december 2011 nucleus web - nesacs · by christine jaworek-lopes with photos by morton z. hoffman...

http://www.nesacs.org

January 2012 Vol. XC, No. 5

90th Anniversary Issue of The NUCLEUS

NORTHEASTERN SECTION • AMERICAN CHEMIC

ALSO

CIET

Y

FOUNDED 1898

NESACS

MonthlyMeeting2008 Nobel Laureate, OsamuShimomura, to speak at Pfizer, Inc.,Cambridge, MAThe Discovery of the GreenFluorescent Protein GFP

2012 Chair’sStatementBy Ruth Tanner

NationalChemistryWeekBy Christine Jaworek-Lopes withphotos by Morton Z. Hoffman

SummerScholar ReportActivation of β-amidoaldeydesToward DiastereoselectiveNucleophilic AdditionBy Shoshana Bachman and DavidHaines, Wellesley College

2 The Nucleus January 2012

The “ACS is a congressionally char-tered independent membership organi-zation which represents professionalsin all fields of chemistry and sciencesthat involve chemistry at all degreelevels”. Currently, there are over162,000 members, of whom approxi-mately 7,300 are in the NortheasternSection of the ACS (NESACS), whichis presently the largest ACS Section. Itis an honor to have been elected as theChair of this Section for 2012 and tohave served as the Chair-Elect andProgram Chair in 2011.

It is likely that the main reasonsyou joined the ACS were to haveaccess to journals (before access wasavailable online) and to connect withother chemists and to other scientists inrelated fields. The ACS connects younationally and globally to members ofyour profession. The programs andactivities of your local Section mirrorthose of the national organization andbring those connections to your localarea and provide a forum for network-ing and collaboration in your geo-graphical area.

In conjunction with this collabora-tion, the Northeastern Section pro-motes industrial and academicresearch, scientific entrepreneurship,high standards of education, studentand young chemist activities, careerservices, government relations, andprofessional ethics, among others. Itprovides you the opportunity toactively engage in all of these areasthrough its monthly meetings and itscommittee network.

In addition, the Section sponsorsnational and local awards to honor out-standing chemists and chemistry edu-cators. NESACS also sponsors grantsand scholarships for students and fac-ulty in support of research, travel andother activities. This award winningSection is very active, not only locally,but also has direct input into the pro-gram decisions and policies of thenational organization.

What is your interest? Connect tothe NESACS through the websitehttp://nesacs.org for a complete listingof all of the program, committees, andactivities of the Section. For upcomingevents and activities, read The Nucleus,which is available monthly by mail, byPDF format on the website, or by emailvia a request form on the website.

In addition, you can join aNESACS discussion group and getupdates on the Section’s activities atthe NESACS LinkedIn® network,which can also be accessed through a

From the New ChairBy Ruth Tanner, 2012 NESACS Chair, [email protected]

continued on page 11

http://nesacs.org

The Nucleus January 2012 3

The Nucleus is published monthly, except June and August, by the Northeastern Section of the AmericanChemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Textmust be received by the editor six weeks before the date of issue.Editor: Michael P. Filosa, Ph.D., ZINK Imaging, Inc., 16 Crosby Drive, Building 4G,

Bedford, MA 01730 Email: Michael.filosa(at)zink.com; Tel: 508-843-9070Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273,

Sheila E Rodman, Konarka Technologies, Inc., 116 John St. Suite 12, Lowell,MA 01852 Email: srodman(at)konarka.com tel 978-569-1414, Mindy Levine, 516-697-9688, mindy.levine(at)gmail.com

Board of Publications: Mary Mahaney (Chair), Mindy Levine, Vivian K. WalworthBusiness Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050,

Email: Manager-vincegale(at)mboservices.net; Tel: 781-837-0424Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews Calendar Coordinator: Sheila Rodman, email: srodman(at)konarka.comPhotographers: Morton Z. Hoffman and James PhillipsProofreaders: Donald O. Rickter, Vivian K. Walworth, Mindy Levine Webmaster: Roy HagenCopyright 2012, Northeastern Section of the American Chemical Society, Inc.

The Northeastern Section of the AmericanChemical Society, Inc.Office: Anna Singer, 12 Corcoran Road,Burlington, MA 01803(Voice or FAX) 781-272-1966.e-mail: secretary(at)nesacs.orgNESACS Homepage:http://www.NESACS.orgOfficers 2012ChairRuth TannerOlney Hall 415BLowell, MA 01854University of Mass LowellRuth_Tanner(at)uml.edu978-934-3662Chair-ElectLiming ShaoSunovion Pharmaceuticals Inc.84 Waterford DriveMarlborough, MA [email protected] Past ChairPatrick M. Gordon1 Brae CircleWoburn, MA 01801Patrick.gordon65(at)gmail.comSecretary:Michael SingerSigma-Aldrich3 Strathmore Rd, Natick, MA 01360774-290-1391, michael.singer(at)sial.comTreasurer:James Piper19 Mill Rd, Harvard, MA 01451978-456-3155, piper28(at)attglobal.netAuditor:Anthony RosnerArchivistTim FrigoTrustees:Peter C. Meltzer, Esther A. H. Hopkins,Michael E. StremDirectors-at-LargeDavid Harris, Stephen Lantos, James Phillips,Ralph Scannell, Alfred Viola, John BurkeCouncilors Alternate CouncilorsTerm Ends 12/31/2012Amy E. Tapper Jerry P. JasinskiCatherine E. Costello Gary R. WeismanPatricia A. Mabrouk Norton P. PeetDorothy J. Phillips Edward J. BrushRuth Tanner Michael HurreyTerm Ends 12/31/2013Thomas R. Gilbert Alfred ViolaMichael Singer Sophia R. SuRobert Lichter Kenneth C. MattesMary Shultz Tim FrigoLeland L. Johnson, Jr. Raj (SB) RajurTerm Ends 12/31/2014Katherine Lee Michaeline ChenMichael P. Filosa C. Jaworek-LopesDoris Lewis Jennifer LareseMorton Z. Hoffman Lawrence ScottPatrick Gordon Marietta SchwartzMary Burgess Andrew Scholte

