acros organics acta n°009
TRANSCRIPT
-
7/28/2019 Acros Organics acta N009
1/20
Acros Organics journalfor chemists
Spring 2002
Acros Organics
actaacta
Acros Organics journalfor chemists
Spring 2002
Acros Organics
A Brief Overview ofCyclopropane Aminoacids . . . . . . . . . 1Nick Kilenyi
Organic Peroxides inRadical Synthesis Reactions . . . . . . . . 6J. Meijer, A.H. Hogt and B. Fischer
(S)- and (R)-N-Boc-N, O-Iso-propylidene--methylserinals . . . . . . . 9
A. Avenozaa, C. Cativielab, F. Corzanaa, J. M.Peregrinaa, D. Sucunzaa and M. M. Zurbanoa
99 ChiroTechproduct range now availableexclusively through Acros Organics
ChiroTechproduct range now availableexclusively through Acros Organics
-
7/28/2019 Acros Organics acta N009
2/20
More product documentationfor your research
Recent product infosheetsN 50: HEB, (S)-Ethyl 3-hydroxybutyrate,
a next building block for asymmetrical
synthesis
N 51: Sodium polytungstate, the NON-TOXIC
alternative high density solvent for sink-
float analysis
N 52: Chiral Glycidols
You can find more infosheets in the
"product info" department of the library
on our website www.acros.com
Chemistry review printsN 1: Solid Phase synthesis of compound libraries
and their application in drug discovery.
N 2: From homogeneous to heterogeneouscatalysis, recent advantages in asymmetricsynthesis with nitrogen containing ligands.
N 3: 1-Hydroxycyclopropanecarboxylic acid -a readily available and efficient precursor.
N 4: Silylated N-Tert-Butyl Aldimines: Versatileorganosilicon reagents for polyenalsynthesis.
N 5:A complete range (C2 to C20) of fullysynthetic sphingosines and ceramides.
No 6: Organic Peroxides in Radical SynthesisReactions.
No 7: CuCl(OH).TMEDA: A Novel, EfficientCatalyst for Aerobic Oxidative CouplingReactions.
NEW No 8: The wonderful world of the
bis(trimethylsilyl) ketene acetalreagents
New publicationsChirals CD
12 more suggestionsfor the Organic Chemist
Drug Discovery brochure
Solid Phase Synthesis brochure
Ionic liquids handbook
Much has happened since the last issue of
Acros Organics Acta. We see new trends
emerging every day, inside as well as outside
the chemistry lab. These are veryinteresting times for a company like Acros
Organics, and we are working hard to keep
apace with all these trends.
Our site in Belgium, for instance, witnessed
an impressive expansion with the building of
new warehouses and offices. The new cata-
logues that we published contain more than
2000 new additions, and more products are
added every day.
We initiated important collaboration projects
with ChiroTech for our drug discovery product
line, and with QUILL for ionic liquids, which
play an important role in green chemistry.
You will find more information on these novel-
ties in this issue of the Acta.
Today, more than ever, Acros Organics delivers
more than just the content of a bottle. We
hope you will enjoy this new issue of our Acta!
ACROS ORGANICSGeel West Zone 2, Janssen Pharmaceuticalaan 3a
B-2440 Geel, Belgium
Tel.: +32(0)14/57.52.11 - Fax: +32(0)14/59.34.34
ACROS ORGANICS USA500 American Road, Morris Plains, NJ 07950Tel.: 1-800-766-7000 - Fax: 1-800-926-1166Internet: http://www.fishersci.com (US orders only)
ACROS ORGANICS on-lineInternet: http://www.acros.com
E-Mail: [email protected]
To receive a copy, fill in
the fax back form on page 16
First words
-
7/28/2019 Acros Organics acta N009
3/20
Introduction
Cyclopropane aminoacids are defined for the purposeof this article as alpha-aminoacids with a bridgingmethylene group forming a cyclopropyl ring.
There are two main families, colloquially named 2,3-methanoaminoacids (1) in which the bridge is connected to thealpha-carbon, and 3,4-methanoaminoacids (2), in which it is oneposition further down the chain. Such compounds are of interest asnatural products, and also as conformationally-restricted analogues ofthe proteinogenic aminoacids. It should be noted that substituted 2,3-
methanoaminoacids can exist in two diastereomeric forms, with thesubstituent either synor anti to the nitrogen. No attempt has beenmade here to provide a comprehensive review of this important field.Instead, emphasis has been placed on the more recent work. Readersdesirous of greater detail should consult the excellent review pub-lished in 1990 by Stammer (ref 1), and the original papers cited here.
Naturally-Occurring CyclopropaneAminoacids
The simplest, and perhaps most important cyclopropane aminoacid isthe parent, 1-aminocyclopropane-1-carboxylic acid (3) (Acc). Thiscompound, originally isolated from apples and pears, is the biogenet-ic precursor of the ripening hormone ethylene in plants. (ref 2)
Coronamic acid (4, R=Et) is a component of the toxins coronatine (5), aplant toxin produced by Pseudomonas corona-facience. The lowerhomologue norcoronamic acid (R=Me) is found in norcoronatine. (ref 3)
Hypoglycine A and B (6), isolated from the Ackee fruit Blighia sapi-da, cause hypoglycaemia in Man and animals. (ref 4)
Applications of CyclopropaneAminoacids
As alluded to above, cyclopropane aminoacids may be regarded asconformationally frozen analogues of the natural aminoacids. It is
therefore of great interest to incorporate them in peptides in order toprobe conformational spaces and reactivity. Enkephalins containing2,3-methanophenylalanine showed very different binding affinitiesand selectivities compared with the native hormone. Furthermore,such peptides were resistant to hydrolysis by chymotrypsin and car-boxypeptidase Y. (ref 5) The dipeptides N-benzoyl-Acc-Phe-OH andN-benzoyl-Acc-Pro-OH inhibited carboxypeptidase A in a time-dependent manner indicative of irreversible covalent binding of thedipeptide to the enzyme. (ref 6) Incorporation of Acc into peptidesfavours folding of the backbone into a C-7 helix or a gamma-turn,unlike the acyclic aminoisobutyric acid residue Aib. (ref 7)
A Brief Overview of Cyclopropane Aminoacids
NH3+
CO2-
H H
HH
Plants
(3)
NH3+
CO2-
R
NH
CO2H
R
O
H
H
OMe
(4)
(5)
CO2-
H3N H
(6)
+
Acros Organics Acta 9 - Spring 2002 1
NH3+
CO2-
H
R
NH3+
CO2-
R
H
(syn) (anti) (1)
H3N
H
CO2 (2)
Nick KilenyiCerise Chemtech sa/nv, Rue de Strasbourg 5,
Da Vinci Science Park, B-1140 Brussels, Belgium.
