Synthesizing a bifunctional

Figure 2. Synthesizing a bifunctional chelating agent from an amino add. In this case, lu-nitrophenylalanine was prepared by nitrating the aromatic ring of L.-phenylalanine. The illustrated steps then lead to the alkylating agent (S)-l -(v>-bromoacetamidobenzyl)-EDTA, which can be attached to bleomycin as shown in Figure 2 (4).

Stadler and coworkers [45] synthesized a bifunctional, or bola form, polyoxyethylene sterol derivative (Fig. 5). This compound was designed as a prototype for a new class of compounds intended to serve as functional equivalents to the antibiotic drug amphotericin B. Analysis of the surface pressure-area isotherm, at the air-water surface, indicated a limiting area of about. 0.60 nm per molecule. This value was consistent with a model in which... 

Heitz reacted low molecular weight PPO with trioxane in the presence of BFj and was able to synthesize a bifunctional PPO 15 by reaction at the terminal phenyl groups. (Scheme 7)... 

Recently, the above mentioned model reaction has been extended to polycondensation reactions for synthesis of polyethers and polysulfides [7,81]. In recent reports crown ether catalysts have mostly been used in the reaction of a bifunctional nucleophile with a bifunctional electrophile, as well as in the monomer species carrying both types of functional groups [7]. Table 5 describes the syntheses of aromatic polyethers by the nucleophilic displacement polymerization using PTC. 

Moreover, Kim and coworkers have shown that a-amino-butyrolactones can be synthesized by a related process employing the amino acid homoserine with an unprotected hydroxy functionality [31]. In a more recent publication by the same research group, morpholin-2-one derivatives of type 9-37 have been prepared (Scheme 9.6) [32]. Herein, glycolaldehyde dimer 9-32 acts as a bifunctional compound, which first reacts with the a-amino acids 9-33 to give the iminium ions 9-34,... 

Sato, S., and Nakao, M. (1981) Cross-linking of intact erythrocyte membrane with a newly synthesized cleavable bifunctional reagent./. Biochem. (Tokyo) 90, 1177. 

Cho et al. describes an alternative synthesis (Scheme 20) of the 2,5 DKP scaffold 92 = 123 via a bifunctional dipeptide 120, an aldehyde 121, and an isocyanide 122 [42]. These commercially available starting materials were added in equimolar amounts to trifluoroethanol at 40°C under nitrogen. The reaction was brought to room temperature and allowed to complete. The standard Ugi workup was used followed by column chromatography. Yields were shown in the range of 21-87%. When this reaction was done in a microwave, time taken for the reaction to complete was decreased significantly and yields increased by a factor of 4. The substitution pattern of this and the previously described (in Scheme 15) are identical however, the reactions use different types of starting materials, for example, dipeptide vs. N- and C-protected amino acids. Thus different stereochemical outcomes can be expected for the two syntheses. 

Lu and coworkers have synthesized a related bifunctional cobalt(lll) salen catalyst similar to that seen in Fig. 11 that contains an attached quaternary ammonium salt (Fig. 13) [36]. This catalyst was found to be very effective at copolymerizing propylene oxide and CO2. For example, in a reaction carried out at 90°C and 2.5 MPa pressure, a high molecular weight poly(propylene carbonate) = 59,000 and PDI = 1.22) was obtained with only 6% propylene carbonate byproduct. For a polymerization process performed under these reaction conditions for 0.5 h, a TOF (turnover frequency) of 5,160 h was reported. For comparative purposes, the best TOF observed for a binary catalyst system of (salen)CoX (where X is 2,4-dinitrophenolate) onium salt or base for the copolymerization of propylene oxide and CO2 at 25°C was 400-500 h for a process performed at 1.5 MPa pressure [21, 37]. On the other hand, employing catalysts of the type shown in Fig. 12, TOFs as high as 13,000 h with >99% selectivity for copolymers withMn 170,000 were obtained at 75°C and 2.0 MPa pressure [35]. The cobalt catalyst in Fig. 13 has also been shown to be effective for selective copolymer formation from styrene oxide and carbon dioxide [38]. 

