Diazotization activation

FIGURE 3.16 Schematic representation of (a) carbamylation and thiocarbamylation reactions, (b) four-component condensation reaction, and (c) diazotization activation. 

Adsorption or glutaraldehyde cross-linking onto activated carbon reaction with diazotized activated carbon derivatives carbodi-imide mediated reaction with activated carbon... 

Active derivatives of glucoamylase immobilized on activated carbon have been prepared by adsorption, glutaraldehyde cross-linking, or covalent attachment by reaction with carbodi-imide-activated or diazotized activated carbon. The effects of a number of pretreatments of the carbon matrix on the efficacy of immobilization were investigated. 

Guaiacols. Cresote, obtained from the pyrolysis of beechwood, and its active principles guaiacol [90-05-1] (1) and cresol [93-51-6] (2) have long been used ia expectorant mixtures. The compounds are usually classed as direct-acting or stimulant expectorants, but their mechanisms of action have not been well studied. Cresol is obtained by the Clemmensen reduction of vanillin (3), whereas guaiacol can be prepared by a number of methods including the mercuric oxide oxidation of lignin (qv) (4), the ziac chloride reduction of acetovanillone (5), and the diazotization and hydrolysis of o-anisidine (6). 

Table 2 summarizes some of the transformations of substituents which have been carried out on azetidines without effect on the ring <79CRV33l). Other transformations of interest are the base catalyzed epimerization, H exchange and alkylation of the activated H-3 in azetidines (26) (69JHC153) and the nitration, reduction, diazotization and hence further modification of the aromatic ring in 3-phenyl-fV-acetylazetidine (27) (61LA 647)83). 

The second point is somewhat less obvious but is readily illustrated by the synthesis of 1,3,5-tribromobenzene. This particular- substitution pattern cannot be obtained by direct brornination of benzene because bromine is an ortho, para director. Instead, advantage is taken of the powerful activating and ortho, para-directing effects of the fflnino group in aniline. Brornination of aniline yields 2,4,6-tribromoaniline in quantitative yield. Diazotization of the resulting 2,4,6-tribromoaniline and reduction of the diazonium salt gives the desired 1,3,5-tribromobenzene. 

Diazotized 3,6-diamino-4-phenylpyrazolo[3,4-6]pyridine-5-carbonitrile 373 reacted with 2-naphthol to give 374 and with active methylene com-... 

Thiazolo[2,3-c][l,2,4]triazines 667 were synthesized by coupling the diazotized thiazole derivative 666 with activated nitriles to give 667 without... 

Experience in PTC with cationic catalysts showed that, in general, the most suitable compounds have symmetrical structures, are lipophilic, and have the active cationic charge centrally located or sterically shielded by substituents. For anionic catalysis sodium tetraphenylborate fulfills these conditions, but it is not stable under acidic conditions. However, certain derivatives of this compound, namely sodium tetra-kis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB, 12.162) and sodium tetrakis[3,5-bis-(l,l,l,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl]borate (HFPB) are sufficiently stable to be used as PTC catalysts for azo coupling reactions (Iwamoto et al., 1983b 1984 Nishida et al., 1984). These fluorinated tetraphenylborates were found to catalyze strongly azo coupling reactions, some of which were carried out with the corresponding diazotization in situ. 

Gold and Linder (17) studied the esterase catalyzed hydrolysis of A-(-)-acetoxymethyl-(l-phenylethyl)nitrosamine. They found that the stereochemistry of 1-phenylethanol produced in the reaction was the same as that observed in the base catalyzed hydrolysis of the nitrosamine and also of N-(l-phenylethyl)nitrosocarbamate. These results indicated that the same diazotate was produced in all three reactions. The fact that no irreversible inhibition of the enzymatic hydrolysis of the nitrosamine was observed, while extensive irreversible inhibition was obtained with the nitrosocarba-mate, led these workers to conclude that the a-hydroxynitro-samine produced by the hydrolysis had sufficient stability to diffuse away from the active site of the enzyme. 

