Imine formation ammonia

It should also be noted that some pathways to be discussed below depend on highly unusual chemical reactions. To give just one example, the formation of the pyridine ring system of vitamin Be depends on a protein that catalyzes a complex series of reactions, including carbohydrate isomerization, imine formation, ammonia addition, aldol-type condensation, cycliza-tion, and aromatization (9). 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

A common technique for minimizing secondary amine formation is to carry out the hydrogenation in the presence of ammonia (21,23,42). Ammonia is thought to complete with the primary amine in attack on the intermediate imine. Anhydrous ammonia is preferred to prevent hydrolysis reactions,... 

Shu and co-workers (35) identified 2-isobutyl-3,5-diisopropylpyridine, 2-pentyl-3,5-dimethylpyridine, and its dihydro derivative obtained under similar conditions. Sultan (29) confirmed the presence of 3,5-diethyl-2-propylpyridine in a model system consisting of butyraldehyde and ammonium sulfide. Our proposed mechanism of their formation (20) consists of three steps 1) aldol condensation of the starting aldehydes to 2,4-alkadienals, 2) imine formation with ammonia, and 3) subsequent cyclization and oxidation to corresponding pyridines. An alternate mechanism, suggested by Shu and co-workers (33), takes into consideration the isolated dihydro derivatives. Hwang and co-workers described another dihydro derivative (19, R = Bu, R = R" = Pr, R= H) (37). 

Ammonia reacts with the ketone carbonyl group to give an imine (C=NH), which is then reduced to the amine function of the a-amino acid. Both imine formation and reduction are enzyme-catalyzed. The reduced form of nicotinamide adenine diphosphonu-cleotide (NADPH) is a coenzyme and acts as a reducing agent. The step in which the imine is reduced is the one in which the chirality center is introduced and gives only L-glutamic acid. 

Intramolecular imine formation between a coordinated aminate ion and a 2-oxo acid has been utilized to synthesize the two racemic amino acids 2-cyclopropylglycine and proline.463 Thus anation of [Co(NH3)5OH2]3+ by Br(CH2)3C0C02H at pH 5 gives two major products (145) and (146). Both are converted to tetraammineiminocarboxylato chelates by attack of an adjacent deprotonated ammonia. The cyclopropylimine complex can, for example, be reduced by alkaline BH4 to give the (RS)-2-cyclopropylglycine complex. 

Reactions proceeding more than once in the transformation of a substrate can be more effective than a single process If the reaction in question is a condensation of an N nucleophile with a carbonyl compound, the combination of the of two such reactions—allows for the synthesis of heterocycles like, the two depicted in Figure 9.27. The synthesis of quinoxaline (B) from glyoxal dihydrate (A) and orfho-phenylene diamine consists of two imine formations. Somewhat more complicated is the synthesis of dimethylpyrrole D from acetonyl acetone (C) and ammonia. After the formation of the first imine, an imine enamine isomerization occurs. A condensation followed by another imine — enamine isomerization leads to the product. 

Ketones and aldehydes also condense with other ammonia derivatives, such as hydroxyl amine and substituted hydrazines, to give imine derivatives. The equilibrium constants for these reactions are usually more favorable than for reactions with simple amines. Hydroxylamine reacts with ketones and aldehydes to form oximes hydrazine and its derivatives react to form hydrazones and semicarbazide reacts to form semicarbazones. The mechanisms of these reactions are similar to the mechanism of imine formation. 

The gas phase acid-catalyzed synthesis of pyridines from formaldehyde, ammonia and an alkanal is a complex reaction sequence, comprising at least two aldol condensations, an imine formation, a cyclization and a dehydrogenation (9). With acetaldehyde as the alkanal, a mixture of pyridine and picolines (methylpyridines) is formed. In comparison with amorphous catalysts, zeolites display superior performance, particularly those with MFI or BEA topology. Because formation of higher alkylpyridines is impeded in the shape-selective environment, the lifetime of zeolites is much improved in comparison with that of amorphous materials. Moreover, the catalytic performance can be enhanced by doping the structure with metals such as Pb, Co or Tl, which assist in the dehydrogenation. 

The original Kabachnik-Fields procedure employing ammonia as the amine component used ammonia in ethanol and the reactions were performed in sealed vessels at circa 100°C.90,123 This method avoids such conditions by using ammonium acetate as the source of ammonia, and it is also thought to act as an acid catalyst for imine formation other ammonium salts were unsatisfactory. Addition of water to produce a homogeneous reaction mixture resulted in diethyl 1-hydroxy-1-benzylphosphonate formation (i.e. from direct attack of diethyl phosphite 25 on benzaldehye, a common side reaction in the Kabachnik-Fields reaction). The yields of this reaction are serviceable, and better for aromatic than aliphatic aldehydes. The product 58 may be further purified by crystallization as the hydrochloride salt by treatment of 58 with hydrogen chloride in ethanol/diethyl ether.122... 

