Monoacyl-1,1-diamines

Mercuric acetate ethylenediaminetetraacetic acid Oxidative N-ring opening Aminoaldehydes s. 28, 92 monoacyl-1,2-diamines from imidazolidines cf. H. Mohrle and C.-M. Seidel, M. 107, 51 (1976)... 

Dehydration of monoacylated diamines using POCl3 yielded substituted imidazolines 16 and 19 (Fig. 5). Selective acylation of the primary amino group of the diamines 14 and 17 was successfully achieved using a... 

Treatment of oxadiazinanes 20 with Zn metal in aqueous HCl afforded the corresponding 1,2-diamines 25 in good yield (Equation 4). Where R = />-MeC6H4CO, the product is a monoacylated diamine such derivatives are accessible by other means only with difficulty <2000J(P1)3292>. 

In a recent puhhcation, an ultrasound-supported procedure for the selective monoacylation of symmetric diamines was presented by Maurya et al. [25j]. The corresponding products are key intermediates in the synthesis of biologically active compounds. However, the selectivity to monoacylated diamines from symmetric diamines remains a major challenge as there are no directing steric or electronic effects. N-Hydroxysuccinimide ester 52 (see Table 6.5) was used as an acylating agent... 

Generally, the monoacylation is 3-15 times faster than second acylation and in the batch procedure the diacylated product 54 was obtained as major product (Table 6.5, entries 6, 7, and 13). In contrast, the monoacylated diamine 53 was obtained as major product when the microfluidic droplet and capillary approaches were applied. Here, the droplet-based protocol leads to slightly better yields and selectivities than the capillary procedure (compare entries 3 and 5), which was attributed to the improved mixing efficacy with additional convection effects within the droplets. But the amount of the continuous phase is certainly a major drawback of the droplet protocol. The capillary procedure was therefore improved by the treatment with ultrasound in a commercially available ultrasonic bath (330 W). Sonication of the capillary during the reaction leads to comparable results as in the droplet procedure in a much shorter residence time of 0.5 min (entry 9, overall flow rate 200pl/min, that is, 0.005 mmol/min). Compared to the silent process, the yield was increased by a factor of 4. With an improved ultrasound-supported continuous capillary protocol, a number of symmetric diamines (e.g., piperazine) were successfidly monoacylated. 

Support-bound 1,2-diamines can be readily converted into imidazolidinones by treatment with carbonyl diimidazole [128,129]. The required diamines have been prepared on cross-linked polystyrene by reduction of peptides bound to MBHA resin with borane. Similarly, bicyclic imidazolines have been prepared from triamines and thiocarbonyl diimidazole (Entry 10, Table 14.3). Dehydration of polystyrene-bound monoacyl ethylene-1,2-diamines yields 4,5-dihydroimidazoles (cyclic amidines, Entry 5, Table 13.18). Several groups have reported the synthesis of 2-aminoimidazol-4-ones from resin-bound amino acid derivatives (e.g., Entry 6, Table 15.11). Most of these compounds are, however, unstable, and slowly decompose if dissolved in DMSO (Jesper Lau, private communication). 

A convenient method for the monoacylation of homopiperazine and other diamines has been described <1999JOC7661>. Under conventional conditions, the bis-acylated product is favored but treatment of homopiperazine with 2 equiv of -butyllithium to form a dianion followed by reaction with 1 equiv of benzoyl chloride provided a 27 1 ratio of mono- to bisacylated derivatives from which the monoacylated compound was isolated in 91% yield. 

Unsymmetric diamines can sometimes be acylated selectively at one amino group only, if one of the amino groups is sterically or electronically deactivated. If the difference in reactivity is only small, acylating agents of low reactivity will usually be required. Some polyamino heteroarenes can be monoacylated or monoalkylated with astonishingly high regioselectivity (Scheme 7.13), which is, however, difficult to predict. 

J. F. Wang, T. Selective monoacylation of symmetrical diamines via prior complexation with boron. Org. Lett. 2003, 5, 3399-3402. 

No benzodiazepine has been obtained from o-phenylenediamine and 3,3-dimethylpentane-2,4-dione (38MI1 40MI1, 40MI2 63JA3354 75TL91) a monoacylated 2,3-diaminophenazine formed by self-condensation of two molecules of the diamine and subsequent reaction with the diketone has been isolated from the reaction mixture. It is possible that diazepine formation requires the presence of some enol form of a diketone. 

Reduction of 101 with lithium aluminum hydride gave the diamine (107) which formed N-methyl and monoacyl derivatives.97... 

One of the more common methods of benzimidazole synthesis is that which cyclizes o-arylenediamines in which one of the amino groups has been acylated or thioacylated. The starting material must be functionalized in such a way that an aromatic product can be formed when cyclization takes place. It is more common with analogous aliphatic diamine derivatives for reduced imidazoles to be formed, but there are a number of synthetically useful processes which cyclize monoacylated alkylenediamines. One example involves niono-acylated diaminomaleonitrile (see below), which can be dehydrated to form imidazoles fl5]. 

The synthesis of purines from monoacyl pyrimidine-4,5-diamines is a commonly used method (for example, [2252]). Similarly, 8-hydroxymethylpurin-6-one is synthesized from S-acylamino-6-aminopyrimidin-4-one and ethyl glycoiate but... 

Monoacylation of 2,3-diaminoquinoxalines has been achieved by reaction with an acid anhydride in THF. Under more vigorous conditions reaction of 2,3-diaminoquinoxalines with acid anhydrides results in ring closure to an imidazo[ ]quinoxaline. Similar ring closures have been carried out with aldehydes, acyl halides, formic acid, orthoesters, and urea. Polycyclic compounds have also been prepared from 2,3-diaminoquinoxaline by reaction with 1,-2-dicarbonyl compounds and 1,2-diamines, as illustrated in Scheme 7. 

Initially, gem-diamines were prepared from iV-protected a-amino azide 14. Intermediate isocyanates 15 obtained by Curtius rearrangement of 14 were immediately trapped with a primary alcohol to afford the corresponding N,N -diacylated-1,1 -diaminoalkane derivatives 16, which were further de-protected to the monoacylated gem-diamine before coupling to carboxylic acids (Scheme 6) [125-128]. 

For fast reactions of the type represented by reaction 13.2, carried out under the conditions stated earlier, micromixing becomes the dominant consideration. However, studies on the effect of micromixing in such reactions are sparse. Some examples are as follows nitration of aromatic componds in general (Schofield, 1980), potassium metal-provoked reactions of aryl halides with amide and acetone enolate ions (Tremelling and Bunnett, 1980X coupling of 1-naphthol with diazotized sulfanilic acid (Bourne et al., 1981, 1985), reactions of o-(3-butenyl)-halobenzenes and 6-bromo-1-hexene with alkali metals in ammonia/terr-butyl alcohol solution (Meijs et al., 1986), and monoacylation of symmetrical diamines (Jacobson et al., 1987). In some fast reactions, hydrogen ions are produced. 

Acylamidines Acylhydrazones a,a-Alkoxyaminonitriles N-Cyaniminoesters Diazo oxides Monoacyl-1,1-diamines... 

Di(azomethine)mono-N-oxides Diazo oxides Ene-N-nitrosamines a-Hydroxyhydrazines a-Hydroxyhydrazones a-Hydroxylaminonitriles Imidoylisocyanates Monoacyl-1,1 -diamines Nitrolamides Osonehydrazones a-Oximinonitriles... 

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