Urethane substituent groups

Recently, polydiacetylenes have been discovered which are soluble in common organic solvents (12). These polymers have urethane substituent groups of the form... 

These polydiacetylenes are soluble in common organic solvents, such as CHCI3, due to the high entropy content of the complicated urethane substituent groups. The discovery of these soluble polymers has lead to a number of interesting developments the first determination of the chain length in a polydiacetylene, [about 1000 repeat units for both polymers(2)], characterization of the chain dynamics for polydiacetylenes in solutlon(3), discovery of the remarkably strong two photon absorption now known to be characteristic of the polydiacetylene backbone(4), and discovery of a conformational transition in the polymer solutions, referred to as a "visual conformational transi-tlon"(1). 

The decrease in rate after 50% reaction is quite apparent in the reaction of tolylene diisocyanate with the polyester at 29°C (Fig. 11). This change in rate illustrates the reduced reactivity of the 2-position isocyanate group, having steric hindrance from the ortho methyl substituent, as well as the lesser activating influence of a meta urethane substituent compared to a meta isocyanate substituent. An increase in reaction temperature favours the slow reaction more than the fast, as would be expected if differences in activation energy accounted for at least part of the difference in rates. Thus at 100°C there was little decrease in rate of reaction with TDI. In the case of 4,4 -diphenylmethane diisocyanate (Fig. 12), there was little change in rate after 50% reaction at any of the temperatures studied. 

The nature of the aromatic substituents is apparently not critical for SSRI activity, as indicated by the structure of duloxetine (23-5), where one ring is replaced by thiophene and the other by naphthalene. The synthesis starts as above by the formation of the Mannich base (23-1) from 1-acetyl thiophene with formaldehyde and dimethyl-amine. Treatment of that intermediate with the complex from lithium aluminum hydride and the 2R,3S entantiomer of dimethylamino-l,2-diphenyl-3-methyl-butane-2-ol gives the S isomer (23-2) in high enantiomeric excess. Treatment of the aUcoxide from (23-2) and sodium hydride with 1-fluoronaphthalene leads to the displacement of halogen and thus the formation of ether (23-2). The surplus methyl group is then removed by yet another variant of the von Braun reaction that avoids the use of a base for saponifying the intermediate urethane. Thus, reaction of (23-3) with trichloroethyl formate leads to the A -demethylated chlorinated urethane (23-4). Treatment of that intermediate with zinc leads to a loss of the carbamate and the formation of the free secondary amine duloxetine (23-5) [23]. 

On the other hand, the group of No wick [29] developed polyurea templates with the general structure 35 in order to nucleate parallel /1-sheet structures. They reported that in a model compound (36) the urethane carbonyls are hydrogen bonding to the adjacent NH and that the orientation of the bonding interactions is controlled by the size of the end substituent, in this case a phenyl group. They also recently prepared 37 and showed by NMR that it adopts mostly the proposed parallel /1-sheet conformation in chloroform [30]. 

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