Contents2012 Chair’s Statement_________________________________2By Ruth Tanner

National Chemistry Week ________________________________4By Christine Jaworek-Lopes with photos by Morton Z. Hoffman

Monthly Meeting _______________________________________52008 Nobel Laureate Osamu Shimomura to speak at Pfizer on“The Discovery of the Green Fluorescent Protein GFP”

Announcements________________________________________7Call for Nominations for the 2012 James Flack Norris Award, The Philip L.Levins Prize

Summer Scholar Report _________________________________8Activation of β-amidoaldeydes Toward Diastereoselective Nucleophilic AdditionBy Shoshana Bachman and David Haines, Department of Chemistry, WellesleyCollege, Wellesley, MA

January Historical Events in Chemistry ____________________11By Leopold May, Catholic University of America

The 2011 Nobel Prize in Chemistry_______________________12By Leopold May

National Recognition for NESACS Student Chapters__________12

Cover: January speaker, 2008 Nobel Laureate, Osamu Shimomura, ProfessorEmeritus, Marine Biological Laboratory, Woods Hole Oceanographic Institute,Woods Hole, MA (Photo courtesy of Dr. Shimomura).

Deadlines: March 2012 Issue: January 15, 2012April 2012 Issue: February 15, 2012

All Chairs of standingCommittees, the editor of THE NUCLEUS, and the Trustees of SectionFunds are members of theBoard of Directors. AnyCoun cilor of the American Chemical Soci-ety residing within the section area is an exofficio member of the Board of Directors.

90th Anniversary Issue of The NUCLEUS


In preparation for National ChemistryWeek 2011, a volunteer preparationday was held at Museum of Science-Boston on Sunday, October 21, 2011.More than 20 individuals attended thisevent, which allowed volunteers topractice the hands-on activities anddemonstrations in advance of the Octo-ber celebration.

On Sunday, October 23, 2011, theNortheastern Section of the AmericanChemical Society sponsored a NationalChemistry Week 2011 Kick-Off Eventat Museum of Science-Boston (MoS).Volunteers ensured that the more than500 visitors to the daylong eventenjoyed a number of hands-on activi-ties. Among the highlights of the daywere the two Phyllis A. BraunerMemorial lectures, presented by Dr.Bassam Shakhashiri, Professor ofChemistry at the University of Wiscon-sin-Madison. These captivating lec-tures were enjoyed by children andadults alike. Approximately 300 indi-

viduals attended these lectures. Atthese lectures, a Salutes to ExcellenceAward was presented by BassamShakhashiri, ACS President Elect, andPatrick Gordon, NESACS chair, toDavid Sittenfeld for his outstandingcontributions to NCW. For the lastseveral years, David has been instru-mental in planning and organizingNCW events at the MoS-Boston.

Approximately 500 students at -tended the High School Science Seriesevent at the MoS-Boston on October27, 2011. The students were from 9different schools in 7 different commu-nities, including Boston, Cambridge,Malden, Abington, Pittsfield, Peabodyand Tynsboro. These students partici-pated in a number of hands-on activi-ties and demonstrations related to theyearly theme and heard lecture demon-strations given by David Sittenfeld.

In addition, an NCW event washeld at the Boston Children’s Museumon Saturday, October 29, 2011.

Approximately 300 individuals partici-pated in NCW hands-on activities anddemonstrations.

The activities and demonstrationsthat were performed throughout theweek included: preparing your ownhand sanitizer, learning how soapworks, making UV bracelets, writingsecret messages using goldenrod paperand ammonia, learning about moodlipsticks, isolating iron from cereal,and testing a variety of foodstuffs forstarch and vitamin C.

Children, grades K-12, were ableto participate in the national postercompetition. Congratulations toCatherine Chen from Newman Ele-mentary School for winning the 3rd-5th

grade category and Emily Chen fromWilliam Pollard Middle School forwinning the 6th-8th grade category.

Special thanks to the Boston Chil-dren’s Museum, Alissa Daniels, SharonHorrigan, Museum of Science-Boston,Northeastern Section of the American

Corporate Patrons $2000 - or moreAstraZeneca PharmaceuticalsEisai PharmaceuticalsEMD SeronoGenzyme Corp.Johnson MattheyMerck & Co.NovartisPfizer Inc.Schering Corp.Strem Chemicals, Inc.Vertex Pharmaceuticals$1000-$1999Boehringer IngelheimGlaxoSmithKlineIrix PharmaceuticalsLyophilization Services of NESundia MeditechYes Bank$300-$999Cambridge Major LabsGirindusMerrimack ConsultantsOrganixPCI SynthesisSigma AldrichWaters Corp.Wilmington PharmaTech


National Chemistry Week The Northeastern Section: Chemistry – Your Health, Your FutureBy Christine Jaworek-Lopes


AbstractThe discovery of the greenfluorescent protein GFPThe green fluorescent protein GFPcontained a fluorophore within its pri-mary peptide chain, differing from allpreviously known fluorescent proteinsthat are complexes of a protein and afluorescent substance. Since GFP con-sists of a single peptide chain, it can becloned and genetically produced in liv-ing organisms. Presently GFP andanalogous fluorescent proteins areextensively used as protein markers inbiological and medical research.

In my study of the bioluminescentjellyfish Aequorea aequorea in 1961, Iwas able to discover the photoproteinaequorin only after disregarding theluciferin-luciferase hypothesis that wascommonly believed at the time. Thephotoprotein aequorin emitted bluelight in the presence of calcium ionseven in the complete absence ofmolecular oxygen.