-
7/28/2019 Acros Organics acta N009
4/20
References1. Stammer, C. H. Tetrahedron1990, 46, 2231
2. Fowden, L.; Lea, P. J.; Bell, E. J., The Non-Protein Aminoacids of Plants, Advancesin Enzymology, ed. A. Meister, Wiley, New York, 1979, 117
3. Ichihara, A.,;Shiraishi, K.; Sato, H.; Sakamura,; S. Nishiyama, K.; Sakai, R.; Furusaki,A.; Matsumoto, T.J. Am. Chem. Soc. 1977, 99, 636
4. Eloff, J.N.; Fowden, L. Phytochemistry1970, 9, 2423 and references therein
5. Mapelli, C.; Kimura, H.; Stammer, C. H. Int.J. Peptide Protein Res. 1986, 28, 347
6. Ner, S. K.; Suckling. C. J.; Bell, A. R.; Wrigglesworth, R. J.J. Chem. Soc. Chem.Commun. 1987, 480
7. Barone, V.; Franternali, B.; Cristinziano, P. L.; Lelj, F.; Rosa, A. Biopolymers1988,27, 1673.
Acros Organics Acta 9 - Spring 20022
N
OH
O
O
O
CH3
CH3
CH3
N
OH
O
O
O
CH3
CH3
CH3
11162 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cyclopropanecarboxylic acid 98%
11163 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cyclopropanecarboxylic acid chloride 98%
34528 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1,1-Cyclopropanedicarboxylic acid 98%
11835 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ethyl cyclopropanecarboxylate 99%
12671 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl cyclopropanecarboxylate 98%
13046 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .trans-2-Phenylcyclopropane-1-carboxylic acid 95%
13492 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(2,4-Dichlorophenyl)cyclopropanecarboxylic acid 95%
16445 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Diethyl 1,1-cyclopropanedicarboxylate 97%
17059 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Phenyl-1-cyclopropanecarbonitrile 97%
17068 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Phenyl-1-cyclopropanecarboxylic acid 97%
17069 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(4-Chlorophenyl)-1-cyclopropanecarboxylic acid 99%
19816 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-Methylcyclopropanecarboxylic acid 98%
20529 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .DL-3-Methylenecyclopropane-trans-1,2-dicarboxylic acid 98%
25534 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl cis-1,2-cyclopropanedicarboxylate 98%
27850 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl 1-methyl-trans-1,2-cyclopropanedicarboxylate 99+%
27851 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl 3-methyl-trans-1,2-cyclopropanedicarboxylate 99%
30142 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Amino-1-cyclopropanecarboxylic acid 99%
30143 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Hydroxy-1-cyclopropanecarboxylic acid 98%
23305 . . . . . . . . . . . . . . . . . . . . . .Methyl 3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane)carboxylate, cis/trans 99%
27520 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl (1R,3S)-2,2-dimethyl-3-(2-oxopropyl)-cyclopropaneacetate 96%30211 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl 1-hydroxy-1-cyclopropane carboxylate
30963 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(Aminocarbonyl)-1-cyclopropanecarboxylic acid 97%
33530 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ethyl 1-hydroxycyclopropanecarboxylate 90%
ADDITIONAL CYCLOPROPANE CARBOXYLIC ACIDS AND DERIVATIVES
Acros Organics Offer: NEW Cyclopropane amino acids
35380
(1R,2R)-N-BOC-1-Amino-2-
phenylcyclopropanecarboxylic
acid
35381
(1R,2S)-N-BOC-1-Amino-2-
phenylcyclopropanecarboxylic
acid
N
OH
O
O
O
CH3
CH3
CH3
N
OH
O
O
O
CH3
CH3
CH3
35379
(1S,2S)-N-BOC-1-Amino-2-
phenylcyclopropanecarboxylic
acid
35382
(1S,2R)-N-BOC-1-Amino-2-
phenylcyclopropanecarboxylic
acid
A Brief Overview ofCyclopropane AminoacidsNick Kilenyi
Cerise Chemtech sa/nv, Rue de Strasbourg 5,Da Vinci Science Park, B-1140 Brussels, Belgium.
-
7/28/2019 Acros Organics acta N009
5/20
Universit de Cergy-Pontoise,Laboratoire de Synthse Organomtallique associ au CNRS,
5 mail Gay Lussac, Neuville sur Oise, F-95031 Cergy-Pontoise Cedex
Acros Organics Acta 9 - Spring 2002 3
Since the work of Mukaiyama1 in 1974 on the aldol reaction using silylenol ethers, silylketene acetals have seen an explosive growth in their useas building blocks in organic synthesis. Among these new reagents, bis (trimethylsilyl) ketene acetals are now the organosilicon compounds ofchoice for type aldol condensations because of their ease of preparation, clean products and high selectivity.
The direct homologation of aldehydes into unsaturated conjugated carboxylic acids with the introduction of two carbon atoms in the resultingchain is a very attractive reaction, since polyethylenic carboxylic acids are very useful intermediates in the total synthesis of natural products.
Indeed, the condensation of reagent 33101 with a wide range of aldehydes in the presence of catalytic amount of catalyst takes place at roomtemperature to give the corresponding ,-ethylenic carboxylic acids in excellent yield and with a total E stereoselectivity2,3. Reagent 33105 hasproven to be suitable for one pot four-carbon homologation of aldehydes4 and imines5. Silylated acetate6 33112 and crotonate7 33111 can be usedfor the construction of many important building blocks.
Queen Substance of honeybee was selected as a targetfor total synthesis of a natural product with the aim todemonstrate the utility of our organosilicon reagents.The following retrosynthetic scheme represents themost efficient total synthesis described up today. Thus,the Queen Substance has been prepared in seven stepsin 34% over yield8.
(1) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96,7503.
(2) Bellassoued,M.; Gaudemar, M. Tetrahedron Lett. 1990, 31, 209.
(3) Bellassoued, M.; Lensen, N.; Bakasse, M.; Mouelhi, S. J. Org. Chem. 1998, 63, 8785.
(4) Bellassoued, M.; Gaudemar, M. J. Organometal. Chem. 1984, 263, C21.
(5) Bellassoued, M.; Ennigrou, R.; Gil, R.; Lensen, N. Synthetic Commun, 1998, 28, 3955.
(6) Bellassoued, M.; Dubois, J. E.; Bertounesque, E. Synthetic Commun, 1987, 17, 1181.
(7) Bellassoued, M.; Ennigrou, R.; Gaudemar, M. J. Organometal. Chem. 1988, 338, 149.
(8) Bellassoued, M.; Majidi, A. Tetrahedron Lett. 1991, 32, 7253.
CO2SiMe3Me3Si
OSiMe3
OSiMe3SiMe3
Me3Si
OSiMe3
OSiMe3CH2-CO2SiMe3
33101 33105 33112 33111
OSiMe3
OSiMe3
Me3Si
OSiMe3
OSiMe3
OCO2H
++CHOO O
Queen Substance of Honeybee
New organosilicon reagentsBis(trimethylsilyl)ketene Acetals:
Versatile Organosilicon Reagents for Aldolisation Reactions.
Request your copy of the Review from Prof. Bel lassoued of
Bis(Trimethylsilyl)Ketene Acetals: A document with a lot of applications,references and many tables of results, complete with the comprehensive list of
these organosilicon reagents available from stock at Acros Organics!
