Diamino compounds

The first work in this area was the synthesis of lO-oxa-lO-deazaAMT (IV.52), which was reported as early as 1954 by Fairbum and co-workers [107]. The key building block in this synthesis was the a-ketoaldehyde diethyl acetal, (IV.54), which on reaction with 2,4,5,6-tetraaminopyrimidine at pH 3.0 (90 °C for 2 h) and subsequent vigorous treatment with HCl (100 °C, 15 min) afforded the diester (IV.53) in low yield. Compound (IV.54) was prepared from diethyl V-(4-hydroxybenzoyl)-L-glutamate by reaction with 2,3-epoxy-1,1-diethoxypropane followed by oxidation of the resultant secondary alcohol with chromic acid. Alkaline hydrolysis of (IV.53) yielded (IV.52). The product was assumed to be 6- rather than 7-substituted on the basis that the 5-amino group in 2,4,5,6-tetraaminopyrimidine is the most nucleophilic and therefore most likely to react with the keto group in (IV.54). Antibacterial activity against S. faecium was observed. 

11-Deaza-ll-oxahomoAMT (IV.62) was synthesized by Nair / a/. [Ill] by a modification of their synthesis of lO-deaza-lO-oxaAMT (IV.52). 1-Bromo-4-[4-(carbomethoxy)phenoxy]-2-butanone (IV.63) was converted successively to the azide (IV.64), the ketal (IV.65), and the acid (IV.66). Mixed anhydride coupling of (IV.66) and diethyl L-glutamate, followed by catalytic hydrogenation of the azido group, yielded the amine (IV.67), which, on addition to 2,4-diamino-6-chloro-5-nitropyrimidine and hydrolysis of the ketal group with acid, gave the key intermediate, (IV.68). Dithionite reduction led 

337 (9,829)]. The UV spectrum of (IV.69) was unlike that of (IV.58) in that, even though (IV.69) similarly contained a sulphur atom on the phenyl ring, an absorption maximum in the 280-290 nm region was absent. This spectral difference between lO-deaza-lO-thiaAMT and 11-deaza-ll-thiahomoAMT suggests that the additional CH2 group in the bridge exerts some as yet unknown influence on the molecular conformation of the chromophore. 

The availabUity of the oxa and thia analogues of AMT and homoAMT allowed comprehensive evaluation of the enzyme inhibitory activity, cellular uptake, and antibacterial and antitumour activity of this series of bridge altered compounds [108-113]. 

In assays against purified DHFR from L. casei, lO-deaza-lO-oxaAMT (IV.52), lO-deaza-lO-thiaAMT (IV.58), and 10-deazaAMT (IV.91 vide infra) all showed an IC50 value of 4 nM, whereas the values observed with 11-deaza- 

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Bis(azol-2-5l)stilbenes (2(i]ll such as (4) have been prepared. 4,4 -Dihydrazinostilbene-2,2 -disulfonic acid, obtained from the diamino compound, on treatment with 2 moles of oximinoacetophenone and subsequent ring closure, leads to the formation of (4) [23743-28 ]. Such compounds are used chiefly as washing powder additives for the brightening of cotton fabrics, and exhibit excellent light- and hypochlorite-stabiUty. 

The compounds 87a and 87b are aminated at position 4, yielding the 4-amino compound (88a, 40%) and the 2,4-diamino compound (88b, 11%) respectively the 2-ethoxy compound (87c), however, undergoes amination at position 4 as well at position 5, giving a mixture of the 4-amino compound (88c, 20%) and the 5-amino compound (89a, 14%).Tlie 2-chloro compound (87d) yields a highly complex reaction mixture from which the 5-amino compound (89b), the 2,4-diamino derivative (88b), and 2,5-diamino-l,8-naphthyridine (89c) could be isolated. l-Ethyl-3-nitro-l,8-naphthyridin-2(lH)-one (90a) and 3,6-dinitro-l-ethyl-l,8-naphthyridin-2(lH)-one (90b) were aminated exclusively in the 4-position to give compounds 91a (62%) and 91b (45%), respectively (93LA471). 

B Nicotine is a diamino compound isolated from dried tobacco leaves. Nicotine has two rings and M + = 162.1157 by high-resolution mass spectrometry. Give a molecular formula for nicotine, and calculate the number of double bonds. 

Aromatic compounds with a functional group containing oxygen ortho to a group containing hydrogen Diamino compounds (loss of NH3)... 

Silylation-amination of 6-acetoxymethyl-5-deazapterine 265 with NH3, HMDS 2, and TsOH for 120 h at 155-160°C in an autoclave affords, after subsequent trans-silylation with boiling methanol, the diamino compound 266 in 74% yield [76]. Silylation-amination-cychzation of the substituted 4-quinolone 267 gives the alkaloid isoaptamine hydrochloride 268 in 51% yield [77, 78] (Scheme 4.30). 

The reaction of an amino acid imidazolide with a diamino compound could be directed so that a mono amide was obtained in good yield,[1091 as shown by the following example ... 

Examples of monoamides from diamino compounds using CDI ... 

Insertion of a C=0 or C=S group between the two amino functions of a 1,3-diamino compound proceeds correspondingly to give six-membered heterocycles. 