During the purification ofaequorin, I discovered a trace amountof GFP as a byproduct. GFP was abeautiful protein that emits emerald-green fluorescence, but it had no prac-tical use at the time. Thus, my effortwas focused on understanding the light-emitting mechanism of aequorin.Despite various technical difficultiesencountered, and also the need formore than a half million jellyfish (over10 tons) for the study, I reached a con-clusion in 1978 that the functionalchromophore of aequorin must be aperoxidized coelenterazine. This con-clusion was confirmed in 2000 by X-ray crystallography.

Ever since the discovery of GFP,the nature of its fluorophore has been amatter of utmost interest. However, myinitial efforts to extract the fluorescentmoiety from GFP all failed, suggestingthat the fluorophore might be cova-lently bound to the protein. Since theyield of GFP from the jellyfish, as abyproduct of aequorin, was very low(1-2 μg per specimen), I for manyyears saved and accumulated theminute amounts of GFP acquired dur-

Monthly MeetingThe 920th Meeting of the Northeastern Section of the AmericanChemical SocietyThursday, January 12, 2012Pfizer, Inc.T2003 Seminar Room, 200 Cambridgepark Drive, Cambridge, MA 02140http://www.pfizer.com

5:30 pm Social Hour

6:30 pm Dinner

7:45 pm Meeting: Ruth Tanner, NESACS Chair, PresidingDr. Katherine L. Lee, Pfizer, Presiding

Welcome Dr. Mark Bunnage, Vice President, Head of BiotherapeuticsChemistry, Pfizer

Speaker Dr. Osamu Shimomura, Professor Emeritus, Marine BiologicalLaboratory, Woods Hole; the 2008 Nobel Prize Laureate in Chem-istryTitle: The Discovery of the Green Fluorescent Protein GFP

Dinner Reservations should be made no later than 12:00 noon, Friday, Jan-uary 6th. Reservations are to be made using PayPal services. Use the fol-lowing link to log on to PayPal. http://acssymposium.com/paypal.html. Selectpay with credit or debit card option and follow the additional instructions on thepage. Members, $30; Non-members, $35; Retirees, $18; Students, $10; Unem-ployed $10. Reservations for new members only, and for additional information, contact thesecretary, Anna Singer between 9 am and 9 pm at (phone/fax 781-272-1966)or [email protected]. Reservations not canceled at least 24 hours in advancemust be paid. THE PUBLIC IS INVITEDDirections to Pfizer:By MBTA: Take the Red Line to Alewife. Go to the end of Cambridge ParkDrive (4 tenths of a mile). Enter the Lobby at 200 Cambridge Park Drive.Security will direct you to the appropriate location.Driving from Boston: Take 93 North to second exit on Storrow Drive West.Continue on Storrow Drive West (~5 miles) to Route 2 (Fresh Pond Parkway).Continue on Route 2 (~2 miles) through the traffic circles. The road namechanges to Alewife Brook Parkway. Continue over the bridge (past the shoppingcenter) and take left at second set of lights (in front of large commuter parkinggarage) to Cambridge Park Drive.Parking Directions:At the end of Cambridge Park Drive, turn right (wide swing) when entering thecul-de-sac. Stop at the intercom and activate button to speak with Security.Security will direct you toward parking. u

zcontinued on page 13


BiographiesMark BunnageHead of ChemistryBiotherapeuticsResearchPfizer, Cambridge,MA, [email protected] studied chemistry at the Univer-sity of Durham, graduating in 1990.Mark then undertook his postgraduatestudies with Professor S. G. Davies atthe University of Oxford. This was fol-lowed by a move to The ScrippsResearch Institute, La Jolla, Californiato work with Professor K C Nicolaouas a NATO post-doctoral fellow.

In 1996, Mark returned to the UKto join Pfizer as a medicinal chemist intheir research laboratories in Sand-wich, Kent. Over the past 15 years atPfizer, Mark has had a number of rolesof increasing responsibility and inNovember 2010 became ExecutiveDirector, Head of Medicinal Chem-istry, Sandwich Laboratories. In April2011, Mark was appointed Vice Presi-

dent, Head of Chemistry, Biotherapeu-tics Research at Pfizer and is nowbased in Cambridge, MA, USA.

Mark has broad interests in DrugDiscovery, is an author or inventor onover 50 publications and patents, andis a member of the editorial board ofMedChemComm.

Osamu ShimomuraOsamu Shimomura was born in 1928in Fukuchiyama near Kyoto, Japan,and raised in Sasebo, NortheasternChina, and Osaka. In 1945, when hewas a high school student, he wit-nessed the Nagasaki atomic bombfrom a factory, in which he was work-ing at the time, about 15 km from theepicenter of the blast.

In the aftermath of the war, heidled for nearly 3 years. In 1948, hewas admitted into the Nagasaki Col-lege of Pharmacy, which had beendestroyed by the atomic bomb andmoved to a temporary campus near hishome. In 1951 he graduated from thecollege and took a position of labassistant under Prof. Shungo Yasunagaat the Pharmacy Department, NagasakiUniversity.

In 1955, Prof. Yasunaga sent Shi-momura to the laboratory of Prof.Yoshimasa Hirata, Nagoya University,to do research on the bioluminescenceof the ostracod Cypridina under thedirection of Prof. Hirata. In 1956, Shi-momura succeeded in the crystalliza-tion of Cypridina luciferin, a stepcrucial in the structural study of thisluciferin which, due its extremelyunstable nature, had been unsuccess-fully pursued at Princeton Universityfor nearly 20 years.

In 1960, Shimomura received hisPh.D. degree in organic chemistryfrom Nagoya University. He was theninvited to work in the lab of Prof.Frank H. Johnson at Princeton Univer-sity. In 1961, he discovered the photo-protein aequorin and the greenfluorescent protein GFP.

