4 -Dimethylamino-4-piperidino

Dialkylaminosulfur trifluorides convert aldehydes and ketones into gtw-difluorides 1 under mild conditions.60-63 The reagent almost exclusively used is the commercially available diethyl-aminosulfur trifluoride (DAST, see Table 2). Other representatives of this class of compounds which have been employed as fluorinating agents for carbonyl compounds are dimethylamino-, piperidino-. and morpholinosulfur trifluoride, which are also commercially available. For the preparation and properties of dialkylaminosulfur trifluorides, see Vol. ElOa. p 406IT. 

OMe, or OH). A more efl cient approach to these 2-amino-heterocycles is the nitration of 2-dimethylamino(piperidino or morpholino)thiazoles, which proceeds in 70—75% yields. ... 

Reactions of polyhydroxyl compounds such as carbohydrates with DAST lead to replacement of one or two hydroxyl groups by fluorine, more fluorine atoms are not introduced even when a large excess of the reagent is used [132, 139, 147] Although diethylaminosulfur tnfluonde (DAST) is the most popular, other dialkylaminosulfuranes, such as diisopropylamino- [95] pyrrolidino [95 109 /27], dimethylamino- [148], piperidino- [148] and particularly morpholinosulfur trifluonde [148,149, ISO], are also used as fluonnating agents to convert alcohols into fluorides... 

Recently195, the hydrogen bond basicity scale (p.K hb as logarithm of the formation constant of 4-fluorophenol/base complexes in carbon tetrachloride, equilibrium 21) has been measured for several nitro derivatives (nitromethane, nitrobenzene, IV-nitrocamphorimine, 2-nitropropane, 4-nitro-o-xylene, 4-nitroanisole, lV,./V-diethyl-4-nitroaniline, l-dimethylamino-2-nitroethylene, l-piperidino-2-nitroethylene) ... 

Complex 1 1 is considered the only complex present, but the hydrogen bond may be either two (76) or three center (77). Nitroenamines are more prone to complex with 4-fluorophenol than the nitroanilines and they form the strongest hydrogen bond presently known for nitro-bases. In particular, l-piperidino-2-nitroethylene (78) and 1-dimethylamino-2-nitroethylene (79) (both in E form) present a hydrogen bond basicity comparable to that of tributylamine. 

An amino alcohol was found to accelerate the addition reaction of diethlylzinc to aldehyde [8], and then chiral amino alcohols were proved to be efficient chiral catalysts for asymmetric alkylation by using dialkylzinc reagents [9], Oguni reported a remarkable asymmetric amplification in chiral amino alcohol-promoted alkylation (Scheme 9.4). In the presence of (-)-l-piperidino-3,3-dimethyl-2-butanol (5) of 11% ee, benzaldehyde is alkylated enantioselectively to give (/ )-l-phenylpropanol with 82% ee [10]. Asymmetric amplification was also observed by Noyori using partially resolved (2.S )-3-exo-(dimethylamino)isobomeol (6) [11]. 

BENZIMIDAZOLE, 1-(2- (DIMETHYLAMINO)-1-METHYLETHYL) -2- (2-PIPERIDINO)ETHYL-, HYDROCHLORIDE... 

Bromo- (35, R = Br) with dimethylamine gave 4-dimethylamino-l,6-naphthyr-idine (35, R = NMe2) (neat reactants, 135°C, sealed, 16 h %)1057 but 4-chloro- (35, R = C1) gave 4-piperidino-l,6-naphthyridine [35, R = N(CH2)5] apparently under milder conditions (neat reactants, 95°C, 5 min %)1067 4-chloro-3-nitro-l,6-naphthyridine (36, R = C1) gave 3-nitro-l,6-naphthyridina-mine (36, R = NH2) (NH3/MeOH, 110°C, sealed, 4h 75%).819... 

Photochromic l-acetoxy-2-piperidino- and l-acetoxy-2-dimethylamino-9,10-anthraquinone also manifested photodegradation.28 The mechanism of these irreversible photochemical transformations includes intermediate 1,10-anthraquinone, which exhibited the photochemical transformations well known for anthraquinones with dialkylamino substituents adjacent to the carbonyl group. 

The sp3 - sp2 hybridization change is shown by similar examples to be more facile for a dimethylamino nitrogen than for a piperidino nitrogen. Thus, the poorer A-basicity of compound 4 relative to 2 is apparently more than balanced by a relative lack of conformational problems upon rehybridization. 

The structure of the basic side chain at N-l is 2-diethylaminoethyl for optimal activity although high activities are achieved with other basic groups such as 2-dimethylamino- and 2-piperidino-ethyl (see 4). Chain lengthening drastically reduces activity. The superiority of NEt, over NMe2 in this respect is in sharp contrast to other analgesics that carry noncyclic NR2 basic functions such as methadone (p. 307). 

Ammoninm (Piperidino-methyl)-trimethyl- -bromid E16a, 1008 (N-Aminomethylier.) Formamidinium N,N -Dimethyl-N,N -dipropyl-(iodid) E5, 94 (N-Alkylier.) N,N,N, N -Tetraethyl- (methylsulfat) E5, 90 (OR - NR2) Piperidinium l-(Dimethylamino-methyl)-l-methyl- -bromid E16a, 1008 (N-Aminomethylier.)... 

---