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Preparation of Labeled Aldehydes and Ketones from Enamides.

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[2] R. Breslow. R. J. Corcoran, 8. B. Snider. R. J. Doll, P. L. Khanna, R. Kaleya,
J . Am Chem. Sac. 99. 905 (1977).
[3] C Hqfle. W Sreglich, Synthesis 1972, 619.
I41 Eutectic mixture of biphenyl and dibenzofuran.
[5] S. A. SzpilfoRel. V. Cerris. Recl. Trav. Chim. Pays-Bas 74. 1462 (1955).
Preparation of Labeled Aldehydes and Ketones from
By Bernard T. Golding and A h Kee Wong[*l
Full exploitation of I70-NMR spectroscopy['] in mechanistic organic chemistry requires efficient, simple methods for
the synthesis of I70-labeled compounds. The classical method for labeling aldehydes and ketones with 1 7 0 or I8O is
based on their reversible hydration['l. However, to obtain by
this method aldehydes or ketones with the atom percentage
of labeled oxygen approaching that of the water used, either
a large excess of labeled water or repeated exchange is required. Several methods have been described in which an aldehyde or ketone is converted into a derivative which can be
hydrolyzed with a stoichiometric amount of water. Suitable
derivatives are a c e t a l ~ ldithioketal~''~,
and a m i n a l ~ ' ~ ~ .
tone was shown to be equivalent to that of the water used (IR
spectroscopy as well as reduction with LiA1H4 and derivatization with cu-CloH7NC0to an cu-naphthylurea that was examined by mass spectrometry).
The advantages of this method for synthesizing labeled aldehydes and ketones are that the precursor enamides (3) are
easy to prepare"' and can be stored (under N2, - 20 "C) until
hydrolysis is effected; the by-product of hydrolysis, Nethyl(or N-benzyl)benzamide, is easy to separate and does
not catalyze further reactions of the aldehyde or ketone'l'l;
pure aldehyde or ketone is readily obtained in acceptable
yield; if desired, oxygen-labeled alcohols (e.g. [ 'XO]-l-pentanol) can be obtained by addition of LiAlH4 to the solution of
(1*) in ether, after filtration of N-ethylbenzamide.
Benzaldehyde reacts with EtNH2/KOH to give N-benzylidene-ethylamine, which with benzoyl chloride gives the adduct PhCHCl-N(Et)-COPH.
This adduct was directly hydrolyzed with 1 equivalent [lXO]water(23 atom-% " 0 ) to
benzaldehyde and N-ethylbenzamide. Extraction of benzaldehyde with ether and final purification by Kugelrohr distillation gave 23 atom-% [ "O]benzaldehyde (86%).
R' H
R' H
R' H
Educt (1)
To (3a) in dry ether (2 ~ m ' / l O - ~mol) was added 1 mol
equiv. 31 atom-% [170]water(BOC Ltd. Prochem) and 0.05
mol equiv. HCl (soln. in ether). The hydrolysis was followed
by TLC and after 2 h/room temperature, diisopropylaminomethyl polystyrene (2 g/mmol HC1) was added. Filtration
and partial evaporation caused crystallization of N-ethylbenzamide which was filtered off. The filtrate was concentrated
and processed by preparative GLC (20% DEGS/chromosorb
WHP, 130 "C) to give ["Olpentanal (la') (52%); IR: v = 1697
(G.lxO), 1711 (C-:Oi7) and 1720 cm-' (rel. int. cu. 5 : 3 : 2 ) ;
54.24-MHz I70-NMR (CDC1,): 6 = 582.9 (relative to external 1:1 H20-D20).
Received September 8, 1980 [Z 650 IE]
German version: Angew Chem 93. 93 (1981)
CAS Registry numbers:
[a] (3e) IS a mixture of (3e') top row and (3e") (bottom row).
