Amino compounds cyclization

Another application of diastereoselective nitro-aldol reactions catalyzed by Bu4NF-3H20 is demonstrated in a simple synthesis of l,4-dideoxy-l,4-imino-D-mannitol (DIM) and amino analogues (Eq. 3.85).134 The nitro-aldol reaction of nitro compounds bearing a-oxy or a-amino function with glyceraldehyde leads to nitrohexitols, which can be reduced to the corresponding amino compounds. Cyclization gives iminopolyols, as shown in Eq. 3.85. 

In contrast to the above-discussed cyclizations, two syntheses including ring closure of the five-membered ring have been described for [l,2,4]triazolo[l,5- ][l,3,5]triazines. The chemical transformations are shown in Scheme 38. Caulkett et al. published that the 2-hydrazino[l,3,5]triazine derivative 188 when treated with acid chlorides underwent ring closure and subsequent treatment with ammonia yielded the 5-amino compound 190 <1995J(P1)801>. 

Chlorooxadiazoles (82) react with amino compounds R NH2 (R = NH2, NHPh, alkyl, or aryl), secondary amines R R NH and azide ion to give products of nucleophilic displacement (76e), (76b), and (54i) respectively <84Mi 406-03, 90AP(323)595>. Reaction with anthranilic acid resulted in nucleophilic displacement with subsequent cyclization to oxadiazoloquinazolone (83) <84JIC436>. 

Most cyclizations described in this chapter involve a carbon-nitrogen bond as the final step. However, the A -amino compound 17 offers an example of a carbon-carbon bond formation to complete ring formation. Treatment of 17 with MeCOCH2COMe gives a mixture of products 18 and 19 (Equation 6) <2003CHE953>, with 19 obtained in very small amounts. 

Cyclization between a 1-amino group and C-4 of an anhydropenti-tol has been achieved 2,5-anhydro-l-azido-l-deoxy-3,4-di-0-p-toIyl-sulfonyl-D-xylitol (48) was hydrogenated to the 1-amino compound and then this was N-p-toluenesulfonylated, giving 49 the product was cyclized by use of sodium methoxide to38,39 the bicyclic compound (50). 

Several amino compounds (170 R1 = H, Me R2 = H,CH2Ph) were obtained from analogous reactions in which the 3-cyano-4-aminotetrahy-dropyridines (169) were treated with hydrazines.153 Cyclization of the enols 171, however, under similar conditions afforded the tetrahydro bicycles 172 (R = H, Me).154,15 5... 

All four isomeric selenolopyridines which can be derived from benzoselenophene (423— 426 Scheme 123) have been described. Ethyl 3-hydroxyselenolo[2,3-fe]pyridine-2-carboxy-late (429) has been prepared as shown in Scheme 124 (73BSF704). Treatment of ethyl 2-chloropyridine-3-carboxylate with methaneselenol yields (427). Nucleophilic displacement of bromine in bromoacetic acid with subsequent loss of methyl bromide yields (428), which after esterification is cyclized under Dieckmann conditions to give (429). The parent compound (423 colorless oil with b.p. 92 °C/1 mmHg) is prepared either by cyclization of compound (430) and subsequent decarboxylation of the intermediate acid (equation 57) or by reduction of 2-nitroselenophene and subsequent condensation of the amino compound with malonaldehyde bis(diethyl acetal) in the presence of zinc chloride (equation 58) (76BSF883). Selenolo[3,2-6]pyridine (426 b.p. 127-129°C/10 mmHg m.p. 35.5-37.0°C) has been obtained in an analogous manner. 

An alternative route, to form the 2-amino compounds, by Meschino and Bond139 used cyanogen bromide to cyclize aminopropanol [Eq. (29)] (see also Meschino and Poos140). 

In a study aimed at the scope and limitations of SET-photoinduced synthesis of indilizidine and quinolizidine ring forming, a-amino radical cyclization reactions are explored.349 It was shown that 2-silyl-pyrrolidyl and piperidyl enones react nicely under DCA-sensitized irradiation (A > 320 nm) in degassed acetonitrile to produce indolizi-dine and quinolizidine compounds. This technique appears as efficient as the preceding one (DCN in protic medium).344... 