In 1963, he was back in Japan asan Associate Professor at Nagoya Uni-versity, but returned to Princeton in1965 as a Senior Research Biochemistto continue his work on various biolu-minescence systems.

In 1982, he moved to the MarineBiological Laboratory in Woods Hole,as a Senior Scientist with an adjunctprofessorship at Boston University,and remained there until his retirementin 2001. He was named DistinguishedScientist at the Marine Biological Lab-oratory in Woods Hole in 2008.

Throughout his active researchcareer, Shimomura’s study has beentargeted on the chemical understandingof bioluminescence. He studied morethan a dozen kinds of different lumines-cent organisms. His accomplishmentsinclude: structure determinations of theluciferins of the ostracod Cypridina, thelimpet Latia and the krills; the discov-ery of coelenterazine that functions asthe luciferins in various marine lumi-nous organisms; the discovery of thegreen fluorescent protein, and the struc-ture determination of its chromophore.

He received the Pearse Prize fromthe Royal Microscopical Society(2004), the Emile Chamot Award fromthe State Microscopical Society of Illi-nois (2005), the Asahi Prize fromAsahi-Shinbun Cultural Foundation(2007), the Nobel Prize in Chemistry(2008), and the Order of Cultural Mer-its, Japan (2008). u

mailto:[email protected]


The 2012 James Flack NorrisAward for OutstandingAchievement in the Teachingof ChemistryDeadline: April 15, 2012Nominations are invited for the 2012James Flack Norris Award, which con-sists of a certificate and an honorariumof $3000, and is given annually by theNortheastern Section of the AmericanChemical Society (NESACS). Thepresentation will take place at a cere-mony and dinner in November, 2012,and will include a formal address bythe awardee. The award was estab-lished in 1950 by NESACS to honorthe memory of James Flack Norris(1871-1940), a professor of chemistryat Simmons College and M.I.T., chairof NESACS in 1904, and ACS Presi-dent in 1925-1926.

Nominees should have servedwith special distinction as teachers ofchemistry at any level: secondaryschool, college, and/or graduateschool. Since the presentation of thefirst award in 1951, awardees haveincluded many eminent teachers at alllevels, whose efforts have had a wide-ranging effect on chemical education.The recipient will be selected from aninternational list of nominees whohave served with special distinction asteachers of chemistry with significantachievements.

A nomination in the form of a let-ter should focus on the candidate’scontributions to, and effectiveness in,teaching chemistry. The nominee’scurriculum vitae should be includedand, where appropriate, a list of hon-ors, awards and publications related tochemical education. Seconding lettersmay also be included: these shouldshow the impact of the nominee’steaching on inspiring colleagues andstudents toward an active life in thechemical sciences and attest to theinfluence of the nominee’s other activi-ties in chemical education such as text-books, journal articles or otherprofessional activity at the local,national and international level.

The nomination materials shouldconsist of the primary nomination let-ter, supporting letters, and the candi-date’s curriculum vitae. Reprints orother publications should NOT beincluded. The material should notexceed thirty (30) pages and should besubmitted electronically in Adobe PDFformat through April 15, 2012 to Ms.Anna Singer, NESACS Administrative

Secretary [email protected]. Formore information about the Award, seehttp://www.nesacs.org/awards_norris.html.

Questions about the award or thenomination process should be directedto the Chair of the Norris Award Com-mittee, Dr. Jerry Jasinski, [email protected].

Nominations for the Philip L. LevinsMemorial Prize for outstanding per-formance by a graduate student on theway to a career in chemical scienceshould be sent to the AdministrativeSecretary of NESACS, 12 CorcoranRoad, Burlington, MA 01803, byMarch 1, 2012.

The graduate student’s researchshould be in the area of organic analyt-ical chemistry and may include suchareas of organic analytical chemistry asenvironmental analysis, biochemicalanalysis, or polymer analysis.

Nominations may be made by afaculty member, or the student maysubmit an application. A biographicalsketch, transcripts of graduate andundergraduate grades, a description ofpresent research activity and three ref-erences must be included. The nomina-tion should be specific concerning thecontribution the student has made tothe research and publications (if any)with multiple authors.The award will be presented at theMay 2012 Section Meeting. u

Philip L. Levins Memorial PrizeDeadline: March 1, 2012

Call for Nominations


http://www.nesacs.org/awards_norris.html



Background:Our work on amino acid analogs, and the biological

effects of their incorporation into biologically active species,has led us to investigate the preparation of a series of α-hydroxy amino acid analogs. While there are a variety ofmethodologies that allow the preparation of such species,we were intrigued by the application of metallic Lewis acidsto the stereospecific addition of aldehydes to activatedmethoxyoxazoles. Some methods, such as Evans’1 use of asalen-Al to catalyze the addition of benzaldehyde to 2-(4-methoxyphenyl)-5-methoxyoxazole, generate the stereose-lectivity from the ligands attached to the metal. We, on theother hand, have studied the stereoselective addition of analdehyde to an activated oxazole, using chirality within thealdehyde to generate high diastereoselectivity. Because chi-rality in a ligand may operate against the chirality of thealdehyde, and because the Evans salen-Al worked well foraromatic aldehydes, but not well for aliphatic aldehydes, wechose to begin our work with the achiral dimethylaluminumchloride. We have utilized the dialkyl aluminum catalyst forthe addition of chiral amidoaldehydes to activated aryl oxa-zoles. The catalyst is a divalent Lewis acid, allowing it tocomplex to the bidentate amidoaldehyde and enforce confor-mational rigidity of the aldehyde. The reaction results in adiastereoselective addition to achieve an oxazoline product.

