Ureas nitroso

Summary MON is prepared by nitrating maltose with 99% nitric acid in the presence of urea, followed by the presence of fuming sulfuric acid. The urea is added to form a urea nitroso intermediate, which aids in the nitration of the maltose. After the reaction, the mixture is refluxed for a short period, and then drowned into ice water to precipitate the product. Recrystallization yields a purity of 99%. 

Nitrocarboxylic acids Nitrodiazome thanes Nitro derivatives of urea N,/V-bis(, p, )-t initrocthyl urea Nitroso compounds... 

Before coupling, excess nitrous acid must be destroyed. Nitrite can react with coupling components to form nitroso compounds causiag deHterious effects on the final dyestuff. The presence of nitrite can be detected by 4,4 -diamiQO-diphenyHnethane-2,2 -sulfone [10215-25-5] (Green reagent) or starch—iodide. Removal of nitrite is achieved by addition of sulfamic acid or urea [57-13-6], however, sulfamic acid [5329-14-6] has been more effective ia kinetic studies of nine nitrous acid scavangers (18). 

Nitrosourea derivatives are alkylating agents that include a nitroso (R-NO) group and a urea. 

Hard evidence for the first category seems to be nonexistent. An educated guess on the potential hazards would combine residue technology [how much of a secondary amine (or amide, urea, carbamate, etc.) might a person consume or otherwise be exposed to ], nitrosation chemistry (what would be the yield of in vivo nitrosation of the pesticide thus consumed ), and toxicology (what would be the toxicological effect and potency of the nitroso compound thus formed ). Frequently, these questions, which simplify to, "What dose—eg., in mg/kg—of a pesticide-derived nitroso compound might a person be exposed to and what would be the result if he were " are not carefully considered. 

OS 50] [R 17] [R 26] [P 36] By nitration of N,N -diefhyl-N-nitroso-urea the target compound for DNDA synthesis N,N -diethyl-N-dinitro-urea was achieved with 100% selectivity [38],... 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

Recently, diazocyclopropane (246) was synthesized from cyclopropyl N-nitroso urea (245) and its reaction with 1 has been studied. The cycloaddition gave a mixture of the unique primary adduct 248 together with the [3]-tri-angulane (247) derived from N2 extrusion (Scheme 40) [62]. 

Into a 3-1., three-necked flask (Note 1) equipped with a reflux condenser and an efficient stirrer is placed 11. of absolute (99.8%) ethanol. To this is added 39.4 g. (1.72 g. atom) of sodium metal, and, after solution is complete (Note 2), 91.5 ml. (97.2 g., 0.86 mole) of ethyl cyano-acetate (Note 3) and 51.5 g. (0.86 mole) of urea are added. The mixture is heated under reflux on a steam bath with vigorous stirring for 1 hours. After about 2 hours, the reaction mixture becomes practically solid, and the stirrer may have to be stopped. At the end of the reac-I ion time, 1 1. of hot (80°) water is added to the reaction mixture, and si i rring is resumed. After complete solution has taken place, the stirred mixture is heated at 80° for 15 minutes and is then neutralized to litmus with glacial acetic acid (Note 4). Additional glacial acetic acid (75 ml.) is then added, followed by cautious addition of a solution of 64.8 g. (0.94 mole) of sodium nitrite dissolved in 70 ml. of water. The rose-red nitroso compound separates almost immediately as an expanded precipitate which almost stops the stirrer. After a few minutes the ni-... 

Enol ether additives were used to probe the protonation of 3-cyclopen-tenylidene (127). Treatment of A-nitroso-A-(2-vinylcyclopropyl)urea (124) with sodium methoxide generates 2-vinylcyclopropylidene (126) by way of the labile diazo compound 125 (Scheme 25). For simplicity, products derived directly from 126 (allene, ether, cycloadduct) are not shown in Scheme 25. The Skat-tebpl rearrangement of 126 generates 127 whose protonation leads to the 3-cyclopentenyl cation (128). In the presence of methanol, cyclopentadiene (130) and 3-methoxycyclopentene (132) were obtained.53 With an equimolar mixture of methyl vinyl ether and methanol, cycloaddition of 127 (—> 131)... 

Experimental studies showed antitumoral effects of raloxifene in different in vitro preparations and animal models. Raloxifene has been able to inhibit the mitogenic effect induced by estrogens on ZR-75-1 cells, an estrogen responsive human breast cancer cell line (Poulin et al. 1989). In a well-accepted rat model of breast cancer induced by nitroso-methyl urea (NMU) raloxifene significantly suppressed the development of breast tumors and acted synergistically with 9 cis-retinoic acid (Anzano et al. 1996). 

