Halogenation of Amines

Tertiary amines, such as N,N-dimethylaniline, can be chlorinated under controlled conditions to yield 2,4,6-trichlorophenylcarbonimidoyl dichloride (LII), which can be further chlorinated in the presence of FeCl3 to yield pentachlorophenylcarbonimidoyl dichloride (LIII). The yields of LII and LIII are 82-87 % and 96-98 %, respectively C ). It is absolutely necessary to conduct the initial chlorination below 60°C, otherwise considerable amounts of intractable tars are formed due to side reactions 

Upon reaction of LII with two equivalents of dimethylamine the corresponding chloroformamidine (LIV) can be obtained, which upon high-temperature chlorination yields the chloroimidoylcarbonimidoyl di-chloride derivative LV ( ). 

The chlorination of aliphatic tertiary amines is less uniform, and hitherto only good results have been obtained in the chlorination of N,N,N, N -tetramethylethylenediamine (LVI), in which all the carbon atoms are in a-position to the nitrogen. Thus, chlorination of LVI in trichlorobenzene produces the bis-carbonimidoyl dichloride LVII in good yield 

Tetrachloroethane 1,2-bis-carbonimidoyl dichloride To a solution of 116g (1 mole) of tetramethylethylenediamine in 1000 ml of 1,2,4-tri-chlorobenzene chlorine is added and the exothermic reaction is controlled at 70-80°C. After the exothermic reaction ceases the temperature is raised at the rate of 10-15°C/hr and chlorination is continued with ultraviolet irradiation. When the temperature has reached 190-210 C, the chlorination is continued for 5 hr, and excess chlorine is removed in a stream of nitrogen. On cooling and concentration tetrachloroethane 1,2-biscarbonimidoyl dichloride, m.p. 166°C is obtained. The yield can range from 30-71%, depending upon temperature control. 

The perhalo compound LVII was also obtained upon chlorination of N,N-dimethylaminoacetonitrile (LVIII), and the nitrile LIX is supposed to be the intermediate, which eliminates cyanogen chloride to yield the final product 

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Elemental chlorine and bromine, and alkali and alkaline-earth hypochlorides are used for JV-halogenation of amines or amides or tert-butyl hypochlorite, 395 may be usec for halogenation in an organic solvent. The Table on p. 598 illustrates uses of the individual halogenating agents. 

C.H.[0].S.Halogen Aryl sulphonyl chlorides C.H.[0].N.S Salts of amines and nitro- ... 

Controlled halogenation can be achieved by halogenation of the A/-acetyl derivative of the aromatic amine, followed by hydrolysis of the acetyl... 

At temperatures near the critical temperature, many organic degradation reactions are rapid. Halogenated hydrocarbons loose the halogen in minutes at 375°C (38). At temperatures typical of nuclear steam generators (271°C (520°F)), the decomposition of amines to alcohols and acids is well known (39). The pressure limits for the treatment of boiler waters using organic polymers reflect the rate of decomposition. 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, aHenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphoms oxychloride [10025-87-3] POCl (H)- Because sulfonic acids are generally not converted directiy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphoms pentachlotide [10026-13-8] and phosphoms pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl haUdes (12,13). The conversion may also be accompHshed by continuous electrolysis of thiols or disulfides in the presence of aqueous HCl [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfutic acid [7789-21-17, or by reaction of the sulfonic acid or sulfonate with fluorosulfutic acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl haUde, can be achieved under oxidative halogenation conditions (15). 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Generally, the addition of chlonne or bromine to tnfluoroacetonitrile leads to a mixture of partially halogenated imines, amines and azo alkanes [270, 271] In special cases, such as the HgF2-mediated addition of bromine, N,N dihaloper-fluoro-2-alkylamines can be obtained in good yields [272]... 

A. Attack by NH2, NHR, or NR2 at an Alkyl Carbon 10-44 Alkylation Of Amines Amino-de-halogenation (alkyl)... 

Treatment with sodium hypochlorite or hypobromite converts primary amines into N-halo- or N,N-dihaloamines. Secondary amines can be converted to N-halo secondary amines. Similar reactions can be carried out on unsubstituted and N-substituted amides and on sulfonamides. With unsubstituted amides the N-halo-gen product is seldom isolated but usually rearranges (see 18-13) however, N-halo-N-alkyl amides and N-halo imides are quite stable. The important reagent NBS is made in this manner. N-Halogenation has also been accomplished with other reagents, (e.g., sodium bromite NaBr02) benzyltrimethylammonium tribromide (PhCH2NMe3 Br3"), and NCS. The mechanisms of these reactions involve attack by a positive halogen and are probably similar to those of 12-47 and 12-49.N-Fluorination can be accomplished by direct treatment of amines °° or... 

Oxidation of thiophene with Fenton-like reagents produces 2-hydroxythiophene of which the 2(570 One isomer is the most stable (Eq. 1) <96JCR(S)242>. In contrast, methyltrioxorhenium (Vn) catalyzed hydrogen peroxide oxidation of thiophene and its derivatives forms first the sulfoxide and ultimately the sulfone derivatives <96107211>. Anodic oxidation of aminated dibenzothiophene produces stable radical cation salts <96BSF597>. Reduction of dihalothiophene at carbon cathodes produces the first example of an electrochemical halogen dance reaction (Eq. 2) <96JOC8074>. 

Karpfen published a study of trends in halogen bonding between a series of amines and halogens and interhalogens [171]. Iodine-containing electron acceptors were not included. This study involved the use of RHF, MP2, and various DFT methods using extended, polarized basis sets and made extensive use of pulsed-nozzle, FT-microwave spectroscopic data (similar to that... 

Aromatic amination by replacement of halogens with amines (example... 

Nucleophilic displacement of halogen by amines is an important method of introducing amino groups into the anthraquinone ring system. In the Ullmann reaction the displacement is catalysed by metallic copper or by copper ions so that relatively mild conditions can be used. Mechanistic studies suggest that copper(I) ions exert a catalytic effect via complex formation. Derivatives of 1,4-diaminoanthraquinone are of considerable industrial significance. Many compounds are prepared from the reduced form of quinizarin (6.6). 

Rappoport and Topol investigated the displacement of the halogen of bromo- and chloromethylenemalonates (287 X= Br, Cl) by several substituted anilines and that of the brosyloxy group of (4-nitrophenyl)(4-bromo-phenylsulfonyloxy)methylenemalonate (289) by morpholine and piperidine, in acetonitrile. A rate-determining nucleophilic addition of the amines was suggested as the mechanism for these reactions. Activation parameters (AH, AS ) were determined [72JCS(P2)1823]. 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

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