In the mechanism of the addition of the aldehyde to theoxazole (Scheme 2), carbon 1 acts as a nucleophile on alde-hyde carbon 2, pushing electron density to oxygen 3 andleaving carbon 6 positively charged. The electron densityfrom oxygen 3 attacks carbon 4, pushing the pi electronstoward the nitrogen. The pi electrons reform the doublebond between carbon 4 and nitrogen, causing the bondbetween carbon 4 and oxygen 5 to break and forming a car-bonyl between oxygen 5 and carbon 6. In this rearrange-ment, a new five membered ring is formed.

The aluminum catalyst is effective for the stereospecificaddition of chiral amidoaldehydes to activated oxazolesbecause it is a divalent Lewis acid, thereby constraining theconformation of the bidentate amidoaldehyde and increasingthe aldehyde’s electrophilicity (Figure 1).5,6 The aldehyde 2may have variable R groups bonded to the amide nitrogen

that will be removed later in the synthesis, and either ahydrogen or methyl group can be bonded to the carbonalpha to both carbonyls. Synthetic Methods: All glassware was oven dried. The 2-(4-methoxyphenyl)-5-methoxyoxazole 1 (0.218 g, 0.001 moles, 1.0 eq) was dis-solved in anhydrous toluene and the reaction flask wasflushed with Ar. The mixture was cooled to -85o C, stirred

Summer Scholar ReportActivation of β-amidoaldeydes Toward Diastereoselective Nucleophilic AdditionShoshana Bachman and David Haines, Department of Chemistry, Wellesley College, Wellesley, MA

Scheme 1. Reaction of oxazole with an aldehyde activatedby an aluminum catalyst

Scheme 2. Mechanism of addition of oxazole to activatedaldehyde.

Scheme 3. Reaction of oxazole with aldehyde.

Figure 1. Aluminum catalyst complexed to the carbonyls ofthe amidoaldehyde, with the spot of nucleophilic attack cir-cled.

for 10 minutes, and (CH3)2AlCl (0.135 mL, 0.134 g, 0.0015mol, 1.5 eq) was added. 2R-N,N-diethyl-2-methyl-3-oxo-propionamide (0.15 g, 0.001 mol, 1.0 eq) was added in 2mL toluene. The reaction was stirred and warmed to roomtemperature over 24 hours, after which MS showed thedesired product. The product was purified by silica gelchromatography in 1:1 to 3:1 ethyl acetate:hexanes. 1HNMR (300 MHz, CDCl3) δ 6.89 (d, J=6.9 Hz, 2 H), 7.89 (d,J=6.9 Hz, 2 H), 5.15 (dd, J=6.6 Hz and J=7.8 Hz, 1 H), 4.74(d, J=6.6 Hz, 1 H), 3.63-2.99 (series of complex multiplets,11 H), 1.9-1.1 (series of multiplets, 9 H, 3 methyl groups). Results and Discussion:

The addition of 1 to 2 generated a single adduct as seenby ‘H NMR, demonstrating that the reaction was stereospe-cific. The relative stereochemistry of the two protons on thefive-membered ring has not been fully elucidated, but can

be predicted based on molecular modeling and a similarreaction done by Evans (Scheme 4).6

In the Evans reaction, a salen-aluminum catalyst wasused to stereospecifically add benzaldehyde to the oxazole,resulting in the two protons on the five-membered ringbeing cis. The coupling constant for the two protons in ourreaction of 1 and 2 is 6.6 Hz, while that of the two protonsin the Evans reaction is 10.8 Hz. Based on the differingcoupling constants, as well as modeling the interaction of 1and 2, we predict the stereochemistry of the two protons onthe five-membered ring in our product to be trans. Theresults of this reaction suggest that the divalent nature of thecatalyst and its ability to act as a Lewis acid are important toachieving stereospecificity.

This aluminum-catalyzed reaction results in the desiredstereospecificity of the adduct, but in low yield, with themajor side product being a result of interactions of the cata-lyst with aldehyde 2. The methyl groups on the catalyst arefairly nucleophilic and react with the aldehyde to form 2R,3?-N,N-diethyl-3-hydroxy-2-methylpropionamide: 1HNMR (300 MHz, CDCl3) δ 4.15 (d, 1 H, J=5.1, -OH), 3.81(complex multiplet, 1 H, proton on alcohol carbon), 3.35 (4H, overlapping -CH2’s on nitrogen), 2.59 (doublet of quar-tets, 1 H, J=6.3 and J=5.1, proton alpha to carbonyl), 1.42-1.0 (series of doublets and triplets, 12 H, 4 methyl groups).The spectrum shows a clean doublet of quartets for the pro-ton alpha to the carbonyl, which suggests that the reaction

resulted in a single diastereomer. The coupling constant of5.1 suggests that the two protons are either 60o or 120o fromone another, based on the Karplus relationship.7 The favoredconformation of the aldehyde will change by 1800 betweenthe aluminum complexed aldehyde and the uncomplexedaldehyde, leading us to predict that nucleophilic attack inthese two states would lead to differing diastereomers.Molecular modeling of the products of the addition of themethyl group to the amidoaldehyde in both the catalyst con-strained conformation and the unconstrained conformation,shows that the protons will exist gauche to each other in theenergy minimized (MM2) conformation in either case. Inconclusion, the side product from this reaction shows stere-ospecific addition of the methyl group, but the applicationof coupling constants in the NMR is inadequate to allow usto determine the absolute stereoisomerism of the addition,and therefore we cannot claim with certainty the mechanismby which the methyl addition product is generated.Future Directions:

An effective catalyst forthis reaction must be rela-tively stable and show biden-tate complexation toamidoaldehydes similar to 2.A bis(oxazoline) (box) cop-per(II) catalyst (Figure 2) is apromising alternative to thealuminum catalyst because ithas shown activation of alde-hydes for stere-ospecific additionof nucleophilesweaker than theoxazole (Table 1)and it is a divalentLewis acid.8

