Prototypical aniline

In a departure from the prototype molecule, the benzylpiperi-done is first converted to the corresponding aminonitrile (a derivative closely akin to a cyanohydrin) by treatment with aniline hydrochloride and potassium cyanide (126). Acid hydrolysis of the nitrile affords the corresponding amide (127). Treatment with formamide followed by reduction affords the spiro oxazinone... 

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

Preparation of the prototype drug departs from the phenylenediamine strategy used in all of the previous examples. Condensation of thiazolo nitrile (53-2) with aniline catalyzed by aluminum chloride affords the amidine addition product (53-3). This is then converted to its reactive A -chloro derivative (53-4) by reaction with sodium hypochlorite. Treatment of that intermediate with a base such as potassium hydroxide leads directly to the cyclization product and thus the benzimidazole thiabendazole (53-6) [56]. The reaction can be rationalized by invoking as the first step the abstraction of chloride to leave behind a nitrene species such as (53-5) this would then readily insert in the CH bond at the ortho position. 

Figure 11.2. The SHMO frontier orbitals of aniline, benzaldehyde, and styrene as prototypes of X -, Z-, and -substituted benzenes.

Cyclisation of ortft(9-(2-oxoalkyl)-anilines by simple intramolecular condensation with loss of water, occurs spontaneously. There are several ways of generating the intermediate amino-ketone, or its equivalent the prototype is the Reissert synthesis. 

Displaying remarkable molecular inventiveness, Butin and colleagues parlayed their basic reaction into a number of novel indole ring constructions (Scheme 2). The novel azulenio[7,8-h]indole salts 7 can also be obtained from the NH anilines corresponding to acetanilides 6 [3, 4], Bis-furans 6 were synthesized from u-nitrobenzaldehydes and two equivalents of furans [4], In a variation of the prototypical synthesis, Butin found that the installation of... 

The commercial preparation of ammonia is accomplished in huge quantities by the Haber process [Equation (16.12)], discussed in Section 16.4 under Nitrogen Fixation. In the laboratory the most common preparation is the treatment of ammonium salts with strong bases, as represented in Equation (16.13).The self-ionization of liquid ammonia (analogous to that of liquid water) is shown in Equation (16.14). NH3(/) is often used as a nonaqueous solvent. As shown in Equation (16.15), NH3 acts as a weak base in water and serves as a prototype for a number of nitrogen-containing bases such as methylamine, pyridine, and aniline, which you may recall from studying acid-base equilibria in earlier courses. 

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