Reaction with formaldehyde and

The hydroxyl groups can be alkylated in the usual manner. Hydroxyalkyl ethers may be prepared with alkylene oxides and chloromethyl ethers by reaction with formaldehyde and hydrogen chloride (86). The terminal chlorides can be easily converted to additional ether groups. 

The resihency and dyeabihty of poly(vinyl alcohol) fibers is improved by a process incorporating -hydroxybenzaldehyde to provide a site for the formation of a stable Mannich base. Hydroxyl groups on the fiber are converted to acetal groups by -hydroxybenzaldehyde. Subsequent reaction with formaldehyde and ammonia or an alkylamine is rapid and forms a stable Mannich base that is attached to the polymer backbone (94). 

Hydrogen bromide adds to acetylene to form vinyl bromide or ethyHdene bromide, depending on stoichiometry. The acid cleaves acycHc and cycHc ethers. It adds to the cyclopropane group by ring-opening. Additions to quinones afford bromohydroquinones. Hydrobromic acid and aldehydes can be used to introduce bromoalkyl groups into various molecules. For example, reaction with formaldehyde and an alcohol produces a bromomethyl ether. Bromomethylation of aromatic nuclei can be carried out with formaldehyde and hydrobromic acid (6). 

An indole protected by a Mannich reaction with formaldehyde and dimethyl-amine is stable to lithiation. The protective group is removed with NaBH4 (EtOH, THE, reflux). The related piperidine analogue has been used similarly for the protection of a triazole. ... 

In a modified approach, the carbolinyl acetate 393 underwent a Mannich reaction with formaldehyde and acetone to give the keto ester 396 which, with base, cyclized to the diketone 397. This diketone (397) has recently been used to prepare a number of interesting pentacyclic compounds. 

The derivative from an isomeric fused system has been described as a sedative-hypnotic compound. The synthesis starts by condensation of the aminopicoline 32 with the haloketone 33. The resulting pyrrolo[l,2-a]pyridine 34 then undergoes a Mannich reaction with formaldehyde and dimethylamine to give the aminomethylated derivative 35. After quatemization of the di-methylamino group in 35 with methyl iodide, the ammonium group is displaced by cyanide to... 

Inclusion of an acetylenic linkage as part of the side chain is apparently consistent with antidepressant activity. Reaction of propargyl magnesium bromide with dibenzocycloheptadieneone leads to carbinol 82. A Mannich reaction with formaldehyde and dimethylamine leads to 83 which, upon dehydration... 

Urine ( -aminolevuli nic acid) Acidification of sample separate -aminolevulinic acid on HPLC reaction with formaldehyde and acetylacetone HPLC/FL 10 pg/L No data Tabuchi et al. 1989... 

Phosphorous acid has also been of use for additions to imines. Originally investigated by Moedritzer and Irani,241 who developed a Mannich-type procedure for the preparation of phosphorus-centered species, the approach was found later to be useful for both primary and secondary amines in reaction with formaldehyde and phosphorous acid. The approach was later used for the preparation of a cationic exchange resin using a polymer substrate.242... 

Ethyl />-nitrophenylacetate, reaction with formaldehyde and hydrogen, 47, 69... 

Fluoride ion promoted cleavage of propynylsilanes and subsequent reaction of the carbanion with carbonyl compounds produces allenic compounds. The reaction with formaldehyde and pivaldehyde fails, but both the allenic and acetylenic products are obtained from the reaction with acrolein and benzaldehyde [49]. Allylsilanes react with carbonyl compounds to produce but-3-en-l-ols [50],... 

The synthesis of zolpidem began with an alkylation/condensation reaction of amino-pyridine 5 and bromide 6 to give imidazopyridine 7 (Scheme 15.1). Mannich-type reaction with formaldehyde and dimethylamine provided 8. Treatment of 8 with methyliodide to form the quaternary salt 9, followed by reaction with sodium cyanide, gave 10. Acidic hydrolysis followed by reaction of the resultant acid 11 with carbonyldiimidazole (GDI) and dimethylamine afforded zolpidem (1) in 46% overall yield (George et al., 1991 Rossey and Long, 1988). 

Regioselective aminomethylation and subsequent cyclization of methyl 2,4-dihydroxybenzoate 517 was accomplished through a Mannich reaction with formaldehyde and primary amines in methanol to yield 3-substituted-3,4-dihydro-2/7-l,3-benzoxazine derivatives 518 (Equation 60). Simultaneous mixing of the reactants resulted in poor yields, but good yields were achieved by the pretreatment of paraformaldehye with a primary amine to form a Schiff base, followed by the addition of compound 517 <2001TL7273>. 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

As a further illustration of the reactivity of the 3 position toward electrophiles, the methoxyindole (25-1) readily undergoes Mannich reaction with formaldehyde and dimethylamine to afford the aminomethylated derivative (25-2). Treatment of that intermediate with potassium cyanide leads to the displacement of dimethylamine and the formation of the nitrile (25-3), possibly by an elimination-addition sequence involving a 3-exomethylene-indolenine intermediate. The protons on the methylene group adjacent to the nitrile are quite acidic and readily removed. Reaction of (25-3) with methyl carbonate in the presence of sodium methoxide gives the carbo-methoxylated derivative (25-4). Catalytic hydrogenation leads to reduction of the nitrile to a primary amine. There is thus obtained the antihypertensive agent indorenate (25-5) [26]. 

Dopamine, the free catechol corresponding to (1-1), plays an important role as a neurotransmitter, particularly in the CNS. The synthesis of a dopamine-related sedative agent starts with the condensation of homoveratramine (1-1) with styrene oxide (1-2) to afford the carbinol (1-3). Treatment of that product with a strong acid leads to an attack on the electron-rich aromatic ring by the resulting carbocation there is thus obtained the benzazocine (1-4). The secondary amine is then methylated by reaction with formaldehyde and formic acid to yield trepipam (1-5) [1]. 

Hauser and Lindsay first showed that ferrocene undergoes a Mannich-type reaction with formaldehyde and dimethylamine to form dimethylaminomethyl-ferrocene (XXIV) (31). This amine is readily converted to a methiodide, and... 

TNT undergoes the Mannich reaction with formaldehyde and various secondary amines (Refs 16 40) ... 

Amines-Reaction with Formaldehyde and Other Aldehydes... 

Alkylation of fluoroolefins is probably the most studied reaction of that kind. Different aspects of this process, such as reaction with formaldehyde and hexamethylenetetramine in HF [3], or condensation of halomethanes with fluoroethylenes, catalyzed by AlCl3 [27] have been reviewed. A recent development in this field mostly associated with the introduction of new catalysts, such as SbF5 [7] or aluminum chorofluoride AlClxFy [12], was covered in two other review articles. Here a brief description of some of these reactions is given. 

The exocyclic amino group of 5-aminotetrazole is reactive in nucleophilic substitution of halogen atoms in halonitrobenzenes. For example, the synthesis of 5-picrylaminotetrazole 406 is based on this process <1999THS(3)467>. Finally, 5-aminotetrazole and l-methyl-5-aminotetrazole 407 undergo a Mannich reaction with formaldehyde and trinitromethane with formation of products 408 (R = H, Me) . 

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