Ketones and nitrogen

Another type of cyclization leading to acetylenylpyrazoles is the interaction between a-acetylenic and -diacetylenic ketones and nitrogen-containing binucleophiles. 

Compound 59 behaves differently from azines toward sensitized photooxidation, showing little reaction after 26 h, whereas azines give the parent ketone and nitrogen.75... 

Hydrophilic molecules are composed of ions (such as sulphonate, sulphate, carboxylate, phosphate and quaternary ammonium), polar groups (such as primary amines, amine oxides, sulphoxides and phosphine oxide) and non-polar groups with electronegative atoms (such as oxygen atom in ethers, aldehydes, amides, esters and ketones and nitrogen atoms in amides, nitroalkanes and amines). These molecules associate with the hydrogen bonding network in water. 

To use reductive amination in synthesis, you must be able to determine what aldehyde or ketone and nitrogen compound are needed to prepare a given amine—that is, you must work backwards in the retrosynthetic direction. Keep in mind the following two points ... 

SampiG ProbiGm 25.2 What aldehyde or ketone and nitrogen cxjmponent are needed to synthesize N-ethylcyclohexylamine by a... 

Diethyl ketone and nitrogen iodide in 2,5 -Diethy 1-3,6-dimethy Ipyrazine 512... 

Both TIN and TTA [Tl(OAc)3] have been known to act as electrophiles toward olefinic double bonds, enolizable ketones and nitrogen-containing compounds to afford a variety of natural products or their synthons. As already shown in Scheme 162, TIN was applied to phenolic oxidation by Yamamura and Nishiyama . In particular, this method which consists of TIN oxidation in MeOH followed by Zn reduction in AcOH is effective for the construction of macrocyclic diaryl ethers from the corresponding open-ring precusors, which are required to possess two o,o -dihalophenol moieties. 

It acts as an acceptor towards alcohols, ethers, esters, ketones and nitrogenous bases as well as towards rc-donors such as benzene as can be seen from the charac-... 

Addition compounds form with those organics that contain a donor atom, eg, ketonic oxygen, nitrogen, and sulfur. Thus, adducts form with amides, amines, and A/-heterocycles, as well as acid chlorides and ethers. Addition compounds also form with a number of inorganic compounds, eg, POCl (6,120). In many cases, the addition compounds are dimeric, eg, with ethyl acetate, in titanium tetrachloride-rich systems. By using ammonia, a series of amidodichlorides, Ti(NH2) Cl4, is formed (133). 

Several blocked diamines or amino-alcohols are commercially available. The aldimine is an aldehyde-blocked diamine. The ketimine is a ketone-blocked diamine. The oxazolidine is a five-membered ring containing oxygen and nitrogen. The oxazolidine ring shown below is an aldehyde-blocked amino alcohol. The basic synthetic concepts of an aldimine, a ketimine, and an oxazolidine are shown below ... 

Diazoketones react with trifluoromcthyl hypofluorite to give a mixture of a,a-difluoro ketones and o-fluoro-a-trifluoromethoxy ketones [70, 71] With elemental fluorine, two fluorine atoms replace the nitrogen in both diazoketones and unactivated diazo eompounds [70, 72, 73] (equation 9)... 

The above considerations presuppose that two important conditions are fulfilled. First the nitrogen must be tertiary, as primary and secondary vinylamines are generally more stable in the imine form (5). Only in the case of enamino ketones and esters are the enamine more stable than the imine forms (7). Secondly, the atoms comprising the tt system must be able... 

Paulsen and Huck also used gas-phase chlorination of ammonia. The mixture, diluted with nitrogen, was led into excess liquid ketone. Diaziridines were obtained from methyl ethyl ketone, diethyl ketone, methyl propyl ketone, and methyl isopropyl ketone. The yields of the crude diaziridines, calculated on the chlorine, were over 90% (Table IV). 

In a 200-ml three-necked flask fitted with a dropping funnel (drying tube) is placed a solution of 13.4 g (0.12 mole) of 1-octene in 35 ml of THF. The flask is flushed with nitrogen and 3.7 ml of a 0.5 M solution of diborane (0.012 mole of hydride) in THF is added to carry out the hydroboration. (See Chapter 4, Section I regarding preparation of diborane in THF.) After 1 hour, 1.8 ml (0.1 mole) of water is added, followed by 4.4 g (0.06 mole) of methyl vinyl ketone, and the mixture is stirred for 1 hour at room temperature. The solvent is removed, and the residue is dissolved in ether, dried, and distilled. 2-Dodecanone has bp 119710 mm, 24571 atm. (The product contains 15 % of 5-methyl-2-undecane.) The reaction sequence can be applied successfully to a variety of olefins including cyclopentene, cyclohexene, and norbornene. 

However, in some cases azines can be converted to hydrazones by treatment with excess hydrazine and NaOH. Arylhydrazines, especially phenyl, p-nitrophenyl, and 2,4-dinitrophenyl, are used much more often and give the corresponding hydrazones with most aldehydes and ketones.Since these are usually solids, they make excellent derivatives and are commonly employed for this purpose. Cyclic hydrazones are also known, ° as are conjugated hydrazones. a-Hydroxy aldehydes and ketones and ot-dicarbonyl compounds give osazones, in which two adjacent carbons have carbon-nitrogen double bonds ... 

Gutsche. It may be noted that this mechanism is essentially the same as in the apparent insertions of oxygen (18-19) and nitrogen (18-16) into ketones. 

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