B/s-diazotized benzidine has been used to create active-hydrogen-reactive spacer arms on chromatographic matrices (Silman et al., 1966 Lowe and Dean, 1971). The compound may be used similarly to o-tolidine for the conjugation of active-hydrogen-containing molecules (see Section 9.1, this chapter, and Chapter 2, Section 6.1). 

Active Hydrogen-Reactive p-Aminobenzoyl Biocytin, Diazotized... 

Azide 367 is prepared from 4-r -butyl-2-nitroaniline in 76% yield by its diazotization followed by treatment with sodium azide. In a 1,3-dipolar cycloaddition with cyanoacetamide, azide 367 is converted to triazole 368 that without separation is directly subjected to Dimroth rearrangement to give derivative 369 in 46% yield. Reduction of the nitro group provides ortfc-phenylenediamine 371 in 91% yield <2000EJM715>. Cyclocondensation of diamine 371 with phosgene furnishes benzimidazol-2-one 370 in 39% yield, whereas its reaction with sodium nitrite in 18% HC1 leads to benzotriazole derivative 372, which is isolated in 66% yield (Scheme 59). Products 370 and 372 exhibit potassium channel activating ability <2001FA841>. 

Attempts to utilize an in situ diazotization procedure (1.2 equiv. isoamyl nitrite, acetic acid, 25 °C, 30 min) [58,60-62] for DNA cleavage were made via generation of diazonium compound 17 directly from commercially available 9-aminofluorene (Fig. 18) [58]. However, addition of this solution to aqueous buffers (pH = 4-7) did not produce any DNA cleavage neither did the addition of cuprous chloride, which had been demonstrated to be successful in activating diazonium compounds for DNA cleavage [60-62]. This may be explained by ... 

The isolation of diazobenzo[fr ]fluorenes as stable antitumor natural products raises several questions about their mode of action. The inability to cleave DNA by diazotization of 9-aminofluorene may imply that if the diazo functionality is involved in the mode of interaction of kinamycins with DNA, its conversion to diazonium and the ensuing reduction may seem to be of negligible importance. An additional possibility, which will be discussed later, is that 9-diazofluorene may not be the ideal model for these natural products. In exploring DNA cleavage as a possible route to the kinamycins role as a stable antitumor agent, which may supplement their speculative and as yet unconfirmed role as alkylating molecules [67], this early model seemed to suggest that the well-established activation of diazonium may not be relevant. 

Type II nitrosamines have two reaction pathways. One pathway involves nucleophilic attack at the carbon of C=0 to generate a tetrahedral intermediate which decomposes to an active diazotate ion (R-N=N-0 ). The other pathway involves the nucleophililc attack on the nitrogen of the nitroso group resulting in denitrosation (Scheme 3.5). The nucleophile can be a biologically prevalent thiol, therefore type II compounds are often used as NO donors for the formation of S-nitrosothiols [67, 68]. 

Heat 85.5 g 3-carbethoxy-2-piperidone and 30 g KOH in 1 L water for twelve hours at 30°. Filter, cool to 0°, add 50 ml 6N HCI. Prepare a fresh solution by diazotizing at 0-5° a mixture of 85 g 3-amino-4-Cl-acetophenone, 250 ml concentrated HCI and 750 ml water with a solution of 36 g Na nitrite in 125 ml water. Add the piperidone solution at 0° to the diazonium salt solution and stir five hours at 10°. Filter, wash precipitate with water to get 80% yield of the hydrazone (1) (recrystallize-95% ethanol). Reflux 62 g (I) in 310 ml 88% formic acid to get 40 g of the carboline (II) (recrystallize-absolute ethanol) (test for activity). Reflux 40 g (II), 100 g KOH, 480 ml ethanol and 360 ml water for eighteen hours and evaporate in vacuum. Add 480 ml water to the residue, cool and adjust pH to 6 with glacial acetic acid. Scratch glass to precipitate filter, wash precipitate with cold water to get 41 g 4-acetyl-2-COOH-7-CI-tryptamine (recrystallize-50% ethanol) which can be alkylated to the active dialkyltryptamine as described elsewhere here. 

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