We have found a convenient, efficient method for preparing oxygen-labeled aldehydes and ketones based on the hydrolysis of enamides (3). N-alkylideneethylamines (obtained
by treating an aldehyde or ketone with EtNH2/KOH)@]or
N-alkylidenebenzylamines (2d), (2e) (from ketone + benzylamine/3A sieves in CH2Clz)[71
are allowed to react with benzoyl chloride/triethylamine181in ether [(2a)-(2c)] or haloalkaneslyl to give enamides (3a)-(3e). These derivatives are
quantitatively hydrolyzed to their parent aldehydes or ketones ( I ) and N-ethyl(or N-benzy1)benzamide by one equivalent of water in ether or haloalkane containing 0.05 mol-%
HCl. The use of [170]- or [I'OIwater in this procedure with
(la) and ( l c ) gives unlabeled N-ethylbenzamide (analysis by
mass spectrometry) and labeled pentanal (la*) or cyclopentanone (lc'). The extent of labeling of the aldehyde or ke('1 Dr. 8. T. Golding, Mr. A. K. Wong
Department of Chemistry and Molecular Sciences
University of Warwick
Coventry, C V 4 7AL (England)
We thank the British Council for an award to A. K. W. Thanks are also due
to Dr. J Srhreiber. ETH Zurich for a gift of diisopropylaminomethylpoly-
Angew. Chem. Inr. Ed. Engl. 20 (1981) No. I
(la), 110-62-3; (Ib). 75-07-0 ( l c ) , 120-92-3; (Id). 108-94-1: (le). 591-78-6; (la)'
("0).75961-85-2; (la)' ("0).75961-86-3; (lb)' ("0).1632-96-8; (IbJ' ("0).
3752-37-2; ( I t ) * ("0).75961-87-4; ( I t ) ' ("0).
27491-23-2; f / d ) *("0).7596188-5; (Id)* ("0).
73007-69-9 (le)' ("0).
75961-89-6: f i e ) * ('"0).75961-90-9:
(20). 10599-76-5; (26). 1190-79-0; ( 2 ~ )54966-05-1;
(Zd), 4471-09-4; (2e). 6345902-9; (3a), 75961-91-0; (36). 75961-92-1; (3c). 75961-93-2; (3d). 30312-24-4; (3e).
75961-94-3; N-ethylbenzamide, 614-17-5; N-benzylbenzamide. 1485-70-7; benzoylchloride. 98-88-4; ethylamine, 75-04-7: benzylamine, 100-46-9
[I] W. G. Klemperer, Angew. Chem. 90, 258 (1978): Angew. Chem. Int. Ed.
Engl. 17. 246 (1978); J. K. Crandall. M. A . Cenreno, S. Bdrresen, J. Org
Chem. 44. t 184 (1979).
121 M. Cohn, H. C. Urey, J . Am. Chem. SOC.60, 679 (1938); H. Dahn. H . - P .
Schlunke, J. Temler, Helv. Chim. Acta 55. 907 (1972).
[3] C. B. Sawyer, J. Org. Chem. 37, 4225 (1972); D. P. Higley. R. W Murray, J .
Am. Chem. Sac. 98,4526 (1976).
141 M. Hojo. R. Masuda. K. Hakorani. Tetrahedron Lett. 1978. 1121
[5] Yu. A. Slrepikheev, L. V. Koualenko. A. B. Balalina, Zh. Obshch Khim. 46.
2468 (1976).
[6] A. I. Ferell, H. Feuer, J. Org. Chem. 43,497 (1978); A. 0. Bedenbaugh, J. H.
Bedenbaugh, J. D. Adkins, W. A . Bergm. ibid. 35, 543 (1970).
[7] Cf. K. Taguchi, F. H Westhermer, J. Org. Chem. 36, 1570(1971).
181 H . Breederveld, Recl. Trav. Chim. Pays-Bas 79. 1197 (1960).
[9] Formation of enamides (30)-(3c) takes place rapidly on addition of ben-
zoyl chloride in ether to a mixture of (20)-(2c) + triethylamine in ice-cold
ether. After filtration of triethylammonium chloride, the filtrate IS concentrated and distilled to give (3a)-(3cJ as colorless/pale yellow oils, whlch
were characterized by their 'H-NMR spectra, mass spectra and by combustion analyses. The formation of (3d) and (3e) from (2d) and (2e) was followed in an NMR tube (solvent CDCll or CCI,).
