Aldehydes Bis

A completely different kind of macro cycle, a calix-salen type macrocycle, was obtained in good yield by microwave irradiation of various dialdehydes and diamines [165]. This was the first example of a calix-type synthesis under microwave conditions and without the presence of a metal template. An example of a [3 -1- 3] cyclocondensed macrocycle 265, obtained from a bis aldehyde and a chiral diamine is reported in Scheme 97. 

The synthesis of quadrupolar chromophores has also been achieved from 2,6-DTT-dicarboxaldehyde 117. Push-push (i.e., bis-donor) compound 118 was prepared via a double Wittig reaction carried out under solid-liquid phase transfer conditions. Pull-pull (i.e., bis-acceptor) compounds 119 were obtained from a symmetrical bis-aldehydes via a double Horner-Emmons-Wittig condensation (Scheme 9) <2002SM17, 1999CC2055>. 

Many synthetic routes have been developed to access the saturated oxazolo[3,2- ]pyridine ring system. Among those, the most efficient ones rely on a similar strategy starting from an amino alcohol 360 and a bis-electrophile 361, the latter being either a bis-aldehyde, a keto-ester, a chloro-ketone, or a chloroalkyne (Scheme 96). Among these electrophiles, the first two have demonstrated their utility and generality over the years and have been used for the preparation of many saturated oxazolo[3,2- ]pyridines 362. 

Amino groups on proteins may be reacted with the bis-aldehyde compound glutaraldehyde to form activated derivatives able to cross-link with other proteins. The reaction mechanism for this modification proceeds by one of several possible routes. In the first option, one of the aldehyde ends can form a Schiff base linkage with e-amines... 

Numerous bis-aldehyde reagents have been used for the conjugation of biomolecules. Nearly every small organic compound containing two aldehyde groups has been at... 

Glutaraldehyde is the most popular bis-aldehyde homobifunctional cross-linker in use today. However, a glance at glutaraldehyde s structure is not indicative of the complexity of its possible reaction mechanisms. Reactions with proteins and other amine-containing molecules would be expected to proceed through the formation of Schiff bases. Subsequent reduction with sodium cyanoborohydride or another suitable re-ductant would yield stable secondary amine linkages (Chapter 2, Section 5.3, and Chapter 3, Section 4). This reaction sequence certainly is possible, but other cross-linking reactions also are feasible. 

Simple iridoids are volatile iridoids of which the best known is the cat-exciting nepetalactone (C5 C50L) from Nepeta cataria (catnip) (Lamiaceae). The lactone nepetalactone, the hemiacetal neomatatabiol (G51G50H), iridodiol (in the ring opened bi-aldehyde... 

More rational syntheses of related fiiran-containing systems involve the condensation of bis-ylides with bis-aldehydes. The simplest such approach involved the condensation of 2,5-diformylfiiran (169) with o-xylylene-bis[triphenylphosphonium bromide] (170) under basic conditions. The result was the production of three isomers of the formal 2 + 2 condensation product (Scheme 27) [146]. Irradiation of the three isomers 171-173 gave a single new isomer 174. Compound 174 may also be generated by the reaction of the bis-ylide 170 with 175 (Scheme 28) [147]. 

Exchange reactions with amines and thiols (X = N, S in Fig. 156) are the most studied (see below) however, interesting C-alkylations, - based on the rather unusual replacement by bis-aldehyde (402, Fig. 157) to give poly( 5-diketone)s 403, have also been performed. 

Fig. 157. Polycondensation reaction between bifunaional Mannich base and bis-aldehyde.

Reductive procedures are seldom sufficiently specific to give high yields of pure aldehydes, and so it is customary to reduce an ester function with lithium aluminium hydride to hydroxymethyl and then reoxidize [11]. A range of 1-substituted 4,5-dicarbethoxyimidazoles have been reduced to the 4,5-bis(hydroxymethyl) derivatives in 50 88% yields oxidation to the bis-aldehydes is reported with 35-45% efficiency [8]. 

First careful studies on benzylic alcohols indicates that it is possible to oxidise stepwise with high selectivity to the aldehyde and then to the ketone. For example oxidation of bis-hydroxymethylguaiacol (precursor for trimethoxybenzaldehyde) can be selectively stopped at the bis-aldehyde stage or pursued to the carboxyvanillin as depicted in Scheme 6.14... 

An important achievement is the synthesis of optically active fusicoccane, in which the key reaction is cyclization of the bis aldehyde (69). 118 Ring closure of the cobalt complex propargyl derivative (70), involving reaction via a cobalt stabilized carbocation gives access to eight-membered rings117 which are also the product of the nickel(0) catalysed [4+4]cycloaddition of the tetraene (71).118... 

In contrast to the sequential introduction of bridging straps, Weiser and Staab used a one-step synthesis to prepare a porphyrin sandwiched between two parallel quinone units. Thus, condensation of the bis-aldehyde 252 with pyrrole in refluxing propionic acid yielded a mixture of oligomers and polymers, and three doubly-strapped porphyrins. The desired cross trans-linked porphyrin, obtained in 0.1%, was easily identified by its characteristic symmetric H-NMR spectrum. Demethylation and oxidation then yielded the desired bis-quinone porphyrin 253 (Scheme 76). 

A couple of additional efforts warrant comment. The reaction between trifluoromethyliodide and 2,5-dimethoxythiophenol should have produced 2,5-dimethoxyphenyl trifluoromethyl sulfide, but it didn t produce anything. And one more. What about a bare thio group at the 4-position in this 2C-T-family Maybe this can be protected through everything as the disulfide, and be reduced at the last step The disulfide, 2,5-dimethoxyphenyl disulfide (see under 2C-T-15) was aimed towards the needed bis-aldehyde with phosphorus oxychloride and N-methylformanilide, but all that came out of this were black oils and tars. This has also been abandoned for now. 

The double hydroformylation reaction was carried out under standard conditions and the bis-aldehyde-azide 53 was obtained in a yield of 76% (Scheme 21). The hydrogenolysis of the azide followed by deprotection of the primary alcohol using TBAF enabled the synthesis of (+)-lupinine with an overall yield of 15% in eight steps. 

Synthesis. The most facile synthetic scheme found for making the accordion polymers involves a Knoevenagel condensation polymerization of two precursors. One is a bis-aldehyde precursor which will form the electron-donating ends of a pair of linked chromophores, e.g. ... 

From Diazo Compounds. Addition of diazomethane or its substituted derivatives to double bonds is a standard approach for the preparation of cyclopropyl compounds. Pyrazolines may be intermediates in such reactions, but are often decomposed in situ without isolation. An example is the addition of diazomethane to the bis-ketal (92). The initially formed pyrazoline extrudes nitrogen at 450 C to give the cyclopropane (93 93%) which can be converted into the bis-aldehyde, or pyrolysed to ring-opened (94) and ring-expanded (95) products, ... 

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