We have syn-thesized a chiralbox-copper catalystthat will be testedon a variety of ami-doaldehydes 2. Thechiral catalyst ispredicted to beeffective when usedwith achiral alde-hyde 2A (Figure3), but introducingchiral aldehydes,such as 2B, to thechiral catalyst maycause unintended stereointeractions. An achiral catalyst isalso being synthesized, that may be effective in activatingchiral amidoaldehydes 2B such that the chirality of the alde-


Continued on page 10

Summer Scholarcontinued from page 8

Scheme 4. Reaction of oxazole with benzaldehyde.1

Figure 2. Bis(oxazoline)copper(II) catalyst.8

Table 1. Nucleophiles used for addi-tion to aldehydes activated by box cat-alyst.8


hyde produces the desired stereoselec-tivity in the product, as was seen with

the aluminum catalysis. When the coupling of the alde-

hyde to the oxazole has been opti-mized, we will use this reaction toprepare a series of stereospecific α-hydroxy amino acid derivatives.Acknowledgements:I would like to thank theNorris/Richards Undergraduate Sum-mer Research Scholarship program,my supervisor, Dr. David R. Haines(Wellesley College), as well as formerstudents who have contributed to thisproject: Lisa Jacob, Halle Ritter,Cecilia Flatley, and Curtis Frantz.

References:1. Evans, D. A.; Janey, J. M.; Magome-

dov, N.; Tedrow, J. S. Chiral Salen-Aluminum Complexes as Catalystsfor Enantioselective Aldol Reactionsof Aldehydes and 5-Alkoxyoxa-zoles: An Efficient Approach to theAsymmetric Synthesis of syn andanti α-hydroxy β-amino Acid Deriv-atives. Angew. Chem. Int. Ed. 2001,40, 1884-1888

2. Centers for Disease Control and Pre-vention. Sexually Transmitted Dis-eases: Chlamydia CDC Fact Sheet.http://www.cdc.gov/std/chlamydia/stdfact-chlamydia.htm (accessedOctober 9, 2010).

3. Dong, F.; Sharma, J.; Xiao Y.;Zhong Y and Zhong G.; Intramolec-ular Dimerization is Required forthe Chlamydia-Secreted ProteaseCPAF to Degrade Host Transcrip-tional Factors. Infect. Immun. 2004,72, 3869-3875.

4. Corey, E. J.; Li, W.D Z.; Nagamitsu,T.; Fenteany, G.; The StructuralRequirements for Inhibition of Pro-teasome Function by the Lacta-cystin-Derived Beta-Lactone andSynthetic Analogs. Tetrahedron Let.

1999, 55, 3305-3316.5. Corey, E.J.; Li, W.D..Z; Nagamitsu,

T.; An Efficient and Concise Enan-tioselective Total Synthesis of Lac-tacystin. Communications, Angew.Chem. Int. Ed. 1998, 37, 1676-1678.

6. Evans, D. A.; Allison, B. D.; Yang,M. G. Chelate-Controlled CarbonylAddition Reactions. The Excep-tional Chelating Ability of Dimethy-laluminum Chloride andMethylaluminum Dichloride. Tetra-hedron Lett. 1999, 40, 4457-4460.

7. Minch, M.J. Orientational depend-ence of vicinal proton-proton NMRcoupling constants: The Karplusrelationship. Concepts in MagneticResonance. 1994, 6(1), 41-56.

8. Evans, D. A.; Johnson J. S. ChiralBis(oxazoline) Copper II Com-plexes: Versatile Catalysts for Enan-tioselective Cycloaddition, Aldol,Michael, and Carbonyl Ene Reac-tions. Acc. Chem. Res. 2000, 33(6),325-335.

9. Soucy, Francois; Grenier, Louis;Behnke, Mark L.; Destree, AntoniaT.; McCormack, Teresa A.; Adams,Julian; Plamondon, Louis. A Noveland Efficient Synthesis of a HighlyActive Analogue of clasto-Lacta-cystin β-Lactone. J. Am. Chem. Soc.1999, 121(43), 9967-9976. u

What’s Yours?DMPK Scientist,

LC/MS Product Specialist, Mass Spec Operator,

Staff Investigator, Process Chemist,

QA Manager, Synthetic Chemist, Lab Instructor . . .

Many local employers post positions on the NESACS job board.

Find yours atwww.nesacs.org/jobs

Summer Scholarcontinued from page 9

Figure 3. Possible amidoaldehydes foraddition to oxazoles activiated by boxcatalyst.

January 1, 1852Eugène A. Demarçay, who was bornon this date, discovered europiumfrom samarium magnesium nitratein 1901 and gave spectroscopicproof of the discovery of radium. Hedid vacuum studies of volatility andlow temperatures followed by hightemperature spark spectra.

January 2, 1889Roger Adams, a researcher inorganic chemical synthesis, wasborn on this date. He directed 184doctoral theses.

January 4, 1891Henry H. Dow prepared brominefrom brine on this date.

January 7, 1794Eilhardt Mitscherlich, who didresearch on crystalline structure,catalysis, and benzene and its deriv-atives, was born on this date. Healso discovered isomorphism.

January 9, 1868Sören P. L. Sörensen, who was bornon this date, is known as the “Fatherof pH”, He did research on proteins,amino acids, and enzymes.

January 10, 1923Chemical and Engineering Newswas started on this day as thebimonthly News Edition of Indus-trial and Engineering News. It waschanged to CEN in 1942 andbecame weekly on January 6, 1947.

January 11, 1875Frederick M. Becket, an inventor inelectrochemistry and electrometal-lurgy, was born on this date. Hereceived more than one hundredpatents covering a wide range ofelectric furnace and chemical prod-ucts, notably ferro-alloys, calciumcarbide, and special chromiumsteels.