Thus, heptafulvalene (522) was isolated in 33 and 65% yield after thermolysis of 517 in diglyme and its photolysis in THF, respectively [193]. An almost quantitative yield of 522 resulted when a mixture of 1-, 2- and 3-chloro-l,3,5-cycloheptatriene (518a) was treated with KOtBu in THF [206]. Even on variation ofthe concentration of the starting material and the temperature of the reaction, 522 turned out to be the exclusive product [207]. Also, the treatment of (trimethylsilyl)tropylium tetrafluoro-borate (519) with tetrabutylammonium fluoride [208] and the gas-phase pyrolysis of 7-acetoxynorbornadiene and 7-acetoxy-l,3,5-cycloheptatriene [209] afforded high yields of 522. Further, 522 was observed on FVT of N-nitroso-N-(7-norbornadienyl)-urea at 350 °C, which is believed to be converted into 7-diazonorbornadiene initially. Its decomposition should proceed via 7-norbornadienylidene to bicyclo[3.2.0]hepta-l(2),3,6,-triene (514) (Scheme 6.103) and then on to 5 [210]. The intermediacy of 514 is also suspected in the formation of 522 from 7-acetoxynorbornadiene. 

Hydrazine salts have been prepared by the action of hypochlorites on ammonia1 or urea 2 by the hydrolysis of salts of sulfohydrazimethylene disulfonic acid 3 by the hydrolysis of triazoacetic acid 4 by the reduction of diazoacetic ester 5 by the reduction of nitroguanidine followed by hydrolysis 6 by the reduction of the nitroso derivatives of hexamethylene tetramine 7 by the reduction of nitrates or nitrites with zinc in neutral solution 8 by the action of sodium bisulfite on hyponitrous acid... 

Guanidines have been prepared by the reaction between an amine, or an amine salt, and a host of other reagents, such as a thiourea in the presence of lead or mercuric oxide [83, 157, 158], carbodi-imides [140, 174, 175],calcium cyanamide [176, 177], isonitrile dichlorides [178—180], chloroformamidines [181], dialkyl imidocarbonates [182], orthocarbonate esters [183], trichloro-methanesulphenyl chloride [184], and nitro- or nitroso-guanidines [185-188]. Substituted ureas can furnish guanidines, either by treatment with amines and phosphorus oxychloride [189], or by reaction with phenylisocyanate [190] or phosgene [191]. 

Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

In view of the various possible pathways for nitrosation of amines as well as of amine derivatives (amides, ureas, carbamates, etc. ), it is not unexpected then for N-nitroso compounds to be found in many different areas of the human environment (11). It is possible that N-nitroso compounds may represent a carcinogenic exposure which most people experience on a daily basis. The list of items that have now been demonstrated to have measurable levels of various N-nitroso compounds present within them has grown considerably over the past decade (, 11, 12). A portion of this list would include air, water, soil, cheese, meats, fish, eggs. 

In studying the reactions betw nitroso-acylamines and diazo esters several expl compds were prepd. Some reactions involved explosion hazards) 4) F. Bucci, AnnChim (Rome), 41, 587-93(1951) CA 47, 3443 (1953) (Reactions of alkali nitrites with some otg amines, such as urea may result in explns) 5) G. Armistead, ChemEngt-Progress 48, 5-10(1952) CA 46, 2298 (1952) (A review of expln hazards)... 

Fig. 1.25. Regulation of alkylation repair in E. coK by methylation of the Ada protein. The effect of methylating agents, such as N-nitroso-N-methyl urea lead to the formation of methyl phospho-triesters (P-Me) of DNA, as well as various base adducts. The Ada protein possesses an N-termi-nal and a C-terminal domain. In one of the first steps of alkylation repair the methyl groups of the phosphotriester is transferred to the Ada protein. The Ada protein is methylated on a Cys residue at its N-terminal domain and thereby transformed into an active transcription activator. In its methylated form the Ada protein binds to the control region of various genes to stimulate their transcription. Among the genes under the control of the Ada protein are its own gene, as well others required for DNA repair (alkB, alkA). After Lindahl et al., 1988.

Substituted ureas have been nitrosated in aqueous systems primarily to obtain intermediates for the preparation of diazoalkanes [47, 48]. The base-induced decomposition of A-nitroso-A-(2,2-diphenylcyclopropyl) urea has been studied [49], and a series of l,3-bis(2-chloroethyl)-l-nitrosoureas and l,5-bis(2-chloroethyl)-l-nitrosobiurets have been studied as potential anticancer agents [50],... 

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