Mannich-type condensation

Functionalization in the 3-position has been accomplished by a Mannich type condensation as shown in Eq. (3.53). The process is initiated by heating binaphthol with N-( -butoxymethyl)morpholine for five days at 150° °. Under these conditions, a mix-... 

The two C—C bond-forming reactions in the trimerization of pyrrole are thus seen to be Mannich-type condensations and find many simple analogies, the most relevant one being that used to prepare 2-2 -pyrrolidinylpyrrole (19)."... 

Sulphoxides also undergo Mannich-type condensation when reacted with aldehydes and secondary amines or their salts. In some cases, stable Mannich bases 462 can be isolated. They undergo amine elimination upon heating to give the corresponding a,/ -unsaturated sulphoxides 463164,529 (equation 276). 

In recent years a number of methods have been developed for the preparation of dialkyl(methylene)ammonium salts (Mannich reagents)and their use in Mannich-type condensation reactions under anhydrous conditions has improved the scope and efficiency of this important synthetic process. However, the orientation of the Mannich reaction may nevertheless be difficult to control. Apart from the work of the submitters, the preparation of isomer-ically pure Mannich bases has only been achieved by indircci... 

Addition of sulfinate ions to the carbonyl group of aldehydes to form c-hydroxy sulfones (Bredereck et al., 1954, Bredereck and Bader, 1954) is also known, as is the participation of sulfinic acids as the acid component in Mannich-type condensation reactions with aldehydes (129) (Rawson and Engberts, 1970 Engberts and Strating, 1964, 1965). 

A large number of nitramine-based explosives have been synthesized via Mannich-type condensation reactions (Section 5.13.2). The amines generated from these reactions often have the powerful electron-withdrawing trinitromethyl or fluorodinitromethyl groups positioned on the carbon a to the amino group. This reduces amine basicity to an extent that A-nitration becomes facile. The energetic nitramines (17), (19) and (21) have been synthesized from the condensation of ethylenediamine with 2,2,2-trinitroethanol, 2-fluoro-2,2-dinitroethanol with ethanolamine, and 2-fluoro-2,2-dinitroethylamine with 2,2-dinitro-l,3-propanediol respectively, followed by A-nitration of the resulting amine bases (16), (18) and (20), respectively. 

Carbazole undergoes a Mannich-type condensation at the nitrogen under mild conditions with formaldehyde and amine in ethanol in this way 66 [R = Me, Et, (CH2)20(CH2)2, and CH2CH2CI] were prepared. An... 

Although a Mannich type condensation of an amine and an aldehyde is involved in this reaction, NCS appears to be a different protein from the genes products involved in STRl-type reactions, since it is a dimer containing 15 kDa subunits. Further characterization of this enzyme suggested it belongs to a new, but uncharacterized family of genes (P. Facchini, personal communication). 

The chemistry of Mannich bases is implied in important spontaneous reactions involving natural products such as the alkaloids,- where a Mannich-type condensation is a key reaction leading to the biogenesis of the final product, as well as in interesting synthetic methods adopted in the laboratory preparation of natural molecules or of structurally related models. The chemical modification of natural compounds and the synthesis of labeled derivatives for biological studies also constitute relevant applications connected with chemistry of Mannich bases. 

Mannich reactions occur frequently in the chemistry of alkaloids. Many key steps in biogenesis are Mannich-type condensations (sec p. 353 in Ref. 2), and several synthetic methods applied to these compounds and related derivatives arc often based on Mannich reaction. ... 

Vinyl ketones. Methyl ketones (1) undergo a Mannich-type condensation with paraformaldehyde (2), when refluxed in THF or dioxane in the presence of N-methylanilinium trifluoroacctate (this volume) to give vinyl ketones. The only... 

Another method of alkylation of A -3-ketones involves a Mannich-type condensation of the enolate anion with formaldehyde and a thiol [166]. The outcome is a selective thio-methylation at C(4>, probably involving nucleophilic attack... 