January 12, 1912Konrad E. Bloch, who waas born onthis date, was a researcher on cho-lesterol and fatty acid metabolism.He shared the Nobel Prize in Physi-ology or Medicine in 1964 withFeodor Lynen for their discoveriesconcerning the mechanism and reg-ulation of the cholesterol and fattyacid metabolism.

January 13, 1780Pierre J. Robiquet, who discoveredasparagine with Nicolas-LouisVauquelin, was born on this date. Healso measured the codeine contentof opium.

January 14, 1851Ludwig Claisen, who developedreactions such as the condensationof esters and the rearrangement ofallyl vinyl ethers, was born on thisday.

January 15, 1784Henry Cavendish presented thequantitative composition of waterbefore the Royal Society on thisdate.

January 17, 1706Benjamin Franklin, who was bornon this date, was a researcher inelectricity, and an inventor, a states-man. He also described marsh gas toPriestley.

January 18, 1861One hundred and fifty years ago,Hans Goldschmidt was born. In1893 he discovered the alumino-thermite process (GoldschmidtProcess) and he patented it in 1895.He was interested in producing very

pure metals by avoiding the use ofcarbon in smelting but realized itsvalue in welding.

January 22, 1936Seventy-Five years ago, Alan J.Heeger was born on this date. Heshared the Nobel Prize in Chemistryin 2000 with Alan G. MacDiarmidand Hidaki Shirakawa for their dis-covery and development of conduc-tive polymers.

January 23, 1929Twenty-five years ago in 1986, JohnC. Polanyi shared the Nobel Prize inChemistry with Dudley R. Hersh-bach and Yuan T. Lee for their con-tributions concerning the dynamicsof elementary chemical processes.Born on this date, he is a researcherusing infrared chemi-luminescenceto follow excited reaction products.

January 26, 1881Claude S. Hudson, who did researchin the chemistry of sugars, was bornon this date.

January 27, 1865August F. Kekulé presented his ben-zene structure to Société Chimique,Paris on this date.

January 28, 1843Henry C. Bolton, who was a writerand bibliographer of the history ofchemistry, was born on this date. Hestudied the action of organic acidson minerals.

. January 31, 1881Irving Langmuir, who was born onthis date, did research on surfacechemistry, for which he received theNobel Prize in 1932. He introducedgas-filled tungsten lamps and theuse of the atomic hydrogen blow-pipe for welding. He and Gilbert N.Lewis evolved the electronic theory.

Additional historical events can befound at Dr. May’s website, faculty.cua.edu/may/history.htm. u


January Historical Events in Chemistryby Leopold May, The Catholic University of America, Washington, DC

link at the NESACS website. Checkout our blog at http://blog.nesacs.org .

This is your Section. Participate!Make connections with other membersthrough the Section’s activities, includ-ing the monthly meetings which offernetworking, connections for collabora-tion, and evenings of cutting-edgechemistry. Stay connected by stayinginvolved. u

Chair’s Statementcontinued from page 2

http://faculty.cua.edu/may/history.htm

http://blog.nesacs.org

Quasicrystals that were supposed notto exist were discovered by DanielShechtman of the Technicon Instituteof Haifa, Israel. Examining the elec-tron diffraction pattern of a rapidlysolidified alloy of aluminum and man-ganese on April 8, 1982, he found thatthe atoms were not packed in symmet-rical patterns which repeated periodi-cally in the crystal. This was incontrast to what was found with crys-tals previously.

He had prepared the first qua-sicrystal. Aperiodic mosaics that arefound in medieval Islamic mosaics ofthe Alhambra Palace in Spain and theDarb-I-Imam Shrine in Iran help to

understand the appearance of qua-sicrystals at the atomic level. The pat-terns are regular but never repeatthemselves.

In the course of defending thisvery controversial discovery, he wasasked to leave his research group. Asmore examples of quasicrystals werefound in the laboratory and in mineralsamples from a Russian river, the con-cept of quasicrystals was accepted,thus leading to the awarding of the2011 Nobel Prize in Chemistry toDaniel Shechtman for the discovery ofquasicrystals. Who said that there isnothing new under the sun? u


Impossible Crystals,Quasicrystals: Nobel Prizein Chemistry, 2011 B y Leopold MayThe Catholic University of AmericaWashington, DC

NationalRecognitionfor NESACSStudentChapters1The ACS Committee on Education hasselected the following student chaptersin the Northeastern Section to receivespecial recognition for the programsand activities described in their 2010-2011 reports:Commendable Recognition• Gordon College, Wenham, MA;

Benjamin Stewart and Ariel Guigu-izian, chapter co-presidents; Prof.Joel Boyd, faculty advisor.

• Northeastern University, Boston,MA; Philip Hamzik and RhiannonThomas, chapter co-presidents; Prof.Victoria Berger, faculty advisor.

Honorable Mention• Bridgewater State College, MA;

Melissa Brulotte and ChristopherGoncalo, chapter co-presidents;Profs. Edward Brush and StevenHaefner, faculty advisors.

• Stonehill College, North Easton,MA; Natalie Dogal and MeghanHarley, chapter co-presidents; Profs.Cheryl Schnitzer and Marilena Hall,faculty advisors.

• Suffolk University, Boston, MA;Andrew Alexander, chapter presi-dent; Prof. Doris Lewis, facultyadvisor.

Student involvement in applying greenchemistry principles and practices isessential to the integration of environ-mentally benign technologies in acade-mia and industry. The ACS GreenChemistry Institute distributes a GreenChemistry Award to ACS student chap-ters who have engaged in at least threegreen chemistry activities during theacademic year. Listed below are the2010-2011 Green Chemistry Award



Chemical Society, David Sittenfeld, Dr.Bassam Shakhashiri, and the Phyllis A.Brauner Memorial Lecture Committee.

