N-allyl derivatives

The allylation of thiadiazole-2-thione 114 with ally 1 bromide gave as the main product the N-allyl derivative 115 with trace amounts of the corresponding S-derivative 116 (Equation 36) <2003CHE228>. Furthermore, it was shown that refluxing the thiadiazole 116 in DMF (3h) gave thiadiazole-2-thione 115 via a thio-Claisen rearrangement. 

Homologation of the N-substituent beyond ethyl generally abolishes activity (22). N,N-dialkylation does not lead to active compounds, even with 3,4-meth-ylenedioxy substitution (197). It should be noted, however, that only a few N,N-dialkyl compounds have been clinically evaluated. N-alkylation also decreases in vitro serotonin receptor affinity (80). Certain N-propyl, N-cyclopropylmethyl, and N-allyl derivatives show weak antagonism against mescaline-induced disruption of swimming behavior in mice (50). 

A similar series of reactions has given the N-allyl derivative (206) of neoechinulin B [87JCS(P1)2473]. However, conversion of this to neoechi-... 

Friedman, A.H., Smith, C.M. 1957 Comparison of the Effects of Tropyl Bensllate and Its N-allyl Derivative with those of Atropine J. Pharmacol. Exp. Therap. 119 147. 

FIGURE 20.21 N-allyl derivatives of hydantoin, thio-hydantoin and dibenzazepine. 

The titanium (Il)-alkene complex reacts with the A-propargylated anthranilic acid derivative to provide the quinolinone 37 <97JA6984>. The reaction also works well with N-allyl derivatives giving the cyclopropyl-fused tetrahydroquinoline. 

As in the ease of eatalytic hydrogenation of an IbP N-allyl derivative into an IbP A-n-propyl, the reduction of an A-isopropylidene substituent in 2-oxo IbP and IcP using hydrogen and palladium led to the formation of the corresponding A-iso-propyl derivatives (69RZC573, 71JHC797). 

Recently a great deal of attention has been focused on the oxymorphone series (III) of morphine derivatives with an axial OH substituent on the C14 position of hydro-morphone. One reason for this interest is that the N-allyl derivative in this series, naloxone (IIIB) has been found to be a pure antagonist, much more potent than its morphine analogue, nalorphine (IB) and with more morphine-like, rather than nalorphine-like side effects and low addiction capacity. The addition of an OH group on Cl4 also causes an apparent two-fold increase in potency from hydromorphone to oxymorphone. Similarly, a six-fold increase in apparent analgesic potency is observed in going from hydrocodone (IIB) to oxycodone (IIIC) [1]. 

However, inspite of such a wide application field, the assortment of used water-soluble polymers is limited. Therefore, a task of creation of the new types of water-soluble polymers based on available raw material, is a quite topical one. N-allyl derivatives of hydrazine, a product requiring utilization, are promising from this point of view. 

The conventional methods for the synthesis of N-vinyl nitrogen-containing heterocycles have been covered in monographs [96,107-109] and reviews [93,95] and involve either dehydration of p-oxyethyl compounds [92,94,458-461], dehydrohalo-genation of haloethyl derivatives [462,463], or the vinylation of NH heterocycles with acetylene [93,95,96,109], vinyl chloride [95,464,465], vinyl bromide [466], dihaloal-kanes [467-469], and vinyl ethers [470]. All these processes have been used mainly for carbazole. Sirotkina et al. have successfully elaborated efficient methods for the preparation of N-vinylcarbazoles via isomerization of N-allyl derivatives [471] and catalytic decomposition of available N-(l-alkoxyalkyl)carbazoles [472]. The credit for the systematic development of direct methods for vinylation of various NH heterocycles, including indole, with acetylene is given to Skvortsova et al. [93,473,474]. 

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