Moncef Bellassouedand Jrme Grugier
-
7/28/2019 Acros Organics acta N009
6/20
First, look for the product(s) youre
interested in by using the search
functions
Call up MSDS data, available in English /
Dutch/ French / German/ Italian / Spanish
(for registered users)
More than 250 info sheets are linked to our
product database. These sheets are also
available under the menu option library.
The molfile allows you to copy and
paste molecule data directly into
programs like ISIS.
View the infrared spectrum of a mole-
cule. Click on the spectrum for more
details.
Click on 3D model to see a 3-dimen-
sional view of the molecules. Rotate,
zoom, move or change the style or addsymbols as you like.
TECHNICAL SERVICE ON THE WEB
Acros Organics on-line
http://www.acros.com ACROS ORGANICS ON THE INTERNETFor Europe and the rest of the world
-
7/28/2019 Acros Organics acta N009
7/20
Registered users can request product specifications
or certificates of analysis through our website.
Use the specifications button to
view product specifications. Just
type in the product code (5 digits).
You can print these forms, or save them as a PDF file
(Acrobat Reader required). Registered users can forward
their technical questions directly to our Technical Service
by clicking the "tech questions" button.
Fill in the Acros
Organics lot code
for the product of
which you want to
view the certificate
of analysis. This lot
code can be found
on the labels of our
products.
TIP
The lot code consists of 7
digits. You may have to omit
the last 3 digits if you see a
10 digits code.(e.g.: A0116441)
TECHNICAL SERVICE ON THE WEB
http://www.fishersci.com/acros ACROS ORGANICS ON THE INTERNET
Select certificates
or specifications
on the home page.
For the US domestic market, Canada & Latin America
-
7/28/2019 Acros Organics acta N009
8/20Acros Organics Acta 9 - Spring 20026
J. Meijer, A.H. Hogtand B. Fischer Akzo Nobel Polymer Chemicals Laboratory Deventer
Zutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.
Introduction
Radicals can be used as synthetic intermediates inreactions which are often difficult to accomplishby other means and which can selectively occurunder very mild conditions. The protection of func-tional groups, often essential for synthetic sequencesof ionic reactions, is mostly not required for radicalreactions.1
Organic peroxides are a very versatile source of radi-cals that are formed after the thermally induced
homolysis of the peroxide bond. The major radical-molecule reactions are additions and SH2 reactions,e.g. H-abstraction, atom transfer, unimolecular reac-tions, e.g. decarboxylation, -scission and rearrange-ments, e.g. 1,5-H-abstraction.2 In synthesis reactions,undesired radical-radical reactions such as radicalcombination and disproportionation can be avoidedby proper choice of the type of peroxide and reactionconditions. Another major application of organic per-oxides in syntheses is oxidation, which is a non-radi-cal reaction.3
Oxidation reactions withorganic peroxides
Peroxyacids are mostly used for the epoxidation of unsaturated com-pounds. Most important are the Baeyer-Villiger reaction of carbonylcompounds, oxidation of nitrogen and sulfur compounds3 (see Fig. 3).It is generally accepted that such oxidations are non-radical reactions.
Radical reactions withorganic peroxides
Through homolytic scission organic peroxides primarily generateoxy-radicals: alkoxy-, acyloxy- and/or oxycarbonyloxy-radicals.4
Oxy-radicals can also be generated from peroxyesters, diacylperox-ides and hydroperoxides by redox systems.5 (see Fig. 4).
An important reaction of alkoxy-radicals is -scission, and of acyloxy-radicals decarboxylation, both reactions resulting in the formation ofcarbon-radicals. In contrast, alkoxycarbonyloxy-radicals do not showdecarboxylation.4 (see Fig. 5).
Organic Peroxides in Radical Synthesis Reactions
O
O
O HRO
BAEYER-VILLIGER
R3N
R2S
R2S(O)n=1,2
R3N(O)
R1C(O)R 2
R1C(O)OR 2
EPOXIDATIONPEROXY ACID
Figure 3. Oxidation via peroxy-compounds.
O
O
HO
OO
O
OO
OO
OOO
O
OO
O
R1OOR2
C14H29
C16H33
*
**
* *
*
**DTBP
DTAP DCP
BPO
CPDC
MPDC TBCPDC
BPIC
Figure 4.
Generation of oxy-radicals via peroxy-compounds.
H
R1OOR2
*
**
* *
*
** DTBP
DTAP TBPIB
TBPP
BPO
LPO BTMHP
TBPEH
CH3
C2H5
C11H23
Figure 5.
Generation of carbon-radicals via peroxy-compounds.
-
7/28/2019 Acros Organics acta N009
9/20
In the presence of a substrate, oxy-radicals (R-H) generate substrate-radicals which may undergo combination reactions, addition reac-tions to unsaturated compounds or atom-transfer reactions. Examplesof such reactions in practical applications are (see Fig. 6): combina-tion of phenylisopropyl-radicals to 2,3-dimethyl-2,3-diphenylbutane,applied as flame-retardant synergist,6 addition of methylphosphorousmono-isobutyl ester to vinylacetic acid ethylester, used in the synthe-sis of the glufosinate herbicide,7 and atom transfer of bromine toa substituted tolyl-radical, yielding a flame retardant.8 In addition,oxy-radicals can be used for the racemization of optically activechrysanthemic acid or its ester used for the synthesis of pyrethrineinsecticides.9
Oxy-radicals can add to unsaturated compounds. They may alsoundergo competitive reactions such as -scission in case of alkoxy-radicals, and decarboxylation in case of acyloxy-radicals. The formedcarbon-radicals will in most cases also add to the unsaturated com-pounds.4,10
Concluding remarks
There are several important parameters for the choice of a peroxidefor use in chemical syntheses. The physical and chemical stabilityaffects the storage and handling properties, the temperature-depen-dent rate of decomposition determines the reactivity at the processconditions. The radicals formed after decomposition must be efficientfor the desired radical reaction. Peroxides may also be selected forspecific rearrangements or specific coupling reactions, which can
introduce functional groups into substrates. Decomposition productsof the peroxides have to be taken in account during the purificationprocess.
Organic peroxides are well established synthetic agents in the manu-facture of many pharmaceutical intermediates, herbicides, insecticidesand various other fine chemicals. Organic peroxides offer opportuni-ties to reduce the number of reaction steps in synthetic routes apply-ing classical synthetic procedures. Moreover, introduction of function-al groups can be achieved by using special organic peroxides. In manycases these reactions are unprecedented in non-radical chemistry.
Organic peroxides combine a number of interesting features for theapplication in organic synthesis:
High purity Good solubility on most organic systems, enabling homogeneous
reaction conditions Well defined and temperature controlled reactivity High efficiency Favorable cost/performance ratio
Acros Organics Acta 9 - Spring 2002 7
Organic Peroxides inRadical Synthesis ReactionsJ. Meijer, A.H. Hogt and B. Fischer
Akzo Nobel Polymer Chemicals Laboratory DeventerZutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.
R H
O P
O
O
O
R1O OR 2* *
R1OH + HOR 2
*RR-X + Y *
ATOM TRANSFER
Br
H
HX
R1OOR2
R-H
ADDITION
ABSTRACTION
[Meiji Saika Kaisha, 1982]
[Tosoh, 1999]
R-R
COMBINATION
[Regitz and Giese, 1989-a]
X-Y2x
Figure 6. Reactions of oxy-radicals with substrates R-H.