The only report on chemoenzymatic synthesis of branched polymers is from Peelers et al. [58], Heterotelechelic PCL macroinimer was synthesized in a one-pot enzymatic procedure by using 2-hydroxyethyl a-bromoisobutyrate as a bifunctional initiator. A polymerizable endgroup was introduced by subsequent in sim enzymatic acrylation with vinyl acrylate. Synthesis of branched polymers by self-condensing ATRP of the macroinimers was successfully conducted with and without the addition of MMA as a comonomer. 

When macrocycle 65 is synthesized, the in/out isomer of [2]catenane 79 is also formed in 11% yield (Figure 29) [46]. A first attempt to methylate both sulfonamide groups by treatment of the DMF solution of 79 with iodomethane and potassium carbonate was successful. By bridging the two sulfonamide units with a bifunctional alkylating reagent, we were able to synthesize the first pretzel-shaped molecule [54]. Considerations of the X-ray structure analysis of amide-linked catenanes [16] and CPK models led to the diiodo compound 95 as a suitable brid-... 

A better, higher yielding approach for the preparation of templates attached to different peptides employs a combination of solid-phase and solution-phase couplings (Scheme ll).121 A peptide chain is synthesized on a low-loading benzhydrylamine resin and reacted with a bifunctional electrophile such as the bis(pentafluorophenyl) ester 4 (R1 = Pfp) (low resin... 

These reactions are particularly useful if a polymer with two (or more) living ends is formed, since a bifunctional (or polyfunctional) polymer formed may be then used to synthesize block polymers via condensation reactions. Interesting examples of such materials have been obtained and the usefulness of this technique is amplified by the fact that each block can be made uniform in size. Of course, living polymers endowed with two active ends can be used directly in such a condensation reaction, if a bifunctional killing agent is added. Examples of such reactions are given in a Thesis by Waack (41) and in a recent publication by Rempp and Stockmayer (42). 

Let us apply Eq. (3.86) to phenol - formaldehyde polymers synthesized in an acid medium with a phenol excess (novolacs). Phenol is a trifunctional reactant (A3), the functional groups being the aromatic hydrogens located in positions 2, 4, and 6 of the phenolic ring. Formaldehyde acts as a bifunctional monomer (B2), forming methylene bridges between the reactive positions of phenol. Novolacs are synthesized with a phenol excess, such that gelation does not occur at full formaldehyde conversion. From Eqs (3.83) and (3.86), we obtain... 

The Shibasaki group developed a broad range of asymmetric catalytic syntheses using bifunctional catalysts. For excellent reviews, see (a) M. Shibasaki in Stimulating Concepts in Chemistry (Eds. F. Vogtle, J. F. Stoddart, M. Shibasaki), John Wiley and Sons, New York, 2000, p. 105-136 (b) M. Shibasaki, N. Yoshikawa, Chem. Rev. 2002, 102, 2187-2210. 

Macromonomers with two methacrylate functionalities (MA-PIB-MA) at both ends of the PIB chain have also been synthesized, by a procedure essentially identical to that reported above, but starting with a bifunctional initiator in the polymerization of IB [103]. Free radical copolymerization of the resulting MA-PIB-MA with 2-(dimethylamino)ethyl methacrylate resulted in amphiphilic networks, with a wide range of mechanical and swelling properties. 

The environmental and economical benefits of one-pot catalytic fine chemical syntheses, in which various successive chemical steps are accomplished in the same reaction vessel, generally over a bifunctional (or multifunctional) catalyst, are obvious. The reduction in the number of synthetic and separation steps has various positive consequences environmentally more sustainable processes (higher atom economy and lower environmental factors), lower operating costs, lower production of wastes and in general an improvement in the safety conditions.[1 31 The environmental advantages are still more remarkable when the transformation of renewable raw materials, such as mixtures of natural terpenes or carbohydrates are concerned. 

A highly original aim, synthesizing a supramolecular cube, was realized by Thomas and co-workers [13] who linked metal corners with bifunctional, rigid, linear spacers. The complete the metals coordination environment the corners were capped with [9]ane-S3 macrocycles. There is a central cavity but it is too small to encapsulate molecules of the size of proteins or genetic material. 

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