Instead of amino-ketones, compounds may be used which are capable of forming amino-ketones as intermediates. Thus, if phenols and phenol ethers are acylated with y- or 8-amino acids in the presence of polyphosphoric acid, the intermediate amino-ketones cyclize to 2-aryl-z31-pyrrolines or 2-aryl-J -piperideines95 (Scheme 1). 

Using similar chemistry l,3-diaryl-2-thiobarbituric acid is acylated with chloroacetyl chloride in the presence of triethylamine. Subsequent (9-alkylation under the mildly basic conditions of sodium acetate yields the 5-oxo derivative <91H(32)907>. It is not necessary to use barbituric acid derivatives to accomplish synthesis of furopyrimidines. Other 6-oxopyrimidines serve well in developing analogues. For example, in a reaction similar to that described above, the acylated pyrimidine (215) undergoes cyclization to a 4-(substituted)amino compound (216) (Equation (74)) <92MI 707-03). 

Muth et al. studied the hydrogenation and cyclization of 2-nitro-2 -carboxy-biphenyl and its carboxy derivatives (22a-22d) over platinum oxide in ethanol (Scheme 9.13).154 IV-Hydroxyphenanthridone (25) was considered to result from the cyclization at the hydroxylamino compound 23, and phenanthridone (26) to result from the amino compound 24 and not via 25, since 25 did not undergo the reduction to yield phenanthridone under the conditions of the reaction. 

There is one example in which part of the amidine system is a C—N bond in a heterocyclic ring. The enamino ketone condensation products (42) of 3-amino-l,2,4-oxadiazoles and 1,3-dicarbonyl compounds cyclize in basic medium to form 60-80% yields of imidazoles. The driving force for this reaction is provided by the well-established, general attack of a nucleophilic centre in the side-chain at N-2 of the heterocyclic ring, but it is unusual in that a carbon nucleophile (rather than an oxygen or nitrogen species) is implicated (Scheme 23). 

The /5-N -benzoylhydrazino esters were readily converted into a variety of N-con-taining compounds. Reductive cleavage of the nitrogen-nitrogen bond of the hydra-zino compounds was successfully conducted by use of Raney Ni under a H2 atmosphere [14] to afford the /8-amino esters. Cyclization of y8-Al -benzoylhydrazino esters was conducted under basic conditions /i-lactams were obtained by treatment with n-BuLi at -78 °C, whereas pyrazolones were produced in the presence of NaOMe in MeOH at room temperature or under reflux (Sch. 4). 

Electrocyclization is the key step in a route to 4//-imidazoles 1187 and imidazoles 1188. Thus, activation of AT-acylamidines 1183 with trifluoromethanesulfonic anhydride and subsequent condensation with amino compounds 1185 produces l-amino-2,4-diazapenta-l,3-dienes 1186. Deprotonation of 1186 by the use of strong organic bases yields the corresponding 4//-imidazoles 1187 or imidazoles 1188 after amine elimination through an anionic 1,5-electrocyclization reaction. For the cyclization to occur, the amino compound 1185 needs to possess electron-withdrawing substituents such as alkoxycarbonyl or fluorenyl groups (Scheme 290) <2004EJO2567>. 

Schnider and Grtissner in the same way prepared 3- and 2- (or 4) hydroxy-N-methylmorphinane, obtained the same compounds from N-methylmorphinane by way of the nitro and amino compounds, and also synthesized the 3-hydroxy-derivative from [liv] by nitration, reduction, diazotization, c., followed by cyclization [25]. They have more recently resolved [lxxih] and prepared 3-hydroxy-N-allyl-morphinane [26], Schnider and Hellerbach [27] prepared an isomer of [lxxiii] and also synthesized dZ-tetrahydrodesoxycodeine [lxxv] by the cyclization of [lxxvi], in which reaction a small amount of 2 3-dihy-droxy-N-methylmorphinane [lxxvii], isomeric with dZ-tetrahydrodes-oxymorphine, was also obtained. Both [lxxhi] and [lxxvii] exhibit marked analgesic properties to about the same extent, whilst the 2- (or 4) hydroxy-compound is much less active [25, 27]. 

N-Amino heterocycles, synthesis of bridgehead N-heterocycles 86BSB973. Annelation of N-heterocycles via Reissert compounds 85H(23)731. Arenediazonium compounds, cyclization of 82YGK752. 

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