Abbreviations
Code Chemical name* CAS nr.
BPIC Tert-butyl peroxy isopropylcarbonate (Trigonox BPIC) 2372-21-6BPO Dibenzoyl peroxide (Lucidol, Cadet) 94-36-0BTMHP Bis(3,5,5-trimethylhexanoyl) peroxide (Trigonox 36) 3851-87-4CPDC Dicetyl peroxydicarbonate (Perkadox 24) 26322-14-5DCP Dicumyl peroxide (Perkadox BC) 80-43-3DTAP Di-tert-amyl peroxide (Trigonox 201) 10508-09-5DTBP Di-tert-butyl peroxide (Trigonox B) 110-05-4EHP Bis(2-ethylhexyl) peroxydicarbonate (Trigonox EHP) 16111-62-9LPO Dilauroyl peroxide (Laurox) 105-74-8MPDC Dimyristyl peroxydicarbonate (Perkadox 26) 53220-22-7TBCPDC Bis(4-tert-butylcyclohexyl) peroxydicarbonate (Perkadox 16) 15520-11-3
TBHP Tert-butyl hydroperoxide (Trigonox A) 75-91-2TBPB Tert-butyl peroxybenzoate (Trigonox C) 614-45-9TBPEH Tert-butyl peroxy-2-ethylhexanoate (Trigonox 21) 3006-82-4TBPIB Tert-butyl peroxyisobutanoate (Trigonox 41) 109-13-7TBPP Tert-butylperoxy pivalate (Trigonox 25) 927-07-1
* Cadet, Laurox, Lucidol, Perkadox, Trigonox are tradenames of Akzo Nobel.
-
7/28/2019 Acros Organics acta N009
10/20
Please check our website http://www.acros.comfor additional events where we will be present.A list of current events can be found on the event page.
Meet Acros Organics at following events:
Are you organising a conference or an event that you would like Acros Organics to attend?Send your request [email protected] and we will get in touch with you.
Acros Organics on tourAcros Organics on tour
References1 Curran, D.P., Porter, N.A., Giese, B., Stereochemistry of Radical Reactions, VCH
Verlagsgesellschaft, Weinheim, Germany (1996), pp. 1-22.
2 Ingold, K.U., Rate constants for free radicals in solution, in: Kochi, J.K. (Ed.), FreeRadicals, Vol. I, Wiley, New York (1973), Chapter 11, pp. 37-112.
3 Rao, A.S. and Mohan, H.R., in: Burke, S.D. and Danheiser, R.L., Handbook ofReagents for Organic Synthesis, Oxidizing and Reducing Agents, Wiley,Chichester, UK (1999), pp. 84-89.
4 Kochi, J.K., Oxygen radicals, in: Kochi, J.K. (Ed.), Free Radicals, Vol. II, Wiley, NewYork (1973), Chapter 23, pp. 665-710 (a).
5 Kochi, J.K, Oxidation-reduction reactions of free radicals and metal complexes, in:Kochi, J.K. (Ed.), Free Radicals, Vol. I, Wiley, NY (1973), Chapter 11, pp. 591-684 (b).
6 Regitz, M. and Giese, B. (Eds.), C-Radikale Band E19a, Methoden der OrganischenChemie(Houben-Weyl), Thieme Verlag, Stuttgart (1989), pp. 547-548 (a).
7 Meiji Seka Kaisha, Ltd, European patent EP18415 (1982).
8 Tosoh Corp., Japanese patent JP 11130708 (1999).
9 Sumitomo Chemical Company, Ltd, European patent EP282221 (1992).
10 Regitz, M. and Giese, B. (Eds.), C-Radikale Band E19a, Methoden der OrganischenChemie(Houben-Weyl), Thieme Verlag, Stuttgart (1989), pp. 31-40 (b).
For the full review article by Meijer, Hogt and Fischer cover-
ing this as well as discussions on reactivity of organic perox-
ides and functionalization reactions with organic peroxides
you can request your free copy of Acros Organics Review 6.
Acros Organics Acta 9 - Spring 20028
34988 . . . . . . . . . . . . . . . . . . . . . . . . . .Dicumyl peroxide
34993 . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl peroxide
21178 . . . . . . . . . . . . . . . . . . . . . . . . .Dibenzoyl peroxide
36131 . . . . . . . . . . . . .1,1-Di(tert-butylperoxy)cyclohexane
34996 . . . . . . . . . . . . . . . . . . . . . . .Cumyl hydroperoxide
34974 . . . . . . . . . . . . . . . . . . . . . . . . . . .Lauroyl peroxide
34994 . . .3,6,9-Triethyl-3,6,9-trimethyl-1,4,7-triperoxonane
34977 . .1,1--Di-(tert-Butylperoxy)-3,3,5-trimethylcyclohexane
34983 . . . . . . . . . . . . . . . . .2,2-Di(tert-butylperoxy)butane
34986 . . . . . . . . . . . . . . . . . . . . . .tert-Butyl peroxyacetate
17014 . . . . . . . . . . . . . . . . . . . .tert-Butyl peroxybenzoate
34985 . . . . . . . . . .tert-Butylperoxy 2-ethylhexyl carbonate
34981 . . . . . .tert-Butyl peroxy-3,5,5-trimethylcyclohexane
34984 . . . . . . . . . . . .tert-Butylperoxy isopropyl carbonate
34989 . . . . . . . . . . . .di(tert-butylperoxyisopropyl)benzene
34991 . . . . . . . . . . . . . . . . . . . . .tert-Butyl cumyl peroxide
34990 . . . . . . .2,5-Dimethyl-2,5-di(tert-butylperoxy)hexane
18034 . . . . . . . . . . . . . . . . . . . . .tert-Butyl hydroperoxide
ORGANIC PEROXIDES FROM ACROS ORGANICS
Event name Location Country Date
Informex New Orleans (LA) USA 26 February - 1 March 2002
ACS National Meeting Orlando (FL) USA 8 - 10 April 2002
Drug Discovery Technology Stuttgart Germany 15 - 18 April 2002
Drug Analysis 2002 Brugge Belgium 21 - 25 April 2002
SECO 39 Saint Jean de Monts France 26 May - 1 June 2002
11th Fechem Conference Barcelona Spain 9 - 12 June 2002Heterocycles in Bio-Organic Chemistry
27th European Peptide Symposium Sorrento Italy 31 August - 6 September 2002
14th International Symposium on Chiralty Hamburg Germany 8 - 12 September 2002
Organic Peroxides inRadical Synthesis ReactionsJ. Meijer, A.H. Hogt and B. Fischer
Akzo Nobel Polymer Chemicals Laboratory DeventerZutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.
-
7/28/2019 Acros Organics acta N009
11/20
This report describes two procedures for the synthesis of (S)- and (R)-N-Boc--methylserinal acetonides 1 and 4.The application of both compounds as valuable chiral building blocks in the asymmetric synthesis of-methyl-amino acids 2 and 3 is also reported.
