Amino reaction scheme

Vollmann found that the reaction between l-imino-3-amino isoin dolenine (124) and 2-amino-4-methylthiazole is catalyzed by ammonium chloride and involves the exocyclic nitrogen (285). This reaction (Scheme 82) was later used to prepare dyes (286). 

The same 3-amino substituent is reactive in condensation reactions (Scheme 235) (701, 726-729). 2-Imino-3-amino-4-thia2oiine reacts, however, in the nicotinoylation reaction through its imino nitrogen (727). 

The rearrangement discovered by Kolosova et al. probably involves such reactivit (159). This reaction provides a good preparative method for various 5-amino-methylthiazoles (Scheme 43). No mechanism is proposed in the report, and it is not easy to understand how the C-5 enamine-like position competes with the very nucleophilic thiocarbonyl group of the formed A-4-thiazoline-2-thione. An alternative mechanism could start with ethanol addition at C-2. leading to the A-4-thiazoline (90) (Scheme 44). In this intermediate, C-5 nucleophilic reactivity would be favored bv the true enaminic structure. After alkylation on C-5,... 

Iminoboianes have been suggested as intermediates in the formation of compounds derived from the pyrolysis of azidoboranes (77). The intermediate is presumed to be a boryl-substituted nitrene, RR BN, which then rearranges to the amino iminoborane, neither of which has been isolated (78). Another approach to the synthesis of amino iminoboranes involves the dehydrohalogenation of mono- and bis(amino)halobotanes as shown in equation 21. Bulky alkah-metal amides, MNR, have been utilized successfully as the strong base,, in such a reaction scheme. Use of hthium-/i /f-butyl(ttimethylsilyl)amide yields an amine, DH, which is relatively volatile (76,79). 

Numerous examples of N—S bond formation using oxidative conditions have been described in the literature. A convenient synthesis of isothiazoles involves the direct oxidation of -y-iminothiols and numerous variations have been studied (see Chapter 4.17), The oxidation of the amidine (248) to give the 3-aminoisothiazole (249) illustrates the reaction scheme (65AHC(4)107, 72AHC(14)1), which has been extended to the synthetically useful 5-amino-4-cyano-3-methylisothiazole (251) obtained by oxidation of (250) with hydrogen peroxide (75JHC883). 

Certain nucleophilic sp ies add to carbonyl groups to give tetrahedral intermediates that are unstable and break down to form a new double bond. An important group of such reactions are those with compounds containing primary amino groups. Scheme 8.2 lists some of the more familiar classes of such reactions. In general, these reactions are reversible, and mechanistic information can be obtained by study of either the forward or the reverse process. 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Bischler-Napieralski reaction of 139 to a 3,4-dihydroisoquinoline, oxidation, dehydrogenation and reduction of the nitro to the amino function gave 140 which was subjected to a Pschorr reaction (Scheme 49). Quaternization was accomplished by methyl iodide to furnish the isoquinolininium salt 141 which underwent an ether cleavage on heating a solid sample or benzene or DMF solution to Corunnine (127) (73TL3617). 

The main polymerization method is by hydrolytic polymerization or a combination of ring opening as in (3.11) and hydrolytic polymerization as in (3.12).5,7 9 11 28 The reaction of a carboxylic group with an amino group can be noncatalyzed and acid catalyzed. This is illustrated in the reaction scheme shown in Fig. 3.13. The kinetics of the hydrolytic polyamidation-type reaction has die form shown in (3.13). In aqueous solutions, die polycondensation can be described by second-order kinetics.29 Equation (3.13) can also be expressed as (3.14) in which B is die temperature-independent equilibrium constant and AHa the endialpy change of die reaction5 6 812 28 29 ... 

There has been a plethora of recent hterature regarding the synthetic manipulations of the 2(lH)-pyrazinone skeleton. Even though the addition-elimination reactions at the C-3 position to decorate the pyrazinone scaffold are well documented [24], the versatihty of such approaches can be found somewhat limited. Selective attack of nucleophiles on the chloroimine group of the pyrazinone system can generate 3-alkoxy- and 3-amino-pyrazinones (Scheme 9) [27,28]. The 3-CN group was introduced via a Rosemund-von Braun reaction with copper(I)cyanide under harsh conditions (heating in NMP at 150 °C) [27] (Scheme 9). 

Fig. 21 Reaction scheme for the detection of aromatics, by means of the reaction sequence, nitration, reduction, diazotization and coupling to an azo dye, and of aliphatic nitro compounds by detection of the primary amino group produced on reduction.

