Secondary or tertiary amines

The reaction proceeds most readily wfth alkylaryl, dialkyl, and cyclic ketones, but the crude product may contain some secondary or tertiary amine. 

A method that achieves the same end result as that desired by alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis Alkyl halides are converted to primary alkylamines without contam mation by secondary or tertiary amines The key reagent is the potassium salt of phthal imide prepared by the reaction... 

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

The preparation of amines by the methods described m this section involves the prior synthesis and isolation of some reducible material that has a carbon-nitrogen bond an azide a nitrile a nitro substituted arene or an amide The following section describes a method that combines the two steps of carbon-nitrogen bond formation and reduction into a single operation Like the reduction of amides it offers the possibility of prepar mg primary secondary or tertiary amines by proper choice of starting materials... 

Reduction of amides (Section 22 9) Lithi um aluminum hydride reduces the car bonyl group of an amide to a methylene group Primary secondary or tertiary amines may be prepared by proper choice of the starting amide R and R may be ei ther alkyl or aryl... 

Weak Base. Weak base anion-exchange resins may have primary, secondary, or tertiary amines as the functional group. The tertiary amine -N(CH2)2 is most common. Weak base resins are frequentiy preferred over strong base resins for removal of strong acids in order to take advantage of the greater ease in regeneration. 

Cycloaliphatic amines are strong bases with chemistry similar to that of simpler primary, secondary, or tertiary amines. Upon reaction with nitrous acid,... 

Phenols. Phenols are unreactive toward chloroformates at room temperature and at elevated temperatures the yields of carbonates are relatively poor (< 10%) in the absence of catalysis. Many catalysts have been claimed in the patent Hterature that lead to high yields of carbonates from phenol and chloroformates. The use of catalyst is even more essential in the reaction of phenols and aryl chloroformates. Among the catalysts claimed are amphoteric metals or thek haUdes (16), magnesium haUdes (17), magnesium or manganese (18), secondary or tertiary amines such as imidazole (19), pyridine, quinoline, picoline (20—22), heterocycHc basic compounds (23) and carbonamides, thiocarbonamides, phosphoroamides, and sulfonamides (24). 

Catalytic hydrogenation of the nitrile function of cyanohydrins can give amines. As in the case of ordinary nitriles, catalytic reduction of cyanohydrins can yield a mixture of primary, secondary, and tertiary amines. Addition of acid or acetic anhydride to the reaction medium minimizes formation of secondary or tertiary amines through formation of the amine salt or acetamide derivative of the primary amine. 

For alkylbenzenes, nitrobenzenes, halogenated benzenes and for secondary or tertiary amines where at least one aromatic group is connected to an amino nitrogen, add the following corrections for each aromatic nuclei is. If N < 16, increase AN by 0.60 if N > 16, increase AN by 3.055 — 0.161N for each aromatic group. For any N, increase AB by (—140.04 + 13.869 ). 

Reductive amination (Section 22.10) Reaction of ammonia or an amine with an aldehyde or a ketone in the presence of a reducing agent is an effective method for the preparation of primary, secondary, or tertiary amines. The reducing agent may be either hydrogen in the presence of a metal catalyst or sodium cyanoborohy-dride. R, R, and R" may be either alkyl or aryl. 

Write structural formulas or build molecular models for all the amines of molecular formula C4H11N. Give an acceptable name for each one, and classify it as a primary, secondary, or tertiary amine. 

The activation energy of substitution of an unactivated aromatic halide (e.g., fiuorobenzene and 2-chloronaphthalene ) is over 30 kcal while that of activated compounds is 5-20 kcal. For the tabulated reactions (Tables II-VIII) with alkoxide and with primary, secondary, or tertiary amines, resonance activation (cf. 278 and 279) by ortho or para nitrogens is found to be greater than inductive activation (cf. 251). This relation is qualitatively demonstrated in... 

The reaction of potassium phthalimide 1 with an alkyl halide 2 leads to formation of a N-alkyl phthalimide 3/ which can be cleaved hydrolytically or by reaction with hydrazine (Ing-Manske variant) to yield a primary amine 5. This route owes its importance as a synthetic method to the fact that primary amines are prepared selectively, not contaminated with secondary or tertiary amines. 

C-coupling is of outstanding importance in the azo coupling reaction for the synthesis of azo dyes and pigments. An aromatic or heteroaromatic diazonium ion reacts with the so-called coupling component, which can be an aromatic primary, secondary, or tertiary amine, a phenol, an enol of an open-chain, aromatic, or heteroaromatic carbonyl compound, or an activated methylene compound. These reactions at an sp2-hybridized carbon atom will be discussed in Chapter 12. In the... 