Acros Organics Acta 9 - Spring 2002 9
(S)- and (R)-N-Boc-N,O-Isopropylidene--methylserinals
Preparation and Synthetic Applications
ONBoc
CHOO
BocN
OHC RS
H2N
HO2C R
NH2
CO2HR
1 42 3
Introduction
Over the last decade, there has been sustained interest in the develop-ment and use of chiral N-protected--amino aldehydes due to their
wide utility in organic synthesis (1). While the (S)-N-Boc-N,O-isopropy-lidene serinal 5, Garner's aldehyde (2), and its enantiomer 6 are wellknown as chiral building blocks in stereocontrolled organic synthesis,it is only very recently the synthesis of their homologues 1 and 4 havebecome appreciated and their chemistry investigated (scheme 1).
In this context, and taking into account the special role that ,-dialkylamino acids have played in the design of peptides withenhanced properties, we have focused our attention on the stereose-
lective synthesis of a-methylamino acids. Indeed, (S)- and (R)--methyl derivatives 1 and 4 can be regarded as ideal precursors for thesynthesis of quaternary-methylamino acids.
Synthesis
The first synthesis (3) of the homologue of serinal 5, the (S)--methylderivative 1, was achieved on a milligram scale starting from (S)--methylserine and using a similar procedure to that described for thesynthesis of Garner's aldehyde (2).
Furthermore, we described a new and more convenient synthesis pro-cedure for (S)- and (R)--methylserinals 1 and 4 on a gram scale start-
ing from (R)-2-methylglycidol (4). Nevertheless, the best method toachieved these serinals on a multigram scale starts from the Weinrebamide of 2-methyl-2-propenoic acid (5), which is easily obtained fromthe commercially available 2-methyl-2-propenoic acid (6)- and uses astereodivergent synthetic route, that involves a Sharpless asymmetricdihydroxylation reaction (AD) (scheme 2).
The AD reaction of Weinreb amide of 2-methyl-2-propenoic acid inthe presence of AD-mix-a proceeded with excellent e.e. to yield thediol 7. The amide group of diol 7 was converted into the methyl estergroup to obtain the corresponding diol in two steps: basic hydrolysis
with LiOH/MeOH and subsequent esterification with AcCl in MeOH.This diol was transformed into its 2,3-cyclic sulfite 9 with thionyl chlo-ride (scheme 2).
O
NBocRCHO
O
BocNR
OHC RS
1: R = Me5: R = H
4: R = Me6: R = H
Scheme 1 N
OS O
O
CO2Me
OH
N3
MeO2C
S
HO
N3
CO2Me
R
S R
7
4
8
9 10
11 12
1
OSO
O
MeO2C
HOHO
SROH
OH
O
O
N
O
ON
O
O
AD-mix-AD-mix-
2. (Boc)2O, Na2CO33. DMP, BF3Et2O
4. LiAlH45. Swern
1. H2, Pd-C
1. NaN3, DMF
2. chromatography
2. AcCl, MeOH
3. SOCl2, CCl4
1. LiOH
Scheme 2
A. Avenozaa, C. Cativielab,F. Corzanaa, J. M. Peregrinaa,D. Sucunzaa and M. M. Zurbanoa
(b) Departamento de Qumica Orgnica, Instituto de Ciencia de Materialesde Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
(a) Departamento de Qumica, Universidad de La Rioja, Grupo de SntesisQumica de la Rioja, UA-CSIC, 26001 Logroo, Spain;
-
7/28/2019 Acros Organics acta N009
12/20Acros Organics Acta 9 - Spring 200210
Reaction of sulfite 9 with NaN3 in the presence of DMF as a solventgave a mixture of azido esters with a regioselectivity of 20/80 in favourto -azido ester 11. Once separated, -azido ester 11 was readilyhydrogenated in the presence of Pd-C to give the corresponding -amino ester, which was subsequently treated with (Boc)2O in a basicmedium to get the N-Boc amino alcohol. This compound was con-
verted into the corresponding oxazolidine by the use of 2,2-dimethoxypropane (DMP) with BF3Et2O and the required buildingblock (S)--methylserinal 1 was obtained from this oxazolidine in twosteps involving a reduction-oxidation sequence (26% overall yieldfrom olefin Weinreb amide, using 8 steps) (scheme 2). The otherenantiomer, the (R)--methylserinal 4, was obtained using the samestrategy described above and also starting from Weinreb amide of 2-methyl-2-propenoic acid, but changing the chiral catalytic ligand to
AD-mix- in the AD reaction (scheme 2).
Synthetic applications
In order to demonstrate that (S)- and (R)-N-Boc--methylserinal ace-tonides 1 and 4 are valuable chiral building blocks in the enantiose-lective synthesis of-methyl -amino acids, we have recently report-ed their use as starting material in the preparation of enantiomericallypure -substituted alanines by transformation of the aldehyde groupinto ethyl, vinyl or ethynyl groups. In this methodology, the oxazoli-dine ring contributes the amino acid moiety and the stereogenic cen-tre was already created in the starting material.
However, more recently we also explored the fact that this oxazoli-dine ring can behave as an excellent chiral inductor to create anothernew stereogenic centre in the asymmetric Grignard addition reactionsto aldehydes. In this way, the synthetic utility of both -methylserinals1 and 4 as chiral building blocks has been proved in the synthesis ofthe four enantiomerically pure -methyl--phenylserines.
1. Reactivity of aldehyde group without generation of newstereogenic centres
Starting from (S)--mehylserinal 1 and (R)--methylserinal 4, andusing five steps, we obtained both enantiomers of Iva 19 and 20 withan overall yield of 61% (scheme 3) (7).
Olefination of aldehyde group was carried out under salt-free Wittigconditions using methyltriphenylphosphonium bromide and potassi-um bis(trimethylsilyl)amide (KHMDS) as base, obtaining olefin 13,
which was hydrogenated using Pd-C to give oxazolidine 15. Thecleavage of the acetonide moiety of 15 was achieved using Sc(OTf)3(10 mol%) to obtain compound 17, which was converted into (R)-Iva19 as follows. It was oxidized by treatment with Jones reagent to givethe corresponding protected amino acid, which was then subjected tohydrolysis using a mixture of concentrated HCl and THF. Liberation ofthe amino acid from its hydrochloride salt was then achieved by treat-ing with propylene oxide in ethanol to furnish (R)-Iva 19 in high yield.
The enantiomer of (R)-Iva: (S)-Iva 20 was obtained using the samestrategy but starting from 4 (scheme 3).
We have also developed a methodology that offers a straightforwardroute to the synthesis of ,-unsaturated -methyl -amino acids.Indeed, we have achieved the synthesis of four interesting quaternary-amino acids in enantiomerically pure form: (R)- and (S)-vinylala-
nines 23 and 24 and (R)- and (S)-ethynylalanines 29 and 30 (7).Starting from olefin 13, we carried out acid hydrolysis, obtaining thecleavage of the acetonide moiety and the hydrolysis of the N-Boc. Thecorresponding aminoalcohol hydrochloride was then protected withBoc2O to give 21. The transformation of this compound into the qua-ternary amino acid (R)--vinylalanine 23 was achieved according tothe protocol described above to transform alcohol 17 into amino acid19. The enantiomer (S)--vinylalanine 24 was obtained using thesame strategy but starting from olefin 14 (scheme 4).