Removal of an iV-amino substituent was also reported in one case <1999KGS796>. Kolos et al. found that heating of the diamino compound 190 in methanol for 20 min results in removal of the iV-amino moiety to give 191 in 27% yield (Scheme 22). 

The fused tetrazoles 10 containing various aryl groups in position 6 were boiled in acetic acid in the presence of either triphenylphosphine or copper and gave rise to the amino-substituted triazines 12. The reaction proceeds obviously via valence bond isomerization of 10 to the azide 11 and is regarded as a useful synthetic route to the diamino compounds 12. 

Another family of technically important diazo components for pigment formation includes a series of aromatic diamino compounds, primarily 3,3 -dichlorobenzidine, and to a lesser extent 3,3 -dimethoxybenzidine (o-dianisidine), 3,3 -dimethylbenzidine (tolidine) and 2,2, 5,5 -tetrachlorobenzidine ... 

Cyclization at a geminal diamino-group can be effected111 by the dichlorosilane, MeHSiCla to give (46). A closely related geminal-diamino-compound is the precursor of a bisphosphazenyl-derivative 13... 

The currently accepted name for (1) in Chemical Abstracts is dibenzothiophene, although biphenylene, diphenylene, or biphenylylene sulfide are still used, especially in the Russian literature. Occasionally 9-thia-fluorene is used and recently, in one instance, dibenzo[6,d]thiophene. An alternative numbering system for (1) is met with on occasions in which C-4 is taken as C-1, as in carbazole. In the absenee of moleeular diagrams this system must be detected by reference to the chemistry described. For example, in a few dyestuff patents 2,7-diaminodibenzothiophene 5,5-dioxide is referred to and this is obviously the 3,7-diamino compound, also known as benzidine sulfone. 

Reduction of 2-amino-3-nitrodibenzothiophene in the presence of acetic acid yields the imidazole (109) and by conducting this reaction in the absence of acetic acid 2,3-diaminodibenzothiophene should be readily accessible. A similar reduction of 3-amino-4-nitrodibenzothio-phene yields 3,4-diaminodibenzothiophene (60%). In addition to the typical reactions described above for the 1,2-diamino compound, 3,4-diaminodibenzothiophene condenses with benzil to give the quinoxaline... 

As the distance between the amino groups increases, the effect of the NH2 on the first protonation diminishes, so that pATai values for the 1,3- and 1,4-diamino compounds are very similar to that of ethylamine. Only in 1,2-diaminoethane do we see the electron-withdrawing effects of the second amino group decreasing basicity. However, for the second protonation, it is clear that an ionized... 

Amides containing nitro groups are reduced to diamino compounds with alane. A, A -Dimethyl-p-nitrobenzamide, on reduction with lithium aluminum hydride in the presence of sulfuric acid in tetrahydrofuran, gave 98% yield of dimethyl-p-aminobenzylamine [1117]. 

Since the first report in 1973, there has been significant growth in the use of rhodium catalysis to cleave strained ethers and amines, particularly in the preparation of enan-tiomericaUy enriched decalins, cyclohexenes, amino alcohols, and diamino compounds. This chapter describes the major advances in synthetic capabihties and outlines the mechanistic evidence pointing to a working model for the reaction pathway in these processes. 

Nucleophilic attack on oxadiazolinone (62b) by diamino compounds NH2(CH2) NH2 (n = 0 or 2) led to oxadiazolotriaza heterocycles (64) <91H(32)237>. Nucleophilic attack followed by ring opening occurred when oxadiazolinones (62c) were treated with amines R R NH, yielding semi-carbazide derivatives R CONHN(Ar)CONR R <82JHC823>. 

Reactions of 1,2,4-thiadiazoles with radicals and electron-deficient species are virtually unknown. Catalytic and dissolving metal reductions usually cleave the nucleus at its N—S bond by a reaction that may be regarded as the reverse of its synthesis by the oxidative cyclization of amidinothiono structures (Section 4.08.9.4). For example, reduction of the diamino compound (37) gives the amidinothiourea (38) from which it may be prepared by oxidation (Equation (8)). 

When 4-bromo- or 4-iododibenzofuran is treated with sodamide or a lithium dialkylamide, cine substitution occurs and the 3-amino derivative results. The 4,6-diiodo derivative similarly gives the 3,7-diamino compound. ... 

From 1,2-Diamino Compounds and their Synthetic Equivalents ( 4+2 Components ). 9.2 From a-Amino Ketones and their Synthetic Equivalents ( 3+3 Components )... 

From 1,2-Diamino Compounds and their Synthetic Equivalents ( 4+2 Components )... 

Two molecules of the acid chloride of l,10-phenanthroline-2-carboxylic acid have been condensed with a number of diamino compounds such as o-phenylenediamine to give novel bifunctional ligands.361 More examples of the decarboxylation of carboxy-substituted... 

Phthalodinitrile is converted by methanolic hydrazine into 1,4-diaminophthalazine (413) (68JHC111), and with excess of hydrazine 1,4-dihydrazinophthalazine (414) is obtained, via the 1,4-diamino compound (59JOC1205). 

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