0 Verlag Chemie, GmbH, 6940 Weinheim, 1981
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1101 We have investigated the hydrolysis of (2) with I equivalent each of water
and HCI as a route to labeled aldehydes and ketones. For aldehydes (e.g.
pentanal) this method is unsatisfactory because of competing aldol condensation. However, the N-ethyliminium hydrochloride of camphor is a satisfactory precursor of oxygen-labeled camphors.--The N-ethylimine of camphor does not react with benzoyl chloride/Et,N in CHCI, at room temperature over several days.
Polymer Model Membranes'"'
By Akira Akimoto, Klaus Dorn, Leo Gros,
Helmut Ringsdorf, and Hans Schuppl'l
The synthesis of stable model membranes which can be
used to study biological processes, for instance cell recognition or cell-cell-interaction, has been a scientific goal for a
long time"]. Especially liposomes-artificial, spherical particles with a bimolecular membrane and an aqueous interior-serve as models for biological membranes; however,
they show a significantly decreased stabilityI21.
To stabilize synthetic double layers Khorana et
synthesized lipids carrying photoreactive groups and could
prove a crosslinking of membrane components. Another
method to stabilize model membranes providing an even
broader scope of possible applications is the polymerization
of lipid-analogous
(Scheme 1).
by adding natural phospholipids the properties of biological
membranes can be imitated to an even greater extent.
The different possibilities shown in Scheme 1 have all
been realized. So far only a few contributions have appeared
in the literature: acrylate and diacetylene systems have already been described by
and by Regen et al.
et al.ISbl,and O'Brien[S'l. Due to the conjugated double bonds
of the polymer chain resulting in a rather rigid conformation
in poly(diacety1ene) compounds no phase transition temperature can be observed, in contrast to biological memb r a n e ~ [ ~ New
~ . ~ ~monomer
systems for the polymerization
according to Scheme 1 are collected in Table 1.
Table 1. Polymerizable and liposome forming lipid analogues Type (a)-(d). cf.
Scheme 1. R=CH2=C(CH,)-C0.
Scheme 1. Possible preparation of polymer model membranes (x = polymerizable
group). (a-c): polymerization preserving head-group properties; d: polymerization preserving chain mobility (Monomer examples, see Table 1).
All four possibilities in Scheme 1, however, alter the physical properties of the membrane: polymerization in the hydrophobic part of the monomers (examples a-c) especially influences the phase transition temperature, while polymerization in the hydrophilic moiety changes the headgroup properties. Nevertheless, in our opinion, the properties of biological membrane systems can be thoroughly achieved by making the right choice of polymerizable groups. Furthermore,
[*]Prof. Dr. H. Ringsdorf, Dr. A. Akimoto, Dip].-Chem. K. Dorn,
Dip1.-Chem. L. Gros, DipLChem H. Schupp
Institut fur Organische Chemie der Universitat
J.-J.-Becher-Weg 18-20, D-6500 Mainz 1 (Germany)
[**I Polyreactions in Oriented Systems, Part 23.-Part 2 2 H. Koch, H. Ringsdorf. Makromolek. Chem. Commun., in press.
0 Verlog Chemre, GmbH, 6940 Weinheim, 1981
M.p. ["C]
The spreading and polymerization behavior of the monomers were investigated at the gas-water interface. The pressure-area diagrams of compounds (3) and (4) qualitatively
resemble those of the corresponding diacetylene derivatives[6"1. However, they already show a liquid-analogous phase
at substantially lower temperatures. The pressure-area diagram of (5) shows a solid-analogous phase at 2 "C, and a liquid-analogous film with transition to a solid phase at 25 "C
(Fig. la).
In contrast to the diacetylenes, which react only topothe butadiene and acrylic derivatives can be
polymerized by UV light at any temperature in the solidanalogous as well as in the liquid-analogous phase. The polymerization can be followed by measuring the contraction of
the film. The pressure-area diagrams of the polymers show a
steeper slope corresponding to the closer packing of the monomer units. This is shown for the butadiene derivative (5)
(Fig. la) and the acrylic system (13) (Fig. lb).
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Chem. I n ( . Ed. Engl 20 (1981) No. I
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preparation, aldehyde, ketone, labeled, enamides
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