O
NBoc
O
BocN
ONBoc
EtO
BocN
Et
EtHOCH 2
BocHN
Et CH2OH
NHBoc
R S
R S
R S
Ph 3PCH3Br,KHMDS , THF
EtHO2C
H2N
Et CO2H
NH2
R S
13
17
H2/Pd-C,AcOEt
Sc(TfO)3CH3CN/H2O
15
1. Jones oxidation2. HCl (conc.)/THF
3. Propyleneoxide, EtOH
19
4
14
18
16
20
1
Scheme 3
(S)- and (R)-N-Boc-N,O-Isopropylidene--methylserinals
Preparation and Synthetic Applications
A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa
(a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain;(b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
-
7/28/2019 Acros Organics acta N009
13/20
The synthesis of (R)- and (S)--ethynylalanines 29 and 30 also startsfrom (S)- and (R)--methylserinals 1 and 4, respectively, and involvesseven steps with an overall yield of 32% (scheme 5). The aldehyde-to-acetylene conversion was undertaken in two steps using a dibro-movinyl intermediate (the Corey-Fuchs strategy). Methylserinals 1 and4 were converted into the corresponding alkynes 27 and 28, using the
vinyl intermediates 25 and 26 (scheme 5).
The conversion of compounds 27 and 28 into (R)- and (S)-ethynylala-nines 29 and 30 was achieved in the same way described above forthe preparation of amino acid 19 from alcohol 17 (scheme 5).
2. Reactivity of aldehyde group with generation of a newstereogenic centre
In order to demonstrate the synthetic utility of both -methylserinals
1 and 4 as chiral building blocks in asymmetric synthesis with gener-ation of a new stereogenic centre, we tried the reaction of thesealdehydes with phenyl nucleophiles under different conditions(scheme 6) (8).
In general, the results obtained indicate that the model proposed toexplain the diastereoselectivity observed in the nucleophile additionsis similar to that described for Garner aldehyde (9). The onlydifference observed is a significant increase of diastereoselectivity in
favor to 31.Starting from enantiomerically pure 31, which was obtained by theattack of PhMgBr on -methylserinal 1, we synthesised (2R,3R)--methyl--phenylserine 35 with an overall yield of 54% (8), using foursteps: intramolecular cyclization in compound 31, promoted by theattack of the alkoxide ion on the carbonylic carbon of the Boc groupto give the bicyclic compound 33, selective deprotection of the ace-tonide moiety of 33 by the action of BF32AcOH to give the corre-sponding oxazolidinone, subsequent Jones oxidation and acidhydrolysis. Liberation of the amino acid 35 from its hydrochloride salt
was achieved by the propylene oxide method. The diastereoisomer
(2R,3S)--methyl--phenylserine 36 was also obtained (8) startingfrom 31 but now by a different type of intramolecular cyclization thatuses triflic anhydride to give the bicyclic compound 34, with inversionof configuration at the benzylic carbon.
HO2C
H2N
CO2H
NH2
R S
HOCH 2
BocHN
R S
2. Na2CO3, Boc2O,1. HCl
H2O-THF
CH2OH
NHBoc
13
21
23
14
22
24
1. Jones oxidation2. HCl (conc.)/THF3. Propylene
oxide, EtOH
Scheme 4
O
NBoc
CHOS
ONBoc
SPh
H OH
R
O
NBoc
SPh
HO H
S1
31
32
+
phenylnucleophile
Scheme 6
Scheme 5
Acros Organics Acta 9 - Spring 2002 11
HOCH 2
BocHN
CH2OH
NHBoc
R S
R S
CO2H
NH2
R S
ONBoc
Br Br
OBocN
BrBr
HO2C
H2N
25
27
1. Jones oxidation2. HCl (conc.)/THF3. Propylene
oxide, EtOH
29
26
28
30
1. BuLi, THF, -78 C2. HCl.3. Na2CO3, Boc2O,
H2O-THF
CH Br3,tBuOK,
PP h3, PhMe
41
(S)- and (R)-N-Boc-N,O-Isopropylidene--methylserinals
Preparation and Synthetic Applications
A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa
(a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain;(b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
-
7/28/2019 Acros Organics acta N009
14/20
Using the same strategy explained to prepare amino acid 35 from 33,the amino acid 36 was obtained from compound 34 in a 43% yield(scheme 7) (8).
The enantiomers (2S,3S)- and (2S,3R)--methyl--phenylserines 40
and 41 were obtained using the same strategy described above inscheme 7, but starting from (R)--methylserinal 4 (scheme 8) (8).
Conclusion
We report a large scale and stereodivergent synthesis of the (S)- and(R)--methylserinals 1 and 4, starting from commercially available(R)-2-methylglycidol 7. These compounds have proved to be valuablestarting materials in a new approach to the synthesis of different qua-ternary-methylamino acids.
We have also developed the asymmetric synthesis of the fourstereoisomers of-methyl--phenylserines, via the highly diastereos-
elective Grignard addition reactions of PhMgBr on the chiral aldehy-des 1 and 4. Indeed, the oxazolidine ring of 1 and 4 has been exploit-ed as the precursor of the amino acid moiety and, moreover, as chiralauxiliary to create another new stereogenic centre in the asymmetricreactions.
References(1) Jurczak, J.; Golebiowski, A. Chem. Rev. 1989, 89, 149.
(2) Garner, P.; Park, J. M. Org. Synth. 1992, 70, 18.
(3) Alas, M.; Cativiela, C.; Daz-de-Villegas, M. D.; Glvez, J. A.; Lapea, Y.Tetrahedron1998, 54, 14963.
(4) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. J. Org.Chem. 1999, 64, 8220.
(5) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Sucunza, D.; Zurbano, M.M. Tetrahedron: Asymmetry2001, 12, 949.
(6) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
(7) Avenoza, A.; Cativiela, C.; Peregrina, J. M.; Sucunza, D.; Zurbano, M. M.
Tetrahedron: Asymmetry1999, 10, 4653.(8) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M.
Tetrahedron: Asymmetry2000, 11, 2195.
(9) Williams, L.; Zhang, Z.; Shao, F.; Carroll, P. J.; Joulli, M. M. Tetrahedron1996, 52,11673.
Acros Organics Acta 9 - Spring 200212
HOOC
H2N
ROH
Ph H
R
Tf2O
O
N
S
O
PhH
O
R O
N
S
O
HPh
O
S
HOOC
H2N
R
OH
H Ph
S
NaH, DMF
1. BF32AcOH2. Jones oxidation3. HCl (conc.)/THF4. Propylene
oxide, EtOH
35
33 34
36
31Scheme 7
HOOC
H2N
SOH
H Ph
S
Tf2O
ON
R
O
HPh
O
SO
NR
O
PhH
O
R
HOOC
H2N
SOH
Ph H
R
NaH, DMF
O
NBoc
R
PhMgBr
Ph
HO H
S
1. BF32AcOH2. Jones oxidation3. HCl (conc.)/THF4. Propylene
oxide, EtOH
40
38 39
41
37
4Scheme 8
16831 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methacrylic acid (2-Methyl-2-propionic acid)
15127 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acetyl Chloride, 98%
21947 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acetyl Chloride, p.a.