Other Mannich and Mannich-type condensations (also see Section II, C, 1) have been used to synthesize 1,5-diazocines. Two groups reported reacting the tetranitro-A-nitroso compound 152 (R = NO) with alkylam-ines and formaldehyde, affording tetranitro-A-nitrosodiazocines 153 (R = NO, R1 = Me) (81IZV1676 83S830) and 153 (R = NO R1 = H, i-Pr)... 

Mannich type condensation. Primary and secondary amines when reacted with formaldehyde and the appropriate RSH nucleophile yield a mixture of mono- and bls-substltuted conjugates and a mono-substltuted conjugate, respectively as Illustrated In Figure... 

A second type of derivative of phosphorus-containing aldehydes and ketones was prepared from a Mannich-type condensation of a phosphorus-containing carbonyl compound, such as 3-(diethyl phosphono)butanal with diethyl phosphonate and diethanol amine, to form a phosphorus-rich diol, l-((diethyl)phosphono]-l-CN,N-di(hyroxyethyl)amino]-3-C(diethyl)phosphono] butane as shown In Eq. 2 of Fig. 2. Examples of the preparation of such diols are shown as Ex 3 and 4 of Table 3. 

The methylcyclopentanoid monoterpenes arise from geranyl-PP via an intramolecular stereocontrolled Mannich type condensation of a dialdehydic or a trialdehydic intermediate, as shown in fig.4. The resulting cyclopentanaldehydic compound has been named iridodial or iridotrial, depending on the nature of the biosynthesized compound and of its biogenetic pathway. 

A partial synthesis of voacamine (and voacamidine, XXVI) was carried out by condensing voacangine and vobasinol in refluxing 1.5% methanolic hydrochloric acid 45, 49). This vinylogous Mannich type condensation (Chart VI) has an analogy in the known dimerization of 1-hydroxy-1,2,3,4-tetrahydrocarbazole 45, 50). 

Despite their great structural variety, isoquinoline alkaloids were, for a long time, considered as a vast, but biosynthetically uniform family of natural products, the common key step of their biogenesis always being the Mannich-type condensation of phenylethylamines with aldehydes or a-ketoacids (7). The preparative imitation of this reaction principle, the Pictet-Spengler-type isoquinoline synthesis (2), has been the basis for countless biomimetic alkaloid syntheses (5). 

The A-[imidazolyl)-iV -(hexan-5-one)urea (108) cyclizes via an acid-catalyzed intramolecular Mannich-type condensation to afford the tricyclic imidazo[4,5-/lpyrido[2,l-i][l,3,5]oxadiazocine (85), shown in Equation (7) <82CPB3088>. 

For example, Porcheddu and co-workers recently reported the synthesis of a series of a,p-unsaturated aldehydes by the dehydrogenative cross-coupling of primary alcohols, which reacted with an amine to form the corresponding imine, followed by a Mannich-type condensation reaction (Scheme 39) [193]. 

A protonated Schiff s base (11) is the presumed intermediate in the Mannich reaction. From the condensation of tryptamine with benzal-dehyde a Schiff s base (10 R = CgHg) has indeed been isolated, which on treatment with acid cyclizes to l-phenyl-l,2,3,4-tetrahydro-j8-carboline(14 R = CeHg). Condensation ofa tryptamine derivative with an aldehyde in the absence of acid leads to the corresponding Schiff s base (10), the structure of which has been proved by reduction to an Ajg-alkyltryptamine derivative (13) with sodium boro-hydride. Reconversion of a l,2,3,4-tetrahydro-j8-carboline (14 R = CH2C6H3-3,4- 0H)2) into the corresponding protonated SchifiF s base of tryptamine (11) has been postulated as a step in the rearrangement in strong acid of this 1,2,3,4-tetrahydro-jS-carboline derivative into an indolenine (see Section IV, B, 3). One instance of a Mannich-type condensation of an aldehyde with a modified tryptamine derivative into the jS-position, rather than into the a-position, of the indole... 

Mannich-type condensation with sulfinic acids... 

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