The events would not have beenpossible without the help of the volun-teers listed below! Individuals fromEmmanuel College, Gordon College,Massachusetts Institute of Technology,Northeastern University, Salem State,Sigma-Aldrich, Stonehill College, Suf-folk University, Tewksbury MemorialHigh School, Tufts University, Univer-sity of Massachusetts-Boston, Whit-man Hanson High School.

Thank you NCW volunteers!*Daniel Adam, Greg Ainsworth, JustinAndrews, Lee Andrews, AlyshaArdagna, Ivan Barrera , Eric Batista,Victoria Berger, Mohini Bhakta, Lau-ren Blair, Joel Boyd, Holly Boyle,Matthew Burris, Hillary Butts, SusanBrauner, Alex Bressette, AmandaCarey, Ruth Chadwick, Christine Cud-demi, Katie Dapsis, Amy D’Entremont,Nick Dibenedetto, Eva Dixon, Chris-tine Dunne, Kristen Entwistle, SarahFaulkner, Carlo Fierimonte, LaurenGagnon, Ariel Guiguizian, KeeveGurkin, Allison Harbottle, CharlieHoyt, Pei Yi Huang, Sarah Iacobucci,Jennifer Ide, Mirian Isreb, Erin John-son, Katie Kelly, Stephanie Laurer,Becky Leifer, Rebecca Leising, BeckyLewis, Doris Lewis, Irv Levy, Yan Lin,Michael Lynch, Leann Mackay, GiannaMancuso, Thomas McGrath, KerryMerchant, Krista Mignon, Mark Nan-iong, Elsy Naveo, Moses Njogu, JackieO’Neil, Brian Pelletier, Anna Piccolo,Maha Ranga, Jayashree Ranga, ChrisRicciardi, Justin Roberts, VictoriaRobinson, Derrick Rousseau, AndreaSchneider, Laura Schneider, MeaghanSebeika, Colleen Shea, Heather Siart,Arianna Smith, Emma St. Marie, StacyStrobel, Kyle Swerdlow, Kelly Tan,Heidi Teng, Kristina Vailonis, C.Danielle Walker, Jenna Whalen, DevanWillans, Jen Winters, Deborah Zorn*I apologize if your name is not on thislist. The 2012 theme for NCW is nanotech-nology. u

NatChem Week 2011continued from page 4

ing the purification of aequorin. In 1979, I finally determined the

accumulated GFP to investigate thenature of the fluorophore. The resultsurprised me; the fluorophore wasfound in the primary structure of theprotein. This implied some possibleimportant uses of GFP.

GFP was cloned by DouglasPrasher in 1992, and successfullyexpressed in living organisms by Mar-tin Chalfie in 2004, which triggered atrend of vigorous study on GFP. Vari-ous forms of modified and improvedGFP were genetically produced byRoger Tsien and other investigators.

Red fluorescent proteins of theGFP family were found in corals in1999, and more recently far-red fluo-rescent proteins were obtained from asea anemone. The improvements andapplications of the GFP-family fluores-cent proteins are still in progress. u

Abstractcontinued from page 5

recipients located within the Northeast-ern Section.• Gordon College, Wenham, MA• Northeastern University, Boston,

MA• Suffolk University, Boston, MA

All chapters receiving special recogni-tion will be honored at the 243rd ACSNational Chemistry Meeting in SanDiego, CA, on Sunday, March 25,2012.1 All information and award descrip-tions from “inChemistry” magazine,November/December 2011 issue. u

National Recognitioncontinued from page 12

Photos from National ChemistryWeek 2011 at the Museum of Sci-ence By Morton Z. Hoffman

(l-r) Zach G., Kyle G., Olivia F., and Sydney F.enjoying chemistry.

Zach L. with Kerry Merchant (at left) and ArielGuiguizian of Gordon College.

Doris Lewis (at left) with Susan Brauner.

Bassam Shakashiri during the Phyllis BraunerMemorial Lecture.


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Check the NESACS home pagefor late Calendar additions:http://www.NESACS.orgNote also the Chemistry Department webpages for travel directions and updates.These include:http://chemserv.bc.edu/seminar.htmlhttp://www.bu.edu/chemistry/events/http://www.chem.brandeis.edu/colloquium.shtmlhttp://www-chem.harvard.edu/events/http://web.mit.edu/chemistry/www.chem.neu.edu/web/calendar/index.htmlhttp://chem.tufts.edu/seminars.html [CHEM.]http://ase.tufts.edu/chemical/seminar.htm

[CHEM. ENGG.]http://www.chem.umb.edu/www.umassd.edu/cas/chemistry/seminars.cfmwww.uml.edu/Dept/Chemistry/speakers.htmlhttp://www.unh.edu/chemistry/seminars.html

Jan. 24 Jimmy Wu, Dartmouth UniversityUniv. New Hampshire, Room N104 (L103)11:10 am

Jan 26Prof. Tohru Fukuyama, Univ. TokyoMIT, 6-1204:00 pm

Jan 27Prof. Tohru Fukuyama, Univ. TokyoBoston College, Merkert 1304:00 pm,

Notices for The NucleusCalendar of Seminars should be sent to:Sheila E Rodman Konarka Technologies, Inc.116 John St. Suite 12, Lowell, MA 01852 email: srodman(at)konarka.com u

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Bassam Shakhashiri with Zach, Olivia, Sydney,and Kyle.

Photos from National Chemistry Week2011 at the Museum of Science ByMorton Z. Hoffman

Bassam Shakhashiri and Doris Lewis presentingthe ACS Salutes to Excellence Award to DavidSittenfeld (Museum of Science Boston) “in appreciation for extraordinary contributions toNational Chemistry Week and in recognition ofexcellence in science education for all ages.”

NatChem Week 2011continued from page 13

http://www.NESACS.org


december 2011 nucleus web - nesacs · by christine jaworek-lopes with photos by morton z. hoffman...

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