Bisamidation

Ak2o has been iastmmental ia developiag a new process for the stereospecific synthesis of 1,4-cyclohexane diisocyanate [7517-76-2] (21). This process, based on the conversion of poly(ethylene terephthalate) [25038-59-9] circumvents the elaborate fractional crystallisation procedures required for the existing -phenylenediamine [108-45-2] approaches. The synthesis starts with poly(ethylene terephthalate) (PET) (32) or phthaUc acid, which is converted to the dimethyl ester and hydrogenated to yield the cyclohexane-based diester (33). Subsequent reaction of the ester with ammonia provides the desired bisamide (34). The synthesis of the amide is the key... 

Amide yields of up to 90—95% are reported from lauric acid and urea (1 1 mole ratio) by ramping the reaction temperature from 140 to 190°C over 4 hours. Oleic, stearic, linoleic, and ricinoleic acids gave similar results (19,20). The reaction does not form significant quantities of bisamides, but rehes on the decomposition of a substituted urea amide, releasing CO2 and NH. ... 

Bisamides. Methylenebisamides are prepared by the reaction of the primary fatty amide and formaldehyde in the presence of an acid catalyst. AijAT-Methylenebisoleamide has been made via this route without the use of refluxing solvent (55). Polymethylenebisamides can be made from fatty acid, esters, or acid haUdes with diamines while producing water, alcohol, or mineral acid by-products. Eatty acids and diamines, typically ethylenediamine, have been condensed in the presence of NaBH and NaH2P02 to yield bisamides (56). When stearic acid, ethylenediamine, and methyl acetate react for 6 h at... 

Many primary fatty amides which are available from various manufacturers are Hsted in Table 3. In 1986 approximately 55,000 metric tons of amides and bisamides were produced world wide (58), the majority of which are bisamides, followed in volume by primary amides. Most of these products are shipped in sohd form in bag or dmm quantities. Major producers of primary fatty amides are Akzo, Glyco, Humko, and Sherex. Bisamides are produced by Akzo, Milacron, and Syntex. There are over 100 producers of alkanolamides in the world, most of which are small specialized manufacturers to a specific industry. GAP, Henkel, Sherex, and Witco are among the principal producers. The most widely used alkanolamides are the Ai,Ai-bis(2-hydroxyethyl) fatty amides, mostly produced from middle-cut coco fatty acids (6% capryflc, 7% capric, 51% lauric, 19% myristic, 9% palmitic, and 2% stearic acids). An estimated 77,000 metric tons of alkanolamide was produced worldwide in 1986 (59). 

Amides can be titrated direcdy by perchloric acid ia a nonaqueous solvent (60,61) and by potentiometric titration (62), which gives the sum of amide and amine salts. Infrared spectroscopy has been used to characterize fatty acid amides (63). Mass spectroscopy has been able to iadicate the position of the unsaturation ia unsaturated fatty amides (64). Typical specifications of some primary fatty acid amides and properties of bisamides are shown ia Tables 5 and 6. 

Eatty bisamides are used primarily to kicrease sHp, reduce blocking, and reduce static ki polymeric systems. Other specialty appHcations kiclude cosolvents or coupling agents for polyamide reskis, fillers for electrical kisulation coatings, additives for asphalt to reduce cold flow, and synthetic waxes for textile treatments (68). Bisamides have been used ki all the traditional primary amide appHcations to kicrease lubricity and have become the amide of choice because of thek better efficiency. Bisamides have the highest commercial value ki the amide market. 

The lack of structural specificity among sedative-hypnotic drugs has been alluded to before. It is perhaps not too surprising that quinazolones, too, show this activity. The prototype, methaqualone (149), is obtained in a single step from the condensation of the"anthranilamide, 148, with o-toluidine.(The reaction may well involve first formation of the bisamide cycli-zation will then give the quinazolone ring system.) Condensation... 

