Primary from formaldehyde

One of the most extensively investigated groups of 1,3-oxazine derivatives is the 5-nitro derivatives of tetrahydro-l,3-oxazine. They were first prepared from 1-nitropropane, aqueous formaldehyde, and ammonia by Hirst et and independently by Senkus from other primary nitroparaffins, formaldehyde, and primary amines. Numerous compounds of the general formula (6) were later prepared from primary nitroparaffins. " ... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Synthetic routes to a-nitroalkenes have been discussed in previous sections. General routes include (1) treating /3-nitroacetates with alkali metal acetates, carbonates or bicarbonates, (2) elimination of water from /3-nitroalcohols via heating with phthalic anhydride or in the presence of a base," ° and (3) degradation of the Mannich products derived from a primary nitroalkane, formaldehyde, and a secondary amine. ... 

Russian chemists have reported the synthesis of A-alkyl-3,4-dinitropyrroles from the cy-clization of primary amines, formaldehyde and the potassium salt of 2,3,3-trinitropropanol. ... 

Simple unactivated Immonlum salts generated In situ from formaldehyde and primary alkyl amines undergo a facile aza Diels-Alder reaction with cyclopentadlene at ambient temperature to afford novel N-alkylated 2-azanorbornenes. The procedure described above Is general and can be applied to a number of primary alkyl amines. Yields of N-alkyl substituted 2-azanorbornenes are good to excellent. Use of ammonium chloride and... 

Experiment 5.39 CYCLOHEXYLMETHANOL (primary alcohol from formaldehyde)... 

The synthetic method (b) combines the formation of a primary or secondary alkynol [from formaldehyde or an aldehyde respectively and an organometallic acetylenic reagent (Section 5.4.2, p. 532)] with the semihydrogenation of the triple bond to a double bond. As noted in Section 5.2.2, p. 493, appropriate selection of catalyst is necessary in the hydrogenation step to ensure the formation of either the ( )- or the (Z)-isomer. The specific formation of the allylic alcohol, CH2=CH-CH(OH),R, is from a vinylmagnesium halide (Expt 6.41) and an aldehyde. 

The mechanism of the reaction is not certain but hydrolysis of the salt may yield the primary amine (5), formaldehyde and ammonia. A hydride ion transfer then probably occurs between the benzylamine and the protonated aldimine (6), derived from formaldehyde and ammonia. Hydrolysis of the resulting aromatic aldimine (7) then yields the required aldehyde. 

The reaction of aldehydes and ketones with Grignard reagents is a useful method of synthesising primary, secondary, and tertiary alcohols (Following fig.). Primary alcohols can be obtained from formaldehydes, secondary alcohols can be obtained from aldehydes, and tertiary alcohols can be obtained from ketones. The reaction involves the formation of a carbon-carbon bond and so this is an important way of building up complex organic structures from simple starting materials. 

Fig. 10.33. Preparation of a primary alcohol from formaldehyde and a Grignard reagent or an organolithium compound.

The subsequent reactions of the hydrogen atom and formyl radical are of considerable importance since they may arise in many systems where formaldehyde is given as a primary product. The ease with which hydrogen atoms may be abstracted from formaldehyde by radicals means that, even when a photooxidation reaction is taken to only 1% conversion, the formaldehyde produced may have reacted further.67... 

Primary alcohols are formed from formaldehyde + Grignard reagent. Secondary alcohols are formed from an aldehyde + Grignard reagent. Tertiary alcohols are formed from a ketone (or an ester) + Grignard reagent. 

In the following subsections experiments are described which indicate that CO2 reduction to methylene-H4MPT is driven by a primary electrochemical Na potential generated by formaldehyde reduction to CH4. These experiments include (1) studies of the mode of energy transduction of the reverse reaction, the exergonic formaldehyde oxidation to CO2 and 2H2 (2) experiments on the effects of ionophores and inhibitors on CH4 formation from CO2/H2 and CH4 formation from formaldehyde/H2, and the determination of stoichiometries of primary Na" translocation. 

Stoichiometries of primary Na translocation. Further support for the conclusion that CO2 activation is driven by A/iNa" came from the determination of stoichiometries of primary Na transport coupled to CH4 formation from CO2/H2 and from formaldehyde/H2. Na" transport experiments were performed with whole cells of Methanosarcina barkeri equilibrated with Na the stoichiometry of Na export was... 

Aldehydes can be prepared by the dehydrogenation of a primary alcohol. Formaldehyde results from the dehydrogenation of methanol at high temperatures with an iron oxide-molybdenum oxide catalyst ... 

The classical Mannich reaction converts phenols to aminomethylated phenols. The reaction involves the addition of phenols to C=N bonds of imines or iminium salts formed from formaldehyde and primary or secondary amines, respectively . Recent modifications employ the reaction of an aminal in the presence of SO3, which gives a sulfonate ester, followed by o-aminomethylation (equation Sc(OTf)3 catalyzed... 

Correspondingly, primary alcohols are formed from formaldehyde and a Grignard reagent. CH2o + RMgX —> RCH2OH... 

CO2, N2O, and formaldehyde were found to elute simultaneously at 1.8-3.8 min. The mass spectrum coincident with the elution at 1.8-2.8 min was characterized by a peak at 29 daltons, which is attributed to a CHO fragment formed from formaldehyde, CH2O. A large amount of formic acid was detected at43.52 min, with a smaller amount of acetic acid detected at 39.79 min. Formaldehyde and formic acid were found to be the primary intermediates formed during the MEO of EG. The same results were obtained with Co(III). 

Simple unactivated fmmonlun salts generated in situ from formaldehyde and primary alkyl amines undergo a facile aza Diels-Alder reaction with... 

The synthesis of Oxyfedrine is based on the Mannich Reaction (see under Organic Name Reactions part J ) wherein one mole each of a ketone i.e., m-methoxy acetophenone reacts with a primary amine i.e., L-norephedrine in the presence of paraformaldehyde to give rise to a product with an additional —CH2— moiety derived from formaldehyde (or paraformaldehyde) i.e., oxyfedrine with the elimination of a mole of water. 

A, A -Bis(benzotriazolylmethyl)alkylamines 249, prepared from formaldehyde, primary amines, and benzotriazole 248, cyclized in the presence of formaldehyde and H2S or Na2S to provide 1,3,5-dithiazines 250 (Scheme 18) <2000SC779, 200SUL185>. 

Compounds capable of forming an enol react with imines from formaldehyde and a primary or secondary amine to yield /3-aminoalkyl carbonyl compounds called Mannich bases. The following reaction of acetone, formaldehyde, and diethylamine is an example ... 

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