CARBON BOND FORMATIONHorner-Wadsworth-WittigO H 3 CO 2 SOPORORCH 3))) THF, 23 o CSO 2 CH 3CH 370-80%

Saponifications in Aqueous Solutions are Enhanced by Ultrasound; Sonochemical EmulsificationOOMe10% aq. NaOHOOHTL, 1979, 3917Reflux, 90 min, 15%Sonication, 23 o C, 96%Formation of anions from heterogenous bases facilitated by sonicationSONaH,)))50 o C, 1h SNaTL, 1966, 6383OCNCO 2 EtBrBrK 2 CO 3, )))PEG-600, ClCH 2 CH 2 ClCNCO 2 EtChin. Chem. Lett. 1991, 517Chem. Abstr. 1992, 116, 193753t85%Nitrogen Protection (Under Phase Transfer Catalysis) Is Enhanced. This is also true for indole protection.NHOH(t-BuOCO) 2 O, NaHCO 3MeOH, ))), 3hNCOOt-BuOHLuche, J.L. etal. Synlett, 1991, 37>80% yieldA Case for "C-H Functionalization"? (JCSCC, 1994, 1425)SiNaNO 2 , AcOHCe(NH 4 ) 2 (NO 3 ) 6CHCl 3 , 23-75 o C))), 4hSiNO 2[O]Si+HNO 2SiNO2REDUCTION REACTIONSMeOBrLAH, DME))), 35 o C, 7hMeO70%Boudjouk etal. TL, 1982, 1643OSiOMeLiAlD 4 , C 6 D 12))), 25 o C, 2hOSiDTL, 1984, 1415• The usual reductive protocols involving heterogenous systems are also facilitated(e.g., nitro to amine, aldehyde to alcohol etc)• Generally, sonochemical reduction chemistry is underexplored

OXIDATION REACTIONSPerfluoroalkylO 2 , Sulfonate salt)))OHMokryi, E.N etal. Akad. Nauk Ukr. 1993, 7, 99Chem. Abstr. 1994, 121, 107751KMnO 4 , H 3 O +PhH,450 torr)))OJCS Perkin Trans. II, 1988, 375HORRTPAP, NMO25 o C, 90 minO>90%RORTL, 1991, 3201OHPCC/SiO 220 min, )))OJOC, 1989, 5387ORGANOMETALLIC SONOCHEMISTRY•This has seen the greatest impact in terms of sonochemical applications•Usually, the influence of ultrasound is to remove passivating coatings on metals (oxides, carbonates, OH etc) -->Depassivation and also to aid in single electron transfer processes which constitute a crucial step in the formation oforganometallic compounds•Recently Reviewed: Luche, J.L.; Cintas, P. (Furstner, A. (ed.)), Activated Metals, VCH, Weinheim, 1997.ALKALI METALS AND MAGNESIUMBogdanovic etal. ACIEE, 1983, 728+ Mg))) )))+Mg*Acyloin Condensation (SynLett, 1990, 89)CO 2 EtMe 3 SiCl, Na, THFMgOSiMe 3Activated Mg* is useful forGrignard reagent prepSONICATION IS GENERALLY USEFULFOR GRIGNARD REACTIONS, HALOGEN-METAL AND TRANSMETAL EXCHANGESCO 2 Et0 o C, 2 h, ))), 82%OSiMe 3OHO90%, ThermalNR 2Li, THFOTL, 1988, 218390%, Sonochemical

• Historically, the first metal to be used in organic chemistryREACTIONS WITH ZINC METAL• Zn-mediated reactions have been the most extensively studied in sonochemical organometallic chemistryREDUCTIONSThe Zn(Ni) Couple (Luche, J.L. etal. JOC, 1989, 5313OZn(Ni) (9:1)EtOH, H 2 OOZn(Ni) (9:1)EtOH, H 2 OO95 %NH 3 -NH 4 ClpH 8,))), 1.5 h23 o C))), 3 h, 23 o C96 %Thermal (12 h, 90 %) Thermal (24 h, 90 %)TL, 1993, 1993, 357OOOZn, AcOH, 25 o C10 min, 100 %)))H5!:5" =1.5:1ORGANOZINC REAGENTSImproved Simmons-Smith Protocol (TL, 1982, 2729)Zn, CH 2 I 2 , DME4h, 90 o C,)))67% (12 % Thermally)Unpredictable induction period suppressedHydroperfluoroalkylation/ Carbometallation (JACS, 1985, 5186)CF 3 I+HOZn, CuI, THFF 3 C23 o C, 2 h, ))) 61 %OHBarbier-Type Processes (Boudjouk etal. JOC, 1982, 751)BrBrRR'Zn, Dioxane)))67-89%RRNo Reaction Thermally!R is electron withdrawing

REFORMATSKY REACTION• Significant rate and yield improvements have been observedMeyers, A.I. JOC, 1991, 2091NOZn(Ag), THFNONRNCBr40 o C, ))), 2 hNR84 %NH 2Jackson etal. JOC, 1992, 3397INHBOCCOOBnZn(Cu), )))DMA, PhH, 30 minIZnNHBOCCOOBn(Ph 3 P) 2 PdCl 2 , )))NNHBocCOOBnNBr• Sn and In seem to predominateAQUEOUS ORGANOMETALLIC COUPLINGSWhitesides, G.M. JOC, 1993, 5500Aq. CH 2 O +BrSn, aq. NH 4 Cl-THF23 o C, 1 h, )))HO60 %Binder etal. Tetrahedron, 1994, 749HOHOOOHOHAllylBr, Sn, )))EtOH-H 2 O (10:1)OH OHOH OH OH60 - 65 %OOCHOAllylBr, In, )))EtOH, 1 hOOOH60 %

OTHER METALS FOR ORGANOMETALLIC SONOCHEMISTRYCu for Ullmann Couplings (Mason etal. Ultrasonics, 1986, 292)NO 2NO 2ONO 2Cu, DMFI))), 60 o C, 90 min95 %Al for Reduction Chemistry (TL, 1993, 353)OHOHOOAl(Hg),10 % aq. HCOONaEtOH, 23 o C, )))OHHOHO80 %(Thermally 23 %)CONCLUSIONS• Sonochemistry is gaining significance based on laboratory results and the availability of scale-up systems• Sonochemical applications can be envisaged in all types of systems, including homogenous reactions• Wide acceptance has been gained at a practical/empirical level, however, the theoretical understanding still lagssignificantly behind• The usefulness of sonochemistry continues to expand into the arena of electrochemistry, photochemistry andbiotechnology• FOR THE ORGANIC CHEMIST: WHEN IN DOUBT, SONICATE!!!!!Useful referencesPrice, G.J. (ed.)., Current Trends in Sonochemistry, Royal Society of Chemistry, Oxford, 1993Mason, T.J. (ed.), Chemistry With Ultrasound, Elsevier Applied Science, London, New York, 1990van Eldik, R.; Hubbard, C.D. (eds.), Chemistry Under Extreme or Non-Classical Conditions, Spektrum/Wiley, 1997Abdulla, R.F. Adrichimica Acta 21, 1988, 31 - 42