The Arndt-Eistert reaction (Scheme 2.1) which involves the Wolff rearrangement of diazoketones 13 (prepared from the corresponding commercially available N-protected-a-amino acids 12 by reaction of their mixed anhydrides with diazomethane a cautionary note is warranted here the generation and handling of diazomethane require special precautions) has been used extensively by Seebach and coworkers for the preparation of N-protected /9 -amino acids 14 and /9 -amino acid esters 15 and 16. 

In this aforementioned Heine reaction the initial ring opening takes place by iodide ions. Subsequent ring closure by S 2 displacement of iodide by reaction with the negative oxygen center then leads to the products. This process proceeds with double inversion at the same carbon atom, thus with net retention. Hydrolysis of these oxazolines gives j9-hydroxy-a-amino acids (Scheme 31) [1,38]. The stereochemical course of ring expansion is the same as that observed in Scheme 29. 

Scheme 1.—Reaction Scheme for the Total, Reductive [ C]Methylation of the 6-Amino Group of Lysine, and the 2-Amino Group of an N-terminal Amino Acid Group.

Figure 1 Reaction scheme for the hydrogenolysis of a Cbz-protected amino acid.

Isoxazolidines can be converted easily to tetrasubstituted cyclobuty-lamines. This transformation involves a one-pot, two-stage reaction involving hydrogenolysis of the isoxazolidine ring on Pd/C in AcOEt and the N-tert-butoxicarbonylation of the resulting amino group (Scheme 4.144).542... 

Protected 6-amino-hexahydro-l,7-dioxopyrazolo[l,2-4]pyrazole-2-carboxylic acid 274 is available by a thermolytic decomposition of diazo compound 273 via the Wolff rearrangement. The starting compound is simply available by alkylation of racemic 272 with the corresponding bromoacetoacetate and subsequent diazo transfer reaction (Scheme 35) <1996TL4891>. 

The bicyclic enamine 383 deviates from the above reaction scheme when interacting with diphenyl cyclopropenone the betaine 384 formed initially does not iso-merize to the amide 385, but to the a-amino cyclopentenone 386, possibly favored by steric reasons248. ... 

Related to the nitrile oxide cycloadditions presented in Scheme 6.206 are 1,3-dipolar cycloaddition reactions of nitrones with alkenes leading to isoxazolidines. The group of Comes-Franchini has described cycloadditions of (Z)-a-phenyl-N-methylnitrone with allylic fluorides leading to enantiopure fluorine-containing isoxazolidines, and ultimately to amino polyols (Scheme 6.207) [374]. The reactions were carried out under solvent-free conditions in the presence of 5 mol% of either scandium(III) or indium(III) triflate. In the racemic series, an optimized 74% yield of an exo/endo mixture of cycloadducts was obtained within 15 min at 100 °C. In the case of the enantiopure allyl fluoride, a similar product distribution was achieved after 25 min at 100 °C. Reduction of the isoxazolidine cycloadducts with lithium aluminum hydride provided fluorinated enantiopure polyols of pharmaceutical interest possessing four stereocenters. 

In a joint paper, Loupy and Gedye [45] reported an investigation of the influence of MW activation on the synthesis of phthalimides by the reaction of phthalic anhydride with several amino compounds (Scheme 4.20) both in the absence of solvent and in the presence of a nonpolar solvent. 

The pH of the oceans forming the primordial soup is important in controlling the charged nature, or otherwise, of the amino and carboxylic acid species and hence their chemistry. Generating reaction schemes for the prebiotic synthesis of molecules requiring basic conditions will not be relevant if the oceans are acidic. Consider dissolving CO2 into water, simply written as ... 

The objective of the preceding equilibrium calculation has been to determine the state of a molecule such as an amino acid in the conditions that prevailed on the early Earth. The pH, degree of dissociation and the extent of the reaction all have a direct effect on the population of the species present. Temperature and cooperative effects have not been considered but serve to complicate the problem. Any prebiotic reaction scheme must take account of that troublesome restriction to chemistry - the second law of thermodynamics. 

The reaction of lithiated 2-(l-chloroethyl)-2-oxazolines (367) with nitrones led to the stereoselective synthesis of oxazolinyl-[1.2] oxazetidines (372a,b) which are important as precursors of o.-hydroxy-j3-amino acids (Scheme 2.160) (601). 

When sulfamate esters 114 are used as substrates, six-membered-ring formation is favored, and results in the selective formation of 1,2,3-oxathiazinane-2,2-dioxide heterocycles 115.251 Nevertheless, five-membered cyclic sulfamidates could be obtained when no alternative cyclization was possible. 1,3-Amino alcohols and related /2-amino acids are thus readily accessible from the same simple alcohols 113 by converting them into sulfamates 114 (Equation (90)). Furthermore, in comparison to the carbamate reaction (Scheme 9), the sulfamate substrates have... 

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