On photolysis in benzene solution, the bisamides 22 (n > 14) form internal [2 + 2] photodimers 23, the maximum quantum yield being noted with n = 26. The shorter alkyl chain analogs 22 (n = 2-12), under the same conditions, form intcrmolccular dimers.236... 

Bisamides (or biscarbamates), which are easily obtainable from the reaction of an aldehyde with two equivalents of a primary amide (carbamate), are converted into the corresponding A-acyliminium ions on heating, often in the presence of strong (Lewis) acids or acylating compounds1 3. 

If R2 contains an a-hydrogen the method cannot be applied as enaminc formation occurs. Bisamides (or -carbamates) are often used in amidoalkylations of aryl and reactive methylene compounds, but the rather harsh reaction conditions severely limit application in the synthesis of more complicated molecules with other functional groups. 

Amides can add to aldehydes in the presence of bases (so the nucleophile is actually RCONH ) or acids to give acylated amino alcohols, which often react further to give alkylidene or arylidene bisamides. If the R group contains an a hydrogen, water may split out. 

The (E/Z) ratio of the product can often be changed by a change in solvent or by the addition of salts. Another way of controlling the stereochemistry of the product is by use of the aforementioned phosphonic acid bisamides. In this case the betaine (42) does form and when treated with water gives the (3-hydroxyphosphonic... 

Attempts to hydroaminate ethylene, aUylbenzene, and norbornene with ArNH2 in the presence of zirconium bisamides Cp2Zr(NHAr)2 (Ar = 2,6-Me2CsH3, o-MeQH4) at temperatures up to 160°C have been unsuccessful [126]. 

In 1992, Bergman et al. reported that zirconium bisamides Cp2Zr(NHR)2 catalyze the intermolecular hydroamination of alkynes with sterically hindered primary amines to give enamines or their tautomeric imines (e.g., Eq. 4.77) [126]. 

Scheme 4-15 Catalytic cycle for the zirconium(bisamide)-catalyzed hydroamination of alkynes...

Although zirconium bisamides Cp2Zr(NHAr)2 do not catalyze the hydroamination of alkenes (see above), they are catalyst precursors for the hydroamination of the more reactive double bond of allenes to give the anti-Markovnikov addition product (Eq. 4.96) [126]. 

The bisbenzotriazolides of terephthalic acid or isophthalic acid react with 2-amino-ethanol to give bisamides selectively in high yield 961... 

The carboxylic groups of hemin are successfully converted into a bisamide by means of ImCSIm without affecting other functional groups of the hemin[127] (see also Table 4—2 in Section 4.1.3) ... 

The water exchange rate is hardly affected by substituents which do not directly interfere in the inner coordination sphere. Different bisamide DTPA derivatives have similar exchange rates.28-30 Substituents on the carbon backbone of DTPA also have little influence on the water-exchange kinetics.31 38 39... 

Gd(DTPA-bisamide)-PEG copolymers52 are also flexible, which explains their low relaxivity. A combined nO NMR, EPR, and NMRD study performed on [Gd(DTPA-BA)-PEG]x concluded that the effective rotational correlation time in the long polymer chain is not higher than that of the same Gd111 monomer unit, Gd(DTPA BMA) restricted to rotate around a single axis (tr for the polymer equals three times the rR for the monomer).52 An interesting feature of this... 

We should note that the water exchange rate remains relatively constant on introducing different substituents on the ligand, which do not directly interfere in the inner coordination shell. Similar rates have been reported for the different bisamide DTPA derivatives (57,59,60,68). Even bulky substituents on the carbon backbone of the DTPA had limited influence on the water... 

Figure 7.21 indicates the several neutral complexes used as MRI imaging agents. Neutrality is accomplished through bisamide substituents on DTPA [Gd(DTPA-BMA)(H20)], Omniscan (Figure 7.21A,B) or via the cyclic ligand HP-D03A [Gd(HP-D03A)(H20)], ProHance (Figure 7.21C.D).

Structures of these unusual aminal bisamides were determined by spectroscopic evidence and chemical degradations. The study of the constituent of A. 

---