18977 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl dicarbonate, 97% [(Boc)2O]19467 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl dicarbonate, 99% [(Boc)2O]
15695 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyltriphenylphosphonium bromide, 98%
11563 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2,2-Dimethoxypropane, 98% [DMP]
36389 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Scandium (III) trifluoromethanesulfonate [Sc(OTf)3]
ADDITIONAL CYCLOPROPANE CARBOXYLIC ACIDS AND DERIVATIVES
(S)- and (R)-N-Boc-N,O-Isopropylidene-a-methylserinals
Preparation and Synthetic Applications
A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa
(a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain;(b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
-
7/28/2019 Acros Organics acta N009
15/20
What is green chemistry all about?
Green chemistry is all about reducing the number and amount ofharmful chemicals that are used and/or generated in research andindustry, by developing harmless, green chemicals and/or process-es. This new field is all about minimising the amount of waste till the
point where you end up with no waste at all.
Where does green chemistry stand now?
The green chemistry principle is still very much in its infancy, it hasnot yet penetrated the mainstream chemical lab in research or indus-try and is not yet part of the curriculum in the education of youngchemists.
However, there are good omens today that green chemistry is startingto pick up speed. For instance, the Royal Society of Chemistry in theU.K. now has a journal that is dedicated to this issue it is called quite
aptly Green Chemistry. The April 2002 issue will be devoted to ionicliquids, for example. In addition, papers on the subject are being wellcited, which is a good meter for the interest in the subject.
What do you think the influenceof green chemistry will be onorganic chemistry?
Well, I am pretty sure that it will revolutionise the way we are doingchemistry now. It is a new vision that creates lots of new challenges.For instance, it is much more difficult to selectively oxidise an organ-
ic substrate with O2, but it is possible, although it requires newapproaches.
Of course, it will take time. Some look at green chemistry as a veryexpensive approach, which is quite a narrow way to view the subject.Indeed, the opposite should be true. There is much more to it thanthat. If I look at the reactions I get whenever I give a lecture on greenchemistry, it gives me a feeling that we will see the interest in this mat-ter grow rapidly in the near future.
How did you get involved withgreen chemistry?
The whole concept of green chemistry comes from Prof. Paul T.Anastas of the White House Office of Science & Technology Policy(OSTP). He wrote all the key textbooks on the subject and defined theterms we currently use. Anastas is also the one who defined the 12basic principles of green chemistry. We owe him a lot.
Another person that played an important role in the development ofthis subject is certainly Professor Roger Sheldon. He is currently the
chairman of the editorial board of the Green Chemistry journal.
What does QUILL stand for?
QUILL is an acronym for the Queens University Ionic LiquidsLaboratory. It is an industry-university collaborative research centrefocusing on ionic liquids. It consists of a consortium of 20 industrialcompanies to support research on ionic liquids.
INTERVIEWwith Professor Ken Seddon
on Green Chemistry / Ionic Liquids
For a free copy of the new
Ionic Liquids Handbook, fill inthe fax form on page 16 orthe registration form on the
Internet: www.acros.com
-
7/28/2019 Acros Organics acta N009
16/20
Solid Phase Synthesis
The use of polymer supports in organic synthesis is
becoming well established as demonstrated by the
massive increase in the number of publications
referring to it.The key reported advantages
for solid-phase synthesis being faster and
simplified procedures for the genera-
tion of a large number of com-
pounds (use of automation/ ease
of purification of intermedi-
ates and products/ use of
excess starting material).
At Acros Organics, we
understand that for a
solid phase synthesis
procedure to fulfill
i t s a d v a n t a g e o u s
promises, it is crucial
to select the correct
resin matrix and link-er(s) for the reaction
under consideration. A
selection of polystyrene
and TentaGel resins for
solid phase synthesis with
a broad variety of linker
groups and narrow-range
loading capacities has been recent-
ly introduced to our stock.
Solution Phase Synthesis
Solution phase synthesis, where a reactive, functional group
specific scavenger, a reagent, a ligand, or catalyst is attached to
a polymer support, has been a fast growing area of synthesis.
This methodology takes advantage of new developments with-
in the field of solid phase synthesis and adapts them to the
existing vast repertoire of chemical reactions.A wide range of
resins for solution-phase synthesis have been introduced to
Acros Organics to respond to the needs of the organic
chemist adopting solution-phase strategies in his synthesis.
NEW RESINS FROM ACROS ORGANICSFOR SOLID SUPPORTED CHEMISTRY
A wide range of resins for Solid Phase and Solution
Phase Synthesis have been introduced by Acros
Organics.Visit www.acros.com for the latest additions.
-
7/28/2019 Acros Organics acta N009
17/20Acros Organics Acta 9 - Spring 2002 15
N CO2H.H2NBn
OH
Boc
36201
OH
36235
MeO2C NHBoc
OH36233
NHBocMeO2C
N CO2Me
OH
Boc
36200
NH
O
OO
36220
MeO2CCO2H
36208
CO2HH2N
F
3630136217
OH
NH2
CO2HFmocHN
Me
36148
We are pleased to announce that research quantities of theChiroTech product range are now available exclusively through
Acros Organics. These products can be ordered through your localAcros Organics distributor or via the internet at www.acros.com.
Through this collaboration with ChiroTech, Acros Organics is able toprovide an unmatched product offering and service level to assist youin your drug design and discovery research.
Over 182 products have been introduced to our product range, includ-ing high added value building blocks, intermediates, and advancedintermediates such as multi-functional single diastereomer scaffoldssuitable for elaboration into potential drug-like compounds.
All compounds are offered with the assurance of robust scaleableprocesses to make larger quantities of material available at minimal leadtimes as your hit compound makes it from discovery to development.
A sample of NEW functionalized cyclopentane and piperidine scaffolds
A sample of NEW building blocks and advanced intermediatesFor further information orfor any questions, pleasecontact Acros Organics [email protected]
For enquiries regarding
larger quantities of ChiroTechproducts, please contactthe ChiroTech SalesAdministrator on+44 1223 728026, ore-mail [email protected]
NEW
NEW
H
N N
O O
Co
+ +
32995
H H
N N
O O
Co
+ +
32996
References
1 Furrow, M. E.; Schaus, S. E.; Jacobsen, E. N. J. Org. Chem. 1998, 63, 6776.
2 Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science1997, 277, 936.
3 Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421.
NEW catalysts for Hydrolytic KineticResolution: (R, R) and (S, S)-(Salen)Co(III) acetate 1
Complexes 1 catalyze the kinetic resolution of racemic, terminal
epoxides. This is a highly desirable reaction leading to the formationof a chiral diol and the unreacted epoxide enantiomer.1,2,3 The Co(III) acetate complexes are generated in situ from the correspondingsalen Co (II) complexes 32995 and 32996 by reaction with 1-2 eq. ofacetic acid and exposure to air.