The application of the same principle to the formation of o-alanine is possible but lacks applicability due to its slowness. In this case, in the presence of ammonia, pyruvate is in equilibrium with its imine. This is reduced at the cathode under formation of racemic alanine. The L-alanine of the racemic mixture is reoxidized by L-alanine dehydrogenase under anodic regeneration of the necessary cofactor NAD to give pyruvate and ammonia, while the o-alanine is not accepted by the enzyme and accumulates in the reaction mixture. The drawback of this reaction is the kinetic control by imine formation, which is very slow, so that a complete inversion of a lOmAf solution of L-alanine would require 140 h [105]. 

Aldehydes and ketones react with one equivalent of phenylhydrazine, forming phenylhydrazones (Section 18.6). Aldoses and ketoses, in contrast, react with three equivalents of phenylhydrazine, forming osazones. One equivalent functions as an oxidizing agent and is reduced to aniline and ammonia. Two equivalents form imines with carbonyl groups. The reaction stops at this point, regardless of how much phenylhydrazine is present. (Recall that the pH at which imine formation is carried out must be carefully controlled Section 18.6.)... 

Finally, the pyridine synthesis is simply a double enamine/imine formation between ammonia and the two carbonyl groups. Probably the aldehyde reacts first. 

Treatment of />w(3-chloropropyl) ether with ammonia affords a modest (36%) yield of 3,4,5,6,7,8-hexahydro-2/f-l,5-oxazocine (74) <85Mi 924-04), while nucleophilic displacement of halide by ammonia, followed by intramolecular imine formation provides a 2% yield of benzoxazocine (62) (Equation (28)) <84AJC129>. 

The aldehyde is the only electrophilic site in the starting material. Cyanide and ammonia are both nucleophiles. Cyanide reacts reversibly with aldehydes, so imine formation is preferred. 

Addition of ammonia or a primary amine to the carbonyl group of an aldehyde or a ketone forms a tetrahedral carbonyl addition compound. Loss of water from this intermediate gives an imine.The mechanism for imine formation involves an initial attack of the nucleophilic nitrogen atom on the carbonyl carbon atom followed by proton transfer to the OH, creating an HjO group that then departs. 

Scheme 10.15. A depiction of the A-chlormation of cyclohexylamine and the subsequent loss of hydrogen chloride (HCl) with imine formation followed by hydrolysis to cyclohexanone and ammonia.

Notice that enamines are the nitrogen counterpart of enols (p. 448). Now comes an important question Why doesn t the iminium ion formed from primary amines or ammonia (Fig. 16.49) also lose a proton from carbon to give an enamine Why is imine formation preferred when there is a choice (Fig. 16.55) The answer is extraordinarily simple Just as the ketone tautomer is more stable than the enol, the imine is more stable than the enamine and so is preferred when possible. It is only in cases where imine formation is not possible, as when secondary amines are used, that enamines are formed. We hope you have noticed that the imine- and enamine-forming reactions are reversible. The reactions work best under slightly acidic conditions with heat applied to drive off water. If water is added to an imine or enamine, the reverse reaction occurs to yield the carbonyl compound and an amine. 

Primary amines cannot be usefully prepared, by reductive alkylation, from lower members of the aliphatic aldehydes and ammonia owing to side-reactions (for instance, formaldehyde and ammonia give hexamethylenetetramine). For aldehydes with more than five carbon atoms, however, conversion to the corresponding amine gives 60% yieldsEven better yields are reported for aromatic aldehydes, presumably because of the greater ease of imine formation With an excess of aromatic aldehyde the reaction with ammonia invariably leads to formation of the secondary amine but with aliphatic compounds a mixture of primary and secondary amines is generally obtained. Alternatively, secondary amines can be prepared directly from primary amines (equation 35). 

Arylmethylamines can be oxidized to the corresponding arylamides by formation of a Schiff base with 2,6-di-t-butylbenzoquinone and base-catalysed oxygenation. Allenic alcohols are oxidized to allenic amides by nickel peroxide at -20 °C in ethereal ammonia. N-Alkyl-amides can be prepared from aldehydes in a four-step procedure consisting of imine formation and subsequent reactions with N-chlorosuccinimide, potassium cyanide, and finally alcoholic HCl. ... 

Begin in a manna- identical to the mechanisms of addition of ammonia and primary amines to give imines. As you proceed step by step, look for the point at which the structure of the secondary amine forces the mechanism to diverge from imine formation. 

Judicious selection of catalyst is necessary to avoid multi-allqrlation ruthenium catalysts tend to provide primary amines from ammonia, while iridium catalysts tend to provide seeondary or tertiary amines (Scheme 12.3). The reasons for the mono-allqrlation seleetivity of ruthenium catalysts have not been thoroughly studied however, Vogt reports that extended reaction times aetually increase the seleetivity for primary amine formation. This observation points toward the reversibility of secondary imine formation, wherein hydrolysis of the seeondary imine is favoured over hydrogenation to the seeondary amine. Both iridium and ruthenium catalysts have proven to be effeetive with aqueous ammonia. 

Benzophenone Process. Benzophenone, (CgH5 )2C=0, reacts with ammonia to form diphenylmethanimine, (CgHg )2C=NH. In the presence of copper catalysts, this is oxidized with oxygen to benzophenone azine, (CgHg )2C=N—N=C(CgHg The formation of the imine and its... 

---