Tetrakis(tripheiiylphosphine)palladium(0) is often used for this reaction. However, Pd(II) complexes such as bis(triphenylphosphine)palladium dichloride or palladium acetate are also commonly employed for convenience, as they are stable in ah. The base is typically a secondary or tertiary amine such as triethy-lamine. Weak bases such as sodium (potassium) acetate, bicarbonate, or carbonate are also used. 

Compounds With Tervalent Chiral Atoms. Atoms with pyramidal bonding might be expected to give rise to optical activity if the atom is connected to three different groups, since the unshared pair of electrons is analogous to a fourth group, necessarily different from the others. For example, a secondary or tertiary amine where X, Y, and Z are different would be expected to be chiral and thus resolvable. Many attempts have been made to resolve such compounds, but until 1968 all of them failed because of pyramidal inversion, which is a rapid oscillation of the unshared pair from one side of the XYZ... 

It is obvious that the primary amines formed in this reaction will be uncontaminated by secondary or tertiary amines (unlike 10-44). The reaction is usually rather slow but can be conveniently speeded by the use of a dipolar aprotic solvent such as DMF or with a crown ether. Hydrolysis of the phthalimide, whether acid or base catalyzed (acid catalysis is used far more frequently), is also usually very slow, and better procedures are generally used. A common one is the Ing-Manske procedure,in which the phthalimide is heated with hydrazine in an exchange... 

A reaction that involves dehydrogenation to an imine, which then reacts further is the reaction of primary or secondary amines with palladium black. The imine initially formed by the dehydrogenation reacts with another molecule of the same or a different amine to give an aminal, which loses NH3 or RNH2 to give a secondary or tertiary amine. An example is the reaction between V-methylbenzylamine and... 

All TCAs are either secondary- or tertiary-amines of a dibenzazepine nucleus (Fig. 20.3), and they all inhibit neuronal reuptake of noradrenaline and/or 5-HT but are much less potent as dopamine reuptake blockers. A common claim is that secondary amines (e.g. desipramine) are preferential inhibitors of noradrenaline uptake whereas the tertiary derivatives (e.g. imipramine, doxepin and amitryptyline) preferentially inhibit 5-HT uptake. However, when Richelson and Pfenning (1984) actually compared the effects of a wide range of antidepressants on the synaptosomal uptake of [ H]monoamines in vitro, and compared their A s, instead of merely ranking /C50S collected from different studies, they found that tertiary- and secondary-substituted compounds were equi-potent inhibitors of [ H]noradrenaline uptake. Moreover, all the TCAs turned out to be more potent inhibitors of [ H]noradrenaline than of [ H]5-HT uptake. Tertiary amines are even less convincing inhibitors of 5-HT reuptake in vivo, because any such action is diminished by their metabolism to secondary amines (e.g. imipramine to desipramine amitriptyline to nortriptyline). Only clomipramine retains any appreciable 5-HT uptake blocking activity in vivo with (an unimpressive) five-fold selectivity for 5-HT versus noradrenaline. 

Adducts of a fatty amine adduct to unsaturated acid in which the product contains only secondary or tertiary amine groups that have a lower toxicity to the environment [391]. 

In summary, the preparation of polyimidazolinones from polyamides containing a-aminoacid units (3, X = NH) can now be considered to be a general reaction provided that Rz and/or R3 are not hydrogen. When the polyamide has additional secondary or tertiary amine functionality in the backbone, cyclodehydration appears to be exceptionally facile. In the absence of amine functionality however, a catalyst is necessary to promote cyclization. Further studies of this new heterocyclic polymer system are ongoing in our laboratories. 

The hindered secondary amines can be highly effective photostabilizers for various polymers (]+.,5.,.6) Various hindered amines have been shown to retard oxidation, but most share the common feature of being secondary or tertiary amines with the a-carbons fully substituted. The most widely exploited representatives of this class are based on 2,2,6,6-tetramethylpiperidine either in the form of relatively simple low molecular weight compounds, or more recently as backbone or pendant groups on quite high molecular weight additives ( i.,5.,6). The more successful commercial hindered amines contain two or more piperidine groups per molecule. Photo-protection by tetra-methylpiperidines (near UV transparent) must result from the interruption of one or more of the reactions 1 to 3. Relatively recent results from our own laboratories, and in the open literature will be outlined in this context. 

Reaction with primary, secondary or tertiary amines proceeds explosively with ignition in absence of a solvent. 

Katti, 1996 Katti et al., 1999). Nucleophiles react with the hydroxymethyl arms by attack on the electron-deficient carbon atom with loss of water to form secondary or tertiary amine bonds (Reaction 16). 

Figure 6.4 THPP reacts with amine-containing molecules to form secondary or tertiary amine bonds.

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