N N
O O
Co
OAc
+ +
(R,R) -1
H2O
OR R
O R OH
OH
+
ChiroTechisaregis
teredtrademarkofChirotechTechnologyLimited.
from Acros OrganicsNew Ligands & Catalysts
for drug discovery and researchNew offerings
To order a copy of the
new Drug Discoverybrochure, fill in the faxform on page 16 or theregistration form on theInternet: www.acros.com
New Ligands & Catalysts
New offerings
NEW
-
7/28/2019 Acros Organics acta N009
18/20
Specialty Catalogues
Acros Organics catalogue Acros Organics catalogue
on CD-Rom
Chirals CD
Substrates Neurochemicals Drug discovery Ionic liquids handbook Chirals
Magazine
Acros Organics Acta
(free subscription)
Review
New N7: A Novel Catalyst
New N8: bis(trimethylsilyl) keteneacetal reagents
N......
Organic Chemistry brochures
12 suggestions
for the Organic
Chemist
12 MORE
suggestions for the
Organic Chemist
For a free copy, fill in this fax form or the registration form on the Internet:
http://www.acros.com
+32(0)14/59.34.34FAX 1-800-926-1166FAX
NAME: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INSTITUTE/COMPANY: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DEPT.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ADDRESS: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
STATE: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
COUNTRY: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TEL.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
FAX: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
E-MAIL: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fax this form
for additional
information :
Catalogue Specialty CatalogueCatalogues on CD-ROM
(Europe & Asia) (USA only)
Solid Phase Synthesis
You will find
a list of all
available
Reviews on
the back of the
inside cover.
-
7/28/2019 Acros Organics acta N009
19/20
A selection of peptide grade reagents, formulations, and solvents
has been recently added to our product range and are listed below.
ReadyMix products are peptide grade reagents and solvents in themost popular formulations used by the peptide synthesis chemists.
They are now available from Acros Organics, in ready to use solutionsor in kits containing pre-weighed amounts of activating agents and
solvents to be mixed immediately prior to use.
Product Nr. Pack. Name Specifications
35480 0025 2.5L Dichloromethane (DCM), peptide synthesis grade. H2O (KF) max 0.005%. Residue on evaporation max 0.0005%.Free amines (Kaiser) max 0.0001%.
35483 0025 2.5L N,N-Dimethylformamide (DMF), peptide synthesis grade. Acidity max 0.001%. Water (KF) max 0.02%. Free amines (Kaiser)max 0.001%. Residue on evaporation max 0.001%. Formaldehydemax 0.002%.
35484 0025 2.5L Methyl sulfoxide (DMSO), peptide synthesis grade. Water (KF) max 0.005%. Residue on evaporation max 0.001%.Peroxides (as H2O2) max 0.001%. Free amines (Kaiser) not detected.
35486 1000 100ml 1,1,1,3,3,3- Hexafluoro-2-isopropanol (HFIPA), Water (KF) max 0.02%. Free amines (Kaiser) not detected.peptide synthesis grade. Residue on evaporation max 0.0005%.
35489 0025 2.5L 1-Methyl-2-pyrrolidone, special automatic peptide Water (KF) max 0.03%. Residue on evaporation max 0.002%.synthesizer grade. Free amines (Kaiser) max 0.001%.
UV absorbance: 285nm max 0.065 AU.300nm max 0.035 AU.325nm max 0.010 AU.350nm max 0.005 AU.
35490 0025 2.5L 1-Methyl-2-pyrrolidone (NMP), peptide synthesis grade. Water (KF) max 0.03%. Residue on evaporation max 0.002%.Free amines (Kaiser) max 0.001%.
35487 1000 100ml 1,1,1,3,3,3- Hexafluoro-2-isopropanol, 10% in Water (KF) max 0.01%.dichloromethane, ReadyMix, peptide synthesis grade.
35491 0010 1L Piperidine, 20% in N-Methyl-2-pyrrolidone, Prepared from peptide grade materials.ReadyMix, peptide synthesis grade.
35481 1000 100ml N,N'-Dicyclohexylcarbodiimide (DCC) Prepared from peptide grade materia ls .0.1M solution in Dichloromethane,ReadyMix, peptide synthesis grade.
35482 2000 200ml N,N'-Dicyclohexylcarbodiimide (DCC) Prepared from peptide grade materia ls .1.0M in N-Methyl-2-pyrrolidone,ReadyMix, peptide synthesis grade.
35485 2000 200ml HBTU 0.1M in (HOBT 0.45M in DMF) 1:1, 3 Bottles kit of pure HBTU, HOBT and DMF to be mixedReadyMix, peptide synthesis grade. prior to use to give 3.79%HBTU in [6.08%HOBT in DMF].
35488 2000 200ml HOBT 0.5M in N,N-dimethylformamide, 2 Bottles kit of pure HOBT and DMF to be mixed prior
ReadyMix, peptide synthesis grade. to use to give 6.76% HOBT in DMF.
Peptide Grade Reagents, Solvents and Formulations
Contact us for special prices and availability
Most Peptide grade solvents are available in 1l and 2.5 l bottles
Ready Mix kits: convenient pack sizes
no tedious preparation
prepared with high quality reagents
complete range of most popular mixes.
-
7/28/2019 Acros Organics acta N009
20/20
ACROS ORGANICSGeel West Zone 2
Janssen Pharmaceuticalaan 3a
B-2440 Geel, Belgium
Tel.: +32(0)14/57.52.11
Fax: +32(0)14/59.34.34
ACROS ORGANICS USA500 American Road,
Morris Plains, NJ 07950Tel.: 1-800-766-7000
Fax: 1-800-926-1166
Internet: http://www.fishersci.com(US orders only)
ACROS ORGANICS on-line
ACROS ORGANICSGeel West Zone 2
Janssen Pharmaceuticalaan 3a
B-2440 Geel, Belgium
Tel.: +32(0)14/57.52.11
Fax: +32(0)14/59.34.34
ACROS ORGANICS USA500 American Road,
Morris Plains, NJ 07950Tel.: 1-800-766-7000
Fax: 1-800-926-1166
Internet: http://www.fishersci.com(US orders only)
ACROS ORGANICS on-line
For more information, please contact your local dealer
Middle EastEgyptIsraelJordanLebanonSaudia Arabia
AfricaAlgeriaMoroccoTunisiaSouth-Africa
North AmericaUnited States
South AmericaArgentinaBrazil
ChileUruguayVenezuela
Far EastHong-KongIndiaPakistanJapanMalaysia
P.R. ChinaSingaporeRepublic of KoreaTaiwan R.O.C.Thailand
Eastern EuropeCzech RepublicCroatiaEstoniaHungaryLatviaPoland
Russian FederationSlovakiaSloveniaUkraineYugoslavia
EuropeAustriaBelgiumDenmarkFinlandFrance
GermanyGreeceItalyNorwayPortugalSpainSwedenSwitzerlandThe NetherlandsTurkeyUnited Kingdom
Australia
AustraliaNew-Zealand