['CHARGE', 'NUMBER:', '2500', 'PROJECT', 'TITLE:', 'Synthesis', 'of', 'Tobacco', 'Additives', 'PROJECT', 'LEADER:', 'Jeffrey', 'I.', 'Seeman', 'PERIOD', 'COVERED:', 'April', '1-30,', '1982', 'DATE', 'OF', 'REPORT:', 'May', '10,', '1982', 'I.', 'Flavor', 'Chemistry', 'We', 'are', 'in', 'the', 'process', 'of', 'examining', 'the', 'relationship:', 'between', 'odor', 'and', 'structure', 'for', 'tobacco', 'flavorants', 'and', 'related', 'compounds.+~?', 'Pyridines', 'and', 'pyrazines', 'are', 'interesting', 'molecules', 'for', 'these', 'types', 'of', 'studies.', 'because', 'of', 'their', 'importance', 'to', 'tobacco', 'flavor', 'and', 'wide', 'range', 'of', 'substituent', 'patterns', 'possible.', 'It', 'is', 'well', 'known', 'that', 'pyridime', 'and', 'benzene', 'have', 'quite', 'different', 'odors.', 'Recently', 'we', 'observed', 'that', '2,6-', 'diisopropylpridine', '(1)', 'and', 'm-diisopropyl-', 'benzene', '(2)', 'have', 'very', 'similar', 'odors.?', 'Based', 'on', 'our', 'structure-activity', 'studies', 'in', 'the', 'nicotine', 'field,', 'we', 'tentatively', 'concluded', 'that', 'nitrogen', 'accessibility', 'was', 'an', 'important', 'factor', 'in', 'pyridine', 'and', 'pyrazine', 'odor', 'characteristics.', 'To', 'test', 'this', 'hypothesis,', 'we', 'have', 'been', 'preparing', 'a', 'series', 'of', '2,6-dialkylpyridines', '3,', 'and', 'm-dialkylbenzenes', '4', 'where', 'the', 'substituents', 'can', 'be', 'the', 'same', 'or', 'different.', 'We', 'have', 'almost', 'completéd', 'the', 'synthesis', 'of', 'this', 'series', 'of', 'compounds.!', '(GY', 'd', ' ', 'Op', 'R,', '»Ro=Me', ',Et,i-Pr,t-Bu', 'This', 'month', 'we', 'prepared', '2-tert-butyl-6-methyIpyridine', '(5)', 'by', 'the', 'rather', 'unusual', 'reaction', 'of', 'isopropyl!', 'pivalamide', 'with', 'phenyl', 'acetamide.', 'We', 'also', 'prepared', '2-isopropyl-6-methylpyridine', '(6)', 'by', 'reacting', '2-picoline', 'with', 'isopropyllithium', 'followed', 'by', 'careful', 'chromatographic', 'purification.', 'We', 'have', 'begun', 'the', 'synthesis', 'of', 'm-tert-buty]isopropy]', 'benzene', '(7)', 'by', 'reacting', 'm-bromoacetophenone', 'with', 'methy]', 'magnesiumbromide', 'to', 'furnish', 'the', 'related', 'tertiary', 'alcohol', 'which', 'will', 'be', 'dehydrated;', 'subsequently,', 'the', 'bromine', 'will', 'be', 'converted', 'to', 'a', 'tert-butyl]', 'group.', '?', 'esozezezoz']