Double carbon-nitrogen

Compounds that contain a carbon—nitrogen double bond are capable of stereoisomerism much like that seen in alkenes The structures... 

Gycloaddition Reactions. Isocyanates undergo cyclo additions across the carbon—nitrogen double bond with a variety of unsaturated substrates. Addition across the C=0 bond is less common. The propensity of isocyanates to undergo cycli2ation reactions has been widely explored for the synthesis of heterocycHc systems. Substrates with C=0, C=N, C=S, and C=C bonds have been found to yield either 2 + 2, 2 + 2 + 2, or 2 + 4 cycloadducts or a variety of secondary reaction products (2). 

Carbon—nitrogen double bonds in imines, hydrazones, oximes, nitrones, azines, and substituted diazomethanes can be cleaved, yielding mainly ketones, aldehydes and/or carboxyHc acids. Ozonation of acetylene gives primarily glyoxal. With substituted compounds, carboxyHc acids and dicarbonyl compounds are obtained for instance, stearoHc acid yields mainly azelaic acid, and a smaH amount of 9,10-diketostearic acid. 

Polyurethane Formation. The key to the manufacture of polyurethanes is the unique reactivity of the heterocumulene groups in diisocyanates toward nucleophilic additions. The polarization of the isocyanate group enhances the addition across the carbon—nitrogen double bond, which allows rapid formation of addition polymers from diisocyanates and macroglycols. 

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

A number of reagents, including perfluoroalkylsulfur trifluorides [191] (equation 29), will add fluorine and sulfur to carbon-nitrogen double bonds [131]... 

II. Structure, Preparation, and Detection of Iminium Salts A. Structure oe Iminium Salts The positively charged carbon-nitrogen double bond... 

Reactions at the carbon-nitrogen double bond of iminium salts are analogous to nucleophilic reactions at the carbonyl group of aldehydes and ketones. This is why free enamines do not react with nucleophilic reagents, whereas their salts can undergo such reactions. 

The isoindole-isoindolenine equilibrium has been studied quantitatively only in the case of certain 1-arylisoindoles. Although two structurally different isoindolenines are possible, only that with the carbon-nitrogen double bond conjugated with both aromatic rings was observed. Investigation of the isoindole-isoindolenine ratios for three compounds by NMR and ultraviolet spectroscopy indicated a... 

Asano and co-workers have reported die kinetic effects of pressure, solvent, and substituent on geometric isomerization about die carbon-nitrogen double bond for pyrazol-3-one azomethines 406 (R = H), 406 (R = NO2) and 407, (Scheme 93). The results demonstrate the versatility of die inversion mechanism. The rotation mechanism has been invalidated. First-wder rate constants and activating volumes for diermal E-Z isomerization for 406 (R = H) and 406 (R = NO2) are given at 25°C in benzene and methanol (89JOC379). 

Ester enolates which contain the chiral information in the acid moiety have been widely used in alkylations (see Section D.1.1.1,3.) as well as in additions to carbon-nitrogen double bonds (sec Section D.1.4.2.). Below are examples of the reaction of this type of enolate with aldehydes720. The (Z)-enolate generated from benzyl cinnamate (benzyl 3-phenylpropcnoate) and lithium (dimethylphenylsilyl)cuprate affords the /h/-carboxylic acid on addition to acetaldehyde and subsequent hydrogenolysis, The diastereoselectivity is 90 10. 

The chemistry of carboxylic acids and esters The chemistry of the carbon-nitrogen double bond The chemistry of amides The chemistry of the cyano group The chemistry of the hydroxyl group (2 parts)... 

The Chemistry of Carboxylic Acids and Esters The Chemistry of the Carbon-Nitrogen Double Bond The Chemistry of the Cyano Group The Chemistry of Amides... 

Ubersicht H. Lund in S. Patai, Electrochemistry of the carbon-nitrogen double bond, Wiley-Interseience,New... 

Compounds containing carbon-nitrogen double bonds can be hydrolyzed to the corresponding aldehydes or ketones. For imines (W = R or H) the hydrolysis is easy and can be carried out with water. When W = H, the imine is seldom stable enough for isolation, and hydrolysis usually occurs in situ, without isolation. The hydrolysis of Schiff bases (W = Ar) is more difficult and requires acid or basic catalysis. Oximes (W = OH), arylhydrazones (W = NHAr), and, most easily, semicarbazones (W = NHCONH2) can also be hydrolyzed. Often a reactive aldehyde (e.g., formaldehyde) is added to combine with the liberated amine. 

The hydrolysis of carbon-nitrogen double bonds involves initial addition of water and elimination of a nitrogen moiety ... 

Related to this process is the hydrolysis of isocyanates or isothiocyanates" where addition of water to the carbon-nitrogen double bond would give an N-substituted carbamic acid (3). Such compounds are unstable and break down to carbon dioxide (or COS in the case of isothiocyanates) and the amine ... 

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 ... 

For reviews of reactions of carbonyl compounds leading to the formation of C=N bonds, see Dayagi, S. Degani, Y. in Patai The Chemistry of the Carbon-Nitrogen Double Bond Ref. 40, p. 64 Reeves, R.L. in Patai, Ref. 2, p. 600. 

An imine is a molecule that contains a carbon—nitrogen double bond. Describe the bonding of the simplest possible imine, H2 CNH, by sketching the a and n bonding systems. 

These enzymes catalyze the addition of the elements of water to carbon-carbon double bonds (C=C), carbon-carbon triple bonds (C C), carbon-nitrogen double bonds (C=N), or carbon-nitrogen triple bonds (C N). These reactions are completely different from oxidoreductases since no redox reactions are involved. Illustrative examples include the following ... 

Mono- and dilithio derivatives of p-tosylmethyl isocyanide 297a were shown to display interesting reactions. Reaction of the monoanion with unsaturated esters was shown to give pyrrole derivatives . Dianion 297b was found to add to the carbon-nitrogen double bonds of isoquinoline, quinoline and quinoxaline affording compounds 298, 299 and 300, respectively. In the reactions with pyridine iV-oxide and pyridazine iV-oxide, unstable open-chain products 301 and 302 were obtained . 

Several functional groups containing carbon-nitrogen double bonds can participate in radical cyclizations. Among these are oxime ethers, imines, and hydrazones.337 Hydrazones and oximes are somewhat more reactive than imines, evidently because the adjacent substituents can stabilize the radical center at nitrogen.338 Cyclization at these functional groups leads to amino- substituted products. 

Efavirenz (1) is the second NNRTI development candidate at Merck. Prior to the development of 1, we worked on the preparation of the first NNRTI development candidate 2 [2]. During synthetic studies on 2, we discovered and optimized an unprecedented asymmetric addition of an acetylide to a carbon-nitrogen double bond. The novel asymmetric addition method for the preparation of 2 also provided the foundation for the process development of Efavirenz . Therefore, in this chapter we will first discuss chemistries for the preparation of 2 in two parts process development of large scale synthesis of 2 and new chemistries. Then, we will move into process development and its chemistries on Efavirenz . 

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